Non-biologic DMARDs Research Articles

Risk of Subsequent Infection Among Patients Receiving Tumor Necrosis Factor Inhibitors and Other Disease-Modifying Antirheumatic Drugs.

To describe the incidence of subsequent serious infections in patients who received systemic drug therapy after an initial serious infection. Patients with rheumatic conditions (rheumatoid arthritis [RA], psoriatic arthritis, ankylosing spondylitis) or psoriasis who experienced a serious infection between January 1, 2006 and December 31, 2011 were identified in a claims database. Patients were required to be continuously enrolled in the Truven Health Analytics MarketScan Research Database for 12 months prior to and at least 60 days after the date of discharge or the end of intravenous antibiotic therapy for the index serious infection. Subsequent serious infection incidence rates per 100 patient-years with 95% confidence intervals (95% CIs) were calculated for up to 18 months post-index, starting 60 days post-index. Cox proportional hazards models were used to adjust for baseline demographic and clinical characteristics, treatment duration, and changes during followup. Among the 21,699 patients who met the inclusion criteria, the majority (84.3%) had RA. Patients who received tumor necrosis factor (TNF) inhibitor therapy after their index infection had a lower rate of subsequent serious infections (18.1 per 100 patient-years for those treated with a TNF inhibitor alone and 17.3 per 100 patient-years for those treated with a TNF inhibitor plus a nonbiologic disease-modifying antirheumatic drug [DMARD]) compared with those treated with a nonbiologic DMARD alone (21.4 per 100 patient-years). Etanercept, either alone (adjusted hazard ratio [HR] 0.87, 95% CI 0.77-0.99) or in combination with a nonbiologic DMARD (adjusted HR 0.76, 95% CI 0.66-0.88), and infliximab (only in combination with a nonbiologic DMARD) (adjusted HR 0.80, 95% CI 0.67-0.95) were associated with a significantly lower risk of subsequent serious infections compared with a nonbiologic DMARD alone. We did not observe an increased risk of subsequent infection in patients who received TNF inhibitor treatment following a serious infection. The risk of a subsequent serious infection was lower in patients treated with both a TNF inhibitor and a nonbiologic DMARD compared with that in patients treated with a nonbiologic DMARD alone.

Relationship of multi-biomarker disease activity score and other risk factors with radiographic progression in an observational study of patients with rheumatoid arthritis.

Objectives. To evaluate the multi-biomarker disease activity (MBDA) score as a predictor of radiographic progression and compare it with other risk factors among patients with established RA receiving non-biologic DMARDs.Methods. For 163 patients with RA, we assessed 271 visits for MBDA score (scale of 1−100), clinical data and subsequent 1-year radiographic progression (change in Sharp−van der Heijde score [SHS]). Scatter plot and non-parametric quantile regression curves evaluated the relationship between the MBDA score and change in SHS. Changes in joint space narrowing and erosions were compared among MBDA categories with Wilcoxon rank-sum tests. The ability of the MBDA score to independently predict progression was determined by multivariate models and cross-classification of MBDA score with other risk factors. Generalized estimating equation methodology was used in model estimations to adjust for same-patient visits, always ≥1 year apart.Results. Patient characteristics included 67% female, 66%/67% RF+/anti-CCP+; mean age 55 years, MBDA score 43 (moderate = 30−44); median disease duration 4.6 years, SHS 23. Radiographic progression was infrequent for low MBDA scores. Relative risk for progression increased continuously as the MBDA score increased, reaching 17.4 for change in SHS >5 with MBDA scores ≥60. Joint space narrowing and erosion progression were associated with MBDA score. MBDA score was associated with radiographic progression after adjustments for other risk factors. MBDA score significantly differentiated risk for progression when swollen joint count, CRP or DAS28–CRP was low, and among seropositive patients.Conclusion. MBDA score enhanced the ability of conventional risk factors to predict radiographic progression in patients with established RA receiving non-biologic DMARDs.

Low rates of biologic-free clinical disease activity index remission maintenance after biologic disease-modifying anti-rheumatic drug discontinuation while in remission in a Japanese multicentre rheumatoid arthritis registry.

