Academic literature on the topic 'Drug study/sulphasalazine'

1 Keratoconjunctivitis sicca (KCS) is an inflammatory eye condition, affecting the cornea and conjunctiva, caused by a deficiency in the aqueous fraction of tears. The condition is relatively common in the dog with a varied aetiology. A number of drugs have been implicated in the production of KCS in the dog including salicylazosulphapyridine (sulphasalazine). 2 This paper details clinically evident KCS in a 12-month oral toxicity study with 5-aminosalicylic acid (5-ASA), the therapeutically active metabolite of sulphasalazine. 3 The condition was first diagnosed at study week 22 and subsequently progressed both in incidence and severity. There was a distinct sex-difference in the response, with treated females being more affected than males. 4 There was a close correlation between the production of KCS and reduced lacrimation as assessed by the Schirmer tear test. 5 Although sulphasalazine causes KCS in dogs there have been no reports of ocular lesions of this type in man with this drug. It is highly probable that the dog is not a predictive model for man with regard to KCS induction by sulphasalazine or its metabolite 5-ASA.

Background: Spondyloarthropathies include a wide spectrum of disease. The study was conducted with the aim of observing the efficacy of SSZ and MTX in different subclasses of spondyloarthropathies and to compare the treatment response of the two drugs. Methods: This study was conducted in the Department of Medicine and Rheurnatology clinic of Bangabandhu Sheikh Mujib Medical University (BSMMU) between January 1999 and July 2001.A total number of one hundred twenty five patients was included in the study. Patients with active disease more than three months, regularly taking NSAIDs and not on DMARD in the last three months were included in the study. Monthly follow up of the patients was done for 6 months. Result: One hundred twenty five patients were included in this study. Male female ratio was 11.5:1. Mean age of patients was 24.17±7.15 years. The mean disease duration was 47.8±32.8 months. The present study categorized the patients into responder and non responder. Among the 78 patients in AS subclass, after completion of 6 month trial 55.6% patients in SSZ group and 39.4% patients in MTX group were categorized responder. The difference of response between drug groups was not significant (p=0.158). In the JCA subclass 81.82% in SSZ and 50% in MTX group were responder. The numbers of patient in Reiter's/Reactive Arthritis in our study were too small to make a definite comment. Conclusion: It can be concluded from this study that both the SSZ and MTX are effective DMARDs for spondyloarthropathies. Statistical analysis did not prove superiority of one drug over another, though the response rates were numerically higher in SSZ group. TAJ 2011; 24(1): 43-47

Background:Methotrexate (MTX) is the recommended first-line drug in EULAR and ACR treatment guidelines for rheumatoid arthritis (RA) and hence the most commonly prescribed DMARD in the treatment of this group of patients. However, lung disease is considered a potential adverse effect of MTX treatment.Objectives:To investigate the risk of interstitial lung disease (ILD) and acute and chronic respiratory failure in RA patients treated with MTX and other medications.Methods:From the Danish National Patient Register (DNPR) and the clinical DANBIO Register for rheumatic diseases, we retrieved data on RA patients registered between 1997 and 2015. Information on ILD and respiratory failure outcomes was obtained from DNPR, and information on redeemed prescriptions for MTX and other medications was obtained through linkage