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Puech, Alain, and Bibiana Quiterio-Mendoza. "Caractérisation des massifs rocheux pour le dimensionnement de pieux forés en mer." Revue Française de Géotechnique, no. 158 (2019): 5. http://dx.doi.org/10.1051/geotech/2019011.
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Les pieux forés et cimentés sont une solution envisagée comme fondations de structures marines dans les roches tendres à dures rencontrées au large des côtes françaises. Le dimensionnement des pieux au rocher est un exercice délicat. L’exécution de séries d’essais de cisaillement d’interface à rigidité constante (dits essais CNS) est considérée comme une approche réaliste pour estimer la résistance au cisaillement de l’interface roche-ciment sous chargements statiques et cycliques. Les essais CNS sont conditionnés par deux paramètres clés qui sont liés aux caractéristiques du massif rocheux : la rigidité du massif et la géométrie de l’interface roche-ciment. Cet article propose une approche méthodologique pour estimer ces paramètres.
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Habib, Pierre. "Utilisation des roches tendres et des roches dures pour l'isolement des dechets radioactifs." Geotecnia, no. 71 (June 20, 1994): 01–24. http://dx.doi.org/10.14195/2184-8394_71_1.
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Le principe de l'isolement des déchets radioactifs dans une formation géologique est simple. L'eau étant le principal vecteur de la migration des ions, il suffit de placer les radionucléides en profondeur au sein d'un milieu tres peu perméable, dans une région ou le gradient hydraulique est tres petit - ce qui signifie, en général, sous une plaine - pour faire en sorte que les nucléides ne puissent s'échapper et rejoindre la biosphere qu'après un temps suffisamment long pour qu'ils aient perdu l'essentiel de leur activité, ce qui peut prendre 100 000 ou 1000000 d'années. II faut ensuite que le milieu géologique garde son intégrité pendant toute cette durée; son ancienneté est évidemment garante de son avenir, mais il faut que les mouvements tectoniques, l'érosion, le climat ne viennent pas altérer son existence ni affecter ses structures. Avant ce long terme pour les déchets de haute activité, l'épisode thermique, avec les dilatations puis les contractions qu'il impose, est susceptible de bousculer les formations géologiques, et les effets thermomécaniques doivent être examinés avec soin pour chaque milieu hôte envisagé, avec une estimation de leurs propriétés rhéologiques à long terme et à tres long terme, ce qui est assez inhabituel en Mécanique des Roches. Le cas des milieux plastiques (sei, argile) et celui des milieux cassants (granite, schiste) posent des problemes différents et doivent être analysés indépendamment.
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Meilliez, Francis, and Jean-Jacques Belin. "Territoire et matériaux, géologie et histoire : visite en pays de Pévèle." Annales de la Société géologique du Nord - (2e Série), Tome 29, no. 29 (December 1, 2022): 121–32. http://dx.doi.org/10.54563/asgn.1932.
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Un territoire, en surface, est déterminé par sa composition et sa structure : la Pévèle rassemble des roches tendres (argiles, sables) au cœur d’une synforme largement ouverte, esquissée par les niveaux crayeux du Crétacé supérieur, discordants sur un socle paléozoïque, structuré par l’orogenèse varisque. L’observation d’églises de plusieurs villages conduit à s’interroger sur la provenance des pierres dures qui ont été nécessaires, et sur leurs conditions d’acheminement il y a environ 1 000 ans.
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Lasm, Théophile, and Moumtaz Razack. "Lois d'échelle dans la fracturation de roches dures cristallines et dans le réseau hydrographique associé." Comptes Rendus de l'Académie des Sciences - Series IIA - Earth and Planetary Science 333, no. 4 (August 2001): 225–32. http://dx.doi.org/10.1016/s1251-8050(01)01632-9.
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Pelegrin, Jacques, Yoshihiro Aita, and Ishiro Yamanaka. "Yokomichi : Une collection du Paléolithique supérieur du Japon abordée selon un œil technologique français." Journal of Lithic Studies 4, no. 2 (September 15, 2017): 447–73. http://dx.doi.org/10.2218/jls.v4i2.2551.
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Depuis les années 1970, l’étude des collections lithiques préhistoriques a vécu en France une profonde modernisation. André Leroi-Gourhan, d’abord intéressé par les techniques traditionnelles, prit pour objectif d’appréhender les activités techniques menées dans un site par un groupe préhistorique, dans une perspective ainsi dénommée « palethnologique ». Il a aussi promu la notion de chaîne opératoire introduite auparavant par Marcel Mauss. Mais ce sont les expérimentateurs de la taille des roches dures, F. Bordes et J. Tixier, qui vont permettre d’enrichir cette notion de ses applications concrètes. J. Tixier, surtout, stabilise la terminologie de la pierre taillée, et systématise la « lecture technologique » qui permet de reconstituer mentalement le déroulement du façonnage d’un outil ou du débitage d’un nucléus. Il introduit aussi une distinction fondamentale entre « méthode » (la démarche -l’agencement des enlèvements successifs- suivie pour atteindre le but de la chaîne opératoire : un type ou une classe de produits) et « technique(s) » (qui réfère aux modalités pratiques d’exécution des enlèvements).
Sur cette base, dès 1980, Tixier et collègues introduisent les notions d’économie des matières premières, du débitage et de l’outillage, corollaires de la notion de règles de gestion. La notion d’intention -entre débitage, supports et (certains) outils- apparaît également, fondant le postulat selon lequel les modalités de la taille sont cohérentes avec la morphologie des produits recherchés. C’est ce postulat que suit la démarche française en technologie lithique : percevoir -comprendre- les intentions de la production lithique, avant de classer et de mesurer.
Cette démarche est ensuite appliquée à la collection lithique de Yokomichi (Dept de Yamagata, NE de Honshu), à débitage laminaire mais antérieure à la production de lamelles, ainsi datable d’environ 18 000 BP. On perçoit d’abord qu’y coexistent deux débitages laminaires : l’un de lames légères et rectilignes à petit talon, tirées de nucléus étroits, et l’autre de fortes lames à talons épais débitées de nucléus plus larges. Parmi les outils retouchés, ce sont les quelques « couteaux de Sugikubo » (des pointes à dos élancées de profil rectiligne) dont les supports correspondent à l’intention première du débitage étroit, quelques autres outils étant réalisés sur des supports de second choix. Un tel couteau de Sugikubo, dans une collection similaire, présente une fracture à longue languette inverse qui suggère fortement qu’il s’agit en fait, au moins pour partie, de pointes de projectile. Le débitage large, lui, avait pour intention première l’obtention de grandes lames pointues, très difficiles à réaliser, tandis que ses nombreux produits de second choix et d’aménagement restent bruts (utilisables comme couteaux) ou se retrouvent dans les « burins de Kamiyama » (en fait, de très probables couteaux ravivés comme les couteaux de Kostienki).
Une expérimentation montre que les deux débitages sont réalisés par percussion directe à la pierre tendre, mais selon des modalités distinctes : par percussion tangentielle pour les lames légères à petit talon, par percussion en retrait pour les lames plus fortes à gros talon.
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Di Bernardini, Gian Luigi. "Roger-Yves Roche, Photofictions. Perec, Modiano, Duras, Goldschmidt, Barthes." Studi Francesi, no. 163 (LV | I) (May 1, 2011): 215. http://dx.doi.org/10.4000/studifrancesi.6102.
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Pinto, Lívia Aparecida Gonçalves, and José Margarida da Silva. "Aprendizagem de máquina na determinação de parâmetros de resistência de filitos brandos." Research, Society and Development 12, no. 1 (January 11, 2023): e19012139693. http://dx.doi.org/10.33448/rsd-v12i1.39693.
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Aspectos geológico-geotécnicos devem ser levados em consideração desde os estudos de exploração geológica, em empreendimentos mineiros. Alguns acidentes ocorridos em minas, nas últimas décadas, poderiam ser evitados, caso as condições geológico-geotécnicas do maciço fossem compreendidas. Ainda existe grande dificuldade em se classificar alguns tipos de rochas, sobretudo as rochas consideradas brandas, por meio dos sistemas de classificação geomecânica conhecidos. A grande maioria das classificações existentes foram desenvolvidos baseadas em características de rochas duras. Para maciços rochosos pouco resistentes, é necessário adaptar os sistemas atuais ou desenvolver novos sistemas de classificação, que sejam específicos para maciços rochosos brandos praticamente contínuos. O objetivo deste artigo é propor a utilização de técnicas de Aprendizagem de Máquina para previsão de parâmetros geotécnicos de rochas brandas, especialmente filito. Foram utilizados dados históricos de resultados de ensaios geotécnicos de laboratório de rochas de minas do Quadrilátero Ferrífero, que, por meio da interação otimizada, e com auxílio de técnica de Inteligência Artificial, como a Rede Neural Artificial e Regressão Linear, sejam capazes de gerar resultados de interesse para análises de estabilidade e modelagens geotécnicas. Das técnicas utilizadas, resultados mostraram que o método de Regressão Linear se mostrou satisfatório na determinação de parâmetros de resistência de filitos brandos e com boas perspectivas de ampliação e utilização para outros parâmetros, assim como outros tipos de rochas.
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Ccopa Ybarra, Luis Antonio, Andre Luis Molisani, Daniel Rodrigues, and Humberto Naoyuki Yoshimura. "O processo de infiltração em ferramentas de perfuração de rochas com o uso dos pós de tungstênio e carboneto de tungstênio: as características e resultados da microestrutura e dureza do cermet." Exacta 7, no. 1 (July 6, 2009): 57–76. http://dx.doi.org/10.5585/exacta.v7i1.1377.
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No processo de infiltração para a fabricação de ferramentas de perfuração de rocha (coroa), analisaram-se três procedimentos com utilização de três pós de matrix: dois à base de carbonetos de tungstênio e um à base de tungstênio, pelos quais se investigaram os efeitos de suas características, os da microestrutura e a dureza de um cermet. As amostras na forma de coroa foram preparadas pela técnica da infiltração, em que o pó matrix, compactado em um molde de grafita, montado com um tubo (carcaça) de aço, foi infiltrado por uma liga de cobre para consolidar o metal duro e ligá-lo à carcaça de aço. Os pós e/ou as seções dos metais duros foram caracterizados por meio de análise química, difração de Raios X, análise granulométrica, densidade, microscopia óptica e eletrônica de varredura, espectroscopia por dispersão de energia e análise térmica diferencial. Além das fases predominantes de carboneto de tungstênio e/ou tungstênio, os pós apresentaram uma pequena fração de partículas de liga metálica. Complementando o estudo iniciado em artigo já publicado, os resultados da análise microestrutural dos metais duros foram correlacionados com as características químicas, de fases, granulométricas, morfológicas e de compressibilidade dos pós investigados. Determinaram-se as micro e macrodurezas dos metais duros, e realizou-se a análise microestrutural da região da interface entre os metais duros e a carcaça de aço e também a diferença de temperatura no processo de infiltração em cada pó de matrix.
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Ccopa Ybarra, Luis Antonio, Andre Luis Molisani, Daniel Rodrigues, and Humberto Naoyuki Yoshimura. "O processo de infiltração em ferramentas de perfuração de rochas com o uso dos pós de tungstênio e carboneto de tungstênio: as características e resultados da microestrutura e dureza do cermet DOI: 10.5585/exacta.v7i1.1377." Exacta 7, no. 1 (July 6, 2009): 57–76. http://dx.doi.org/10.5585/exactaep.v7i1.1377.
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No processo de infiltração para a fabricação de ferramentas de perfuração de rocha (coroa), analisaram-se três procedimentos com utilização de três pós de matrix: dois à base de carbonetos de tungstênio e um à base de tungstênio, pelos quais se investigaram os efeitos de suas características, os da microestrutura e a dureza de um cermet. As amostras na forma de coroa foram preparadas pela técnica da infiltração, em que o pó matrix, compactado em um molde de grafita, montado com um tubo (carcaça) de aço, foi infiltrado por uma liga de cobre para consolidar o metal duro e ligá-lo à carcaça de aço. Os pós e/ou as seções dos metais duros foram caracterizados por meio de análise química, difração de Raios X, análise granulométrica, densidade, microscopia óptica e eletrônica de varredura, espectroscopia por dispersão de energia e análise térmica diferencial. Além das fases predominantes de carboneto de tungstênio e/ou tungstênio, os pós apresentaram uma pequena fração de partículas de liga metálica. Complementando o estudo iniciado em artigo já publicado, os resultados da análise microestrutural dos metais duros foram correlacionados com as características químicas, de fases, granulométricas, morfológicas e de compressibilidade dos pós investigados. Determinaram-se as micro e macrodurezas dos metais duros, e realizou-se a análise microestrutural da região da interface entre os metais duros e a carcaça de aço e também a diferença de temperatura no processo de infiltração em cada pó de matrix.
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Higham, Charles. "Bérénice Bellina. Cultural Exchange between India and Southeast Asia: production and distribution of hard stone ornaments (VI c. BC – VI c. AD)/Echanges culturels entre l'Inde et l'Asie du Sud-Est: production et distribution des parures en roches dures du VIè siècle avant notre ère au VIè siècle de notre ère. 126 pages, 3 maps, CD-ROM. 2007. Paris: Maison des sciences de l'homme/Epistèmes; 978-2-7351-1127-5 paperback €29." Antiquity 82, no. 315 (March 1, 2008): 230–31. http://dx.doi.org/10.1017/s0003598x00096691.
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Nascimento, Vandetania Xavier, Claúdia Maria Salvador Vasconcelos, and Marcela Rejane Silva Ferreira. "ESTUDO DA EROSÃO MARINHA NA PRAIA DE BARRA DE MAXARANGUAPE/RN." Revista da Casa da Geografia de Sobral (RCGS) 21, no. 2 (September 30, 2019): 33–37. http://dx.doi.org/10.35701/rcgs.v21n2.598.
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A zona costeira é uma área que está em um equilíbrio dinâmico em decorrência da intermediação de fatores naturais e antrópicos, no entanto as consequências nocivas promovidas pelos agentes naturais tem sua dinâmica própria, e causa múltiplas reações que independem da ação humana, contudo, muitas vezes acelerados ou aumentados pela intervenção do homem. Geologicamente, toda faixa costeira do estado potiguar é constituída por rochas sedimentares de idade Cretácea, recoberta por rochas da Formação Barreiras e sedimentos Quaternários, como dunas, rochas praiais, terraços marinhos e aluvionares com coberturas arenosas diversas. Este trabalho busca entender os efeitos causados pela erosão costeira na vida dos moradores locais. Para atingir os objetivos propostos foi realizado uma visita in loco, onde aplicamos uma entrevista com 10 pescadores da área, os resultados obtidos demostram que a erosão da praia tem provocado o desequilíbrio na economia local, desapropriação de residências e pousadas, desemprego e a ausência de turismo. O assoreamento no estuário do rio Maxaranguape, tem alterado a dinâmica das embarcações pesqueiras que ali ficam atracadas, prejudicando os rendimentos financeiros dos pescadores.Palavras-chave: Maxaranguape; Zona costeira; Erosão ABSTRACT The coastal zone is an area that is in a dynamic equilibrium due to the effect of natural and anthropic factors; however, the harmful consequences promoted by natural agents have their own dynamics, and cause multiple reactions that are independent of human action, many times increased by man's intervention. Geologically, all the coastal zone of the Potiguar state is constituted by sedimentary rocks of Cretaceous age, covered by Rocks of the Barreiras Formation and Quaternary sediments, like dunes, beach rocks, marine and alluvial terraces. This work want to understand the effects caused by coastal erosion on the lives of local residents. To achieve the proposed objectives, an on-site visit was carried out, where we interviewed ten fishermen from the area. The results show that beach erosion has caused an imbalance in the local economy, expropriation of homes and inns, unemployment and lack of tourism. The siltation in the estuary of the Maxaranguape river has altered the dynamics of the fishing boats that are there, damaging the financial income of the fishermen.Keywords: Maxaranguape; Coastal zone; Erosion.
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Ritschl, V., T. Stamm, D. Aletaha, J. W. Bijlsma, P. Boehm, R. Dragoi, E. Dures, et al. "SAT0608-HPR EULAR POINTS TO CONSIDER FOR THE DETECTION, ASSESSMENT AND MANAGEMENT OF NON-ADHERENCE IN PEOPLE WITH RHEUMATIC AND MUSCULOSKELETAL DISEASES." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1264.2–1264. http://dx.doi.org/10.1136/annrheumdis-2020-eular.787.
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Background:Non-adherence to medication and non-pharmacological interventions precludes reaching an optimal outcome. 30 to 80% of patients with rheumatic and musculoskeletal diseases (RMDs) do not adhere to their recommended treatment regimens.Objectives:The objective of this EULAR task force was to establish recommendations/points to consider (PtC) for the detection, assessment and management of non-adherence in people with RMDs.Methods:A EULAR task force (TF) was established, and the EULAR standardised operating procedures for the development of PtCs were followed. The TF included rheumatologists, health professionals in rheumatology (HPRs), and patient-representatives from 12 countries. A systematic literature review of reviews was conducted in advance to support the TF in formulating the PtC. Agreement was obtained by Delphi technique in three rounds (0-10 rating scale).Results:A definition of adherence, 4 overarching principles and 9 PtC were formulated (table).Conclusion:The PtCs can help health-care providers to support people with RMDs to adhere to the agreed treatment plan.Table.Overarching principles and points to consider.Definition of AdherenceAdherence is defined as the extent to which a person’s behaviour corresponds with the agreed prescription.Overarching principlesAgreement1Adherence impacts the outcomes of people with RMDs.992Shared decision making is key, since adherence is a behaviour following an agreed prescription.963Adherence is influenced by multiple factors.984Adherence is a dynamic process that requires continuous evaluation.96Points to considerAgreement1All HCPs involved in the management of people with RMDs should take responsibility for promoting adherence.992Effective patient-health professional communication should be applied to enhance adherence.993Barriers and facilitators of adherence of a specific patient to a specific prescription should be appropriately evaluated.954Patient education should be provided for people with RMDs as an integral part of standard care.965Care should be tailored to patient preferences and goals to enhance adherence.986Adherence should be discussed regularly based on open questions and particularly when disease is not well controlled.997The HCP should explore which factors might negatively influence adherence, including: opportunity (e.g., availability or cost), capability, (e.g., memory problems), motivation (e.g., concerns).948Together with the patient, the HCP should tailor the approach to overcome individual barriers to adherence, e.g.,98- simplifying the regimen,- using reminders,- providing education,- discussing the patient’s beliefs on treatments.9When specific expertise or interventions for adherence are needed, they should be made available to patients.98HCP, health-care providers; RMDs, rheumatic and musculoskeletal diseasesDisclosure of Interests:Valentin Ritschl: None declared, Tanja Stamm Grant/research support from: AbbVie, Roche, Consultant of: AbbVie, Sanofi Genzyme, Speakers bureau: AbbVie, Roche, Sanofi, Daniel Aletaha Grant/research support from: AbbVie, Novartis, Roche, Consultant of: AbbVie, Amgen, Celgene, Lilly, Medac, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi Genzyme, Speakers bureau: AbbVie, Celgene, Lilly, Merck, Novartis, Pfizer, Sanofi Genzyme, UCB, Johannes WJ Bijlsma Grant/research support from: Roche, Speakers bureau: Roche, Lilly, Peter Boehm: None declared, Razvan Dragoi Speakers bureau: MSD, AbbVie, Novartis, Roche, Pfizer, Myllan, Sandoz, Emma Dures Grant/research support from: Independent Learning Grant from Pfizer, combined funding for a research fellow from Celgene, Abbvie and Novartis, Paid instructor for: A fee from Novartis to deliver training to nurses., Fernando Estévez-López: None declared, Laure Gossec Grant/research support from: Lilly, Mylan, Pfizer, Sandoz, Consultant of: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis, UCB, Annamaria Iagnocco Grant/research support from: Abbvie, MSD and Alfasigma, Consultant of: AbbVie, Abiogen, Alfasigma, Biogen, BMS, Celgene, Eli-Lilly, Janssen, MSD, Novartis, Sanofi and Sanofi Genzyme, Speakers bureau: AbbVie, Alfasigma, BMS, Eli-Lilly, Janssen, MSD, Novartis, Sanofi, Michal Nudel: None declared, Andrea Marques: None declared, Ellen Moholt: None declared, Bart van den Bemt Grant/research support from: UCB, Pfizer and Abbvie, Consultant of: Delivered consultancy work for UCB, Novartis and Pfizer, Speakers bureau: Pfizer, AbbVie, UCB, Biogen and Sandoz., Kirsten Viktil: None declared, Marieke Voshaar Grant/research support from: part of phd research, Speakers bureau: conducting a workshop (Pfizer), Annette de Thurah Grant/research support from: Novartis (not relevant for the present study)., Speakers bureau: Lily (not relevant for the present study)., Loreto Carmona Grant/research support from: Novartis Farmaceutica, SA, Pfizer, S.L.U., Merck Sharp & Dohme España, S.A., Roche Farma, S.A, Sanofi Aventis, AbbVie Spain, S.L.U., and Laboratorios Gebro Pharma, SA (All trhough institution)
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Burmester, G. R., J. M. Alvaro-Gracia, N. Betteridge, J. Calvo, B. Combe, P. Durez, R. J. O. Ferreira, et al. "THU0579 “EVOLVING THE MANAGEMENT OF RA” PROGRAMME: EDUCATIONAL TOOLS TO SUPPORT DAILY PRACTICE." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 531.1–531. http://dx.doi.org/10.1136/annrheumdis-2020-eular.1219.