To examine in detail the outcomes of biologic DMARD (bDMARD) discontinuation while in remission occurring in daily clinical practice settings. We examined a multicentre longitudinal registry of RA patients. We utilized data from the NinJa multicenter registry in Japan. Patients who used bDMARDs and had one or more successive visits in remission (defined by the clinical disease activity index (CDAI) ≤2.8) before discontinuation were included. The outcome of failing bDMARD-free disease control was defined as a composite of the following: re-use of bDMARDs, intensification of non-biologic DMARDs or of oral glucocorticoids, or loss of CDAI remission. Among 1037 patients who initially achieved remission on bDMARDs, 46 patients discontinued bDMARDs while remaining in remission. Of these 46 subjects, 41 (89.1%) were female, the median disease duration was 6.0 years and 31 (70.5%) had reported radiographical erosions. At the baseline, 27 (58.7%) used MTX and 19 (41.3%) used oral glucocorticoids. The bDMARD-free remission failure rate was estimated to be 67.4% at 1 year and 78.3% at 2 years. Loss of remission and reuse of bDMARDs were the more common reasons for failure. Lower CDAI within the remission range was associated with fewer failures. We found a high rate of failing bDMARD-free CDAI remission, indicating difficulty of maintaining disease control, even in patients who were in remission. Modification of non-biologic treatment was observed in some of the patients who remained in remission. Considering the cost of bDMARDs, such strategies for maintaining disease control after bDMARD discontinuation may be an important option.

Safety of biologic and nonbiologic disease-modifying antirheumatic drug therapy in veterans with rheumatoid arthritis and hepatitis B virus infection: a retrospective cohort study.

IntroductionWe evaluated the safety of current treatment regimens for patients with RA and HBV in a large US cohort.MethodsWe identified biologic and nonbiologic treatment episodes of RA patients using 1997 to 2011 national data from the US Veterans Health Administration. Eligible episodes had evidence of HBV infection (HBV surface antigen, HBV core antibody, HBV e-antibody and/or HBV DNA) and had a baseline alanine aminotransferase (ALT) <1.5 times the upper limit of laboratory normal within 90 days prior to initiation of a new biologic or nonbiologic DMARD. The main outcome of interest was hepatotoxicity, defined as ALT elevation >100 IU/mL. Results were reported as the cumulative incidence of treatment episodes achieving hepatotoxicity at 3, 6 and 12 months post biologic exposure.ResultsFive hundred sixty-six unique RA patients with HBV contributed 959 treatment episodes. Mean age was 62.1 ± 10.3 years; 91.8% were male. Hepatotoxicity was uncommon, with 26 events identified among 959 episodes (2.7%) within 12 months. Hepatotoxicity was comparable between biologic and nonbiologic DMARDs (2.6% vs. 2.8%, P = 0.87). The median time between HBV screening and starting a new RA drug was 504 days (IQR 144, 1,163). Follow-up HBV testing occurred among 14 hepatotoxicity episodes (53.8%) at a median of 202 days (IQR 82, 716) from the date of ALT elevation. A total of 146 (15.2%) treatment episodes received at least one test for HBV DNA at any point in the observation period.ConclusionsAmong US veterans with RA and HBV the risk of hepatotoxicity is low (2.7%), and comparable between biologic and nonbiologic DMARDS (2.8% vs. 2.6%, P = 0.87). HBV testing associated with DMARD initiation or hepatotoxicity was infrequent.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0628-z) contains supplementary material, which is available to authorized users.

Left ventricular morphology and function in rheumatoid arthritis patients without cardiac symptoms, using a cardiac magnetic resonance imaging