to the Danish Prescription Register. Associations between MTX and lung disease outcomes were analyzed in Cox regression models adjusted for age, calendar time, sex and use of other medications possessing the potential for pulmonary toxicity. Standardized Incidence Ratios (SIRs) of lung disease were calculated to compare RA patients to the general population.Results:Of the 30,512 RA patients identified, 60% patients had redeemed at least one prescription for MTX, 35% had redeemed a prescription for sulphasalazine, 6% had redeemed a prescription of either amiodarone or nitrofurantoin, and 27% had not received any of the included drugs at the end of the 5-year follow-up for ILD and respiratory failure. MTX treatment was not associated with an increased risk of lung disease (≥1 redeemed prescription(s) compared to no prescriptions), HR 1.00 (95% CI 0.78 to 1.27) for ILD and 0.54 (95%CI 0.43 to 0.67) for respiratory failure at 5-year follow-up (Table). The SIR was 3-4 times increased for ILD in MTX-treated RA patients, but this was no different from the RA population in general compared to the background population.Table.Hazard ratios (HR) with 95% confidence intervals (95%CI) for the risk of interstitial lung disease (ILD) and acute or chronic respiratory failure in 30,512 patients with rheumatoid arthritis up to 5 years after diagnosis.ILD (incl. drug-induced cases)1 year of follow up5 years of follow upEvents, NHR (95% CI)Events, NHR (95% CI)Methotrexate, ≥1 redeemed prescription(s) vs. none621.03 (0.71 to 1.48)1661.00 (0.78 to 1.27)Sulphasalazine, ≥1 redeemed prescription(s) vs. none210.88 (0.54 to 1.43)901.14 (0.89 to 1.48)Amiodarone and/or nitrofurantoin, ≥1 redeemed prescription(s) vs. none10.57 (0.08 to 4.10)70.65 (0.31 to 1.38Women72Ref.155Ref.Men551.51 (1.06 to 2.16)1301.74 (1.38 to 2.21)Acute or chronic respiratory failure1-year of follow up5-years of follow upEvents, NHR (95% CI)Events, NHR (95% CI)Methotrexate, ≥1 redeemed prescription(s) vs. none360.48 (0.32 to 0.73)1580.54 (0.43 to 0.67)Sulphasalazine, ≥1 redeemed prescription(s) vs. none140.70 (0.39 to 1.26)991.09 (0.86 to 1.38)Amiodarone and/or nitrofurantoin, ≥1 redeemed prescription(s) vs. none63.01 (1.31 to 6.94)221.33 (0.86 to 2.06)Women71Ref.239Ref.Men381.07 (0.72 to 1.59)1201.04 (0.83 to 1.29)Conclusion:RA patients had an increased risk of ILD compared to the general population, but that risk was not further increased in patients treated with MTX compared to non-MTX treated.Disclosure of Interests:None declared

Background: To analyse the usage pattern of pharmacological agents in the treatment of rheumatoid arthritis in Eastern India at a community level before reaching a specialized rheumatology clinic.Methods: Total 200 patients earlier diagnosed to be RA on treatment were selected and their demographic details, duration of treatment, agents prescribed, adverse drug reactions (ADRs) were analysed.Results: At the end of the study analysis, we observed that HCQ (24.4%) and Sulphasalazine (20.9%) were the commonest disease modifying anti-rheumatoid drug (csDMARD) used, followed by Methotrexate (16.9%). Dual combination csDMARD (33.1%) was preferred. Biological therapy was a rarity (0.5%). Steroids (21.0%) and NSAIDs (22.5%) was commonly used. Complementary and Alternative Medicines (CAM) (44.0%) was used often. Polypharmacy was the trend. Not all patients diagnosed as RA met the 2010 ACR/EULAR classification criteria of RA.Conclusions: In 15% patients, the diagnosis of RA was inappropriate according to the recent classification criteria. csDMARD was preferred either as monotherapy or combination therapy. Use of steroids and NSAID was a common practice. ADR were mild in severity.