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Background:The eRA (evolving the management of RA) programme was initiated in Europe to provide practical educational tools that address unmet needs in the management of rheumatoid arthritis (RA). Several eRA tools – covering early access to care, management of comorbidities, treat-to-target strategies, and patient empowerment – are available to the rheumatology community. Through ongoing activities, the eRA Steering Committee (SC) identified a need for tools on non-pharmacological management of RA.Objectives:To improve accessibility to eRA tools for rheumatology professionals; to review the evidence base of non-pharmacological interventions to create new eRA resources that may support management decisions.Methods:A web platform providing information on eRA programme and tools was developed in 2019. The platform collects survey-based metrics to quantify perception of eRA and use of eRA tools in clinical practice. Platform and tools are translated to further support access and use across Europe.To address unmet needs in non-pharmacological patient management, the eRA SC reviewed the core literature on agreed priority interventions, including physical activity, diet, patient education and self-management, psychosocial interventions, occupational therapy and orthotics, hand exercises, and hydrotherapy/balneotherapy. Available evidence for each intervention was assessed and graded according to the Oxford Centre for Evidence-based Medicine Levels of Evidence.Results:The eRA web platform is now live in 3 countries (www.evolvingthemanagementofRA.com), hosting translated copies of the eRA tools, with additional countries launching throughout 2020.From a review of core literature on non-pharmacological interventions, the eRA SC determined that strong evidence exists to support use of physical activity, patient education and self-management, psychosocial interventions, and occupational therapy and orthotics. Evidence was lacking or conflicting for diet and nutrition, hand exercises, and balneotherapy/hydrotherapy. A set of educational slides was produced by the eRA SC to summarise the evidence (Fig. 1) and provide top-line guidance on use of interventions in practice that should engage relevant members of the multi-disciplinary team. These slides are available through eRA dissemination activities.Conclusion:The eRA programme content is now freely available to health care professionals in several countries on a web platform, supported by translations of the eRA tools. An additional slide set on non-pharmacological management serves to further increase the practical guidance of this programme’s educational offering.Acknowledgments:The eRA programme is funded by Sanofi Genzyme. Programme direction and content creation are driven by an independent Steering CommitteeDisclosure of Interests:Gerd Rüdiger Burmester Consultant of: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Speakers bureau: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Jose-Maria Alvaro-Gracia Grant/research support from: Abbvie, Elli-Lilly, MSD, Novartis, Pfizer, Consultant of: Abbvie, BMS, Janssen-Cilag, Elli-Lilly, MSD, Novartis, Pfizer, Sanofi, Tigenix, Roche, UCB, Paid instructor for: Elli-Lilly, Pfizer, Roche, Speakers bureau: Abbvie, BMS, Janssen-Cilag, Elli-Lilly, Gedeon Richter, MSD, Novartis, Pfizer, Sanofi, Tigenix, Roche, UCB, Neil Betteridge Consultant of: Amgen, Eli Lilly and Company, Grunenthal, GSK, Sanofi Genzyme, Jaime Calvo Grant/research support from: Lilly, UCB, Consultant of: Abbvie, Jansen, Celgene, Bernard Combe Grant/research support from: Novartis, Pfizer, Roche-Chugai, Consultant of: AbbVie; Gilead Sciences, Inc.; Janssen; Eli Lilly and Company; Pfizer; Roche-Chugai; Sanofi, Speakers bureau: Bristol-Myers Squibb; Gilead Sciences, Inc.; Eli Lilly and Company; Merck Sharp & Dohme; Pfizer; Roche-Chugai; UCB, Patrick Durez Speakers bureau: AbbVie, Bristol-Myers Squibb, Celltrion, Eli Lilly, Pfizer, Sanofi, Ricardo J. O. Ferreira Grant/research support from: Abbvie, Consultant of: Sanofi Genzyme, Amgen, MSD, Paid instructor for: UCB, Bruno Fautrel Grant/research support from: AbbVie, Lilly, MSD, Pfizer, Consultant of: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celgene, Lilly, Janssen, Medac MSD France, Nordic Pharma, Novartis, Pfizer, Roche, Sanofi Aventis, SOBI and UCB, Annamaria Iagnocco Grant/research support from: Abbvie, MSD and Alfasigma, Consultant of: AbbVie, Abiogen, Alfasigma, Biogen, BMS, Celgene, Eli-Lilly, Janssen, MSD, Novartis, Sanofi and Sanofi Genzyme, Speakers bureau: AbbVie, Alfasigma, BMS, Eli-Lilly, Janssen, MSD, Novartis, Sanofi, Carlomaurizio Montecucco: None declared, Mikkel Ǿstergaard Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Merck, and Novartis, Consultant of: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Sofia Ramiro Grant/research support from: MSD, Consultant of: Abbvie, Lilly, Novartis, Sanofi Genzyme, Speakers bureau: Lilly, MSD, Novartis, Andrea Rubbert-Roth Consultant of: Abbvie, BMS, Chugai, Pfizer, Roche, Janssen, Lilly, Sanofi, Amgen, Novartis, Tanja Stamm Grant/research support from: AbbVie, Roche, Consultant of: AbbVie, Sanofi Genzyme, Speakers bureau: AbbVie, Roche, Sanofi, Zoltán Szekanecz Grant/research support from: Pfizer, UCB, Consultant of: Sanofi, MSD, Abbvie, Pfizer, Roche, Novertis, Lilly, Gedeon Richter, Amgen, Peter C. Taylor Grant/research support from: Celgene, Eli Lilly and Company, Galapagos, and Gilead, Consultant of: AbbVie, Biogen, Eli Lilly and Company, Fresenius, Galapagos, Gilead, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer Roche, and UCB, Mart van de Laar Consultant of: Sanofi Genzyme, Speakers bureau: Sanofi Genzyme
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Tâmega, Frederico Tapajós de Souza, and Marcia Abreu de Oliveira Figueiredo. "DISTRIBUIÇÃO DAS ALGAS CALCÁRIAS INCRUSTANTES (CORALLINALES, RHODOPHYTA) EM DIFERENTES HABITATS NA PRAIA DO FORNO, ARMAÇÃO DOS BÚZIOS, RIO DE JANEIRO." Rodriguésia 56, no. 87 (May 2005): 123–32. http://dx.doi.org/10.1590/2175-78602005568709.
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RESUMO As algas calcárias incrustantes ocupam grande variedade de habitats nos substratos duros. Neste estudo as características morfológicas destas algas foram relacionadas à influência de fatores ambientais. Coletas foram realizadas na Praia do Forno (RJ) utilizando transectos de linha com 10 m de comprimento com 30 pontos aleatórios para quantificação das algas calcárias. Aspectos morfológicos externos foram observados no estereomicroscópio e seções histológicas preparadas para identificação dos grupos/táxons. Seis grupos morfo-funcionais foram identificados sendo quatro mais abundantes: Hydrolithon samoënse (Foslie) D. Keats & Y. Chamberlain dominou naregião do mesolitoral(53%)eno sublitoral(57-87%)junto à clorofícea Codium spongiosum Harvey e em locais desprovidos de outras algas, expostos à ação das ondas e alta densidade de ouriços herbívoros. Spongites sp. foi abundante próximo às fendas nas rochas do mesolitoral(39-40%). Lithophyllum sp. dominou desde o mesolitoral (44%) até o sublitoral junto à Codium (43-74%) e Sargassum (74-93%). Houve discreta variação temporal na distribuição de H. samoënse e Lithophyllum sp. Talos protuberantes em Lithophyllum dominaram em locais de maior sedimentação enquanto talos planos de H. samoënse e Spongites sp. dominaram em locais de maior herbivoria. A distribuição dos grupos morfo-funcionais nos diferentes habitats concorda com padrões associados aos distúrbios bióticos e abióticos, previstos para comunidades de costões rochosos.
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Castro, David Lopes de, João Andrade dos Reis Júnior, Washington Luiz Evangelista Teixeira, Victor De Albuquerque Silva, and Francisco Pinheiro Lima Filho. "GROUND-PENETRATING RADAR IMAGING TECHNIQUES APPLIED IN 3D ENVIRONMENT: EXAMPLE IN INACTIVE DUNES." Revista Brasileira de Geofísica 32, no. 2 (June 2, 2014): 273. http://dx.doi.org/10.22564/rbgf.v32i2.482.
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ABSTRACT. The increased use of Ground-Penetrating Radar (GPR) in several areas of knowledge has introduced an impressive number of new methodologicalprocedures, adapted from other areas, such as seismic reflection, or developed specifically for the GPR. A summary of the advances in acquisition, processing andinterpretation of GPR data is presented in this paper. Some of the techniques were applied to a 3D GPR survey in a study area, whose substrate is composed bysedimentary sequences of paleodunes or inactive dunes, located in the outer courtyard of the Department of Geology (DEGEO) of the Universidade Federal do Rio Grandedo Norte (UFRN), Brazil. A GPR cube was generated from a regular grid of GPR in-lines and cross-lines, spaced 0.5 m. A filtering routine was applied. For eachprocessing step, the changes in the signal content in the time and frequency domains were analyzed. Common midpoint (CMP) sections and hyperbolas of buried pipesconstrained the construction of a subsurface velocity model, allowing the migration and time/depth conversion of the radargrams. Analysis of instantaneous, amplitude,and geometrical attributes and concepts of seismic stratigraphy were applied in the migrated GPR cube to define five stratigraphic sequences and their paleo-reliefs.Based on the radar facies internal geometry, some considerations were established about the depositional environment of the surveyed area.Keywords: GPR, 3D imaging, processing, attribute analysis.RESUMO. A expansão do uso do GPR nas mais diversas áreas do conhecimento tem contribuído para o desenvolvimento de novos procedimentos metodológicos,decorrentes da adaptação de outros métodos geofísicos, principalmente a sísmica de reflexão, ou desenvolvidos especialmente para o GPR. Uma síntese dos avanços nas etapas de aquisição, processamento e interpretação é descrita no presente artigo. Algumas das técnicas analisadas foram aplicadas em dados GPR obtidos em umlevantamento realizado segundo uma malha retangular, em uma área de estudo situada no interior do campus da Universidade Federal do Rio Grande do Norte (UFRN).O substrato imageado é constituído por camadas de sedimentos arenosos siliciclásticos, de origem eólica costeira, depositados sobre rochas do Grupo Barreiras. Um volume GPR foi gerado a partir de uma malha regular de linhas longitudinais e transversais, espaçadas de 0,5 m. Uma rotina de filtragem dos dados GPR é proposta, sendo as alterações no conteúdo do sinal eletromagnético (EM) analisadas nos domínios do tempo e frequência para cada etapa do processamento. Seções de ponto médio comum (CMP) e hipérboles de tubulações soterradas permitiram a confecção de um modelo de velocidades da subsuperfície e a migração e conversão tempo/profundidade dos radargramas. Análise de atributos instantâneos, de amplitude e geométricos, além de técnicas de interpretação sismoestratigráficas foram aplicadas no volume GPR migrado para definir cinco sequências estratigráficas e seus paleorelevos. Com base nas geometrias internas das radarfácies, foram tecidasalgumas considerações sobre a geometria e arquitetura dos depósitos investigados.Palavras-chave: GPR, imageamento 3D, processamento, análise de atributos.
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Robson, J., C. Almeida, J. Dawson, E. Dures, R. Greenwood, C. Guly, S. Mackie, A. Bromhead, S. Stern, and M. Ndosi. "POS0003 DEVELOPMENT AND VALIDATION OF A DISEASE SPECIFIC PATIENT REPORTED OUTCOME FOR GIANT CELL ARTERITIS." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 214.2–214. http://dx.doi.org/10.1136/annrheumdis-2022-eular.1769.
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BackgroundGiant cell arteritis (GCA) is caused by inflammation of the blood vessels of the head and neck; patients can present with cranial, ocular or large vessel vasculitis involvement. Treatment is with glucocorticoids, steroid sparing agents and biologics to control inflammation and protect sight.ObjectivesThe aim of this study was to produce a validated disease specific PROM for patients with GCA, to capture the impact of GCA and its treatment on health-related quality of life.MethodsPatients with clinician- confirmed GCA from the UK, either diagnosed in the last three years or with a flare in the last year, were included in the survey. A longlist of 40 candidate questionnaire items, each with a 5-point Likert scale, had previously been developed, based on a qualitative study with patients from the UK and Australia [1]. In this cross-sectional survey, patients completed the 40-item draft GCA-PROM alongside EQ5D-5L, CAT-PRO5 and self-report of GCA disease activity. Rasch and factor analysis were used in an iterative manner to determine the underlying construct validity of the new PROM. Items were fitted to the Rasch model to determine its construct validity, reliability, unidimensionality and statistical sufficiency of the total score from the scale. Factor analysis was used to establishing factor structure. Item reduction decisions were be based on clinical importance, lack of fit to the Rasch model, and redundancy detected during principal component analysis. External validity was tested by comparing the scores of the newly validated GCA-PROM (i) in participants who self-identify as having ‘active disease’ versus patients ‘in remission’ (known groups validity) (ii) with scores derived from EQ5D-5L and CAT-PRO5 (convergent validity).ResultsThe survey included 428 patients; 327 (76%) cranial GCA, 114 (26.6%) large vessel vasculitis and 142 (33.2%) ocular involvement. 285 (67%) of participants were female with a mean age (SD) of 74.2 (7.2). 167 (39%) temporal artery biopsies and 177 (41.4%) temporal artery ultrasounds, and 51 (11.9%) Positron Emission Tomography and Computed Tomography (PET-CT)s were reported as positive. 108 (25%) received second-line immunosuppressants, and 34 (7.9%) anti-IL6 therapy. Active disease was reported in 197 (46%). Four factors (domains) were identified after deletion of 10 redundant items: Acute symptoms (8 items), Activities of daily living (7 items), Psychological (7 items) and Participation (8 items). The four domains were analysed as ‘super-items’ and shown to fit the Rasch model. The overall scale had an adequate fit to the Rasch model: X2 = 25.219, DF=24, p=0.394 including reliability PSI=0.828. The raw-to-linear transformation scale was calibrated to enable parametric analyses if desired. Each domain was shown to have known-groups validity (p<0.001 patients reporting active versus inactive disease) and correlation with EQ5D-5L and CAT-PRO5 (Rs) ranging between 0.4.42 and 0.778.ConclusionThe GCA-PROM is a new patient reported outcome measure for patients with GCA which demonstrates good internal and external validity.References[1]Robson JC, Almeida C, Dawson J, Bromhead A, Dures E, Guly C, Hoon E, Mackie S, Ndosi M, Pauling J, Hill C. Patient perceptions of health-related quality of life in giant cell arteritis; international development of a disease-specific Patient-Reported Outcome Measure. Rheumatology (Oxford). 2021:keab076. http://dx.doi.org/10.1093/rheumatology/keab076Disclosure of InterestsJoanna Robson Speakers bureau: Vifor Pharma EULAR 2021 Symposium, Consultant of: Vifor Pharma Advisory board 2021, Grant/research support from: Vifor Pharma Steroid PRO grant, Celia Almeida: None declared, Jill Dawson: None declared, Emma Dures: None declared, Rosemary Greenwood: None declared, Catherine Guly: None declared, Sarah Mackie Speakers bureau: Roche/Chugai Educational talk on GCA., Consultant of: Roche/ChugaiSanofiAbbvie (2021-)AstraZeneca (2021-), Grant/research support from: Vifor Pharma Steroid PRO 2020Vifor Pharma GTI Validation 2020Roche GCA Tocilizumab Registry 2019, Alison Bromhead: None declared, Steve Stern: None declared, Mwidimi Ndosi: None declared
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Dures, E., B. Farisogullari, E. Santos, A. Moltó, C. Feldthusen, C. Harris, C. Elling-Audersch, et al. "POS0370 2023 EULAR RECOMMENDATIONS FOR THE MANAGEMENT OF FATIGUE IN PEOPLE WITH INFLAMMATORY RHEUMATIC AND MUSCULOSKELETAL DISEASES." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 437–38. http://dx.doi.org/10.1136/annrheumdis-2023-eular.2793.
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BackgroundFatigue is prevalent in people with inflammatory rheumatic and musculoskeletal diseases (I-RMDs) and recognised as one of the most challenging symptoms to manage [1]. The existence of multiple factors associated with fatigue, the lack of clarity around underlying pathophysiological mechanisms and the limited evidence about what helps have led to a multifaceted and often fragmented approach to symptom management. However, there are no recommendations for fatigue management in people with I-RMDs, and this lack of guidance has been challenging for those living with fatigue as well as for healthcare professionals delivering clinical care.ObjectivesTo develop EULAR recommendations for the management of fatigue in people with I-RMDs.MethodsA multi-disciplinary taskforce comprising 26 members from 14 European countries was convened and two systematic reviews were conducted. The taskforce developed recommendations based on evidence from the systematic reviews and taskforce members’ personal and professional experience of fatigue in I-RMDs.ResultsFour overarching principles and four recommendations were developed (Table 1), including health professionals’ awareness that fatigue should be monitored and assessed and that people with I-RMDs should be offered management options. Shared decisions about fatigue management should consider the needs and preferences of individuals, their clinical disease activity, comorbidities and other psychosocial and contextual factors (Table 1).ConclusionThese 2023 EULAR recommendations provide consensus and up-to-date guidance on the management of fatigue in people with I-RMDs.Reference[1]Dures E, et al. Fatigue in inflammatory arthritis. Best Pract Res Clin Rheumatol 2020;34.Table 1.EULAR overarching principles and recommendations for the management of fatigue in people with I-RMDs.Overarching principles1. Health professionals should be aware that fatigue encompasses multiple and mutually interacting biological, psychological and social factors.2. In people with I-RMDs, fatigue should be monitored, and management options should be offered as part of their clinical care.3. Management of fatigue should be a shared decision between the person with an I-RMD and healthcare and well-being professionals.4. Management of fatigue should be based on the needs and preferences of people with I-RMDs, as well as their clinical disease activity, comorbidities and other individual psychosocial and/or contextual factors.RecommendationsLoEGoR1. Healthcare professionals should incorporate regular assessment of fatigue severity, impact and coping strategies into clinical consultations.5D2. As part of their clinical care, people with I-RMDs and fatigue should be offered access to tailored physical activity interventions and encouraged to engage in long-term physical activity.1aA3. As part of their clinical care, people with I-RMDs and fatigue should be offered access to structured and tailored psychoeducational interventions.1aA4. The presence or worsening of fatigue should trigger evaluation of inflammatory disease activity status and consideration of immunomodulatory treatment initiation or change, if clinically indicated.1aAI-RMDs, inflammatory rheumatic and musculoskeletal diseases; GoR, Grade of recommendation; LoE, Level of Evidence. GoR and LoE as per 2011 Oxford Centre for Evidence Based Medicine Levels of Evidence.AcknowledgementsB Farisogullari and E Santos contributed equally to the manuscript.Disclosure of InterestsEmma Dures: None declared, Bayram Farisogullari: None declared, Eduardo Santos: None declared, Anna Moltó: None declared, Caroline Feldthusen: None declared, Claire Harris: None declared, Corinna Elling-Audersch: None declared, Deirdre Connolly: None declared, Elena Elefante: None declared, Fernando Estevez-Lopez: None declared, Ilaria Bini: None declared, Jette Primdahl: None declared, Kirsten Hoeper Speakers bureau: AbbVie, Novartis, Galapagos, Consultant of: AbbVie, Novartis, Galapagos, Marie Urban: None declared, Mart van de Laar: None declared, Marta Redondo: None declared, Peter Böhm: None declared, Raj Amarnani: None declared, Rhys Hayward Speakers bureau: Abbvie, Rinie Geenen: None declared, Simona Rednic: None declared, Susanne Pettersson: None declared, Tanja Thomsen: None declared, Till Uhlig: None declared, Valentin Ritschl: None declared, Pedro Machado Speakers bureau: Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, Consultant of: Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB.
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Fleischmann, R., I. H. Song, J. Enejosa, E. Mysler, L. Bessette, P. Durez, A. Ostor, J. Swierkot, Y. Song, and M. C. Genovese. "THU0201 LONG-TERM SAFETY AND EFFECTIVENESS OF UPADACITINIB OR ADALIMUMAB IN PATIENTS WITH RHEUMATOID ARTHRITIS: RESULTS AT 72 WEEKS FROM THE SELECT-COMPARE STUDY." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 323. http://dx.doi.org/10.1136/annrheumdis-2020-eular.1418.
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Background:In the SELECT-COMPARE study in rheumatoid arthritis (RA) patients with inadequate response to methotrexate (MTX), upadacitinib (UPA), a Janus Kinase (JAK) 1-selective inhibitor, showed significant improvements in treatment of signs and symptoms when compared to placebo (PBO) and adalimumab (ADA) up to 48 weeks.1Objectives:To report safety and efficacy of UPA vs ADA up to 72 weeks in patients with RA from the ongoing long-term extension (LTE) of SELECT-COMPARE.Methods:Patients were randomized to once daily (QD) UPA 15 mg, PBO, or ADA 40 mg every other week, with all patients continuing background MTX. The study was double-blind for 48 weeks. Between Weeks 14-26, patients were rescued (from PBO to UPA, UPA to ADA, or ADA to UPA) if there was <20% improvement in tender/swollen joint count at Weeks 14/18/22 or if Clinical Disease Activity Index (CDAI) was >10 at Week 26; all PBO patients who were not rescued were switched to UPA at Week 26. Patients continued UPA or ADA in a blinded manner until the last patient completed the Week 48 visit; patients received open-label treatment thereafter. Study visits occurred at Week 60, 72, and every 12 weeks thereafter. Treatment-emergent adverse events (TEAEs) per 100 patient years (PY) were summarized up to December 26, 2018. Efficacy was analyzed by randomized group.Results:In total, 651, 651 and 327 patients were randomized at baseline to receive UPA, PBO, and ADA, respectively. Subsequently, 252 patients were switched from UPA to ADA, 159 were switched from ADA to UPA, and all PBO patients were switched to UPA. 1403 patients entered the LTE at Week 48 (UPA: 1091 [565 switched from PBO; 66 rescued from ADA; 460 on continued UPA]; ADA: 312 [110 rescued from UPA; 202 on continued ADA]). The cumulative exposures were 1396.7 and 515.1 PYs for UPA and ADA, respectively. UPA + MTX was generally well-tolerated as assessed by the frequency of AEs, including serious AEs, AEs leading to discontinuation of study drug, and AEs of special interest ([AESIs] including serious and opportunistic infections, malignancy, adjudicated major adverse cardiac events or venous thromboembolism; Figure 1). The event rates of AESIs were generally comparable between UPA + MTX and ADA + MTX, except for herpes zoster, lymphopenia, hepatic disorder, and CPK elevation, which were numerically higher with UPA + MTX. At both Weeks 60 and 72, significantly greater proportions of patient receiving UPA + MTX achieved ACR20/50/70 (P ≤.01/.001/.001), low disease activity (P ≤.001) and remission (P ≤.001) compared to those receiving ADA + MTX; Figure 2). Similarly, improvements in pain and function were significantly greater in the UPA vs ADA group through Week 72 (P ≤.01).Conclusion:The safety profile for UPA + MTX was consistent with that reported previously and with the integrated Phase 3 safety analysis.1,2UPA + MTX maintained significantly higher levels of clinical response, including remission compared to ADA + MTX through Week 72.References:[1]Fleischmann R, et al.Annals of the Rheumatic Diseases.2019;78:744-745.[2]Cohen SB, et al. Thu0167.Annals of the Rheumatic Diseases. 2019;78:357.Disclosure of Interests: :Roy Fleischmann Grant/research support from: AbbVie, Akros, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer, IngelhCentrexion, Eli Lilly, EMD Serono, Genentech, Gilead, Janssen, Merck, Nektar, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Roche, Samsung, Sandoz, Sanofi Genzyme, Selecta, Taiho, UCB, Consultant of: AbbVie, ACEA, Amgen, Bristol-Myers Squibb, Eli Lilly, Gilead, GlaxoSmithKline, Novartis, Pfizer, Sanofi Genzyme, UCB, In-Ho Song Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Jeffrey Enejosa Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Eduardo Mysler Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Roche, Eli Lilly, Novartis, Janssen, Sanofi, and Pfizer., Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Roche, Eli Lilly, Novartis, Janssen, Sanofi, and Pfizer, Louis Bessette Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sanofi, Patrick Durez Speakers bureau: AbbVie, Bristol-Myers Squibb, Celltrion, Eli Lilly, Pfizer, Sanofi, Andrew Ostor Consultant of: MSD, Pfizer, Lilly, Abbvie, Novartis, Roche, Gilead and BMS, Speakers bureau: MSD, Pfizer, Lilly, Abbvie, Novartis, Roche, Gilead and BMS, Jerzy Swierkot Grant/research support from: AbbVie, Sandoz, Pfizer, Roche, BMS, UCB, MSD, Accord, Janssen, Consultant of: AbbVie, Sandoz, Pfizer, Roche, BMS, UCB, MSD, Accord, Janssen, Speakers bureau: AbbVie, Sandoz, Pfizer, Roche, BMS, UCB, MSD, Accord, Janssen, Yanna Song Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Mark C. Genovese Grant/research support from: Abbvie, Eli Lilly and Company, EMD Merck Serono, Galapagos, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, Pfizer Inc., RPharm, Sanofi Genzyme, Consultant of: Abbvie, Eli Lilly and Company, EMD Merck Serono, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, RPharm, Sanofi Genzyme
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Farisogullari, B., E. Santos, E. Dures, and P. Machado. "POS1087 EFFICACY OF PHARMACOLOGICAL INTERVENTIONS: A SYSTEMATIC REVIEW INFORMING THE 2023 EULAR RECOMMENDATIONS FOR THE MANAGEMENT OF FATIGUE IN PEOPLE WITH INFLAMMATORY RHEUMATIC AND MUSCULOSKELETAL DISEASES." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 867.1–867. http://dx.doi.org/10.1136/annrheumdis-2023-eular.1591.