Background Patients with rheumatoid arthritis (RA) experience an excess risk of congestive heart failure (CHF), chronic inflammation plays a pivotal role in this increased risk. Despite the growing body of research on cardiovascular (CV) disease in RA, the key pathways underlying the development of abnormalities in myocardial structure and function associated with CHF remain obscure. Cardiac magnetic resonance imaging (CMR) has been used to identify early functional and structural changes in the left ventricle (LV) before development of clinically overt CHF. We evaluated LV function and structure using a CMR in RA patients (pts) without cardiac symptoms, and determined the impact of non-biologic DMARDs and biologic DMARDs. Methods Consecutive RA pts and healthy control were enrolled. RA pts received biologic DMARDs (bDMARDs) or non-biologic DMARDs (nbDMARDs). All subjects underwent evaluation of LV function and structure using non-contrast CMR. LV function was based on LV ejection fraction (EF), end-systolic volume (ESV), end-diastolic volume (EDV), stroke volume (SV), and cardiac output (CO). LV hypertrophy was measured by absolute LV mass (LVM) and LV mass index (LVMI) determined by LVM/body surface area. Subjects were classified into four categories based on LVMI and LVM/EDV of control subjects, with the mean + 2 SD of each measure defined as elevated LVMI and LVM/EDV. Results We compared 90 female RA pts (mean age, 55.9±7.1 years) with a matched 20-patient control group (mean age, 52.7±4.6 years). 46 RA pts received nbDMARDs [43, methotrexate (MTX); 3, other drugs)] and 44 RA pts received bDMARDs [(18, infliximab; 26, tocilizumab) plus MTX]. The Simplified Disease Activity Index (SDAI) was significantly higher in the nbDMARDs group than in the bDMARDs group (p=0.002). Compared to the control group, the nbDMARDs group showed significantly higher LVMI and lower EF (p 1.02 (2) concentric hypertrophy (LVMI>66.9 and LVM/EDV>1.02 (3) eccentric hypertrophy (LVMI>66.9 and LVM/EDV <1.02 and (4) normal geometry (LVMI<66.9 and LVM/EDV<1.02. Among those with abnormal LV geometry, 32% of RA patients in the nbDMARDs group showed eccentric hypertrophy. 98% of RA patients in the bDMARDs group showed normal geometry. LVMI and EF were significantly associated with SDAI (r=0.567, p<0.001; r=0.412, p=0.02, respectively). Mass/EDV tended to be associated with SDAI (p=0.07). Adjustment for ESR did not modify the association of SDAI with EF and LVMI (p=0.017, p=0.005, respectively). Conclusions Biologics treatment may reduce progression of subclinical LV dysfunction and normalize LV structure in association with the reduction in disease activity. It can be presumed that active RA may be an important contributor to the development of myocardial abnormalities.

Safety, Tolerability, and Efficacy of Tocilizumab in Rheumatoid Arthritis: An Open-Label Phase 4 Study in Patients from the Middle East

This open-label study investigated the safety and efficacy of tocilizumab in Middle Eastern patients with rheumatoid arthritis (RA). Patients whose Disease Activity Score based on 28 joints (DAS28) was >3.2 received tocilizumab 8 mg/kg intravenously every 4 weeks for 24 weeks. Patients receiving aTNF ± nonbiologic disease-modifying antirheumatic drug(s) (DMARD(s)) switched to tocilizumab; patients receiving nonbiologic DMARD monotherapy added tocilizumab. Primary end points were adverse events (AEs), serious AEs (SAEs), and laboratory parameters; secondary end points were DAS28, Health Assessment Questionnaire-Disability Index, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Eighty-eight of 95 patients completed 24 weeks. Overall, 125 AEs were reported in 43 (45%) patients; the most common were increased hepatic enzymes (16%) and cholesterol (11%). Eight patients experienced SAEs. Significant changes from baseline to week 24 occurred for hemoglobin, neutrophils, platelets, total cholesterol, and liver enzymes (P < 0.05). DAS28, CRP, and ESR decreased significantly from baseline at each visit (P < 0.0001). At week 24, the proportions of patients reporting DAS28 clinically meaningful improvement (decrease ≥1.2), low disease activity (DAS28 ≥2.6 to ≤3.2), and remission (DAS28 <2.6) were 92%, 23%, and 64%, respectively. Safety and efficacy of tocilizumab were consistent with values reported in Western patients.

Structural and functional outcomes of a therapeutic strategy targeting low disease activity in patients with elderly-onset rheumatoid arthritis: a prospective cohort study (CRANE).