Background:For inflammatory arthritis, drug retention is accepted as an important indicator of the effectiveness and safety of biological drugs.Objectives:The objective of this study was to determine of the effects first and overall bDMARD drug retention rate during concomitant csDMARD in psoriatic arthritis (PsA).Methods:HUR-BIO (Hacettepe University Rheumatology Biologic Registry) is a prospective, single center database of biological treatments since 2005. All PsA patients (469) who enrolled in HUR-BIO registry and prescribed at least once biologic DMARD (bDMARD) were included in the study. The subjects were divided into two groups depending on whether or not to use csDMARDs (methotrexate, sulphasalazine or leflunomide) at the last control visit. Demographic, clinical and therapeutic data were collected from this database. Baseline disease activity before the first bDMARD initiation was assessed with DAPSA and PsAID-12.Table.Demographics, baseline and follow-up clinical characteristics of PsA patientsWith concomitant csDMARD n=288Without concomitant csDMARD n=167pAge (mean, SD)48.9 (12.1)45.1 (12.4)0.002Female n (%)204 (70.8)113 (67.7)0.48PsA disease duration (med, IQR)7 (13)7 (14.5)0.53Age at PsA diagnosis (mean, SD)39 (11.7)40.8 (12.9)0.81BMI (mean, SD)29.6 (6.0)29.2 (5.9)0.53Axial involvement n (%)68 (34.0)37 (44.6)0.09HLA-B 27 (+) n (%)21/76 (27.6)17/69 (24.6)0.68Duration of use first bDMARD (months) (med, IQR)22.4 (51.3)14.1 (31.4)0.003Duration of use overall bDMARD (months) (med, IQR)56.8 (69.4)24.4 (57.7)<0.001Switching bDMARD (+) n (%)148 (52.5)71 (42.8)0.04Initial DAPSA1(med, IQR)19.4 (11.7)17.3 (10.2)0.04Initial PSAID2(med, IQR)5.7 (3)5.6 (2.8)0.55Final visit PSAID3(med, IQR)2.8 (3.8)2 (5.7)0.41Final visit DAPSA4(med, IQR)Remission (n,%)Low disease activityModerate disease activityHigh disease activity10.2 (12.4)12.5 (12.5)0.01Remission (n,%)61 (23.9)111 (43.5)72 (28.2)11 (4.3)27 (17.6)59 (38.6)58 (37.9)9 (5.9)0.13Low disease activity111 (43.5)59 (38.6)Moderate disease activity72 (28.2)58 (37.9)High disease activity11 (4.3)9 (5.9)1: n=249,2: n=214,3: n=109,4: n=408p<0.001p=0.003Results:HUR-BIO PsA registry included 469 PsA patients. Baseline, clinical characteristics and follow-up parameters were given in Table. The using overall bDMARD were adalimumab 294 (62.0%), etanercept 135 (28.8%), infliximab 119 (25.4%), certolizumab pegol 107 (22.8%), secukinumab 67 (14.3%), golimumab 58 (12.4%), ustekinumab 25 (5.3%) and tofacitinib 11 (2.3%). Two hundred eighty eight (61.4%) patients used concomitant cDMARDs [methotrexate 176 (37.5%), leflunomide 94 (20.0%), sulphasalazine 35 (7.5%) and two csDMARD combination 17 (3.6%)]. The first-year retention rate of first bDMARD with or without concomitant csDMARDs were 88% and 80%, respectively. The median duration of first bDMARD retention with or without concomitant csDMARDs were 131.7 and 91.4 months, respectively (Figure). The first-year retention rate of overall bDMARDs with or without concomitant csDMARDs were 92% and 85%, respectively. The median drug retention rate of overall bDMARD in using csDMARD and not using csDMARD were 141.5 and 131.5 months, respectively. Retention rates (both for first bDMARD and overall bDMARDs) were significantly higher in concomitant csDMARDs using group (p=0.003 for first bDMARD retention, p<0.001 for overall bDMARDs retention, log-rank; Figure). In concomitant csDMARD using group, no differences were identified methotrexate or other csDMARDs.Conclusion:In this study, csDMARDs, either methotrexate or leflunomide/sulphasalazine have additional effect for both retention rate and treatment response of bDMARDs. On the other hand, using bDMARD monotherapy is relatively higher than rheumatoid artritis (1).Figure.Drug retention rate of the first bDMARD and overall bDMARDs according to concomitant csDMARD use (csDMARD:conventional synthetic Disease Modifiying Antirheumatic Drug)Disclosure of Interests:Emine Duran: None declared, Emre Bilgin: None declared, Ertugrul Cagri Bolek: None declared, Gözde Kübra Yardimci: None declared, Bayram Farisoğullari: None declared, Levent Kiliç: None declared, Ali Akdoğan: None declared, Omer Karadag: None declared, Şule Arpaş Bilgen: None declared, Sedat Kiraz: None declared, Ali İhsan Ertenli: None declared, Umut Kalyoncu Consultant of: Abbvie, Amgen, Janssen, Lilly, Novartis, UCB