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BackgroundThere is evidence that pharmacological interventions, including biologic therapies, can improve inflammation, disease activity and function in inflammatory rheumatic and musculoskeletal diseases (I-RMDs), and fatigue has increasingly been included as a secondary outcome of I-RMDs clinical trials. However, no systematic review (SR) has established the evidence for the pharmacological management of fatigue in people with I-RMD [1,2].ObjectivesTo identify the best evidence on the efficacy of pharmacological interventions in reducing fatigue in people with I-RMDs and to summarise their safety in the identified studies to inform EULAR recommendations for the management of fatigue in people with I-RMD.MethodsSystematic review of adults with I-RMD conducted according to the Cochrane Handbook. Search strategy ran in Medline, Embase, Cochrane Library, CINAHL Complete, PEDro, OTseeker and PsycINFO. Assessment of risk of bias, data extraction, and synthesis performed by two reviewers independently. Data pooled in statistical meta-analyses.ResultsFrom a total of 4,150 records, 454 were selected for full-text review, 105 fulfilled the inclusion criteria, and 19 RCTs were included in meta-analyses. Adalimumab was superior to placebo in reducing fatigue at 52 and 12 weeks (wk) in rheumatoid arthritis (RA) (mean difference [MD]=-2.25, p=0.03; MD=-3.03, p<0.001; respectively) and psoriatic arthritis (MD=-3.16, p=0.26). Golimumab (24wk: MD=-5.27, p<0.001), baricitinib (24wk: MD=-4.06, p<0.001), sarilumab (24wk: MD=-3.15, p<0.001), tocilizumab (24wk: MD=-3.69, p<0.001) and tofacitinib (12wk: MD=-4.44, p<0.001) were also superior to placebo in reducing fatigue in RA. A dose/effect relationship was observed for sarilumab, tocilizumab and tofacitinib. In spondyloarthritis, secukinumab was superior to placebo in reducing fatigue at 16wk (MD=-4.15, p<0.001), with a dose/effect relationship also observed (Figure 1). The narrative results of the RCTs not included in the meta-analysis indicated that several other pharmacological interventions were efficacious in reducing fatigue, with reassuring safety results.ConclusionPharmacological interventions are efficacious and safe for the management of fatigue in people with I-RMD.References[1]Almeida C, Choy EH, Hewlett S, et al. Biologic interventions for fatigue in rheumatoid arthritis.The Cochrane database of systematic reviews. 2016;2016:Cd008334.[2]Choy EH. Effect of biologics and targeted synthetic disease-modifying anti-rheumatic drugs on fatigue in rheumatoid arthritis.Rheumatology. 2019;58:v51-v5.Figure 1.The summary of the meta-analyses, PsA: Psoriatic arthritis, RA: Rheumatoid arthritis, SpA: Spondyloarthritis, wk: weeksAcknowledgementsB Farisogullari and E Santos contributed equally to the manuscript.Disclosure of InterestsBayram Farisogullari: None declared, Eduardo Santos: None declared, Emma Dures: None declared, Pedro Machado Speakers bureau: Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, Consultant of: Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB.
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Burmester, G. R., D. Aletaha, J. Pope, Y. Tanaka, P. Durez, A. Gomez-Centeno, A. Pechonkina, et al. "THU0194 CHARACTERISATION OF DEPTH OF RESPONSE, INCLUDING 50% IMPROVEMENT IN ACR COMPONENTS AT WEEK 12 AND REMISSION AT WEEK 24, FOLLOWING TREATMENT WITH FILGOTINIB COMPARED WITH METHOTREXATE OR ADALIMUMAB IN PATIENTS WITH RHEUMATOID ARTHRITIS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 316.1–317. http://dx.doi.org/10.1136/annrheumdis-2020-eular.2236.
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Background:The oral, potent, selective JAK1 inhibitor filgotinib (FIL) showed favorable efficacy at week (W)12 and W24 of treatment for rheumatoid arthritis (RA) compared with methotrexate (MTX) monotherapy (mono) in FINCH 3 (NCT02886728) and with placebo (PBO) or adalimumab (ADA) in FINCH 1 (NCT02889796).Objectives:50% clinical improvement from baseline at W12 is a key checkpoint for RA treatment.1These post hoc analyses evaluated FIL treatment effect on improvement in ACR components at W12 and remission at W24 in FINCH 3 and FINCH 1.Methods:FINCH 3 and FINCH 1 were global, phase 3, double-blind studies in patients (pts) with active RA. In FINCH 3, MTX-naïve pts were randomised 2:1:1:2 to once-daily (QD) oral FIL 200 mg + weekly MTX, FIL 100 mg + MTX, FIL 200 mg mono + PBO, or PBO + MTX mono up to W52. In FINCH 1, pts with inadequate response to MTX (MTX-IR) on a background of stable MTX were randomised (3:3:2:3) to oral FIL 200 or 100 mg QD, subcutaneous ADA 40 mg Q2W, or PBO up to W52. Post hoc analyses evaluated proportions of pts with 50% improvement from baseline in each ACR component and in all 7 ACR components (ACR50c) at W12, and proportions of pts with ACR50c at W12 achieving clinical remission at W24. Comparisons between treatments were not adjusted for multiplicity; subgroup comparisons are descriptive.Results:Analyses included 1249 pts in FINCH 3 and 1755 pts in FINCH 1. Greater proportions of pts receiving FIL 200 mg + MTX, FIL 100 mg + MTX, or FIL mono (FINCH 3) vs MTX mono (FINCH 3) or PBO + MTX (FINCH 1)—and numerically higher proportions of pts receiving FIL 200 mg + MTX vs FIL 100 mg + MTX (both studies) or ADA + MTX (FINCH 1)—achieved ACR50c and individual components at W12 (Table). Proportions of pts achieving CDAI ≤2.8 (Figure 1) or Boolean remission (Figure 2) at W24 were higher for pts with vs without ACR50c at W12 (Figures 1–2).Table.Proportions of patients with 50% improvement in each ACR component and ACR50c at week 12ACR componentSJC66TJC68PainPGASGAHAQ-DIhsCRPACR50cFINCH 3FIL 200 mg + MTX82.2***76.9***59.2***72.8***56.5***54.9***59.1***26.2***FIL 100 mg + MTX81.2***74.4***48.5*68.1*46.9**49.5***58.5***19.3***FIL 200 mg mono82.9***75.7***47.6*66.2*47.1**47.3**59.5***22.9***MTX mono67.159.639.258.435.635.633.76.0FINCH 1FIL 200 mg + MTX83.2***,+77.9***,+50.1***,+67.4***48.2***42.1***,+67.2***,+++18.5***FIL 100 mg + MTX77.9***72.3***45.1***62.9***43.2***35.2***55.0***12.5***ADA + MTXa76.970.541.561.542.034.455.713.8PBO + MTX66.759.228.050.928.023.125.92.5aNot formally compared vs PBO + MTX.*, p <0.05;**, p <0.01;***, p <0.001 vs MTX mono (FINCH 3) or PBO + MTX (FINCH 1);+, p <0.05;+++, p <0.001 vs ADA + MTX (FINCH 1); not adjusted for multiplicity.ACR50c, 50% improvement from baseline in all ACR components; ADA, adalimumab; FIL, filgotinib; MTX, methotrexate; mono, monotherapy; PBO, placebo.Conclusion:In MTX-naïve and MTX-IR pts with RA, FIL treatment was more effective vs MTX (FINCH 3) or PBO (FINCH 1) for achieving ACR50c at W12—a potential predictor of remission at W24. Proportions of pts achieving ACR50c at W12 were numerically higher for pts receiving FIL 200 mg + MTX vs FIL 100 mg + MTX (both studies) or ADA + MTX (FINCH 1).References:[1]Smolen JS, et al.Ann Rheum Dis. 2017;76:960–77.Disclosure of Interests:Gerd Rüdiger Burmester Consultant of: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Speakers bureau: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Daniel Aletaha Grant/research support from: AbbVie, Novartis, Roche, Consultant of: AbbVie, Amgen, Celgene, Lilly, Medac, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi Genzyme, Speakers bureau: AbbVie, Celgene, Lilly, Merck, Novartis, Pfizer, Sanofi Genzyme, UCB, Janet Pope Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly & Company, Merck, Roche, Seattle Genetics, UCB, Consultant of: AbbVie, Actelion, Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eicos Sciences, Eli Lilly & Company, Emerald, Gilead Sciences, Inc., Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB, Speakers bureau: UCB, Yoshiya Tanaka Grant/research support from: Asahi-kasei, Astellas, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, Bristol-Myers, UCB, Daiichi-Sankyo, Eisai, Pfizer, and Ono, Consultant of: Abbvie, Astellas, Bristol-Myers Squibb, Eli Lilly, Pfizer, Speakers bureau: Daiichi-Sankyo, Astellas, Chugai, Eli Lilly, Pfizer, AbbVie, YL Biologics, Bristol-Myers, Takeda, Mitsubishi-Tanabe, Novartis, Eisai, Janssen, Sanofi, UCB, and Teijin, Patrick Durez Speakers bureau: AbbVie, Bristol-Myers Squibb, Celltrion, Eli Lilly, Pfizer, Sanofi, Antonio Gomez-Centeno: None declared, Alena Pechonkina Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Beatrix Bartok Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Franziska Matzkies Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Lei Ye Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Zhaoyu Yin Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Robin Besuyen Shareholder of: Galapagos, Employee of: Galapagos, William Rigby Grant/research support from: Bristol-Myers Squibb, Consultant of: AbbVie, Bristol-Myers Squibb, Genentech, Pfizer, Bernard Combe Grant/research support from: Novartis, Pfizer, Roche-Chugai, Consultant of: AbbVie; Gilead Sciences, Inc.; Janssen; Eli Lilly and Company; Pfizer; Roche-Chugai; Sanofi, Speakers bureau: Bristol-Myers Squibb; Gilead Sciences, Inc.; Eli Lilly and Company; Merck Sharp & Dohme; Pfizer; Roche-Chugai; UCB
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Ostendorf, L., P. Enghard, P. Durek, F. Heinrich, M. F. Mashreghi, G. R. Burmester, A. Radbruch, F. Hiepe, and T. Alexander. "AB0138 INCREASED CD38 EXPRESSION LEVELS ON IMMUNE CELL SUBSETS IN SYSTEMIC LUPUS ERYTHEMATOSUS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1369.2–1370. http://dx.doi.org/10.1136/annrheumdis-2020-eular.6531.
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Background:Plasma Cells (PCs) are implicated in the pathogenesis of Systemic Lupus erythematosus (SLE) and their targeting proved a promising treatment modality. As there is a monoclonal therapeutic antibody targeting CD38 licensed for clinical use in multiple myeloma, plasma cell depletion via CD38 seems to represent a promising path in SLE treatment. While CD38 Is highly expressed on plasmacells, it is present on the surface of subsets of T and B lymphocytes as well as myeloid cells.Objectives:Here we aim to identify the differential expression of CD38 on peripheral blood leukocytes in SLE compared to healthy controls (HC) investigate the function of CD38+ T lymphocytesMethods:We performed flow cytometry to investigate the expression of CD38 on peripheral blood mononuclear cells of SLE patients (n=36) and HCs (n=20). We additionally analyzed the expression of T lymphocytes within the urine of patients with lupus nephritis as well as the skin of SLE patients. We investigated the inflammatory potential of CD38 positive memory T lymphocytes after stimulation and performed single-cell RNA sequencing analyses.Results:CD38 Expression is increased on certain immune cell subsets: Plasmablasts and unswitched Memory B cells, as well as plasmacytoid dendritic cells and CD16+ non-classical monocytes. We observed a drastic increase CD38 in both memory CD4 and CD8 T lymphocytes in SLE patients. These cells were mostly effector T cells (and not regulatory T cells) and expressed other markers of T cell activation and proliferation. We found an enrichment of CD38+ memory T cells in the urine of patients with lupus nephritis. After polyclonal stimulation of T cells, CD38+ produced less inflammatory cytokines. Preliminary single-cell sequencing results indicate that CD38+ CD8+ T-lymphocytes have decreased clonal diversity and that these cells express genes associated with exhaustion and type 1 interferon response.Conclusion:Increased CD38 expression on various lymphocyte subsets provides an additional rationale for investigating CD38-directed therapies in SLE. Targeting CD38 could not only deplete plasma cells but also has the potential to target interferon alpha producing plasmacytoid dendritic cells and modulate inflammatory T cell functions.Disclosure of Interests:Lennard Ostendorf: None declared, Philipp Enghard: None declared, Pawel Durek: None declared, Frederik Heinrich: None declared, Mir-Farzin Mashreghi: None declared, Gerd Rüdiger Burmester Consultant of: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Speakers bureau: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Andreas Radbruch: None declared, Falk Hiepe: None declared, Tobias Alexander: None declared
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Santos, E., B. Farisogullari, E. Dures, and P. Machado. "OP0182-HPR EFFICACY OF NON-PHARMACOLOGICAL INTERVENTIONS: A SYSTEMATIC REVIEW INFORMING THE 2023 EULAR RECOMMENDATIONS FOR THE MANAGEMENT OF FATIGUE IN PEOPLE WITH INFLAMMATORY RHEUMATIC AND MUSCULOSKELETAL DISEASES." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 120.1–120. http://dx.doi.org/10.1136/annrheumdis-2023-eular.1627.
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BackgroundSeveral EULAR recommendations for the management of people with specific inflammatory rheumatic and musculoskeletal diseases (I-RMDs) have highlighted the importance of some non-pharmacological interventions in the management of fatigue [1-3]. However, these recommendations are either disease-specific or focusing on a single intervention, and lack an integrated view of the overall evidence for fatigue management with non-pharmacological therapies in the wider context of all I-RMD.ObjectivesTo identify the best evidence on the efficacy of non-pharmacological interventions in reducing fatigue in people with I-RMDs and to summarise their safety in the identified studies to inform EULAR recommendations for the management of fatigue in people with I-RMD.MethodsSystematic review of adults with I-RMD conducted according to the Cochrane Handbook. Search strategy ran in Medline, Embase, Cochrane Library, CINAHL Complete, PEDro, OTseeker and PsycINFO. Assessment of risk of bias, data extraction, and synthesis performed by two reviewers independently. Data pooled in statistical meta-analyses.ResultsFrom a total of 4,150 records, 454 were selected for full-text review, 82 fulfilled the inclusion criteria, and 55 RCTs were included in meta-analyses. Physical activity or exercise were efficacious in reducing fatigue in rheumatoid arthritis (RA) (SMD=-0.23, p<0.001), systemic lupus erythematosus (SLE) (SMD=-0.54, p=0.04) and spondyloarthritis (SpA) (SMD=-0.94, p<0.001). A reduction in fatigue was also observed in Sjögren’s syndrome and systemic sclerosis, although not statistically significant (SMD=-0.83, p=0.21; SMD=-0.66, p=0.06, respectively). Psychoeducational interventions were efficacious in reducing fatigue in RA (SMD=-0.32, p<0.001), but not in SLE (SMD=-0.19, p=0.18). Follow-up models in consultations and multicomponent interventions reduced fatigue in RA, although the effect was not statistically significant (SMD=-0.05, p=0.71; SMD=-0.20, p=0.24, respectively) (Figure 1). The narrative results of the RCTs not included in the meta-analysis indicated that several other non-pharmacological interventions were efficacious in reducing fatigue, with reassuring safety results.ConclusionNon-pharmacological interventions are efficacious and safe for the management of fatigue in people with I-RMD.References[1] Smolen JS, et al. Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force.Annals of the rheumatic diseases. 2015;75:3.[2] Rausch Osthoff A-K, et al. 2018 EULAR recommendations for physical activity in people with inflammatory arthritis and osteoarthritis.Annals of the Rheumatic Diseases. 2018;77:1251.[3] Nikiphorou E, et al. 2021 EULAR recommendations for the implementation of self-management strategies in patients with inflammatory arthritis.Annals of the rheumatic diseases. 2021;80:1278.Figure 1.The summary of the meta-analysesAcknowledgementsE Santos and B Farisogullari contributed equally to the manuscript.Disclosure of InterestsEduardo Santos: None declared, Bayram Farisogullari: None declared, Emma Dures: None declared, Pedro Machado Speakers bureau: Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, Consultant of: Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UC.B.
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Fleischmann, R., E. Mysler, L. Bessette, C. Peterfy, P. Durez, Y. Tanaka, J. Swierkot, et al. "POS0087 LONG-TERM SAFETY AND EFFICACY OF UPADACITINIB OR ADALIMUMAB IN PATIENTS WITH RHEUMATOID ARTHRITIS: RESULTS AT 3 YEARS FROM THE SELECT-COMPARE STUDY." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 251.1–252. http://dx.doi.org/10.1136/annrheumdis-2021-eular.535.
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Background:In the SELECT-COMPARE study, the Janus kinase inhibitor, upadacitinib (UPA), demonstrated significant improvements in the signs and symptoms of rheumatoid arthritis (RA) when administered at 15 mg once daily (QD) on background methotrexate (MTX) compared with adalimumab (ADA) plus MTX at Week 12 that were maintained through 72 weeks in patients with prior inadequate response to MTX.1Objectives:To assess the long-term safety and efficacy of UPA vs ADA over 3 years in the ongoing long-term extension (LTE).Methods:Patients receiving background MTX were randomized 2:2:1 to UPA 15 mg QD, placebo (PBO), or ADA 40 mg every other week. Between Weeks 14-26, rescue was mandated for either lack of response (<20% improvement in tender or swollen joint counts: Weeks 14, 18, 22) or failure to achieve a targeted disease outcome (CDAI low disease activity: Week 26). Patients who completed the 48-week double-blind period could enter an LTE for up to 10 years total. This analysis describes patients through 3 years of treatment. Treatment-emergent adverse events (TEAEs) per 100 patient years (PY), including events of special interest (AESI), were summarized up to 3 years based on exposure to UPA and to ADA. Efficacy was analyzed by original randomized groups. Patients who were rescued or prematurely discontinued study drug were categorized as non-responders for visits after rescue or discontinuation. Descriptive analyses were performed without formal statistical comparisons.Results:In total, 651, 651, and 327 patients were randomized at baseline to receive UPA, PBO, and ADA, respectively. Between Weeks 14-26, 252 (39%) patients were rescued from UPA to ADA, 159 (49%) were rescued from ADA to UPA, and all PBO patients were switched to UPA by Week 26.1 A higher proportion of patients randomized to UPA completed 3 years without rescue compared to those randomized to ADA (47% vs 36%, respectively). UPA was generally well-tolerated as assessed by the rates of TEAEs, including serious AEs, AEs leading to discontinuation of study drug, and AESIs, including serious and opportunistic infections, malignancies, adjudicated major adverse cardiac events or venous thromboembolism; Figure 1). Consistent with previous analyses, the event rates of AESIs were generally comparable between the UPA and ADA groups, while herpes zoster, lymphopenia, hepatic disorder, and CPK elevation were reported at higher rates with UPA. Consistent with earlier time points, greater proportions of patients randomized to UPA achieved low disease activity and remission at 3 years based on CDAI, as well as DAS28(CRP) ≤3.2 or <2.6, compared with patients randomized to ADA (Table 1).Conclusion:The safety profile of UPA was consistent with the results reported previously and with the integrated Phase 3 safety analysis.1,2 Higher levels of clinical response continued to be observed with UPA vs ADA through 3 years of treatment.References:[1]Fleischmann R, et al. Ann Rheum Dis 2020;79:323.[2]Cohen SB, et al. Ann Rheum Dis 2020; doi: 10.1136/annrheumdis-2020-218510.Table 1.Efficacy Endpoints at 3 Years (NRI)Endpoints, % (95% CI)UPA 15 mg QDN=651*ADA 40 mg EOWN=327*CDAI ≤1039 (36, 43)29 (24, 34)CDAI ≤2.824 (21, 28)17 (12, 21)DAS28(CRP) ≤3.237 (33, 41)26 (21, 31)DAS28(CRP) <2.632 (29, 36)22 (17, 26)ADA, adalimumab; CI, confidence interval; DAS28(CRP), Disease Activity Score for 28-joints C-Reactive Protein; CDAI, clinical disease activity index; EOW, every other week; NRI, non-responder imputation; QD, once daily; UPA, upadacitinib.*Patients who were rescued prior to/at Week 26 were considered non-responders. 252/651 and 159/327 patients were rescued of those randomized to UPA and ADA, respectively.Acknowledgements:AbbVie and the authors thank the patients, trial sites, and investigators who participated in this clinical trial. AbbVie, Inc was the trial sponsor, contributed to trial design, data collection, analysis & interpretation, and to writing, reviewing, and approval of final version. No honoraria or payments were made for authorship. The authors thank Dr. Tim Shaw of AbbVie Inc. for his support with the interpretation of the data. Medical writing support was provided by Ramona Vladea, PhD, of AbbVie, Inc.Disclosure of Interests:Roy Fleischmann Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, GSK, Janssen, Novartis, Pfizer Inc, Sanofi-Aventis, and UCB, Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Genentech, Janssen, Novartis, Pfizer Inc, Regeneron, Roche, Sanofi-Aventis and UCB, Eduardo Mysler Consultant of: AbbVie, AstraZeneca, Lilly, Pfizer, Roche, BMS, Sandoz, GSK, Janssen, Grant/research support from: AbbVie, AstraZeneca, Lilly, Pfizer, Roche, BMS, Sandoz, GSK, Janssen, Louis Bessette Consultant of: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Eli Lilly, Novartis, Gilead, Grant/research support from: Amgen, BMS, Janssen, Roche, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Eli Lilly, Novartis, Gilead, Charles Peterfy Shareholder of: Spire Sciences, Inc, Speakers bureau: Amgen, Bristol-Myers Squibb, Consultant of: Aclaris, Centrexion, Daiichi Sankyo, EMD, Serono, Five Prime, Flexion Therapeutics, Genentech, Gilead, GlaxoSmithKline, Istresso, Eli Lilly, Myriad Genetics, Novartis, Roche, SetPoint, Sorrento, UCB, Employee of: Spire Sciences, Inc, Patrick Durez Speakers bureau: BMS, Sanofi, Eli Lilly, Celltrion, Yoshiya Tanaka Speakers bureau: Daiichi-Sankyo, Astellas, Chugai, Eli Lilly, Pfizer, AbbVie, YL Biologics, Bristol-Myers, Takeda, Mitsubishi-Tanabe, Novartis, Eisai, Janssen, Teijin, Consultant of: Daiichi-Sankyo, Astellas, Chugai, Eli Lilly, Pfizer, AbbVie, YL Biologics, Bristol-Myers, Takeda, Mitsubishi-Tanabe, Novartis, Eisai, Janssen, Teijin, Grant/research support from: Asahi-kasei, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, Bristol-Myers, UCB, Daiichi-Sankyo, Eisai, Ono, Jerzy Swierkot Speakers bureau: AbbVie, Sandoz, Pfizer, Roche, BMS, UCB, MSD, Accord, Janssen, Consultant of: AbbVie, Sandoz, Pfizer, Roche, BMS, UCB, MSD, Accord, Janssen, Grant/research support from: AbbVie, Sandoz, Pfizer, Roche, BMS, UCB, MSD, Accord, Janssen, Nasser Khan Shareholder of: AbbVie, Employee of: AbbVie, Xianwei Bu Shareholder of: AbbVie, Employee of: AbbVie, Yihan Li Shareholder of: AbbVie, Employee of: AbbVie, In-Ho Song Shareholder of: AbbVie, Employee of: AbbVie.
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Peterfy, C., V. Strand, M. C. Genovese, A. Friedman, J. J. Enejosa, S. Hall, E. Mysler, et al. "THU0211 RADIOGRAPHIC OUTCOMES IN PATIENTS WITH RHEUMATOID ARTHRITIS RECEIVING UPADACITINIB AS MONOTHERAPY OR IN COMBINATION WITH METHOTREXATE: RESULTS AT 2 YEARS FROM THE SELECT-COMPARE AND SELECT-EARLY STUDIES." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 330–31. http://dx.doi.org/10.1136/annrheumdis-2020-eular.1869.