The aim of this study was to evaluate structural damage and physical disability in patients with elderly-onset RA (EORA) who were treated in clinical practice with a therapeutic strategy targeting low disease activity (LDA). Data from 151 MTX-naive patients (mean age 74.9 years) with EORA from a prospective, monocentric registry were analysed. Treatment was adjusted every 3 months targeting LDA [28-joint DAS using ESR (DAS28-ESR) <3.2]. Treatment was initiated with non-biologic DMARDs (nbDMARDs), followed by TNF inhibitors (TNFis) or tocilizumab. The primary outcome was change from week 0 to week 52 in the modified total Sharp score (ΔmTSS). Secondary outcomes were derived from the HAQ Disability Index (HAQ-DI) and DAS28 at week 52. Predictors of clinically relevant radiographic progression [CRRP; ΔmTSS/year more than the smallest detectable change (2.1 points)] were examined using multivariate logistic regression models. Adherence to the treat-to-target strategy was observed in 83.4% of the 151 patients at week 24 and in 75.5% at week 52. At week 52, 67.6% of the patients were receiving a nbDMARD alone, 31.0% a TNFi with or without MTX and 1.4% tocilizumab. At week 52, structural remission (ΔmTSS/yr ≤0.5) was achieved in 49.7% of the patients, functional remission (HAQ-DI ≤0.5) in 63.4% and LDA in 51.0%. Clinical responses at weeks 12 and 24 were significant independent predictors of CRRP. Cumulative disease activity during the first 12 weeks predicted CRRP with a C-statistic of 0.888. Achieving structural remission, functional remission and LDA in clinical practice in EORA patients are realistic goals. Our results indicate significant benefits for a therapeutic strategy targeting LDA for EORA patients in clinical practice.

Pharmacologic treatment of psoriatic arthritis and axial spondyloarthritis with traditional biologic and non-biologic DMARDs.

This manuscript focuses on the pharmacologic treatment of psoriatic arthritis and axial spondyloarthritis - including ankylosing spondylitis - using traditional biologic and non-biologic disease-modifying antirheumatic drugs. Early treatment of psoriatic arthritis and axial spondyloarthritis/ankylosing spondylitis as well as the treat-to-target concept receive particular attention. This review also surveys recent national and international guidelines for the treatment of both psoriatic arthritis and couches practice recommendations for axial spondyloarthritis/ankylosing spondylitis within the context of various international guidelines.

First episode of chronic anterior uveitis in patients with juvenile idiopathic arthritis and relationship with administrated treatments

Fifty-six (80.0%) patients were female and 14 (20.0%) males. The categories ILAR were: 42 (60.0%) oligoarticular, 10 (14.3%) extended oligoarticular, 15 (21.4%) poliarticular and 3 (4.3%) associated with psoriasis. The average age at diagnosis was 3.5 SD 1.6 years (median 3 years). ANA positive were found in 41 (58.6%) patients. The mean follow-up of patients was 4.44 SD 3.65 years. There were 5 new cases of uveitis during treatment (3 MTX, 2 MTX-ETN or ETN and 0 with ADM only) and 10 cases presented to debut or before starting DMARDs or biologic therapy. The incidence was 0.15 and 0.11 cases per 100 patient / year, respectively (p> 0.05, t Student test). The accompanying table describes the distribution of new cases according to the ILAR category and administered treatment during the follow up period. Conclusion The incidence of occurrence of uveitis in our series of JIA patients at high risk of uveitis is comparable to that described in the literature (22.8%) and similar between patients who received MTX as monotherapy and those who received MTX and ETN or ETN. We reported no new cases of uveitis in patients treated with ADM, although in 85% of cases ADA was recomended in patients diagnosed with uveitis, with studies that have shown that it is more effective than treating this complication with ETN. The number of cases that occurred during treatment with ETN in our series of cases is too small to infer a causal relationship, the stratification by immunological profile, sick time, age or baseline severity of the symptoms could influence the development of this complication. Prospective comparative studies of biological and non-biological DMARDs are needed to assess the increase or decrease in the risk of uveitis associated with JIA.

Childhood Arthritis and Rheumatology Research Alliance Consensus Treatment Plans for New‐Onset Polyarticular Juvenile Idiopathic Arthritis

There is no standardized approach to the initial treatment of polyarticular juvenile idiopathic arthritis (JIA) among pediatric rheumatologists. Understanding the comparative effectiveness of the diverse therapeutic options available will result in better health outcomes for polyarticular JIA. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed consensus treatment plans (CTPs) for use in clinical practice to facilitate such studies. A case-based survey was administered to CARRA members to identify the common treatment approaches for new-onset polyarticular JIA. Two face-to-face consensus conferences employed modified nominal group technique to identify treatment strategies, operational case definition, end points, and data elements to be collected. A core workgroup reviewed the relevant literature, refined plans, and developed medication dosing and monitoring recommendations. The initial case-based survey identified significant variability among treatment approaches for new-onset polyarticular JIA. We developed 3 CTPs based on treatment strategies for the first 12 months of therapy, as well as case definitions and clinical and laboratory monitoring schedules. The CTPs include a step-up plan (nonbiologic disease-modifying antirheumatic drug [DMARD] followed by a biologic DMARD), an early combination plan (nonbiologic and biologic DMARD combined within a month of treatment initiation), and a biologic only plan. This approach was approved by 96% of the CARRA JIA Research Committee members attending the 2013 CARRA face-to-face meeting. Three standardized CTPs were developed for new-onset polyarticular JIA. Coupled with data collection at defined intervals, use of these CTPs will enable the study of their comparative effectiveness in an observational setting to optimize initial management of polyarticular JIA.