BackgroundThe effects of fish oil (FO) in rheumatoid arthritis (RA) have not been examined in the context of contemporary treatment of early RA. This study examined the effects of high versus low dose FO in early RA employing a ‘treat-to-target’ protocol of combination disease-modifying anti-rheumatic drugs (DMARDs).MethodsPatients with RA <12 months’ duration and who were DMARD-naïve were enrolled and randomised 2:1 to FO at a high dose or low dose (for masking). These groups, designated FO and control, were given 5.5 or 0.4 g/day, respectively, of the omega-3 fats, eicosapentaenoic acid + docosahexaenoic acid. All patients received methotrexate (MTX), sulphasalazine and hydroxychloroquine, and DMARD doses were adjusted according to an algorithm taking disease activity and toxicity into account. DAS28-erythrocyte sedimentation rate, modified Health Assessment Questionnaire (mHAQ) and remission were assessed three monthly. The primary outcome measure was failure of triple DMARD therapy.ResultsIn the FO group, failure of triple DMARD therapy was lower (HR=0.28 (95% CI 0.12 to 0.63; p=0.002) unadjusted and 0.24 (95% CI 0.10 to 0.54; p=0.0006) following adjustment for smoking history, shared epitope and baseline anti–cyclic citrullinated peptide. The rate of first American College of Rheumatology (ACR) remission was significantly greater in the FO compared with the control group (HRs=2.17 (95% CI 1.07 to 4.42; p=0.03) unadjusted and 2.09 (95% CI 1.02 to 4.30; p=0.04) adjusted). There were no differences between groups in MTX dose, DAS28 or mHAQ scores, or adverse events.ConclusionsFO was associated with benefits additional to those achieved by combination ‘treat-to-target’ DMARDs with similar MTX use. These included reduced triple DMARD failure and a higher rate of ACR remission.

Background:Cytopenia is a known side-effect of conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) in rheumatoid arthritis (RA). There is a lack of data on the comparative risk of cytopenia with different csDMARDs.Objectives:To assess the comparative risk of leukopenia and pancytopenia for the most frequently used first-line csDMARDs: methotrexate (MTX), hydroxychloroquine (HCQ), sulphasalazine (SSZ), and leflunomide (LEF).Methods:The study used data from 7 databases from 4 countries: CCAE, MDCR, Optum, IQVIA Ambulatory EMR (US); IQVIA THIN IMRD EMR (UK); IQVIA Disease Analyzer EMR (Germany); and SIDIAP (Spain). Cohorts included adult patients with a diagnosis of RA from 2005 to 2019 with at least one-year prior follow-up, no prior inflammatory arthritis, initiaton of first-line csDMARD, and no cytopenia in the preceding 30 days. Participants were followed from one day after treatment initiation to the earliest of event occurrence, treatment discontinuation/switching plus 14 days in the on-treatment analysis, five years in the intent-to-treat (ITT) analysis, or loss to follow-up. MTX was used as reference group. Cox models were fitted with propensity score stratification for observed confounding and negative control outcomes calibration for residual error. Estimates across database were pooled where I2<40% was seen.Results:Overall 166,347 patients were included. Pooled rates of leukopenia and pancytopenia for MTX were 10.9 and 3.2 per 1,000 person years, respectively. Figure 1 and 2 show the results for the different databases and pooled estimates where applicable. Database estimates are not reported where adequate covariate balance not attained, and meta-analysis not shown where I2>0.4. MTX showed slightly higher hazards of leukopenia and of pancytopenia compared to LEF but no consistently differential risks compared to HCQ or SSZ.Figure 1.Calibrated hazard ratios (95% CI) vs MTX, on-treatment analysisConclusion:Cytopaenia is rare, and apparently more frequent with MTX and less with LEF. Since prior full blood counts were inconsistently obtained in fewer than 50% of csDMARD new users (e.g. more frequent in MTX [42%] than HCQ [32%] in CCAE and Optum; roughly equal in MDCR), these results should inform future monitoring recommendations.Figure 2.Calibrated hazard ratios (95% CI) vs MTX, ITT analysisDisclosure of