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Background:For patients with rheumatoid arthritis (RA), long-term prevention of structural joint damage is a key treatment goal.1In the SELECT-EARLY and SELECT-COMPARE trials, upadacitinib (UPA), an oral JAK inhibitor, inhibited the progression of structural joint damage at 6 months and 1 year when used either as monotherapy or in combination with methotrexate (MTX) in patients (pts) with active RA.2Objectives:To describe the radiographic progression up to 2 years (96 wks) among pts with RA receiving UPA either as monotherapy or in combination with MTX.Methods:Both the SELECT-EARLY and SELECT-COMPARE phase 3, randomized controlled trials enrolled pts at high risk for progressive structural damage with baseline (BL) erosive joint damage and/or seropositivity.3,4In SELECT-EARLY, MTX-naïve pts (N=945) were randomized to UPA 15 mg or 30 mg once daily (QD) or MTX monotherapy. In SELECT-COMPARE, pts with an inadequate response to MTX (N=1629) were randomized to UPA 15 mg, placebo (PBO), or adalimumab (ADA) 40 mg every other wk, with all pts continuing background MTX; at wk 26, all pts receiving PBO were switched to UPA 15 mg, regardless of response. In both trials, mean changes from BL in modified Total Sharp Score (mTSS), joint space narrowing, and joint erosion as well as the proportion of pts with no radiographic progression (change in mTSS ≤0) were evaluated based on X-rays taken at wks 24/26, 48, and 96 for those patients in whom wk 96 X-rays were available. Data are reported as observed (AO).Results:BL demographics have been reported previously.3,4In the SELECT-EARLY study, at wk 96 UPA monotherapy (15 mg and 30 mg doses) significantly inhibited radiographic progression compared with MTX as measured by mean change in mTSS and by the proportion of patients with no radiographic progression (Figures 1 and 2). When patients who were rescued (MTX added to UPA or UPA added to MTX) were removed from the analysis, changes in mTSS from baseline remained similar. By the same measures, in SELECT-COMPARE, the degree of inhibition of structural progression observed was comparable between UPA and ADA. Following the switch of all PBO patients to UPA, the rate of progression slowed and was comparable to that observed in pts receiving UPA from BL. Among pts from both studies that had no radiographic progression at wk 24/26, >90% remained without radiographic progression at wk 48 and 96.Conclusion:UPA was effective in inhibiting the progression of structural joint damage through 2 years both in MTX-naïve patients receiving UPA monotherapy and MTX-inadequate responder patients receiving UPA in combination with MTX.References:[1]Smolen, et al.Ann Rheum Dis2017;76(6):960-77.[2]Peterfy, et al.Ann Rheum Dis2019;78(suppl 2):369-370.[3]Fleischmann, et al.Arthritis Rheumatol2019;71(11):1788-1800.[4]Van Vollenhoven, et al.Arthritis Rheumatol2018;70(suppl 10).Disclosure of Interests: :Charles Peterfy Consultant of: AbbVie, Acerta, Amgen, AstraZeneca, Bristol Myers Squibb, Centrexion, Daiichi Sankyo, Five Prime Therapeutics, Genentech, Gilead, Hoffman-La Roche, Janssen, Lilly USA, MedImmune, Merck, Myriad, Novartis, Plexxikon, Pfizer, Sanofi, Salix Santarus, Samsung, Samumed, Setpoint, Sorrento, UCB, Vorso, Employee of: founder and CEO of Spire Sciences, which provides imaging services to multiple pharmaceutical companies, Speakers bureau: Amgen, Vibeke Strand Consultant of: AbbVie, Amgen, Biogen, Celltrion, Consortium of Rheumatology Researchers of North America, Crescendo Bioscience, Eli Lilly, Genentech/Roche, GlaxoSmithKline, Hospira, Janssen, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi, UCB, Mark C. Genovese Grant/research support from: Abbvie, Eli Lilly and Company, EMD Merck Serono, Galapagos, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, Pfizer Inc., RPharm, Sanofi Genzyme, Consultant of: Abbvie, Eli Lilly and Company, EMD Merck Serono, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, RPharm, Sanofi Genzyme, Alan Friedman Shareholder of: AbbVie Inc, Employee of: AbbVie Inc, Jose Jeffrey Enejosa Shareholder of: AbbVie, Employee of: AbbVie, Stephen Hall Grant/research support from: Abbvie, UCB, Janssen, Merck, Eduardo Mysler Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Roche, Eli Lilly, Novartis, Janssen, Sanofi, and Pfizer., Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Roche, Eli Lilly, Novartis, Janssen, Sanofi, and Pfizer, Patrick Durez Speakers bureau: AbbVie, Bristol-Myers Squibb, Celltrion, Eli Lilly, Pfizer, Sanofi, Xenofon Baraliakos Grant/research support from: Grant/research support from: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Consultant of: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Tim Shaw Shareholder of: AbbVie, Employee of: AbbVie, Yanna Song Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Yihan Li Shareholder of: AbbVie, Employee of: AbbVie, In-Ho Song Shareholder of: AbbVie Inc., Employee of: AbbVie Inc.
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Durez, P., E. Feist, R. Blanco, V. Rajendran, N. Verbruggen, K. Van Beneden, and J. Galloway. "POS0663 THE USE OF EXPOSURE-ADJUSTED EVENT RATES VERSUS EXPOSURE-ADJUSTED INCIDENCE RATES IN ADVERSE EVENT REPORTING: INSIGHTS FROM FILGOTINIB INTEGRATED SAFETY DATA IN RHEUMATOID ARTHRITIS." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 604.1–604. http://dx.doi.org/10.1136/annrheumdis-2022-eular.138.
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BackgroundReporting of treatment-emergent adverse events (TEAEs) in rheumatoid arthritis (RA) clinical trials can be summarized as exposure-adjusted incidence rates (EAIRs) or exposure-adjusted event rates (EAERs). Censored EAIR (EAIR), weighing exposure up to a patient’s first event, is commonly reported; uncensored EAIR (EAIRu), using total exposure time for all patients, can also be used. For EAIR, exposure time can vary by event. In contrast to EAIR(u), the total number of events are used to calculate EAER. The three methods account for different exposures and/or multiple events, which can impact the outcome evaluation. Studies of filgotinib (FIL) in RA1 report safety data as EAIR/100 patient-years of exposure (PYE) for TEAEs, which is uncensored.ObjectivesTo describe the outcome of long-term FIL integrated safety data in RA by applying different statistical methodologies: EAER, EAIRu and EAIR.MethodsIntegrated FIL safety data from seven clinical trials were assessed1. Predefined adverse events of special interest (AESI) included serious infections (any), herpes zoster (HZ), major adverse cardiac events (MACE), malignancies (excluding nonmelanoma skin cancer [NMSC]), NMSC and venous thromboembolism (VTE). The number of patients with an event, number of events, EAER, EAIRu and EAIR were summarized. The data extraction date was January 2021 for the DARWIN 3 (NCT02065700) long-term extension (LTE) and November 2020 for the FINCH 4 (NCT03025308) LTE.ResultsIn total, 3691 patients received ≥1 FIL dose for 8085 PYE. In this population, 176 serious infections were reported in 137 patients, 125 HZ events were reported in 112 patients, 39 MACE were reported in 33 patients, 20 cases of VTE were reported in 15 patients, 60 malignancies excluding NMSC were reported in 49 patients and 21 cases of NMSC were reported in 20 patients. Within each treatment arm (FIL 200 mg [FIL200], FIL 100 mg [FIL100] or combined FIL), rates for most AESI were similar when reported as EAER, EAIRu or EAIR (Table 1). For serious infections, EAER was higher than EAIRu or EAIR. The total exposure time to first event (censored PYE) was high and comparable to total exposure (PYE) (>2700 years and >5100 years for the total populations in the FIL100 and FIL200 groups, respectively).Table 1.Exposure-adjusted event and incidence rates for AESIFIL200FIL100FIL combinedNumber of patients/PYE2267/5302.51647/2782.63691/8085.1Serious infectionsEAER1.9 (1.5, 2.4)3.2 (2.2, 4.5)2.0 (1.7, 2.4)EAIRu1.5 (1.1, 1.9)2.7 (1.9, 3.9)1.6 (1.3, 2.0)EAIR1.5 (1.2, 1.9)2.8 (1.9, 4.0)1.7 (1.4, 2.0)HZEAER1.6 (1.3, 2.1)1.3 (0.9, 1.8)1.5 (1.2, 1.8)EAIRu1.5 (1.2, 2.0)1.1 (0.8, 1.5)1.4 (1.1, 1.7)EAIR1.6 (1.2, 2.0)1.1 (0.8, 1.6)1.4 (1.1, 1.7)MACEEAER0.3 (0.2, 0.5)0.6 (0.4, 1.0)0.4 (0.3, 0.6)EAIRu0.3 (0.2, 0.5)0.5 (0.3, 0.8)0.4 (0.2, 0.6)EAIR0.3 (0.2, 0.5)0.5 (0.3, 0.9)0.4 (0.2, 0.6)VTEEAER0.3 (0.2, 0.5)0.1 (0.1, 0.4)0.2 (0.2, 0.4)EAIRu0.2 (0.1, 0.4)0.1 (0.1, 0.4)0.2 (0.1, 0.3)EAIR0.2 (0.1, 0.4)0.1 (0.1, 0.4)0.2 (0.1, 0.3)Malignancies excluding NMSCEAER0.8 (0.5, 1.1)0.8 (0.5, 1.2)0.7 (0.2, 2.8)EAIRu0.6 (0.4, 0.9)0.6 (0.4, 1.0)0.6 (0.4, 0.8)EAIR0.6 (0.4, 0.9)0.6 (0.4, 1.0)0.6 (0.4, 0.8)NMSCEAER0.3 (0.2, 0.5)0.2 (0.1, 0.5)0.3 (0.2, 0.4)EAIRu0.3 (0.2, 0.5)0.2 (0.1, 0.4)0.2 (0.2, 0.4)EAIR0.3 (0.2, 0.5)0.2 (0.1, 0.4)0.2 (0.2, 0.4)Data are rate (95% CI) unless otherwise stated.ConclusionThese data confirm that using different methods to analyze FIL safety data (EAER, EAIRu, EAIR) does not result in different safety outcomes, reinforcing the previously reported FIL safety profile in patients with RA. As the AESI reported in the long-term safety database with FIL are rare, patients commonly have long exposure times before experiencing an event, which are often associated with end of treatment. As such, EAIRu, EAIR and EAER are similar.References[1]Winthrop KL et al. Ann Rheum Dis 2021, doi: 10.1136/annrheumdis-2021-221051.AcknowledgementsThis study was co-funded by Galapagos NV (Mechelen, Belgium) and Gilead Sciences, Inc. (Foster City, CA, USA). Medical writing support was provided by Iain Haslam, PhD (Aspire Scientific Ltd, Bollington, UK), and funded by Galapagos NV.Disclosure of InterestsPatrick Durez Speakers bureau: AbbVie, Galapagos, and Lilly, Eugen Feist Speakers bureau: AbbVie, Galapagos, Lilly, Novartis, Pfizer, Roche, and Sobi, Consultant of: AbbVie, Galapagos, Lilly, Novartis, Pfizer, Roche, and Sobi, Grant/research support from: Lilly, Pfizer, and Roche, Ricardo Blanco Speakers bureau: AbbVie, Amgen, Bristol-Myers, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, and Sanofi, Consultant of: Astra-Zeneca, Galapagos, Janssen, Novartis, and Pfizer, Grant/research support from: AbbVie and Roche, Vijay Rajendran Employee of: Galapagos, Nadia Verbruggen Employee of: Galapagos, Katrien Van Beneden Shareholder of: Galapagos, Employee of: Galapagos, James Galloway Speakers bureau: AbbVie, Biogen, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, Galapagos, Gilead, Janssen, Lilly, Novartis, and Pfizer, Grant/research support from: Astra-Zeneca, Celgene, Gilead, Janssen, Medicago, Novavax, and Pfizer
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Fleischmann, R. M., J. Swierkot, S. Penn, P. Durez, L. Bessette, X. Bu, N. Khan, et al. "POS0849 LONG-TERM SAFETY AND EFFICACY OF UPADACITINIB OR ADALIMUMAB IN PATIENTS WITH RHEUMATOID ARTHRITIS: 5-YEAR DATA FROM THE SELECT-COMPARE STUDY." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 725–26. http://dx.doi.org/10.1136/annrheumdis-2023-eular.2615.
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BackgroundUpadacitinib (UPA) is an oral reversible Janus kinase inhibitor. In patients (pts) with RA, UPA 15 mg once daily (QD) demonstrated better clinical responses at 12 weeks (wks) vs adalimumab (ADA) 40 mg every other week (EOW) in the phase 3 SELECT-COMPARE study; these were maintained through 3 years (yrs) in the ongoing long-term extension (LTE), along with an acceptable safety profile.[1,2]ObjectivesTo assess the safety and efficacy of UPA vs ADA through 5 yrs in the SELECT-COMPARE LTE.MethodsPts receiving background methotrexate were randomized 2:2:1 to UPA 15 mg QD, placebo (PBO), or ADA 40 mg EOW. Rescue (PBO to UPA, UPA to ADA, or ADA to UPA) was mandated for lack of response (<20% improvement in tender or swollen joint counts at wks 14, 18, or 22), or failure to achieve Clinical Disease Activity Index (CDAI) low disease activity (LDA) at wk 26. All remaining PBO pts switched to UPA at wk 26. Pts who completed the 48-wk double-blind period could continue to receive open-label UPA or ADA in the LTE for up to 10 yrs total. Rates of treatment-emergent adverse events (TEAEs) and AEs of special interest were calculated per 100 pt-yrs through 5 yrs for all pts receiving UPA or ADA. Efficacy assessments at 5 yrs were performed by original randomized group for CDAI LDA (≤10) and remission (≤2.8), and disease activity score for 28-joints C-reactive protein (DAS28[CRP]) ≤3.2 and <2.6. Radiographic progression (change from baseline in modified total Sharp score [mTSS]) and proportion of pts with no radiographic progression (change from baseline in mTSS ≤0) were assessed at 192 wks (latest available timepoint; data collected at wks 96/192/520 only) by treatment sequence. No formal statistical comparisons were performed.ResultsThrough 5 yrs, 1417 pts were exposed to UPA (4497 pt-yrs) and 579 to ADA (1472 pt-yrs). UPA was generally well tolerated, with similar rates of TEAEs, serious TEAEs, TEAEs leading to discontinuation of study drug, and COVID-related TEAEs vs ADA (Figure 1). Rates of most AEs of special interest with UPA were similar vs ADA, except for numerically higher rates of herpes zoster, creatine phosphokinase elevation, lymphopenia, and hepatic disorder (mainly transaminase elevations) with UPA. In the 651 and 327 pts originally randomized to UPA and ADA, respectively, greater proportions of pts achieved CDAI LDA and remission, and DAS28(CRP) scores ≤3.2 and <2.6, with UPA vs ADA (Table 1). Through 192 wks, similar proportions of pts treated with UPA vs ADA had no radiographic progression; mean changes from baseline in mTSS were similar, except for a numerically smaller change with continuous UPA (Table 1).ConclusionThe safety profile of UPA over 5 yrs was consistent with the 3-yr results and the integrated phase 3 safety analysis.[1,2]Consistent with the 3-yr analyses,[2]UPA continued to show numerically better clinical responses than ADA at 5 yrs. Radiographic progression remained similarly low through 192 wks with UPA and ADA.References[1]Cohen SB, et al.Ann Rheum Dis2020. doi:10.1136/annrheumdis-2020-218510[2]Fleischmann R, et al.RMD Open2022. doi:10.1136/rmdopen-2021-002012Table 1.Efficacy endpointsAt 5 yrs, by original randomized group (non-responder imputation)UPA N=651a,bADA N=327a,cCDAI ≤1036.4 (32.7, 40.1)26.9 (22.1, 31.7)CDAI ≤2.824.6 (21.3, 27.9)18.7 (14.4, 22.9)DAS28(CRP) ≤3.234.7 (31.1, 38.4)24.8 (20.1, 29.4)DAS28(CRP) <2.631.8 (28.2, 35.4)23.2 (18.7, 27.8)At 192 wks, by treatment sequence (as observed)PBO to UPA N=442UPA N=288UPA to ADA N=150ADA N=109ADA to UPA N=111Radiographic progression (change from baseline in mTSS, mean [95% CI])1.3 (0.8, 1.7)0.5 (0.2, 0.9)1.7 (0.7, 2.8)1.2 (0.5, 1.9)0.9 (0.2, 1.5)No radiographic progression (mTSS change from baseline ≤0)77.1(73.2, 81.1)80.9(76.4, 85.4)74.0(67.0, 81.0)78.0(70.2, 85.8)77.5(69.7, 85.2)Data are % of pts (95% confidence interval) unless otherwise stated.aPts rescued at or before wk 26 were considered non-responders.b252 rescued.c159 rescued.AcknowledgementsAbbVie funded this trial and participated in the trial design, research, analysis, data collection, interpretation of data, and the review and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Laura Chalmers, PhD, of 2 the Nth (Cheshire, UK), and was funded by AbbVie.Disclosure of InterestsRoy M. Fleischmann Consultant of: AbbVie, Amgen, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galapagos, Galvani, Gilead, GSK, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Biosplice, Bristol-Myers Squibb, Flexion, Gilead, Horizon, Eli Lilly, Galvani, Janssen, Novartis, Pfizer, Sanofi-Aventis, Selecta, Teva, UCB, Viela, and Vorso, Jerzy Swierkot Speakers bureau: AbbVie, Accord, BMS, Janssen, MSD, Pfizer, Roche, Sandoz, and UCB, Consultant of: AbbVie, Accord, BMS, Janssen, MSD, Pfizer, Roche, Sandoz, and UCB, Grant/research support from: AbbVie, Accord, BMS, Janssen, MSD, Pfizer, Roche, Sandoz, and UCB, Sara Penn Employee of: AbbVie, and may hold stock or options, Patrick Durez Speakers bureau: AbbVie, Galapagos, Lilly, Nordimed, and Thermofischer, Louis Bessette Speakers bureau: AbbVie, Amgen, Bristol-Meyers Squibb, Celgene, Eli Lilly, Fresenius Kabi, Gilead, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi-Aventis, Teva, and UCB, Consultant of: AbbVie, Amgen, Bristol-Meyers Squibb, Celgene, Eli Lilly, Fresenius Kabi, Gilead, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi-Aventis, Teva, and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Meyers Squibb, Celgene, Eli Lilly, Fresenius Kabi, Gilead, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi-Aventis, Teva, and UCB, Xianwei Bu Employee of: AbbVie, and may hold stock or options, Nasser Khan Employee of: AbbVie, and may hold stock or options, Yihan Li Employee of: AbbVie, and may hold stock or options, Charles Peterfy Shareholder of: Spire Sciences, Inc, Consultant of: Daiichi Sankyo, Eli Lilly, Five Prime, Genentech, Gilead, GlaxoSmithKline, Istesso, Labcorp, Paradigm, SetPoint, Sorrento, and UCB, Employee of: Spire Sciences, Inc, Yoshiya Tanaka Speakers bureau: AbbVie, Asahi Kasei, Astellas, BMS, Chugai, Daiichi-Sankyo, Eisai, GSK, Janssen, Lilly, Mitsubishi Tanabe, MSD, Novartis, Ono, Pfizer, Sanofi, Taisho Toyama, Takeda, UCB, and YL Biologics, Grant/research support from: AbbVie, Asahi Kasei, Astellas, BMS, Chugai, Daiichi-Sankyo, Eisai, GSK, Janssen, Lilly, Mitsubishi Tanabe, MSD, Novartis, Ono, Pfizer, Sanofi, Taisho Toyama, Takeda, UCB, and YL Biologics, Eduardo Mysler Speakers bureau: AbbVie, Amgen, AZ, BMS, Janssen, Lilly, Novartis, Pfizer, Roche, Sandoz, and Sanofi, Paid instructor for: AbbVie, Amgen, AZ, BMS, Janssen, Lilly, Novartis, Pfizer, Roche, Sandoz, and Sanofi, Grant/research support from: AbbVie, Amgen, AZ, BMS, Janssen, Lilly, Novartis, Pfizer, Roche, Sandoz, and Sanofi.
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Bridgewater, S., J. Dawson, M. Ndosi, R. J. Black, J. T. L. Cheah, E. Dures, N. Ghosh, et al. "AB0834 DEVELOPMENT OF A CONCEPTUAL FRAMEWORK FOR A PATIENT REPORTED OUTCOME MEASURE TO CAPTURE PATIENTS’ PERCEPTIONS OF GLUCOCORTICOID THERAPY DURING TREATMENT FOR RHEUMATIC DISEASES." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 1441.1–1441. http://dx.doi.org/10.1136/annrheumdis-2021-eular.164.
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Background:Glucocorticoids (GCs) are a key treatment for the autoimmune rheumatic diseases; however, they produce numerous physical and psychological side effects.1 The Outcome Measures in Rheumatology (OMERACT) Glucocorticoid Working Group have identified that there are no Patient Reported Outcome Measures (PROMs) for assessing the impact of systemic GC therapy across multiple rheumatic diseases from the patient’s perspective.2,3Objectives:The aim is to explore the impact of GCs on the symptoms and health-related quality of life of adults with rheumatic inflammatory diseases, to inform items for inclusion in a PROM. Key considerations will include patient perceptions of GC therapy at diagnosis and over the course of treatment, for use in future randomised controlled trials or in clinical practice.Methods:An international steering committee comprising researchers, rheumatology clinicians, methodologists and patient partners in the UK, Australia and USA developed an initial conceptual framework informed by a review of the literature. Semi-structured interviews were conducted in each country with patients who had an autoimmune rheumatic disease and had received GC therapy. The interviews explored salient aspects of health-related quality of life associated with being treated with GCs.Results:Interviews have been completed in three continents with patients who had a range of demographic features, rheumatological conditions and duration and dosage of GC therapy. Figure 1 shows the initial conceptual framework for developing the GC PROM (Steroid PRO).Figure 1.Conclusion:This conceptual framework will act as an evolving guide in the development of a PROM for assessing patients’ perspectives of systemic glucocorticoid therapy. Future work will include inductive analysis of qualitative transcripts to inform candidate questionnaire items, cognitive interviewing, linguistic translatability assessment, and an international validation survey to define the final PROM questionnaire and its measurement properties.References:[1]Cheah JTL, Robson JC, Black RJ, et al. The patient’s perspective of the adverse effects of glucocorticoid use: A systematic review of quantitative and qualitative studies. From an OMERACT working group. Semin Arthritis Rheum. 2020 Oct; 50(5):996-1005.[2]Black RJ, Robson JC, Goodman SM, et al. A Patient-reported Outcome Measure for Effect of Glucocorticoid Therapy in Adults with Inflammatory Diseases Is Needed: Report from the OMERACT 2016 Special Interest Group. J Rheumatol. 2017; 44(11):1754-8.[3]Cheah JTL, Black RJ, Robson JC, et al. Toward a Core Domain Set for Glucocorticoid Impact in Inflammatory Rheumatic Diseases: The OMERACT 2018 Glucocorticoid Impact Working Group. J Rheumatol. 2019; 46(9):1179-1182.Disclosure of Interests:Susan Bridgewater Grant/research support from: Grant from Vifor Pharma for an independent investigator-led study to develop a PRO for steroids, Jill Dawson: None declared, Mwidimi Ndosi: None declared, Rachel J Black: None declared, Jonathan T.L. Cheah: None declared, Emma Dures: None declared, Nilasha Ghosh: None declared, Elizabeth A Hoon: None declared, Iris Navarro-Millan Consultant of: Received consultant fees from SOBI, Diyu Pearce-Fisher: None declared, Pamela Richards: None declared, Carlee Ruediger: None declared, Christine Silverthorne: None declared, Joanna Tieu Grant/research support from: Vifor Pharma, Sarah Mackie Consultant of: Consultancy on behalf of institution for Roche/Chugai, Sanofi, AbbVie and AstraZeneca, Grant/research support from: Educational grant from Roche to attend EULAR2019, Susan Goodman: None declared, Catherine Hill: None declared, Joanna Robson Speakers bureau: Vifor Pharma for educational webinar, Grant/research support from: Grant from Vifor Pharma for an independent investigator-led study to develop a PRO for steroids
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Dobson, J., D. Dockrell, K. Berg, S. Ralston, and H. Harris. "POS0801-HPR GREAT EXPECTATIONS: A FATIGUE MANAGEMENT PROGRAMME CAN ALSO IMPROVE SLEEP QUALITY AND MENTAL WELL-BEING IN RHEUMATIC DISEASE PATIENTS." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 694.2–695. http://dx.doi.org/10.1136/annrheumdis-2023-eular.2507.