SAT0038 Factors Predicting Pain and Early Discontinuation of Tumour Necrosis Factor-Alpha-Inhibitors in People with Rheumatoid Arthritis: Results from the British Society for Rheumatology BIOLOGICS Register

BackgroundPain is a major problem in RA, but is not fully explained by inflammation.ObjectivesWe investigated factors predicting bodily pain 1 year after initiation of anti-TNF or conventional DMARD therapy change...

FRI0257 A Retrospective Database Analysis Describing Recurrent Infection Risk among Patients Using Tnf-Inhibitors, Other Biologic DMARDS and Non-Biologic Dmards

BackgroundPatients with inflammatory rheumatic conditions and psoriasis are often treated with immunosuppressive medications that can increase risk for infections but relatively little research has focused on the risk of recurrent...

THU0147 Tofacitinib, an Oral Janus Kinase Inhibitor: Analysis of Malignancies across the Rheumatoid Arthritis Clinical Programme

BackgroundTofacitinib is a novel, oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA).ObjectivesAn evaluation of malignancies in the tofacitinib RA programme from the Phase (P) 2, P3, and...

THU0441 Adherence and Persistence with Triple Non-Biologic Disease Modifying Antirheumatic Drug Therapy and Etanercept-Methotrexate Combination Therapy in US Patients with Rheumatoid Arthritis

BackgroundA recent randomized controlled trial in patients with rheumatoid arthritis (RA) showed non-inferiority of clinical benefit when starting on triple therapy (sulfasalazine (SSZ)+hydroxychloroqiune (HCQ)+methotrexate (MTX)) as compared to etanercept (ETN)...

FRI0325 The Use of Intravenous Expanded Allogeneic Adipose-Derived Mesenchymal Stem Cells in Refractory Rheumatoid Arthritis Patients. A Phase Ib/Iia Study

BackgroundExpanded adipose-derived stem cells (eASCs) are shown to have immune-modulatory effects in vitro and in animal models of arthritis. eASCs are currently under investigation as potential treatments targeting auto-immune and...

THU0174 Comparison of Switching to Reduced Dose VS Continuation of Standard Dose Etanercept for Rheumatoid Arthritis Patients in the Corrona Registry

BackgroundBoth patients and doctors are interested in information exploring the lowest effective dose of a drug. Clinical trials have recently demonstrated that the achievement of low disease activity (LDA) or...

THU0249 Early Therapeutic Intervention with Methotrexate (MTX) Prevents Development of Rheumatoid Arthritis (RA) in Patients with Undifferentiated Arthritis (UA), Even in the Presence of Smoking or the HLA-DR B1-Shared Epitope

BackgroundPreviously we reported that the patients with early-onset UA (EUA) showing high-titer anti-citrullinated peptide antibodies (ACPA) (>15 U/ml) developed RA within a year at high-rate (>80%) (ref. 1).ObjectivesTo examine whether...

THU0120 Is Early DMARD Use Associated with Less Joint Replacement Surgery? an Analysis of 5,199 Incident Rheumatoid Arthritis (RA) Patients

BackgroundEarly DMARD use in RA may prevent damage and possibly, need for joint replacement.ObjectivesTo assess joint replacements within incident RA patients in Quebec, Canada, and potential associations with early DMARD...

AB0376 Neither RA Disease Activity nor TNFI Increase the Incidence of Lymphoma in A Large, US RA Registry

BackgroundThe incidence of lymphoma is increased in patients with rheumatoid arthritis. There is controversy; however, regarding whether disease activity influences the incidence of lymphoma in this disease. Likewise, the effect...

FRI0206 Effectiveness of First, Second or Third Biologic DMARDS – Clinical Characteristics Are More Important than Choice of the Substance

BackgroundAt least one third of patients with long-standing RA starting treatment with a biologic (b)DMARD will have to change the substance within three years due to inefficacy or adverse events....