Interests: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), James Weaver Shareholder of: J&J Shares, Grant/research support from: Full-time employment salary from Janssen, Consultant of: Janssen employee, Employee of: Janssen, Paid instructor for: Janssen employee, have instructed at conferences, Speakers bureau: Janssen employee, have spoken at conferences, Edward Burn: None declared, Ben Illingens: None declared, David Vizcaya Employee of: Bayer, Ruta Sawant Shareholder of: AbbVie, Employee of: AbbVie, Talita Duarte-Salles: None declared, Patrick Ryan: None declared, Daniel Prieto-Alhambra Grant/research support from: Professor Prieto-Alhambra has received research Grants from AMGEN, UCB Biopharma and Les Laboratoires Servier, Consultant of: DPA’s department has received fees for consultancy services from UCB Biopharma, Speakers bureau: DPA’s department has received fees for speaker and advisory board membership services from Amgen

Background:Biosimilar infliximab (bio-INF) was approved for all indications of the reference product in several countries. It has been marketed since 2014 in Turkey and used in the same indications with its bio-originator.Objectives:Herein, we aimed to analyse clinical features and the drug survival rates of spondyloarthritis patients who have recieved bio-INF.Methods:This multicenter, prospective observational cohort study used the TReasure database in which web-based registration of rheumatoid arthritis and SpA patients are being performed in 13 centers across different regions of Turkey. Age, gender, and acute phase responses (erythrocyte sedimentation rate and C-reactive protein), HAQ scores, VAS patient global, VAS fatigue, VAS pain, VAS physician global, BASDAI, BASFI, ASDAS ESH and ASDAS CRP values, clinical findings of SpA patients, number of patients who has received bio-INF as first line therapy or after switch, treatments which are used before bio-INF, the reasons for switching bio-INF to another biologic DMARD and drug survival rates were retrospectively evaluated.Results:A total number of 231 SpA (94 (40.7 %) female, 137 (59.3%) male, mean age 43±11 yrs) patients have received biosimilar infliximab in the database. Of the 231 patients 127 (55%) had received bio-INF as first line therapy, whereas 104 (46 (19.9%) 2ndchoice, 58 (25.1%) 3rdchoice) patients used switching after another biologic DMARD. Previously used biologic and synthetic DMARDs were adalimumab (28.6%), etanercept (22.5%), golimumab (9.1%), original infliximab (8.2%), secukinumab (13.4%), methotrexate (23.8%), leflunamid (10.4%), sulphasalazine (60.6%). The baseline and first visit (3. Months) diseases activity scores were shown in Table 1. Drug survival rates were 79.1 in 12. months, 65.5 in 24. months and 54.6 in 60. months. (Figure 1). The most common reasons for switching from biosimilar infliximab to another biologic DMARD is secondary (25(10.8%)), and primary ineffectiveness (22(9.5%)). Other reasons to discontinuation of treatment are psoriasis (5 (2.1%)), infusion reaction (3(1.2%)), allergic reaction (22(8.8 %)), chest pain (3(1.2%)), dyspnea (1 (0.4%)), vasculitis (1 (0.4%)) and patient or doctor wish (7 (3.4%)).Conclusion:The results of this real life data provides evidence that biosimilar infliximab is an effective and safe treatment option with long term use in SpA patients. Drug survival rates of bio-INF is similar to its bio-originator.Table 1.Disease activity scoresBaseline visit3.monthpmedian (Q1-Q3)median (Q1-Q3)HAQ score0,63 (0,4-1)0,25 (0-1)<0,001BASDAI6,2 (4,8-7)2,8 (1-5)<0,001BASFI5,05 (3,3-6)2,1 (0,45-4)<0,001VAS Patient Global70 (50-80)30 (10-50)<0,001VAS Doctor Global60 (40-70)30 (20-40)<0,001VAS Pain50 (3-80)30 (10-50)0,572VAS fatigue70 (50-80)40 (10-65)<0,001ESR24 (11-45)11 (6-23)<0,001CRP12,1 (4,4-30)3,91 (2,19-9)<0,001ASDAS ESR3,12 (2,51-4)2,05 (1,39-3)<0,001ASDAS CRP3,53 (2,86-4)2,21 (1,5-3)<0,001*Wilcoxon Signed Rank TestFigure 1.Drug survival ratesDisclosure of Interests:Nazife Sule Yasar Bilge: None declared, Timuçin Kaşifoğlu: None declared, Sedat Kiraz: None declared, Ali İhsan Ertenli: None declared, Ediz Dalkiliç: None declared, Cemal Bes: None declared, Hakan Emmungil: None declared, Belkis Nihan Seniz: None declared, Burcu Yağiz: None declared, Muhammet Çinar: None declared, Servet Akar: None declared, Önay Gerçik: None declared, Duygu Ersözlü: None declared, Gezmiş Kimyon: None declared, Ridvan Mercan: None declared, Omer Karadag: None declared, Yavuz Pehlivan: None declared, Levent Kiliç: None declared, Umut Kalyoncu Consultant of: Abbvie, Amgen, Janssen, Lilly, Novartis, UCB