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BackgroundFatigue is a significant problem for patients with Rheumatic diseases and yet remains overlooked and undertreated[1-3]. It is known to be associated with increased sleep disturbance in this patient group[4]and with poorer mental health[5]. A fatigue management programme (FMP) was developed with the aim of reducing the impact of fatigue on patients. Outcome measures were used to determine whether an improvement in fatigue scores also resulted in an improvement in sleep and mental health.ObjectivesThe primary objective was to evaluate whether a reduction in fatigue corresponded with an improvement in sleep quality following attendance at a virtual FMP. The secondary objective was to evaluate the impact of the FMP on patient mental well-being.MethodsThe FMP was based on the RAFT study[6]and patient-reported outcome measures (PROMs) were assessed before and after enrolment to the FMP. The Visual Analogue Scale (Fatigue) (VAS-F) was used to evaluate fatigue scores. The Pittsburgh Sleep Quality Index (PSQI) was used to assess changes in sleep quality. The Patient Health Questionnaire 9-Item (PHQ-9) and the Generalised Anxiety Disorder Assessment (GAD-7) were used to measure depression and anxiety scores respectively.ResultsGender ratio 5:1 females to males, age range 25-81 with a mean of 51.6 ± 12.3. Patient’s diagnoses were equally divided between Rheumatoid Arthritis, Systemic Lupus Erythematosus and other Rheumatic Diseases. Both primary and secondary objectives have been met.Table 1.PROM scores reported before and after the FMP. Data is shown as mean and standard deviation.n = 43Pre-FMPPost-FMPp valueVAS-F74.3 ± 18.452.3 ± 22.1<0.0001PSQI11.8 ± 4.89.1 ± 4.1<0.0001PHQ-913.8 ± 6.28.9 ± 5.4<0.0001GAD-78.5 ± 6.45.7 ± 5.30.0005Patient‘s scores significantly improved in all of the PROMs collected for the purposes of this service evaluation (see Table 1). There was a correlation between improvements in VAS-F scores and improvements in PSQI scores (r = 0.365) which was statistically significant (p = 0.016).ConclusionAn FMP is effective at significantly reducing fatigue, improving sleep quality and mental wellbeing. We have shown that there is a correlation between a reduction in fatigue and an improvement in sleep and this work highlights the importance of such a programme as part of routine care and management of these chronic conditions.References[1]Primdahl, J., Hegelund, A., Lorenzen, A.G., Loeppenthin, K., Dures, E. and Esbensen, B.A., 2019. The experience of people with rheumatoid arthritis living with fatigue: a qualitative metasynthesis.BMJ open,9(3), p.e024338.[2]Kier, A.Ø., Midtgaard, J., Hougaard, K.S., Berggreen, A., Bukh, G., Hansen, R.B. and Dreyer, L., 2016. How do women with lupus manage fatigue? A focus group study.Clinical rheumatology,35(8), pp.1957-1965.[3]Hewlett, S., Cockshott, Z., Byron, M., Kitchen, K., Tipler, S., Pope, D. and Hehir, M., 2005. Patients’ perceptions of fatigue in rheumatoid arthritis: overwhelming, uncontrollable, ignored.Arthritis care & research,53(5), pp.697-702.[4]Miyauchi, K., Fujimoto, K., Abe, T., Takei, M. and Ogawa, K., 2021. Cross-sectional assessment of sleep and fatigue in middle-aged Japanese women with primary Sjogren syndrome or rheumatoid arthritis using self-reports and wrist actigraphy.Medicine,100(37).[5]Matcham, F., Rayner, L., Steer, S. and Hotopf, M., 2013. The prevalence of depression in rheumatoid arthritis: a systematic review and meta-analysis.Rheumatology,52(12), pp.2136-2148.[6]Hewlett, S., Almeida, C., Ambler, N., Blair, P.S., Choy, E.H., Dures, E., Hammond, A., Hollingworth, W., Kadir, B., Kirwan, J.R. and Plummer, Z., 2019. Reducing arthritis fatigue impact: two-year randomised controlled trial of cognitive behavioural approaches by rheumatology teams (RAFT). Annals of the rheumatic diseases, 78(4), pp.465-472.Acknowledgements:NIL.Disclosure of InterestsJoanne Dobson: None declared, Dervil Dockrell: None declared, Kathryn Berg: None declared, Stuart Ralston Speakers bureau: UCB Pharma (fees paid to University of Edinburgh).Novartis (fees paid to University of Edinburgh).Janssen (fees paid to University of Edinburgh), Paid instructor for: Abbvie, Alexion, Amgen, Bristol Myers-Squibb, Celgene, Consilient Health, Janssen, Eli-Lilly, Novartis, Pfizer, Roche, Sandoz, Sanofi-Genzyme, Thornton & Ross, UCB: All provided sponsorship of 14th Scientific Symposium on Bone and Joint disease 2022 (Fees paid to University of Edinburgh)., Grant/research support from: Astra-Zeneca (Local investigator on clinical study, fees paid to NHS Lothian).Kyowa Kirin (Local investigator on clinical study, fees paid to NHS Lothian).Eli Lilly (donation of IMP for clinical trial), Helen Harris Speakers bureau: Galapagos Ltd, Paid instructor for: Galapagos Ltd.
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Ostendorf, L., U. Schneider, M. Urbicht, P. Enghard, F. Heinrich, P. Durek, G. Heinz, et al. "AB0385 TARGETING CD38 IN SYSTEMIC LUPUS ERYTHEMATOSUS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1493.3–1493. http://dx.doi.org/10.1136/annrheumdis-2020-eular.5052.
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Background:Depletion of long-lived plasma cells (PC) resembles a novel concept for the treatment of antibody-mediated autoimmune diseases, such as systemic lupus erythematosus (SLE). Therapeutic approaches such as autologuos stem-stem cell transplantation and proteasome inhibition are limited by significant treatment-related toxicity. A novel target for PC depletion is CD38, a surface protein that is highly expressed on plasma cells (PCs) but also activated T-cells and most myeloid cells. Daratumumab is a monoclonal antibody targeting CD38 that is licensed for the treatment of multiple myeloma.Objectives:Here, we aimed to ascertain clinical safety and efficacy of Daratumumab for the treatment of refractory SLE, as well as to gain insights into effects of Daratumumab on the immune system.Methods:We treated two SLE patients with life- and organ-threatening SLE with four weekly dosis of 16 mg/kg Daratumumab. We performed integrative analyses of clinical, serological and immunological effects over a follow-up period of 6 months. Using flow cytometry and single-cell RNA and T-cell receptor sequencing we followed CD38 expression and composition of peripheral blood leukocytes with a special focus on memory T cells.Results:Patient 1, a 50-year old woman, suffered from active biopsy-proven class III lupus nephritis (LN) with nephrotic syndrome, pericarditis, arthritis and skin rash. Upon Daratumumab treatment, her glomerular filtration rate normalized within 3 months and proteinuria gradually declined from 6.4 to 1.9g/g Creatinine during the 180-day follow-up period. Pericarditis, arthritis and skin rash completely resolved. Patient 2, a 32-year-old woman, presented with autoimmune hemolytic anemia requiring blood transfusions, immune thrombocytopenia and cutaneous vasculitis. Her direct antiglobulin test normalized within 3 months and remained negative throughout follow-up with consecutive recovery of the hemolytic anemia. Immune thrombocytopenia stabilized and vasculitic skin lesions completely resolved. Infusions were well tolerated without severe adverse drug reactions. NK cells and Dendritic Cells were transiently depleted, while numbers of T cells, B cells and Monocytes in the peripheral blood remained stable. CD38+ memory T cells that were expanded prior to treatment were virtually undetectable early after treatment. Their single cell transcriptomics demonstrated an upregulation of genes associated with activation, cytotoxicity and type 1 interferon response. CD38+ CD8+ memory T-cells showed marked oligoclonality. These prominent clones persisted upon treatment but their transcription profile gradually normalized.Conclusion:Daratumumab appears to be a safe and effective treatment for refractory SLE. Further investigations are warranted to establish the efficacy in a clinical trial and to gain further insights into the pathophysiologic mechanism of action.Disclosure of Interests:Lennard Ostendorf: None declared, Udo Schneider: None declared, Marie Urbicht: None declared, Philipp Enghard: None declared, Frederik Heinrich: None declared, Pawel Durek: None declared, Gitta Heinz: None declared, Henrik Mei: None declared, Mir-Farzin Mashreghi: None declared, Gerd Rüdiger Burmester Consultant of: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Speakers bureau: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Andreas Radbruch: None declared, Falk Hiepe: None declared, Tobias Alexander: None declared
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Machado, P. M., S. Lawson-Tovey, K. Hyrich, L. Carmona, L. Gossec, E. Mateus, A. Strangfeld, et al. "LB0002 COVID-19 VACCINE SAFETY IN PATIENTS WITH RHEUMATIC AND MUSCULOSKELETAL DISEASE." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 199–200. http://dx.doi.org/10.1136/annrheumdis-2021-eular.5097.
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Background:The consequences of the COVID-19 outbreak are unprecedented and have been felt by everyone around the world, including people with rheumatic and musculoskeletal diseases (RMDs). With the development of vaccines, the future is becoming brighter. Vaccines are a key pillar of public health and have been proven to prevent many serious diseases. However, vaccination also raises questions, especially for patients with inflammatory RMDs and/or treated with drugs that influence their immune system.Objectives:Our aim was to collect safety data among RMD patients receiving COVID-19 vaccines.Methods:The EULAR COVID-19 Vaccination (COVAX) Registry is an observational registry launched on 5 February 2021. Data are entered voluntarily by clinicians or associated healthcare staff; patients are eligible for inclusion if they have an RMD and have been vaccinated against SARS-CoV-2. Descriptive statistics are presented.Results:As of 27 April 2021, 1519 patients were reported to the registry. The majority were female (68%) and above the age of 60 (57%). Mean age was 63 years (SD 16), ranging from 15 to 97 years. A total of 28 countries contributed to the registry, with France (60%) and Italy (13%) as the highest contributors. The majority (91%) had inflammatory RMDs. Inflammatory joint diseases accounted for 51% of cases, connective tissue diseases 19%, vasculitis 16%, other immune mediated inflammatory diseases 4%, and non-inflammatory/mechanical RMDs 9%. The most frequent individual diagnoses were rheumatoid arthritis (30%), axial spondyloarthritis (8%), psoriatic arthritis (8%), systemic lupus erythematosus (SLE, 7%) and polymyalgia rheumatica (6%). At the time of vaccination, 45% were taking conventional synthetic DMARDs, 36% biological DMARDs, 31% systemic glucocorticoids, 6% other immunosuppressants (azathioprine; mycophenolate; cyclosporine; cyclophosphamide; tacrolimus), and 3% targeted synthetic DMARDs. The most frequent individual DMARDs were methotrexate (29%), TNF-inhibitors (18%), antimalarials (10%) and rituximab (6%). The vaccines administered were: 78% Pfizer, 16% AstraZeneca, 5% Moderna and 1% other/unknown; 66% of cases received two doses and 34% one dose. Mean time from 1st and 2nd dose to case report was 41 days (SD 26) and 26 days (SD 23), respectively. COVID-19 diagnosis after vaccination was reported in 1% (18/1519) of cases. Mean time from first vaccination until COVID-19 diagnosis was 24 days (SD 17). Disease flares were reported by 5% (73/1375) of patients with inflammatory RMDs, with 1.2% (17/1375) classified as severe flares. Mean time from closest vaccination date to inflammatory RMD flare was 5 days (SD 5). The most common flare types were arthritis (35/1375=2.5%), arthralgia (29/1375=2.1%), cutaneous flare (11/1375=0.8%) and increase in fatigue (11/1375=0.8%). Potential vaccine side effects were reported by 31% of patients (467/1519). The majority were typical early adverse events within 7 days of vaccination, namely pain at the site of injection (281/1519=19%), fatigue (171/1519=11%) and headache (103/1519=7%). Organ/system adverse events were reported by 2% (33/1519) but only 0.1% (2/1519) reported severe adverse events, namely a case of hemiparesis in a patient with systemic sclerosis/SLE overlap syndrome (ongoing at the time of reporting), and a case of giant cell arteritis in a patient with osteoarthritis (recovered/resolved without sequelae).Conclusion:The safety profiles for COVID-19 vaccines in RMD patients was reassuring. Most adverse events were the same as in the general population, they were non-serious and involved short term local and systemic symptoms. The overwhelming majority of patients tolerated their vaccination well with rare reports of inflammatory RMD flare (5%; 1.2% severe) and very rare reports of severe adverse events (0.1%). These initial findings should provide reassurance to rheumatologists and vaccine recipients, and promote confidence in COVID-19 vaccine safety in RMD patients, namely those with inflammatory RMDs and/or taking treatments that influence their immune system.Acknowledgements:EULAR COVID-19 Task Force; European Reference Network on rare and Complex Connective Tissue and Musculoskeletal Diseases; European Reference Network on Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases Network; all rheumatologists contributing to the EULAR COVAX Registry.Disclosure of Interests:Pedro M Machado Consultant of: Abbvie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this manuscript., Grant/research support from: Orphazyme, unrelated to this manuscript., Speakers bureau: Abbvie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this manuscript., Saskia Lawson-Tovey: None declared, Kimme Hyrich Grant/research support from: BMS, UCB, and Pfizer, all unrelated to this manuscript., Speakers bureau: Abbvie, Loreto Carmona Consultant of: her institute works by contract for laboratories among other institutions, such as Abbvie Spain, Eisai, Gebro Pharma, Merck Sharp & Dohme España, S.A., Novartis Farmaceutica, Pfizer, Roche Farma, Sanofi Aventis, Astellas Pharma, Actelion Pharmaceuticals España, Grünenthal GmbH, and UCB Pharma, all unrelated to this manuscript., Laure Gossec Grant/research support from: AbbVie, Amgen, BMS, Biogen, Celgene, Gilead, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, UCB, all unrelated to this manuscript., Speakers bureau: Amgen, Lilly, Janssen, Pfizer, Sandoz, Sanofi, Galapagos, all unrelated to this manuscript., Elsa Mateus Grant/research support from: LPCDR received support for specific activities: grants from Abbvie, Novartis, Janssen-Cilag, Lilly Portugal, Sanofi, Grünenthal S.A., MSD, Celgene, Medac, Pharmakern, GAfPA; grants and non-financial support from Pfizer; non-financial support from Grünenthal GmbH, outside the submitted work., Anja Strangfeld Speakers bureau: AbbVie, MSD, Roche, BMS, and Pfizer, all unrelated with this manuscript., BERND RAFFEINER: None declared, Tiphaine Goulenok: None declared, Olilvier Brocq: None declared, Martina Cornalba: None declared, José A Gómez-Puerta Speakers bureau: AbbVie, BMS, GSK, Janssen, Lilly, MSD, Roche and Sanofi., Eric Veillard: None declared, Ludovic Trefond: None declared, Jacques-Eric Gottenberg: None declared, Julien Henry: None declared, Patrick Durez: None declared, Gerd Rüdiger Burmester: None declared, Marta Mosca: None declared, Eric Hachulla: None declared, Hans Bijlsma: None declared, Iain McInnes: None declared, Xavier Mariette Consultant of: BMS, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sanofi-Aventis, UCB, and grant from Ose, all unrelated to this manuscript.
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Favalli, E. G., M. H. Buch, J. Galloway, A. Constantin, P. Durez, P. Van Hoek, C. Watson, et al. "AB0454 SAFETY OF FILGOTINIB IN PATIENTS WITH RA: LABORATORY ANALYSIS RESULTS FROM A LONG-TERM EXTENSION STUDY." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 1417–18. http://dx.doi.org/10.1136/annrheumdis-2023-eular.2129.
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BackgroundFilgotinib (FIL) is a Janus kinase (JAK) 1 preferential inhibitor, approved for treatment of moderate to severe active RA in Europe, the UK, and Japan. Graded laboratory abnormalities from placebo-controlled analyses and long-term data on lymphocytes have been reported previously.ObjectivesReport the effect of FIL on laboratory parameters in the FINCH 4 long-term extension (LTE).MethodsSafety was assessed from LTE baseline (BL) to data cutoff (1 Jun 2020) in patients (pts) receiving ≥1 FIL dose (FIL 200 mg [FIL200] or 100 mg [FIL100]) in FINCH 4 (NCT03025308). Laboratory abnormalities were graded per Common Terminology Criteria for Adverse Events v4.03. Frequencies and exposure-adjusted incidence rates (EAIRs)/100 pt-years of exposure (PYE) for graded abnormalities are reported. Median laboratory parameters are reported to LTE Week (W) 48.ResultsIn FINCH 4, 2729 pts received FIL for 4198.08 PYE (mean 80.3 weeks); exposure was similar between dose groups. Frequency and EAIR of laboratory abnormalities were similar for anemia, decreased platelets, and increased alanine aminotransferase (ALT), aspartate aminotransferase (AST), and serum creatinine, and higher in the FIL200 vs FIL100 group for neutropenia, increased creatinine kinase (CK), hypophosphatemia, and cholesterol (high) (Table 1; graded data not shown). No Grade 4 decreased phosphate laboratory abnormalities were observed and hypophosphatemia was not associated with adverse events. Laboratory abnormalities led to discontinuation of FIL in 7 pts: ALT and AST increased, 3 (0.2%, FIL 200); ALT increased, 1 (<0.1%, FIL 100); and neutropenia 3 (0.3%, FIL 100). From LTE BL to W48, hemoglobin, platelets, ALT, and AST were relatively stable, with no clear differences between doses, or between pts with or without prior FIL. Neutrophil count was relatively stable from LTE BL to W48. Neutrophils decreased for the FIL200 group with no prior FIL exposure, remaining stable from W24. CK and serum creatinine were relatively stable from LTE BL to W48 in pts with prior FIL exposure; in pts with no prior FIL, initial increases plateaued by W6 and W12, respectively, remaining stable. Changes in phosphate levels from LTE BL were small, remaining within normal range (2.2–5.1 mg/dL). Triglycerides were stable over time with no differences between groups. Total cholesterol, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) levels were stable in pts with prior FIL exposure. In pts with no prior FIL exposure, small increases in total cholesterol, HDL, and LDL plateaued by W24, remaining stable. The LDL:HDL ratio was stable, with no differences between groups (Figure 1).ConclusionLaboratory abnormalities were generally mild to moderate, similar to previous observations. Frequency and EAIR were higher in the FIL200 vs FIL100 group for neutropenia, increased CK, hypophosphatemia, and high cholesterol.Table 1.Treatment-emergent laboratory abnormalities* (any Grade ≥1; safety analysis set†)n/N (%); EAIR (95% confidence interval)FIL200 (n=1530; PYE=2346.0)FIL100 (n=1199; PYE=1852.1)Anemia264/1526 (17.3); 11.3 (10.0, 12.7)227/1193 (19.0); 12.3 (10.8, 14.0)Platelets (decreased)44/1525 (2.9); 1.9 (1.4, 2.5)24/1189 (2.0); 1.3 (0.9, 1.9)Neutropenia194/1526 (12.7); 8.3 (7.2, 9.5)101/1193 (8.5); 5.5 (4.5, 6.6)ALT (increased)349/1526 (22.9); 14.9 (13.4, 16.5)287/1193 (24.1); 15.5 (13.8, 17.4)AST (increased)338/1526 (22.1); 14.4 (13.0, 16.0)273/1193 (22.9); 14.7 (13.1, 16.6)Serum creatinine (increased)80/1526 (5.2); 3.4 (2.7, 4.2)62/1193 (5.2); 3.3 (2.6, 4.3)Creatine kinase (increased)448/1526 (29.4); 19.1 (17.4, 20.9)259/1193 (21.7); 14.0 (12.4, 15.8)Hypophosphatemia103/1526 (6.7); 4.4 (3.6, 5.3)50/1193 (4.2); 2.7 (2.0, 3.6)Hypertriglyceridemia307/1497 (20.5); 13.1 (11.7, 14.6)268/1164 (23.0); 14.5 (12.8, 16.3)Cholesterol (high)125/1497 (8.4); 5.3 (4.5, 6.3)73/1164 (6.3); 3.9 (3.1, 5.0)*Defined as an increase of ≥1 toxicity grade from BL up to 30 days post last study drug dose;†Pts who received ≥1 dose of study drug.AcknowledgementsWe thank the physicians and patients who participated in these studies. The FINCH studies were co-funded by Gilead Sciences Inc. (Foster City, CA, USA) and Galapagos NV (Mechelen, Belgium). Publication coordination was provided by Fabien Debailleul, PhD, of Galapagos NV. Medical writing support was provided by Stephanie Rippon, MBio (Aspire Scientific, Bollington, UK) and funded by Galapagos NV.Disclosure of InterestsEnnio Giulio Favalli Speakers bureau: AbbVie, BMS, Celltrion, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, UCB, Consultant of: AbbVie, BMS, Celltrion, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, UCB, Maya H Buch Speakers bureau: AbbVie (paid to host institution), Consultant of: AbbVie, CESAS Medical, Galapagos, Gilead, Pfizer (all paid to host institution), Grant/research support from: Gilead (paid to host institution), James Galloway Speakers bureau: AbbVie, Biogen, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Roche, UCB, Consultant of: AbbVie, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Grant/research support from: AstraZeneca, Celgene, Gilead, Janssen, Medicago, Novavax, Pfizer, Arnaud Constantin Speakers bureau: AbbVie, Amgen, Biogen, BMS, Boehringer, Celltrion, Fresenius-Kabi, Galapagos, Janssen, Lilly, Medac, MSD, Novartis, Pfizer, Roche, Sanofi, Sandoz, UCB, Viatris, Consultant of: AbbVie, Boehringer, Celltrion, Galapagos, Janssen, Lilly, Novartis, Pfizer, UCB, Patrick Durez Speakers bureau: AbbVie, Eli Lilly, Galapagos, Paul Van Hoek Consultant of: Galapagos, Aspen, AOP Health, Sanofi-Genzyme, Astellas, Employee of: Schering Plough, MSD, Janssen, Chris Watson Shareholder of: Galapagos, Employee of: Galapagos, Pieter-Jan Stiers Employee of: Galapagos, Vijay Rajendran Shareholder of: Galapagos, Employee of: Galapagos, Katrien Van Beneden Shareholder of: Galapagos, Employee of: Galapagos, Tsutomu Takeuchi Speakers bureau: AbbVie GK, AYUMI, BMS, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Gilead Sciences, Inc., Janssen Pharm KK, Mitsubishi Tanabe, Pfizer Japan, Sanofi KK, Consultant of: AbbVie GK, Astellas, Chugai, Eli Lilly Japan, Gilead Sciences, Inc., Janssen Pharm KK, Mitsubishi Tanabe, Pfizer Japan, Grant/research support from: Astellas, AYUMI, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, AbbVie GK, Asahi Kasei Pharma, Mitsubishi Tanabe, Nippon Kayaku, UCB Japan, Bernard Combe Speakers bureau: AbbVie, Celltrion, Galapagos, Janssen, Lilly, Pfizer, Roche-Chugai, Consultant of: AbbVie, Galapagos, Gilead, Janssen, Lilly, Novartis, Roche-Chugai.
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Bridgewater, S., M. Ndosi, J. Dawson, P. Richards, C. Silverthorne, E. Dures, S. Goodman, C. Hill, S. Mackie, and J. Robson. "OP0280-HPR VALIDATION OF A NEW GLUCOCORTICOID-SPECIFIC PATIENT REPORTED OUTCOME QUESTIONNAIRE (THE STEROID PRO)." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 184.2–184. http://dx.doi.org/10.1136/annrheumdis-2023-eular.3705.
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BackgroundGlucocorticoids are used in the treatment of a broad range of rheumatic conditions but can have a significant impact on health-related quality of life[1]. In-depth qualitative interviews with patients who have experience of glucocorticoid treatment for their rheumatic disease, from the UK, USA and Australia, were used to develop candidate items for a treatment-specific Patient Reported Outcome Measure (PROM): the Steroid PRO.ObjectivesWe aimed to complete the development and validation of the Steroid PRO through use of a cross-cultural validation study.MethodsThis was a cross-sectional online study of adults taking glucocorticoids for a rheumatic disease, from the UK, USA, Australia and New Zealand. A steering committee comprising methodologists, clinicians and patient research partners (PRPs) oversaw the study. The survey was distributed via social media with support from patient groups. Baseline data included: (i) demographics - age, gender, country, ethnicity, educational level; (ii) clinical information - diagnosis, glucocorticoid dose; (iii) 40 candidate items for the Steroid-PRO, developed in a previous qualitative study; (iv) EQ5D-5L. Optional follow-up data collected 3-5 days later: (i) the Steroid PRO candidate items; (ii) a condition change question. After descriptive analysis, iterative testing with Rasch measurement model and exploratory factor analysis (EFA) informed item reduction and established structural validity, reliability and unidimensionality of the final Steroid PRO. Item reduction was based on clinical importance, lack of fit to the Rasch model, and redundancy. Evidence of discriminative validity of the Steroid PRO was established by comparing its scores for participants receiving lower dose glucocorticoid (up to 10 mg) versus higher dose (>10 mg). Intraclass correlation (ICC) between baseline and follow-up was calculated for patients who reported ‘no change’ compared with 3-5 days ago.ResultsA total of 946 patients returned complete responses at baseline (follow-up: 447 responses). They were from UK, n=743 (78.5%); USA, n=139 (14.7%); Australia, n=59 (6.2%). Their mean age was 57.6 (SD=13.6); 833 (88%) were women. They were treated for inflammatory arthritis (n=194), connective tissue disease and/or vasculitis (n=398), and giant cell arteritis and/or polymyalgia rheumatica (n=341). A total of 25 items were removed due to floor effects and lack of fit to the Rasch model. Iterative discussions between statisticians, clinicians and PRPs ensured that items of high clinical importance were retained. The remaining 15 items showed a satisfactory fit to the model. EFA suggested a scale structure with four domains: Participation (4 items), Appearance (3 items), Psychological (5 items), and Treatment concerns (3 items). PRPs were involved in naming the domains. The 4-domain structure was supported by the Rasch model, confirming construct validity; χ2=47.82 (DF=36), p=0.899; and reliability (Person Separation Index, PSI=0.757). Total scores also fitted the Rasch model, therefore both domain and total scores will be psychometrically appropriate for use as a repeated measure. A good fit to the Rasch model was also seen across the disease groups with items distributed equally across the three groups. Patients on a lower glucocorticoid dose had lower Steroid PRO domain scores than those receiving higher dose (discriminant validity). ICC between baseline and follow-up ranged from 0.892 to 0.942 (95%CI 0.868 to 0.953) suggesting excellent (test-retest) reliability.ConclusionThe final Steroid PRO is a 15-item, valid and reliable 4-domain scale measuring the impact of glucocorticoid therapy on HRQoL of people with rheumatic diseases.Reference[1]Cheah, J. T. L.; Robson, J. C.; Black, R. J.; Goodman, S. M.; Lester, S.; Mackie, S. L.; Hill, C. L., The patient’s perspective of the adverse effects of glucocorticoid use: A systematic review of quantitative and qualitative studies. From an OMERACT working group. Seminars in arthritis and rheumatism 2020 50 (5), 996-1005.Acknowledgements:NIL.Disclosure of InterestsSusan Bridgewater Grant/research support from: Vifor Pharma, Mwidimi Ndosi Grant/research support from: Vifor Pharma, Jill Dawson: None declared, Pamela Richards: None declared, Christine Silverthorne: None declared, Emma Dures Grant/research support from: Vifor Pharma, Susan Goodman Consultant of: UCB, Grant/research support from: Novartis, Catherine Hill: None declared, Sarah Mackie Speakers bureau: Roche/Chugai, Vifor Pharma and Pfizer on behalf of her institution (no personal remuneration), Consultant of: Roche/Chugai, Sanofi, AbbVie, AstraZeneca and investigator on clinical trials for Sanofi and GSK on behalf of her institution (no personal remuneration), Grant/research support from: Vifor Pharma as research grant co-applicant (partial salary support) paid to her institution, Joanna Robson Speakers bureau: Vifor Pharma, Consultant of: Vifor Pharma, Grant/research support from: Vifor Pharma.
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Felten, R., P. M. Duret, E. Bauer, M. Ardizzone, H. J. Djossou, J. H. Salmon, C. Fabre, et al. "OP0282 RITUXIMAB ASSOCIATED WITH SEVERE COVID-19 AMONG PATIENTS WITH INFLAMMATORY ARTHRITIDES: A 1-YEAR MULTICENTER STUDY IN 1116 SUCCESSIVE PATIENTS RECEIVING BIOLOGIC AGENTS." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 170.1–171. http://dx.doi.org/10.1136/annrheumdis-2021-eular.1521.
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Background:At a time when vaccines are being prioritized for individuals most at risk, there is currently no clear evidence that risk of SARS-CoV-2 infection is higher for patients with than without inflammatory arthritides (IA). Biologic use was not associated with worse COVID-19 outcomes for yet but the case of rituximab (RTX) remains an issue, given its immunological long term effect, the role of humoral response against SARS-CoV-2 and its indirect effect on T-cell response. A potential association between rituximab and worse COVID-19 outcomes was raised by case reports and retrospective, declarative studies (with few data on the total number of patients exposed).Objectives:To address differently the issue of the risk of COVID-19 related to RTX and limit biases, we examined the occurrence of severe COVID-19 in all patients receiving intravenous biologic agents at day-hospitals during the pandemic in France.Methods:From 1st September 2019 to 1st January 2021, we analyzed patients with IA prospectively treated with intravenous biologic agents (RTX, abatacept, infliximab or tocilizumab) in 7 clinical centers in France. We obtained the list of patients receiving intravenous biologic agents in each center from the pharmacist of the hospitals. Therefore, all consecutive patients receiving 1 of the 4 drugs at the time of the study were included in each center. Patients with no follow-up after September 2020 were systematically contacted by phone. The occurrence of a severe COVID -19 (i.e. resulting in death, hospitalization or increase in length of hospitalization related to COVID-19) was the primary outcome criteria.Results:In total, 1116 patients receiving intravenous biologic agents were included: 449 with infliximab, 392 RTX, 170 tocilizumab and 105 abatacept. From 1st September 2019, the median follow-up time was 15 months (interquartile range 14-16). In total, 10 cases of severe COVID-19 occurred, 9 treated with RTX and 1 with infliximab (supplementary Table 1). Four deaths occurred in our cohort during follow-up but none was related to COVID-19 (1 patient treated by tocilizumab, 1 by RTX and 2 by infliximab). In univariate analysis, the proportion of severe COVID-19 was significantly higher for patients receiving RTX than other biologic agents (9/392 vs 1/724, p=0.0003, OR [95%CI] 17.0 [2.1-134.6]). To take into account potential confounders, we performed multivariate analysis accounting for baseline parameters that differed between RTX and other biologic groups. RTX remained significantly associated with risk of severe COVID-19 (p=0.019) (Table 1).Patient characteristicsRituximab (n= 392)Other bDMARDs (n= 724)Univariate analysis, p-valueMultivariate analysis, p-valueMedian age (years), — [IQR]64 [56-71]57.3 [47.0-67.0]< 0.00010.51Female — n (%)285 (72.7)426 (58.8)< 0.00010.58IA diagnosis< 0.00010.12Median follow-up from 1st September to last news14 [13-15]15 [14-16]< 0.00010.86Confirmed severe COVID-19 cases —n (%)9 (2.3)1 (0.1)0.00030.019Comorbidities** (history of) — n (%) Cardiovascular disease60 (15.4)167 (23.1)0.00250.77 Chronic lung disease,92 (23.5)84 (11.6)0.00010.88Median BMI (kg/m2) — [IQR]25.8 [23.2-29.4]27.3 [23.4-31.2]0.0150.80Treatments — n (%) Methotrexate179 (45.8)322 (44.5)0.71 Leflunomide41 (10.5)39 (5.4)0.00230.43 Hydroxychloroquine35 (8.9)24 (3.3)0.00010.15 Glucocorticoids127 (41.8)100 (19.4)< 0.00010.36 Median dose (mg/day) — [IQR]1 [0-5]0 [0-0]< 0.0001No significant difference in terms of baseline gammaglobulins (p=0.46) or number of previous RTX infusions (p=0.57) was observed among patients receiving RTX with or without a severe COVID-19.Conclusion:The present results highly indicate increased risk of severe COVID-19 with RTX. Among patients with inflammatory arthritides, those receiving RTX should be prioritized for vaccination against SARS-CoV-2, sufficiently long before infusion/reinfusion and the immunization checked, or an alternative targeted therapy proposed.Acknowledgements:We thank Dr. Karine Demesmay and all the pharmacists who helped us for this study.Disclosure of Interests:Renaud FELTEN Speakers bureau: Abbvie, Biogen, BMS, Lilly, Novartis, Pfizer, Pierre-Marie Duret: None declared, Elodie BAUER: None declared, Marc Ardizzone: None declared, H Julien Djossou: None declared, Jean-Hugues Salmon: None declared, Cassandre Fabre: None declared, Julia Walther: None declared, Isabelle CHARY VALCKENAERE: None declared, marion geoffroy: None declared, Laurent Messer: None declared, Francis Berenbaum: None declared, Martin SOUBRIER: None declared, Jérémie SELLAM Speakers bureau: MSD, Pfizer, Abbvie, Roche, BMS, Lilly, Janssen, Novartis, Galapagos, Sandoz, Fresenius Kabi, Grant/research support from: Roche, MSD, Pfizer, Jacques-Eric Gottenberg: None declared
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Daien, C., M. Krogulec, P. Gineste, J. M. Steens, L. Desroys Du Roure, S. Biguenet, D. Scherrer, J. Santo, H. Ehrlich, and P. Durez. "POS0688 PHASE 2A STUDY IN PATIENTS WITH MODERATE-TO-SEVERE RHEUMATOID ARTHRITIS AND INADEQUATE RESPONSE TO MTX AND/OR ANTI-TNFΑ THERAPEUTICS SHOWS THAT ORAL ABX464 50 MG ONCE DAILY IS SAFE, WELL TOLERATED AND SHOWS PROMISING EFFICACY RESULTS." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 623.1–623. http://dx.doi.org/10.1136/annrheumdis-2022-eular.2286.
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BackgroundABX464 upregulates the expression of the anti-inflammatory microRNA miR-124 and is a first-in-class drug candidate as an oral treatment for moderate-to-severe Rheumatoid Arthritis (RA).ObjectivesThis phase 2a randomized, double blind, placebo controlled, parallel group 12-week study evaluated the safety and preliminary efficacy of ABX464 (50 and 100 mg q.d.), in combination with methotrexate (MTX) in 60 patients (1:1:1 ratio) with moderate-to-severe active RA who have inadequate response to MTX or/and to an anti-TNFα therapy. Patients who completed the 12-week induction phase could roll over into a 52-week open-label maintenance study to evaluate the long-term safety and efficacy of 50 mg q.d oral ABX464 in RA.MethodsThe primary end point was the safety of ABX464; efficacy endpoints included the proportion of patients achieving ACR20/50/70 responses, disease activity scores (DAS28, SDAI, CDAI), EULAR response, DAS28 low disease activity (DAS28-CRP ≤ 3.2) or remission. Blood samples from patients were used to measure the expression of miR-124 and the relative concentrations of cytokines (baseline and week 8).ResultsPatients baseline characteristics were well balanced in terms of disease severity and demographics (mean ± SD DAS28-CRP: 5.43 ± 0.78; RA duration: 6.43 ± 7.43 years). ABX464 50 mg was safe and well tolerated. Two serious adverse events (SAEs) were reported (one on placebo group and one on ABX464 100 mg). Eleven patients were withdrawn for AEs (9 patients on 100 mg, 1 on 50 mg and 1 on placebo). An increased incidence of largely mild-to-moderate gastrointestinal AEs in the 100 mg treatment group led to a higher drop-out rate of patients. The nature of these AEs was consistent with what has been observed in more than 1023 subjects who have so far been treated in other clinical trials with ABX464 across different indications. No cases of opportunistic infection, no malignancies and no death were reported.Although the sample size of this proof-of-concept study was not powered to show efficacy, multiple early efficacy endpoints showed signs of promise with the ABX464 50 mg daily dose. Compared to placebo, ABX464 50 mg showed significantly higher proportions of patients achieving ACR20 and ACR50 responses at week 12 in the per protocol population (PP). DAS28-CRP and DAS28-ESR decreased significantly (Intent-to-Treat Population, ITT) and rates of categorical DAS28-CRP response (PP) or CDAI remission (ITT) increased significantly on ABX464 at week 12 (Table 1). Compared to placebo, a significant upregulation of miR-124 expression and a decrease in IL-6 blood levels were observed for every patient dosed with ABX464.Table 1.Efficacy endpoints.Placebo50 mg100 mgPPITTPPITTPPITT(n=19)(n=20)(n=16)(n=21)(n=7)(n=19)Early discontinuations due to AE119 ACR20 n (%)4 (21%)4 (20%)9 (56%) *9 (43%)3 (43%)3 (16%) ACR50 n (%)1 (5%)1 (5%)5 (31%) *5 (24%)2 (29%)2 (11%) ACR70 n (%)1 (5%)1 (5%)4 (25%)4 (19%)1 (14%)1 (5%)DAS28-CRP-0.63-0.60-1.79 *-1.41 *-1.94 *-0,72Mean change from baselineDAS28-ESR-0.65-0.59-1.86 *-1.43 *-2.0 **-0.74Mean change from baselineLow Disease Activity2 (11%)2 (10%)4 (25%)4 (19%)3 (43%)3 (16%)(DAS28-CRP ≤ 3.2) n (%)Categorical DAS28-CRP response8 (42%)8 (40%)14 (88%) **14 (67%)6 (86%) *6 (32%)n (%)CDAI ≤ 10 n (%)2 (11%)2 (10%)5 (31%)5 (24%)3 (43%)3 (16%)CDAI Remission n (%)003 (19%) *3 (14%) *00* P < 0.05, ** P < 0.01 Chi-squared test ABX-464 versus placebo40 patients enrolled in the ongoing open-label maintenance study with ABX464 50 mg q.d.At week 52, the drop-out rate of patients was 44 % (17/39), including 7 drop-outs due to AE (18 %). Preliminary maintenance efficacy data, defined as Low Disease Activity, were obtained from 22 patients who reached 52 weeks of treatment: 44 % patients achieved LDA according to ITT.ConclusionEfficacy and safety findings of the first-in-class drug candidate ABX464 warrant further exploration at 50 mg q.d. or less as an oral treatment for RA patients.Disclosure of InterestsClaire Daien Speakers bureau: Abivax, Consultant of: Abivax, Abbvie, Amgen, BMS, Fresenius-Kabi, MSD, Novartis, Pfizer, Sandoz, Sanofi, Roche-Chugai, UCB, Grant/research support from: punctual links or research grant from Abbvie, Amgen, BMS, Fresenius-Kabi, MSD, Novartis, Pfizer, Sandoz, Sanofi, Roche-Chugai, UCB, Marek Krogulec: None declared, Paul Gineste Employee of: Abivax, Jean-Marc Steens Employee of: Abivax, Laurence Desroys Du Roure Employee of: Abivax, Sophie Biguenet Employee of: Abivax, Didier Scherrer Employee of: Abivax, Julien Santo Employee of: Abivax, Hartmut Ehrlich Employee of: Abivax, Patrick Durez: None declared
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Kalmar, Alexandra, Gitta Szabo, Orsolya Galamb, Barbara Kinga Bartak, Zsofia Brigitta Nagy, Sara Zsigrai, Krisztina Andrea Szigeti, et al. "Abstract 2945: Comprehensive analysis of tissue and plasma-related genetic alterations in Hungarian colorectal cancer patients." Cancer Research 82, no. 12_Supplement (June 15, 2022): 2945. http://dx.doi.org/10.1158/1538-7445.am2022-2945.
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Abstract Background: Analysis of circulating cell-free DNA (cfDNA) of colorectal cancer (CRC) patients provides an ideal approach to explore genetic alterations in a minimally invasive way. Aims: We aimed to perform a comprehensive analysis of tissue-originated genomic DNA and plasma-derived cfDNA from CRC patients by whole-exome and targeted panel sequencing. Materials & methods: DNA was isolated from tissue and plasma samples of 55 [7 healthy (N), 16 adenomas (AD), and 32 CRC] patients using the High Pure PCR Template Kit (Roche) and the Quick cfDNA Serum & Plasma Kit (Zymo). cfDNA quality was assessed with the High Sensitivity DNA kit on BioAnalyzer 2100 and quantified by the Qubit dsDNA HS assay. Exome libraries from tissue samples were constructed by the Nextera DNA Exome Kit (Illumina). For the cfDNA samples, we used the QIAseq cfDNA All-in-One kit combined with the QIASeq Human Exome Kit, and in the case of 12 patients, CRC-specific oncogenes were further analyzed with a solution developed by QIAGEN for reliable calling of low frequency variants in cfDNA samples. Exome libraries were quantified with the KAPA Library Quantification Kit and the QIAseq™ Library Quant Assay Kit (Qiagen) and were sequenced using the NextSeq 500/550 High Output v2 kit on a NextSeq 500 Instrument (Illumina). Raw data analysis and demultiplexing were completed on the BaseSpace Sequence Hub. Variants of the tissue and cfDNA samples were determined by the Mutect2 and Haplotype caller algorithms of GATK 4.1.4.1, respectively. Clinical significance was evaluated according to the OncoKB database. Results: The most frequently mutated genes were APC, KRAS, DYNC1H1, KCNO5, and MARCH6 in the colorectal adenoma tissue samples, while those in CRC samples were APC, TP53, TTN, KRAS, and DYNCC2H1. CfDNA quantity was significantly higher in the CRC group compared to the AD (p<0.02) and N (p<0.005) patients. Based on the plasma exome results, 4.4-59.4% of the tumor somatic variants could be found in 12.5% of the patients. These patients were above 60 years of age and had Dukes D stage CRC. Panel sequencing of the circulating DNA samples detected tumor somatic variants in 8 out of the 12 enrolled patients. This method could identify 60% of all tumor somatic variants falling on its targeted regions, while whole-exome sequencing recovered only 20% of tumor somatic variants in the respective regions in cfDNA of the same patients. Conclusion: We have performed a comprehensive genetic analysis on CRC tissue and cfDNA samples in the Hungarian population. Exome sequencing offers a broad overview of the coding regions, however, targeted panel sequencing with a higher coverage depth can detect tumor somatic variants more reliably in cfDNA, therefore, it can hold a relevant clinical potential. Citation Format: Alexandra Kalmar, Gitta Szabo, Orsolya Galamb, Barbara Kinga Bartak, Zsofia Brigitta Nagy, Sara Zsigrai, Krisztina Andrea Szigeti, William Kothalawala, Peter Igaz, Istvan Takacs, Bela Molnar. Comprehensive analysis of tissue and plasma-related genetic alterations in Hungarian colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2945.
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Bettiol, A., I. Mattioli, M. L. Urban, F. Bello, R. Padoan, M. Groh, G. Lopalco, et al. "OP0304 BENRALIZUMAB FOR EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS (EGPA): RESULTS FROM A EUROPEAN MULTICENTER STUDY ON 121 PATIENTS." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 196.1–197. http://dx.doi.org/10.1136/annrheumdis-2023-eular.1510.
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BackgroundEosinophilic granulomatosis with polyangiitis (EGPA) is an ANCA-associated vasculitis characterized by asthma, ear-nose-throat (ENT) manifestations, peripheral hypereosinophilia and systemic vasculitic involvement [1]. Increased serum levels of interleukin 5 (IL-5) have been observed in eosinophilic disorders, including EGPA, and a genome-wide association study identified the IL-5 region as a major EGPA-associated loci [2]. On these bases, an increasing interest is focusing on benralizumab (an IL-5 receptor antagonist approved for severe eosinophilic asthma at the dosage of 30mg every 4 weeks for 3 administrations, then every 8 weeks) as a new potential therapy for EGPA.Following the promising results of a pilot study on 10 patients [3], a randomized double-blind trial is ongoing to assess the efficacy and safety of benralizumab at a higher dosage (30mg/4 weeks), as compared to mepolizumab (another IL-5 inhibitor approved for EGPA) in patients with EGPA (NCT04157348). In the meanwhile, isolated cases of patients with refractory EGPA, successfully treated with benralizumab, have been described in the literature [4,5].ObjectivesThis study aimed to assess the efficacy and safety of benralizumab in a multicenter European cohort of patients with EGPA.MethodsThe study included patients with EGPA treated with benralizumab at 28 centers belonging to the European EGPA Study Group. Efficacy and safety outcomes were assessed after 3, 6 and 12 months of treatment. Complete response (CR) was defined as no disease activity (Birmingham Vasculitis Activity Score [BVAS] = 0) and a daily prednisone equivalent dose ≤4 mg. Respiratory outcomes included asthma, ENT manifestations and lung function.ResultsA cohort of 121 patients with EGPA was included. All were treated with benralizumab at the dosage approved for eosinophilic asthma (30mg every 4 weeks for 3 administrations, then every 8 weeks). The proportion of patients meeting the criteria for CR was 16% at 3 months, 26% at 6 months and 46% at 12 months of follow-up (Table 1). During follow-up, a drop in BVAS was recorded, from a median score of 3 (IQR 2-8) at baseline to 0 (0-2) at month 3 and 6 and to 0 (0-1) at month 12 (p<0.001 at all timepoints). Regarding respiratory outcomes, the proportion of patients reporting active asthmatic decreased from 94% at baseline to 39% at 3 months (p<0.001), and that of patients with active ENT manifestations decreased from 70% at baseline to 49% at 3 months (p<0.001), with concomitant improvements in lung function. 19 patients experienced adverse events, three requiring hospitalization.ConclusionThe results from this large European real-world study suggest that benralizumab, at the dosage approved for severe eosinophilic asthma, could be effective and safe to control respiratory EGPA manifestations and overall disease activity.References[1]Trivioli, Rheumatol 2020[2]Lyon, Nat Commun 2019[3]Guntur, JACI Pract 2021[4]Bormioli, JIACI 2021[5]Menzella, Multidisciplinary Respir Med 2021Table 1.Efficacy outcomesBenralizumab beginning (t0)3 monthsp-value (t3 vs t0)6 monthsp-value (t6 vs t0)12 monthsp-value (t12 vs t0)N patients12112110185Complete response-15/96 (15.6%)23/87 (26.4%)32/69 (46.4%)BVAS, median (IQR)3 (2-8)0 (0-2)[n=96]<0.001*0 (0-2)[n=87]<0.001*0 (0-1)[n=69]<0.001*Respiratory involvementPulmonary114 (94.2)43/111 (38.7)<0.001*36 (35.6)<0.001*33 (38.8)<0.001*ENT85 (70.3)54/111 (48.6)<0.001*46 (45.5)<0.001*40 (47.1)<0.001*BVAS= Birmingham Vasculitis Activity Score; ENT= ear-nose-throat; IQR= interquartile range.AcknowledgementsWe acknowledge drs./profs. Francesco Cinetto, Marco Caminati, Pavel Novikov, Alvise Berti, Paolo Cameli, Pascal Cathébras, Angelo Coppola, Cécile-Audrey Durel, Marco Folci, Alberto Lo Gullo, Carlo Lombardi, Sara Monti, Paola Parronchi, Carlos Martinez Rivera, Roser Solans, Angelo Vacca, Maria Cinta Cid, and Domenico Prisco, who contributed to this study.Disclosure of InterestsAlessandra Bettiol: None declared, Irene Mattioli: None declared, Maria Letizia Urban: None declared, Federica Bello: None declared, Roberto Padoan Consultant of: GSK, Matthieu Groh: None declared, Giuseppe Lopalco: None declared, Allyson Egan: None declared, Vincent Cottin Consultant of: Astra Zeneca and GSK., Paolo Fraticelli: None declared, Claudia Crimi Speakers bureau: Honoraria for lectures from GSK, Sanofi, Astra Zeneca, Novartis, Resmed, Fisher & Paykel., Stefano Del Giacco: None declared, Jan Schroeder: None declared, Laura Moi: None declared, David Jayne Consultant of: Astra-Zeneca, Aurinia, BMS, Boehringer-Ingelheim, Chemocentryx, Chugai, CSL, GSK, Infla-RX, Janssen, Novartis, Roche/Genentech, Takeda and Vifor, Augusto Vaglio Consultant of: GSK, Giacomo Emmi Consultant of: GSK.
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Contreras, Carlos Andrés, Samuel Yniesta, Abtin Jahanbakhshzadeh, and Michel Aubertin. "Correction: calibration of the PM4Sand model for hard-rock mine tailings based on laboratory and field testing results." Canadian Geotechnical Journal, October 12, 2023. http://dx.doi.org/10.1139/cgj-2023-0509.