Background:Among patients with psoriatic arthritis (PsA), there remains a considerable confusion regarding the effectiveness of conventional synthetic DMARDs (csDMARDs), especially methotrexate (MTX). The availability of biologic DMARDs and targeted synthetic DMARDs have revolutionised the management of psoriatic disease; however, it comes with a significant cost burden. We believe that combination of DMARDs, especially combining MTX and Leflunomide (LEF) provides a valuable low-cost treatment option for patients with PsA after failure of MTX monotherapy. Hence, in our practice, we are inclined to use combination of potent DMARDs after MTX failure, prior to considering biologic therapies. Little is known about the combination use of LEF and MTX in PsA, especially in the context of drug retention time and tolerability.Objectives:We aimed to review our PsA cohort data especially examining the drug retention of first-line csDMARD monotherapy and combination csDMARDs.Methods:In our centre, MTX is a preferred first line csDMARD, unless contraindicated, and patients are followed up with a protocol on 4-6 weekly basis unless complete remission is achieved. MTX if needed is escalated to the maximum tolerated dose (up to 25mg/week), and if PsA is still active then preferably LEF is added (usual starting dose for add-on therapy is 10mg a day and if needed escalated to 20mg a day, without any loading dose). Other csDMARDs, such as sulphasalazine are used, if needed. For this study, after written-informed consent, only those adult patients were included who had a follow up of at least 6 months with our rheumatology services, and were fulfilling CASPAR criteria. Moreover, only patients who were DMARD-naïve (no prior DMARD therapy for any cause, including psoriasis), and initiated DMARD as monotherapy after 1 April 2018 were included. If any patient had already been on any DMARDs prior to attending our rheumatology services was excluded.Results:A total of 81 PsA patients [mean age 45.6±6 years; 52% male; mean PsA disease duration=9±4 years; 35% with dactylitis, 42% with enthesitis, 17% with sacroiliitis, median current PASI=2.6, median number of swollen joints=8.0, median number of tender joints= 11.0] fulfilled the inclusion and exclusion criteria. As regards first-line csDMARD monotherapy, 88% (n=71) of patients were commenced on MTX. In total, 79% (n=56 out of 71) of patients who were started on MTX as their first-line csDMARD therapy failed this monotherapy during follow-up (51=ineffective, 5=intolerance). After a median follow-up of 22 months, MTX median drug retention among all MTX monotherapy users (n=71) was only 7 months (IQR 5-7); and among MTX failures (n=56), MTX monotherapy median drug retention was 6.0 months (IQR 4-8). Eighty percent (n=45 out of 56) of the MTX monotherapy failure cohort was started on combination therapy of MTX and LEF (combo MTX+LEF); among them, only 7 patients needed escalation of therapy to bDMARDs, and the rest are still using combo MTX+LEF. It was noted that to date median drug retention time of combo MTX+LEF has been 8 months (IQR 7-11), and 84% (n=38 out of 45) of these patients are still using this combo therapy. Significantly more patients managed to continue the combo MTX+LEF therapy compared to MTX monotherapy (84% vs. 21%, p<0.001)Conclusion:Among csDMARD naïve PsA patients, 79% of patients failed MTX monotherapy with median drug retention time of only 6 months. Combination of MTX and LEF was well tolerated and had good drug retention time, with 84% of patients having ongoing treatment to date. Our data provides initial evidence that MTX and LEF combination therapy could be an effective treatment option for PsADisclosure of Interests:Muhammad Haroon Speakers bureau: Roche, Novartis, Grant/research support from: Abbvie, Pfizer, Shabnam Batool: None declared., Sadia Asif: None declared., Farzana Hashmi: None declared., Saadat Ullah: None declared.