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Résumé Une campagne d“essais en laboratoire et sur le terrain a été réalisée pour caractériser le comportement des résidus miniers de roche dure. Des essais cycliques triaxiaux, de cisaillement direct simple et de cisaillement simple triaxial ont montré que les résidus contractants sont susceptibles de se liquéfier et que leur comportement est similaire à un sable lâche malgré leur pourcentage de fines plus élevé. Afin de modéliser le comportement des parcs à résidus dans des simulations dynamiques, la loi de comportement PM4Sand est calibré à partir de l”ensemble de données présenté ici. Certains des paramètres du modèle sont définis sur la base d“essais de consolidation et de compression, tandis que la ligne d”état critique est définie sur la base des résultats d“essais de cisaillement direct et triaxial monotones. La ligne d”état critique est plus basse pour les résidus que pour la plupart des sables naturels, ce qui est cohérent avec les études précédentes. Le modèle calibré peut reproduire de manière raisonnable le comportement monotone, et fournit un excellent ajustement des courbes de résistance cyclique mesurées en laboratoire à différentes pressions de confinement et indices de densité. Les résultats présentés dans l'article indiquent que la loi de comportement PM4Sand peut être utilisée pour simuler le comportement cyclique des résidus de mines en roches dures de faible plasticité. La procédure proposée fournie aussi des lignes directives générales pour calibrer le modèle pour d'autres types de résidus miniers.1 Ceci est une traduction fournie par l'auteur du résumé en anglais.
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Denes, Dominique. "Un lieu à l’oeuvre : « La chambre noire » de Marguerite Duras." Voix Plurielles 5, no. 1 (April 1, 2008). http://dx.doi.org/10.26522/vp.v5i1.477.
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Partant du constat que chez Duras la poétique de l’espace oscille entre l’« outside » du
« monde extérieur » et l’inside de « la vie matérielle » et domestique - autant de formules dont
elle a fait des titres - comme elle-même se partage physiquement entre ses trois lieux de l’écrit,
nous nous demanderons comment et jusqu’où ses lieux informent ses livres, et à l’inverse,
comment l’écriture investit le lieu et se l’approprie. Emblématique est à cet égard la chambre des
Roches noires érigée en concept de « chambre noire » de la création, cette chambre-livre avec
vue se prêtant à la réflexion poétique comme à la projection dans l’imaginaire.
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Vieira, Fabrício Thiengo, and Júlio D’Auria Braga. "Caracterização de parâmetros de desempenho explosivos: ANFO e emulsão explosiva." International Seven Journal of Multidisciplinary 1, no. 1 (May 26, 2023). http://dx.doi.org/10.56238/isevmjv1n2-008.
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Os explosivos mais utilizados, para fins civis, na construção e mineração são o óleo combustível de nitrato de amônio (ANFO) e as emulsões explosivas. Ambos são à base de nitrato de amônio e detonam sob a mesma reação química entre nitrato e óleo mineral, uma vez que o ANFO é composto de minúsculos grãos de nitrato poroso com óleo difuso, e a emulsão está na forma de uma fase líquida, contínua, viscosa e oleosa e a fase aquosa descontínua. O estudo de parâmetros que medem o desempenho explosivo é fundamental para compreender o comportamento da explosão. Parâmetros importantes são a velocidade e pressão de detonação, o calor da explosão (energia), e o volume de gás produzido. Estas propriedades ajudam a julgar se um determinado explosivo é conveniente ou não para a situação em questão, pois, em algumas aplicações, é necessária alta velocidade para aumentar a capacidade de fragmentação, por exemplo, quando se deseja fragmentar rochas duras. Entretanto, não há necessidade de fragmentar em alguns momentos, mas de deslocar. Outras propriedades, como o volume de gás, tornam-se mais relevantes em tais casos.
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Humby, Frances C., Myles Lewis, Patrick Durez, Maya H. Buch, Michele Bombardieri, Hasan Rizvi, Felice Rivellese, et al. "O07 Randomised, open labelled clinical trial to investigate synovial mechanisms determining response: resistance to rituximab versus tocilizumab in RA patients failing TNF inhibitor therapy." Rheumatology 59, Supplement_2 (April 1, 2020). http://dx.doi.org/10.1093/rheumatology/keaa110.006.
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Abstract Background Biologic therapies have transformed the outlook for RA but the significant health economic impact of these therapies has highlighted the need to define predictive markers of response. Rituximab (RTX) is licensed for use following failure of csDMARDs and TNF inhibitor (TNFi) therapy. However, in this increasing therapeutically resistant cohort only 30% of patients achieve an ACR50 response. The observation in early RA that 50% of patients show low/absence of synovial B-cells prompted us to test the hypothesis that in these patients a biologic agent targeting alternative pathways maybe more effective. We report results from the first pathobiology-driven randomised controlled trial (RCT) in RA (R4RA) evaluating whether patient stratification according to the synovial B-cell rich/poor status enriches for response/non response to RTX. Methods R4RA is a phase IV open-label RCT conducted in 19 European centres recruiting patients failing or intolerant to csDMARD therapy and at least one TNFi. Synovial tissue was obtained at trial entry and used to classify patients as B-cell rich or poor using both histological and RNA-seq classification criteria. Patients were randomised to receive RTX or tocilizumab (TCZ). The study was powered to test in the B cell poor population superiority of TCZ over RTX at 16 weeks. The primary and co-primary end-points were defined respectively as Clinical Disease Activity Index (CDAI) ≥50% improvement from baseline and Major Treatment response (MTR)= CDAI improvement ≥ 50% and CDAI ≤10.1. Results The trial recruited to target (n = 164) with a power of 89.5%. In the B cell poor cohort a numerically higher number of patients achieved the primary endpoint and a significantly higher number of patients achieved co-primary endpoint (MTR). Classification of patients as B cell poor/rich according to RNA-seq criteria enhanced the difference between TCZ and RTX, with a significantly higher number of TCZ treated patients reaching both CDAI 50% improvement and CDAI MTR in the B-cell poor group. Conclusion In a RA B cell poor population failing csDMARDs and TNFi therapy, TCZ is more effective than RTX. This first biopsy-driven RCT suggests clinical utility for integrating molecular pathology profiling into treatment algorithms to allocate targeted therapies. Disclosures F. Humby: Honoraria; Roche, Pfizer. Grants/research support; Pfizer. P. Durez: BMS,Bristol-Myers Squibb, Celltrion, Eli Lilly, Hospira, Mundipharma, Pfizer, Samsung, Sanofi, UCB. M. Buch: Consultancies; Pfizer, Roche, UCB, AbbVie, Eli Lilly, Sandoz, and Sanofi. Grants/research support; Pfizer, Roche, UCB, AbbVie, Eli Lilly, Sandoz, and Sanofi. M. Lewis: None. M. Bombardieri: None. H. Rizvi: None. S. Kelly: None. L. Fossati: None. R. Hands: None. G. Giorli: None. A. Mahto: None. C. Montecucco: None. B. Lauwerys: None. V.C. Romao: None. A.G. Pratt: Member of speakers’ bureau; Eli Lilly and Janssen-Cilag Ltd. Grants/research support; Pfizer. S. Bugatti: None. N. Ng: None. F. Rivellese: None. P. Ho: None. M. Bellan: None. P. Sainaghi: None. P. Verschueren: None. N. Gendi: None. B. Dasgupta: Abbvie, BMS, GSK, Roche, Roche Chugai, Sanofi, Sanofi Aventis, Sanofi-Aventis. A. Cauli: BMS, Celgene, Lilly, Lilly MSD, MSD, Novartis, Pfizer, Sanofi, Sigma Wesseumen, UCB. C. John: None. A. Nerviani: None. G. Thornborn: None. D. Holroyd: None. M. Congia: None. C. Thompson: None. P. Reynolds: None. J. Cañete: None. R. J. Moots: Biogen, Bristol-Myers Squibb, Chugai, Novartis, Pfizer Inc, Roche, Sandoz, UCB. P.C. Taylor: AbbVie, Biogen, Celgene, Eli Lilly and Company, Fresenius, Fresenius SE & Co, Galapagos, Gilead. GlaxoSmithKline, Janssen, Lilly, Nordic Pharma, Pfizer, Pfizer Inc, Roche, Sanofi, UCB. C. Edwards: Abbvie, Biogen, BMS, Fresenius, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, UCB. J. Isaacs: None. P. Sasieni: None. J. E. Fonesca: None. E. Choy: AbbVie, Abbvie, Roche, Chugai, Amgen, Eli Lilly, Janssen, Novartis, Regeneron, R-Pharm and Sanofi, Amgen, Amgen, Roche, Chugai, Bristol-Myers Squibb, Eli-Lilly Janssen, Pfizer, Regeneron, Sanofi and UCB., AstraZeneca, Bio-Cancer, Bio-Cancer, Biogen, Novartis, Sanofi, Roche, Pfizer and UCB ,Biogen, BMS, Boehringer Ingelheim, Celgene, Chugai Pharma, Eli Lilly, Ferring Pharmaceuticals, GSK, Hospira, Janssen, Jazz Pharmaceuticals, Merck Sharp & Dohme, Merrimack Pharmaceutical, Napp, Novartis, Novimmune, ObsEva, Pfizer, Regeneron, Roche, R-Pharm, Sanofi, SynAct Pharma, Tonix, Union Chimique Belge. C. Pitzalis: None. NIHR have funded the study.
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Durez, Patrick, Eugen Feist, Ricardo Blanco, Vijay Rajendran, Nadia Verbruggen, Katrien Van Beneden, and James Galloway. "P119 The Use of Exposure-Adjusted Event Rates versus Exposure-Adjusted Incidence Rates in Adverse Event Reporting: Insights from Filgotinib Integrated Safety Data in Rheumatoid Arthritis." Rheumatology 62, Supplement_2 (April 1, 2023). http://dx.doi.org/10.1093/rheumatology/kead104.160.
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Abstract Background/Aims Reporting of treatment-emergent adverse events (TEAEs) in rheumatoid arthritis (RA) clinical trials can be summarized as exposure-adjusted incidence rates (EAIRs) or exposure-adjusted event rates (EAERs). Censored EAIR (EAIR), weighing exposure up to a patient’s first event, is commonly reported; uncensored EAIR (EAIRu), using total exposure time for all patients, can also be used. For EAIR, exposure time can vary by event. In contrast to EAIR(u), the total number of events are used to calculate EAER. The three methods account for different exposures and/or multiple events, which can impact the outcome evaluation. Studies of filgotinib (FIL) in RA report safety data as EAIR/100 patient-years of exposure (PYE) for TEAEs, which is uncensored. Objective: To describe the outcome of long-term FIL integrated safety data in RA by applying different statistical methodologies: EAER, EAIRu and EAIR. Methods Integrated FIL safety data from seven clinical trials were assessed. Predefined adverse events of special interest (AESI) included serious infections (any), herpes zoster (HZ), major adverse cardiac events (MACE), malignancies (excluding nonmelanoma skin cancer [NMSC]), NMSC and venous thromboembolism (VTE). The number of patients with an event, number of events, EAER, EAIRu and EAIR were summarized. The data extraction date was January 2021 for the DARWIN 3 (NCT02065700) long-term extension (LTE) and November 2020 for the FINCH 4 (NCT03025308) LTE. Results In total, 3691 patients received ≥1 FIL dose for 8085 PYE. In this population, 176 serious infections were reported in 137 patients, 125 HZ events were reported in 112 patients, 39 MACE were reported in 33 patients, 20 cases of VTE were reported in 15 patients, 60 malignancies excluding NMSC were reported in 49 patients and 21 cases of NMSC were reported in 20 patients. Within each treatment arm (FIL 200 mg [FIL200], FIL 100 mg [FIL100] or combined FIL), rates for most AESI were similar when reported as EAER, EAIRu or EAIR. For serious infections, EAER was higher than EAIRu or EAIR. The total exposure time to first event (censored PYE) was high and comparable to total exposure (PYE) (>2700 years and >5100 years for the total populations in the FIL100 and FIL200 groups, respectively). Conclusion These data confirm that using different methods to analyze FIL safety data (EAER, EAIRu, EAIR) does not result in different safety outcomes, reinforcing the previously reported FIL safety profile in patients with RA. As the AESI reported in the long-term safety database with FIL are rare, patients commonly have long exposure times before experiencing an event, which are often associated with end of treatment. As such, EAIRu, EAIR and EAER are similar. Disclosure P. Durez: Member of speakers’ bureau; AbbVie, Galapagos, Lilly. E. Feist: Consultancies; AbbVie, Galapagos, Lilly, Novartis, Pfizer, Roche, and Sobi. Member of speakers’ bureau; AbbVie, Galapagos, Lilly, Pfizer, Roche, Novartis and Sobi. Grants/research support; Lilly, Pfizer and Roche. R. Blanco: Consultancies; AstraZeneca, Galapagos, Janssen, Novartis and Pfizer. Member of speakers’ bureau; AbbVie, Amgen, Bristol-Myers, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Roche and Sanofi. Grants/research support; AbbVie, Roche. V. Rajendran: Other; Galapagos. N. Verbruggen: Other; Galapagos. K. Van Beneden: Shareholder/stock ownership; Galapagos. Other; Galapagos. J. Galloway: Consultancies; AbbVie, Galapagos, Gilead, Janssen, Lilly, Novartis and Pfizer. Member of speakers’ bureau; AbbVie, Biogen, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche and UCB. Grants/research support; AstraZeneca, Celgene, Gilead, Janssen, Medicago, Novavax and Pfizer.
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Walker, David, Ilias Kouris, Thorsten Holzkämper, Marco W. Wu, Ricardo Xavier, Josef Smolen, Patrick Durez, et al. "P220 An updated safety profile of baricitinib for the treatment of RA up to 7 years." Rheumatology 59, Supplement_2 (April 1, 2020). http://dx.doi.org/10.1093/rheumatology/keaa111.215.
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Abstract Background Baricitinib (BARI) is a selective inhibitor of janus kinase (JAK) 1 and JAK2, approved for the treatment of moderately to severely active rheumatoid arthritis (RA) in adults in over 50 countries. Objective: To evaluate the long-term safety of BARI in patients with RA with a specific focus on malignancies, major adverse cardiovascular events (MACE), serious infections and herpes zoster (HZ) events. Methods Data from nine completed studies (5 Phase 3, 3 Phase 2, 1 Phase 1b) and 1 long term extension (LTE) study were pooled for this analysis (data cut-off date: 13-Feb-2018). The all BARI data set included all patients exposed to any BARI dose. Results A total of 3,770 patients with RA were treated with BARI (10,127 patient years [PY]) with a maximum exposure of 7 years. Of these, 2,938 (78%) and 1,754 (47%) were on concomitant methotrexate or corticosteroids (CS; mean dose 6.2 mg/day), respectively. The incidence rates (IR) of malignancy (excluding non-melanoma skin cancer) were 0.8 (2-mg) and 1.0 (4-mg; as-randomized analysis) in the LTE. The IRs for MACE were similar between the all BARI and PBO group; however, the IR for DVT/PE were numerically higher in the BARI 4mg group during the PBO-controlled period. IRs for MACE remain stable over time. The IR of serious infections were numerically higher in the PBO group; the IR of tuberculosis and other opportunistic infections were similar between the all BARI and PBO group. During the PBO-controlled period, HZ IR was significantly higher for BARI 4-mg versus PBO (4.4 vs 1.1) (Table 1). Amongst 323 HZ patients, 11 (4%) had received prior HZ vaccination. Twenty-six [8%] cases were multidermatomal, and no visceral disease was reported. Multivariate analyses showed that older age and some geographical regions (Asia, especially Japan, Taiwan and South Korea) were associated with a higher risk of HZ. Conclusion This integrated analysis in patients with active RA exposed to BARI for up to 7 years shows that the safety profile of BARI is like that reported previously. The IRs of malignancies, MACE (including DVT/PE), serious infection, and HZ did not increase over time. Disclosures D. Walker: Honoraria; Lilly, Pfizer, Giliad, Novartis, Roche. Member of speakers’ bureau; Lilly, Pfizer, Roche. I. Kouris: Other; Lilly employee. T. Holzkämper: Shareholder/stock ownership; Lilly. Other; Lilly employee. M.W. Wu: Other; Lilly employee. R. Xavier: None. J. Smolen: Consultancies; Abbvie, Amgen, Astra Zeneca, Astro, BMS. Grants/research support; Abbvie, Eli Lilly, Novartis, Pfizer, Roche, Samsung, Sanofi-Aventis, UCB. P. Durez: Member of speakers’ bureau; Abbvie, BMS, Celltrion, Eli Lilly. Y. Chen: None. J. Zhong: Corporate appointments; Eli Lilly Contractor. R. Liao: Other; Lilly employee. M.C. Genovese: Consultancies; Eli Lilly. K. Winthrop: Consultancies; Pfizer, UCB, Eli Lilly, Gilead, Abbvie, Roche, BMS.
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Almeida, Celia, Catherine Guly, Sarah Mackie, Alison Bromhead, Steve Stern, Emma Dures, Jill Dawson, Mwidimi Ndosi, Rosemary Greenwood, and Joanna C. Robson. "P301 Patient reported outcome measure for giant cell arteritis: clinical testing." Rheumatology 61, Supplement_1 (April 23, 2022). http://dx.doi.org/10.1093/rheumatology/keac133.300.
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Abstract Background/Aims Giant cell arteritis (GCA) presents in people over 50, with headaches, visual involvement and large vessel vasculitis. A 30-item GCA-specific patient reported outcome measure (GCA PRO) was developed and tested in a clinical setting to pilot its feasibility and acceptability to patients and clinicians as a communication tool. Methods Patients seen in rheumatology or ophthalmology departments in Bristol and Leeds completed the GCA PRO prior to their consultation. Items referred to patients’ health-related quality of life over the past 7 days. Clinicians were given a copy of patients’ responses and a summary sheet highlighting overall scores which they referred to during the consultation. After the appointment, patients and clinicians completed short answer questionnaire (SAQ) plus free-text feedback forms reporting on the experience of use of the GCA PRO within the consultation. Results The GCA PRO was piloted during 16 clinic appointments. 16 patients, mean age (SD) of 74.7 (7.0), 11 (68.8%) female, 7 (43.8%) active disease and 5 (31.3%) with ocular involvement took part. Seven clinicians participated - 5 rheumatologists and 2 ophthalmologists. 87% percent of patients agreed that the GCA PRO had helped them to explain their condition; clinicians agreed that the GCA PRO had helped them to understand the patient’s condition 88% of the time (Table 1). Clinicians noted that “it was easier for the patient to convey his anxiety and feelings towards the disease and treatment” and that the GCA PRO “indirectly helped via prompting discussion of patient’s anxieties and worries”. However, they were more equivocal on its impact on decision making: “management plan was informed by symptoms, bloods and stage of illness”. Patients commented that “it helped us to plan how to manage my GCA based on my answers”, and that “the questions seemed relevant and it was helpful to me to be able to think about them before the appointment”. Conclusion The GCA-PRO was found to be an acceptable tool for use in clinic by patients and clinicians, especially in terms of explaining and understanding the patient’s condition. Disclosure C. Almeida: None. C. Guly: None. S. Mackie: Honoraria; Sept 2021: Roche/Chugai payment to my institution for delivering a talk on giant cell arteritis at an educational day. Grants/research support; MRC Confidence in Concept scheme, 2021 to develop early diagnosis methods for giant cell arteritis, 2018: MRC Proximity to Discovery: Protein biomarkers for polymyalgia rheumatica and giant cell arteritis. (PI: Morgan, University of Leeds), 2019: Roche: giant cell arteritis tocilizumab registry (PI: Morgan, University of Leeds). Other; Site Sub-Investigator on clinical trial in giant cell arteritis for Roche, Site Principal Investigator on clinical trial in giant cell arteritis for GSK, Site Principal Investigator and UK Chief Investigator on clinical trials (giant cell arteritis and polymyalgia rheumatica) for Sanofi. A. Bromhead: None. S. Stern: None. E. Dures: None. J. Dawson: None. M. Ndosi: None. R. Greenwood: None. J.C. Robson: None.
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Almeida, Celia, Catherine Guly, Sarah Mackie, Alison Bromhead, Steve Stern, Emma Dures, Jill Dawson, Mwidimi Ndosi, Rosemary Greenwood, and Joanna C. Robson. "P301 Patient reported outcome measure for giant cell arteritis: clinical testing." Rheumatology 61, Supplement_1 (April 23, 2022). http://dx.doi.org/10.1093/rheumatology/keac133.300.
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Abstract Background/Aims Giant cell arteritis (GCA) presents in people over 50, with headaches, visual involvement and large vessel vasculitis. A 30-item GCA-specific patient reported outcome measure (GCA PRO) was developed and tested in a clinical setting to pilot its feasibility and acceptability to patients and clinicians as a communication tool. Methods Patients seen in rheumatology or ophthalmology departments in Bristol and Leeds completed the GCA PRO prior to their consultation. Items referred to patients’ health-related quality of life over the past 7 days. Clinicians were given a copy of patients’ responses and a summary sheet highlighting overall scores which they referred to during the consultation. After the appointment, patients and clinicians completed short answer questionnaire (SAQ) plus free-text feedback forms reporting on the experience of use of the GCA PRO within the consultation. Results The GCA PRO was piloted during 16 clinic appointments. 16 patients, mean age (SD) of 74.7 (7.0), 11 (68.8%) female, 7 (43.8%) active disease and 5 (31.3%) with ocular involvement took part. Seven clinicians participated - 5 rheumatologists and 2 ophthalmologists. 87% percent of patients agreed that the GCA PRO had helped them to explain their condition; clinicians agreed that the GCA PRO had helped them to understand the patient’s condition 88% of the time (Table 1). Clinicians noted that “it was easier for the patient to convey his anxiety and feelings towards the disease and treatment” and that the GCA PRO “indirectly helped via prompting discussion of patient’s anxieties and worries”. However, they were more equivocal on its impact on decision making: “management plan was informed by symptoms, bloods and stage of illness”. Patients commented that “it helped us to plan how to manage my GCA based on my answers”, and that “the questions seemed relevant and it was helpful to me to be able to think about them before the appointment”. Conclusion The GCA-PRO was found to be an acceptable tool for use in clinic by patients and clinicians, especially in terms of explaining and understanding the patient’s condition. Disclosure C. Almeida: None. C. Guly: None. S. Mackie: Honoraria; Sept 2021: Roche/Chugai payment to my institution for delivering a talk on giant cell arteritis at an educational day. Grants/research support; MRC Confidence in Concept scheme, 2021 to develop early diagnosis methods for giant cell arteritis, 2018: MRC Proximity to Discovery: Protein biomarkers for polymyalgia rheumatica and giant cell arteritis. (PI: Morgan, University of Leeds), 2019: Roche: giant cell arteritis tocilizumab registry (PI: Morgan, University of Leeds). Other; Site Sub-Investigator on clinical trial in giant cell arteritis for Roche, Site Principal Investigator on clinical trial in giant cell arteritis for GSK, Site Principal Investigator and UK Chief Investigator on clinical trials (giant cell arteritis and polymyalgia rheumatica) for Sanofi. A. Bromhead: None. S. Stern: None. E. Dures: None. J. Dawson: None. M. Ndosi: None. R. Greenwood: None. J.C. Robson: None.
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Lim, Joyce, Emma Dures, Lawrence Bailey, Celia Almeida, Carlee Ruediger, Catherine Hill, Joanna Robson, and Sarah L. Mackie. "OA32 Jaw claudication - does the textbook description need updating?" Rheumatology 62, Supplement_2 (April 1, 2023). http://dx.doi.org/10.1093/rheumatology/kead104.032.
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Abstract Background/Aims Recognition of jaw claudication is crucial to expedite diagnosis and treatment of giant cell arteritis (GCA). The ACR 1990 criteria defined claudication of the jaw, tongue or deglutition as “development or worsening of fatigue or discomfort in muscles of mastication, tongue, or swallowing muscles while eating”. We sought to describe the diverse ways in which patients may describe this key GCA symptom and its impact on health-related quality of life. Methods Secondary analysis of a qualitative dataset originally created for the development of a patient-reported outcome measure for GCA. Participants (n = 36) with GCA confirmed by biopsy/imaging were recruited using purposive sampling from two rheumatology clinics and one ophthalmology clinic in the UK (n = 25) and Australia (n = 11). Interviews transcripts from the original study were organised within QSR NVivo 12 software and analysed using template analysis. Themes were refined through discussion among researchers including a patient partner. Results 20 of 36 participants (56%) reported jaw symptoms. Of these 20, the median age was 76.5 years; 60% were female. Five main themes were identified in the data: physical sensations; impact on function; impact on diet; symptom response to steroids; attribution to other causes (see Table 1). Whilst a large proportion of patients described jaw pain, jaw cramp, jaw stiffness and lockjaw had also been described. Symptom resolution following commencement of steroids varied among participants. Jaw symptom was misjudged as due to dental cavity, ear infection and teeth grinding by healthcare professionals in some cases. Some patients did not seek immediate help from healthcare professionals regarding their jaw symptoms as they were thought to be related to arthritis, age or viral illnesses. Conclusion Patients with GCA described their jaw symptoms in various ways, not exclusive to chewing. When Horton originally described jaw claudication, he also observed that some patients reported ‘lockjaw’. For early recognition and prompt diagnosis of GCA, we suggest that textbooks and teaching should be updated to reflect this. Patient education on the potential significance of jaw symptoms is also crucial to avoid delay in seeking help. Disclosure J. Lim: None. E. Dures: None. L. Bailey: None. C. Almeida: None. C. Ruediger: None. C. Hill: None. J. Robson: None. S.L. Mackie: Consultancies; Roche/Chugai, Sanofi, AbbVie, AstraZeneca. Other; SLM has given talks on behalf of her institution for Pfizer, Vifor and UCB. In all cases fees were paid to her institution and no personal fees were received, SLM was supported by Roche to attend EULAR2019 and by Pfizer to attend ACR2021 virtually, SLM has been an investigator on clinical trials for Sanofi and GSK, As a research grant co-applicant, SLM has received research funding (partial salary support) from Vifor, paid to her institution.
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Peterfy, Charles, Mark C. Genovese, In-Ho Song, Alan Friedman, Stephen Hall, Eduardo Mysler, Patrick Durez, et al. "P225 Inhibition of structural joint damage with upadacitinib as monotherapy or in combination with MTX in patrients with RA: one-year outcomes from the select Phase 3 programme." Rheumatology 59, Supplement_2 (April 1, 2020). http://dx.doi.org/10.1093/rheumatology/keaa111.220.
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Abstract Background Long-term prevention of structural joint damage is a key treatment goal in the management of RA. Upadacitinib (UPA), a JAK1-selective inhibitor, inhibited the progression of structural joint damage at 6 months as monotherapy in methotrexate (MTX)-naïve RA patients and in combination with MTX in patients with inadequate response (IR) to MTX. Objectives: To evaluate the progression of structural joint damage (radiographic) through Week 48 in patients with moderately to severely active RA treated with UPA monotherapy or in combination with MTX. Methods Radiographic progression was assessed in 2 phase 3 randomized controlled trials (RCTs). MTX-naïve patients were randomized to UPA 15 or 30mg QD or MTX monotherapy [SELECT-EARLY, N = 945], while MTX-IR patients were randomized to UPA 15mg QD or adalimumab (ADA) 40 mg eow or placebo (PBO), with continuous background MTX [SELECT-COMPARE, N = 1629]. Both RCTs specifically enrolled patients at high risk for progression of joint damage (high disease activity including elevated hsCRP, presence of baseline erosions and ACPA and/or RF positivity). The mean changes (D) from baseline (BL) in modified Total Sharp Score (mTSS), joint space narrowing (JSN), and erosion scores (ES) as well as the proportion of patients with no radiographic progression (ΔmTSS ≤0) at Weeks 24/26 and 48 were determined in both RCTs. Data were analyzed by linear extrapolation (LE) for missing data imputation and treatment switching, and as observed (AO). Results BL demographics have been reported previously. At Weeks 24/26, UPA as monotherapy and in combination with background MTX significantly inhibited radiographic progression measured by mean DmTSS and the proportion of patients with no radiographic progression vs MTX and PBO, respectively. The significant inhibition of radiographic progression with UPA was maintained through Week 48 vs MTX (LE and AO) in EARLY and vs PBO (LE) in COMPARE. Following the switch of all PBO patients to UPA in COMPARE by Week 26, no further change in mean mTSS was observed through Week 48. The inhibition of radiographic progression vs comparators was not only observed for the overall mTSS scores but also its components - the JSN and ES in both RCTs (LE and AO). Conclusion UPA both as monotherapy, and in combination with background MTX, was effective in inhibiting the progression of structural joint damage through Week 48 in MTX-naïve, and MTX-IR patients, respectively. Disclosures C. Peterfy: Consultancies; AbbVie, Acerta, Amgen, AstraZeneca, Bristol-Myers Squibb, Centrexion, Daiichi Sankyu, Five Prime Therapeutics, Genentech, Hoffmann-La Roche, Janssen, Lilly USA, MedImmune, Merck, Novartis, Plexxikon, Pfizer, Sanofi, Salix-Santarus, Samsung. M.C. Genovese: Consultancies; Consultant for and has received grants from AbbVie Inc, Lilly, Pfizer, Galapagos, and Gilead. I. Song: Corporate appointments; Employee of AbbVie. A. Friedman: Corporate appointments; Employee of AbbVie. S. Hall: Consultancies; Received research grants and consultancy fees from AbbVie Inc, BMS, Lilly, Janssen, Pfizer, UCB, and Novartis. E. Mysler: Grants/research support; Received research grants and speaker’s bureau fees from Bristol-Myers Squibb, Roche, Eli Lilly, AbbVie, Novartis, Janssen, and Pfizer. P. Durez: Member of speakers’ bureau; Bristol-Myers Squibb, Samsung, Pfizer, UCB, Mundipharma, Hospira, and Eli Lilly. X. Baraliakos: Grants/research support; AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Chugai, Janssen, MSD, Novartis, Pfizer Inc, Roche and UCB. J. Enejosa: Corporate appointments; Employee of AbbVie. T. Shaw: Corporate appointments; Employee of AbbVie. Y. Li: Corporate appointments; Employee of AbbVie. S. Chen: Corporate appointments; Employee of AbbVie. V. Strand: Consultancies; Consultant for AbbVie, Amgen, AstraZeneca, BMS, Celltrion, Celgene, Genentech, GSK, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Samsung, Sanofi, and UCB.
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Janagan, Shalini, Kian Wah Lim, Rayna Bhogal, Susan Bridgewater, Christine Silverthorne, Pamela Richards, Jill Dawson, et al. "P041 Health-related quality of life in patients receiving glucocorticoids for a rheumatic disease and associated factors : a cross-sectional study." Rheumatology 63, Supplement_1 (April 1, 2024). http://dx.doi.org/10.1093/rheumatology/keae163.083.
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Abstract Background/Aims Glucocorticoids (GCs) used in the treatment of inflammatory rheumatic conditions can impact on patients in different ways. The objective of this study was to identify socio-demographic and clinical factors associated with health-related quality of life (HRQoL) in patients undertaking GCs for a rheumatic disease. Methods This was a cross-sectional study using online survey methods. Participants taking GCs for a rheumatic disease from Australia, United Kingdom and the United States of America were included. HRQoL was measured using the EQ-5D-5L converted into a linear EQ5D index value. Eight explanatory factors (age, sex, country, educational level, employment status, disease group, self-reported disease state, and dose of GCs) were tested for potential association with HRQoL using univariable and multivariable (hierarchical) analyses. Factors found to have a significant association with EQ5D index at a P < 0.05 level in the multivariable model were considered to be independently associated with HRQoL. Results A total of 945 patients completed the EQ-5D-5L with no missing values: UK n = 742 (79%); USA n = 139 (15%); Australia/New Zealand n = 64 (7%); mean age 57.6 (SD = 13.6); 833 (88%) women. Participants with inflammatory arthritis n = 197 (21%), connective tissue disease and/or vasculitis n = 402 (43%), giant cell arteritis and/or polymyalgia rheumatica n = 346 (37%) were included. Those with self-reported active disease were 726 (77%). Mean (SD) EQ5D index was 0.64 (0.25); there were significant differences between groups in EQ-5D-5L index by age (median split, t=-3.77, p < 0.001); sex (t = 3.40, p < 001); educational level (F[3]=10.51, p < 0.001); employment status (F[6]=37.67, P < 0.001); disease group (T[2]=20.23, p < 0.001); disease state (T=-8.46, p < 0.001); and the dose of GCs(T = 2.95, p < 0.001). Worse HRQoL was associated with older age, being female, low educational attainment, being unemployed, having an inflammatory arthritis or a CTD, disease being active, and taking a higher dose of GC. Of the eight factors that were tested in the multivariable model, five were found to be independently associated with HRQoL. These were: disease state (β = 0.12, p < 0.001), disease group (β = 0.06, p < 0.001), employment status (β = 0.05, p < 0.001), sex (β = 0.05, p < 0.001), and educational level (β = 0.04, p < 0.001). This 5-factor model explained 18% of the variance in EQ5D index scores (F[1, 926] = 4.97, P = 0.026). The excluded factors in the model were age, dose, and country. Conclusion In our data, we identified 5 factors independently associated with worse HRQoL in patients being treated with GCs. Over 80% of the variance was not explained by our model likely due to use of a generic HRQoL measure (EQ-5D-5L) as outcome variable, and the small number of explanatory variables tested within this survey. Further research is required to identify potential targets to support interventions. Disclosure S. Janagan: None. K. Lim: None. R. Bhogal: None. S. Bridgewater: Grants/research support; Vifor pharma. C. Silverthorne: None. P. Richards: None. J. Dawson: None. E. Dures: Grants/research support; Vifor pharma. C. Hill: None. S. Goodman: Consultancies; UCB. Grants/research support; Novartis. S.L. Mackie: Consultancies; Consultancy on behalf of her institution for Roche/Chugai, Sanofi, AbbVie, AstraZeneca, Pfizer. Other; Investigator on clinical trials for Sanofi, GSK, Sparrow, speaking/lecturing on behalf of her institution for Roche/Chugai, Vifor, Pfizer, UCB, Novartis and AbbVie, ; chief investigator on STERLING-PMR trial, funded by NIHR; patron of the charity PMRGCAuk, No personal remuneration was received for any of the above activities. Support from Roche/Chugai to attend EULAR2019 in person and from Pfizer to attend ACR Convergence 2021 virtually., SLM is supported in part by the NIHR Leeds Biomedical Research Centre., The views expressed in this article are those of the authors and not necessarily those of the NIHR,the NIHR Leeds Biomedical Research Centre, the National Health Service or the UK Department of Health. M. Ndosi: Grants/research support; Vifor pharma. J.C. Robson: Consultancies; Vifor Pharma. Member of speakers’ bureau; Vifor Pharma. Grants/research support; Unrestricted Grant/research support from: Vifor Pharma.
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Bridgewater, Susan, Mwidimi Ndosi, Jill Dawson, Pamela Richards, Christine Silverthorne, Emma Dures, Susan Goodman, Catherine Hill, Sarah L. Mackie, and Joanna C. Robson. "E038 A common measure of the impact of glucocorticoids in patients with inflammatory and autoimmune conditions - the Steroid PRO: A cross-cultural validation study with Rasch models." Rheumatology 62, Supplement_2 (April 1, 2023). http://dx.doi.org/10.1093/rheumatology/kead104.287.
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Abstract Background/Aims Systemic glucocorticoids are key in the management of life- and organ-threatening rheumatic diseases, but have wide-ranging adverse effects of concern to patients and clinicians. We aimed to validate a Patient Reported Outcome (PRO) measure (the Steroid PRO) for assessing the impact of glucocorticoids on health-related quality of life (HRQoL) in patients receiving glucocorticoids for rheumatic disease. Methods This was a cross-sectional study of adults from the UK, USA, Australia and New Zealand, taking glucocorticoids for a rheumatic disease. An online survey was conducted at two time points: Time 1: (i) demographics - age, gender, country, ethnicity, educational level; (ii) clinical information - diagnosis, glucocorticoid dose; (iii) 40 candidate items for the Steroid-PRO, developed in a previous qualitative study; (iv) EQ5D-5L. Time 2 (optional, completed 3-5 days later): (i) the Steroid PRO candidate items; (ii) a condition change question. The survey was distributed via social media and patient organisations. After descriptive analysis, iterative testing with Rasch measurement model and exploratory factor analysis (EFA) informed item reduction and established structural validity, reliability and unidimensionality of the final Steroid-PRO. Item reduction was based on clinical importance, lack of fit to the Rasch model, and redundancy. Evidence of discriminative validity of the Steroid-PRO was established by comparing its scores for participants receiving lower dose glucocorticoid (up to 10 mg) versus higher dose (>10 mg). Intraclass correlation (ICC) between Time 1 and Time 2 was calculated for patients who reported ‘no change’ compared with 3-5 days ago. Results A total of 946 patients returned complete responses at Time 1 (Time 2: 447 responses). They were from UK, n = 743 (78.5%); USA, n = 139 (14.7%); Australia, n = 59 (6.2%). Their mean age was 57.6 (SD = 13.6); 833 (88%) were women. They were treated for inflammatory arthritis (n = 194), connective tissue disease and/or vasculitis (n = 398), and giant cell arteritis and/or polymyalgia rheumatica (n = 341). A total of 25 items were removed due to floor effects and lack of fit to the Rasch model. The remaining 15 items showed a satisfactory fit to the model. EFA suggested a scale structure with four domains: Participation (4 items), Appearance (3 items), Psychological (5 items), and Treatment concerns (3 items). This 4-domain structure was supported by the Rasch model, confirming construct validity; χ2=47.82 (DF = 36), p = 0.899; and reliability (Person Separation Index, PSI=0.757). Patients on a lower glucocorticoid dose had lower Steroid-PRO domain scores than those receiving higher dose (discriminant validity). ICC between Time 1 and Time 2 ranged from 0.892 to 0.942 (95%CI 0.868 to 0.953) suggesting excellent (test-retest) reliability. Conclusion The final Steroid-PRO is a 15-item, valid and reliable 4-domain scale measuring the impact of glucocorticoid therapy on HRQoL of people with rheumatic diseases. Disclosure S. Bridgewater: Grants/research support; S.B. has received funding for research from Vifor Pharma. M. Ndosi: Grants/research support; M.N. has received funding for research from Vifor Pharma. J. Dawson: None. P. Richards: None. C. Silverthorne: None. E. Dures: Grants/research support; E.D. has received funding for research from Vifor Pharma. S. Goodman: Consultancies; S.G. reports consultancy for UCB. Grants/research support; S.G. has received research support from Novartis. Other; S.G. has given talks for NYU, Case Western, ACR Rheumatology Courses. C. Hill: None. S.L. Mackie: Consultancies; S.L.M. has provided consultancy on behalf of her institution for Roche/Chugai, Sanofi, AbbVie, AstraZeneca. Grants/research support; S.L.M. has been an investigator on clinical trials for Sanofi and GSK, as a research grant co-applicant, S.L.M. has received research funding (partial salary support) from Vifor, paid to her institution. Other; S.L.M. has given talks on behalf of her institution for Pfizer, Vifor and UCB. In all cases fees were paid to her institution and no personal fees were received, S.L.M. was supported by Roche to attend EULAR2019 and by Pfizer to attend ACR2021 virtually. J.C. Robson: Consultancies; J.C.R. reports: Consultancy for Vifor Pharma. Grants/research support; Funding for research from Vifor Pharma. Other; Speaking fees from Vifor Pharma.
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van der Heijde, Désirée M. F. M., Cynthia E. Kartman, Li Xie, Scott Beattie, Douglas E. Schlichting, Patrick Durez, Yoshiya Tanaka, and Roy Fleischmann. "P134 Radiographic progression of structural joint damage over 5 years of baricitinib treatment in patients with RA: results from RA-BEYOND." Rheumatology 60, Supplement_1 (April 1, 2021). http://dx.doi.org/10.1093/rheumatology/keab247.130.
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Abstract Background/Aims Baricitinib (BARI) is an oral, reversible, selective JAK1/2 inhibitor. Treatment with once-daily oral BARI resulted in low rates of radiographic progression for up to 2 years in patients with rheumatoid arthritis (RA). Here, we evaluate the radiographic progression of structural joint damage in patients with RA over 5 years of treatment with BARI. Methods This included patients who completed three Phase 3 trials, RA-BEGIN (DMARD-naive), RA-BUILD (csDMARD-IR), or RA-BEAM (MTX-IR), and enrolled in long-term extension study, RA-BEYOND. Patients receiving blinded BARI at the conclusion of Phase 3 trials remained on that dose (2mg/4mg, once daily) in RA-BEYOND. At 52 weeks, DMARD-naive patients receiving methotrexate(MTX) or combination therapy(BARI 4mg+MTX) were switched to BARI 4mg monotherapy; MTX-IR patients receiving adalimumab(ADA) were switched to BARI 4mg on background MTX. At 24 weeks, csDMARD-IR patients receiving placebo(PBO) were switched to BARI 4mg on background csDMARD. Analysis population included patients who had baseline and at least one radiograph collected after 2 years. Radiographic progression of structural joint damage (Years 3-5) was determined by changes from baseline in van der Heijdemodified Total Sharp Score(ΔmTSS), erosion score, and joint space narrowing. Proportion of patients showing no progression was assessed based on change from baseline mTSS(ΔmTSS) from originating study, using thresholds of 0.5 or smallest detectable change(SDC). Mixedmodel repeatedmeasures and logistic regression models were used to analyze continuous variables and categorical variables, respectively; linear extrapolation was used for imputation of missing data(maximum of 1 year). Results 82.6% (2125/2573) of patients entered long-term extension study. Among DMARD-naive patients, those on initial BARI monotherapy or in combination with MTX had significantly slower radiographic progression(ΔmTSS) versus those on initial MTX at Years 3, 4, 5 (p ≤ 0.05). They had significantly fewer erosions at these time points (p ≤ 0.05). A greater proportion of patients who received initial BARI therapy and BARI+MTX had no radiographic progression versus initial MTX monotherapy using thresholds of 0.5 (p ≤ 0.05). Among MTX-IR patients, those on initial BARI treatment had slower radiographic progression compared to PBO and results were comparable to those on initial ADA treatment at Years 3, 4, 5. A greater proportion of patients who received initial BARI therapy had no radiographic progression versus initial PBO using thresholds of SDC (p ≤ 0.05). Among csDMARD-IR patients, although differences between groups were small, patients on initial BARI 4mg had slowest radiographic progression compared to initial PBO and initial BARI 2mg. At least 74% of the structure data used in the analyses are based on observed data. Conclusion Treatment with once-daily oral BARI maintained low rates of radiographic progression for up to 5 years in different patient populations with RA. Disclosure D.M.F.M. van der Heijde: Consultancies; AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Cyxone, Daiichi Sankyo, Eli Lilly and Company, Galapagos NV, Gilead Sciences, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, and UCB Pharma. C.E. Kartman: Shareholder/stock ownership; Eli Lilly and Company. L. Xie: Shareholder/stock ownership; Eli Lilly and Company. S. Beattie: Shareholder/stock ownership; Eli Lilly and Company. D.E. Schlichting: Shareholder/stock ownership; Eli Lilly and Company. P. Durez: Member of speakers’ bureau; Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, and Sanofi. Y. Tanaka: Member of speakers’ bureau; AbbVie, Asahi-kasei, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly and Company, GlaxoSmithKline, Janssen, Mitsubishi-Tanabe, Novartis, Pfizer, Sanofi, Takeda, UCB, and YL Biologics. Grants/research support; AbbVie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi-Tanabe, MSD, Ono, and Taisho-Toyama and Takeda. R. Fleischmann: Consultancies; AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Novartis, Pfizer, Roche, Sanofi-Aventis, and UCB.
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ANGULO, Rodolfo José, and Maria Cristina De SOUZA. "MAPA GEOLÓGICO DA PLANÍCIE COSTEIRA ENTRE O RIO SAÍ-GUAÇU E A BAÍA DE SÃO FRANCISCO, LITORAL NORTE DO ESTADO DE SANTA CATARINA." Boletim Paranaense de Geociências 55 (December 31, 2004). http://dx.doi.org/10.5380/geo.v55i0.4280.
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A geologia de superfície da região costeira, entre o Rio Saí-Guaçu e a Baía de São Francisco, litoral norte de Santa Catarina, é constituída por rochas do embasamento cristalino Pré-Cambriano e pela cobertura sedimentar do Cenozóico. O objetivo deste trabalho é apresentar um novo mapa geológico dessa cobertura, na escala 1:50.000, com ênfase na planície costeira. Na área, foram identificadas as seguintes unidades: Fm. Mina Velha do Mioceno Inferior; colúvios, leques aluviais e depósitos fluviais, do Quaternário indiferenciado; terraços costeiros do Pleistoceno Superior (120.000 anos A.P.) e do Holoceno (< 7.000 anos A.P.); planícies paleoestuarinas do Holoceno; dunas, praias e mangues atuais. A distribuição em superfície e subsuperfície e o empilhamento das fácies dos depósitos costeiros permitem compreender alguns aspectos da evolução geológica e paleogeográfica da área durante o Quaternário. A ocorrência de extensos terraços do Pleistoceno e Holoceno, a presença de paleolagunas na retaguarda dos terraços e a ocorrência de sedimentos argilosos lagunares sob os terraços permitem inferir que, durante os ciclos transgressivos regressivos do Pleistoceno superior e Holoceno, existiram na região barreiras transgressivas e regressivas. A extensão das planícies paleoestuarinas indica que durante o máximo transgressivo do Holoceno existiam grandes estuários e lagunas. A morfologia dos cordões litorâneos evidencia que no Holoceno houve a formação de esporões paralelos à costa, que teriam crescido para o norte sob o efeito da deriva litorânea predominante. O crescimento desses esporões teria desviado a desembocadura do Rio Saí-Mirim para o norte. Durante essa migração, o rio erodiu a parte interna desses esporões e, provavelmente, as barreiras transgressivas do Holoceno. GEOLOGICAL MAP OF THE COASTAL PLAIN BETWEEN THE SAÍ-GUAÇU RIVER AND SÃO FRANCISCO BAY, NORTHERN COAST OF THE STATE OF SANTA CATARINA Abstract The studied area is located in the northeastern area of the State of Santa Catarina between 25o57' S and 26o14' S. The surface geology of the area is composed by rocks from the Precambrian basement and from the Cenozoic sedimentary cover. In conventional geological maps, the Cenozoic sedimentary package appears as an undifferentiated unit (e.g. Siga Jr. et al. 1993). Martin et al. (1988) presented the first map of the coastal Quaternary of the State of Santa Catarina, in 1:200,000 scale. Later, Horn Filho (1997) presented a map, in the scale 1:50,000, of the São Francisco do Sul region. The objective of this study is to present a new geological map, in the scale 1:50,000, of the coastal plain between the Saí-Guaçu River and the São Francisco Bay. In the studied area the following Cenozoic age units were identified: Mina Velha Formation, probably of Lower Miocene; colluvium and alluvial fans of undifferentiated Quaternary; fluvial deposits of undifferentiated Quaternary; Upper Pleistocene coastal terraces (120,000 years B.P.); Holocene coastal terraces (< 7,000 years B.P.); Holocene paleoestuarine plains; dunes; beaches and mangroves. The distribution on the surface and subsurface and the layers of facies of the coastal deposits allow an understanding of some aspects of the geological and paleogeographical evolution of the area during the Quaternary. There are extensive Pleistocene and Holocene terraces, the presence of paleolagoons on the terrace backs and also fine lagoon sediments below the terraces makes one infer that during the Upper Pleistocene and Holocene there were transgressive barrier and regressive beach/foredune ridges in the region, similar to those described by Lessa et al. (2000) in the State of Paraná. The extension of the paleoestuarine plains indicates that during the Holocene transgressive maximum there were large estuaries and lagoons. The morphology of the beach/foredune ridges provides evidence that in the Holocene spits parallel to the coast foreland that would have grown northward due to the effect of the dominant littoral drift. The growth of these spits caused the migration of the inlet of Saí-Mirim River more than 6 km northward throughout the last 5,000 years. During this migration the river eroded the internal part of these spits and the Holocene transgressive barriers.