Background Disease-modifying Antirheumatic Drugs Research Articles

Urinary prostanoids are elevated by anti-TNF and anti-IL6 receptor disease-modifying antirheumatic drugs but are not predictive of response to treatment in early rheumatoid arthritis

BackgroundDisease-modifying antirheumatic drugs (DMARDs) are widely used for treating rheumatoid arthritis (RA). However, there are no established biomarkers to predict a patient’s response to these therapies. Prostanoids, encompassing prostaglandins, prostacyclins, and thromboxanes, are potent lipid mediators implicated in RA progression. Nevertheless, the influence of DMARDs on prostanoid biosynthesis in RA patients remains poorly understood. This study aims to assess the impact of various DMARDs on urinary prostanoids levels and to explore whether urinary prostanoid profiles correlate with disease activity or response to therapy.MethodsThis study included 152 Swedish female patients with early RA, all rheumatoid factor (RF) positive, enrolled in the NORD-STAR trial (registration number: NCT01491815). Participants were randomized into four therapeutic regimes: methotrexate (MTX) combined with (i) prednisolone (arm ACT), (ii) TNF-α blocker certolizumab pegol (arm CZP), (iii) CTLA-4Ig abatacept (arm ABA), or (iv) IL-6R blocker tocilizumab (arm TCZ). Urine samples, collected before start of treatment and at 24 weeks post-treatment, were analyzed for tetranor-prostaglandin E metabolite (tPGEM), tetranor-prostaglandin D metabolite (tPGDM), 2,3-dinor thromboxane B2 (TXBM), 2,3-dinor-6-keto prostaglandin F1a (PGIM), leukotriene E4 (LTE4) and 12-hydroxyeicosatetraenoic acid (12-HETE) using liquid chromatography–mass spectrometry (LC–MS). Generalized estimating equation (GEE) models were used to analyze the change in urinary eicosanoids and their correlations to clinical outcomes.ResultsPatients receiving MTX combined with CZP or TCZ exhibited significant elevations in urinary tPGEM and TXBM levels after 24 weeks of treatment. Other eicosanoids did not show significant alterations in response to any treatment. Baseline urinary eicosanoid levels did not correlate with baseline clinical disease activity index (CDAI) levels, nor with changes in CDAI from baseline to week 24. Their levels were also similar between patients who achieved CDAI remission and those with active disease at week 24.ConclusionsTreatment with anti-TNF or anti-IL6R agents in early RA patients leads to an increased systemic production of proinflammatory and prothrombotic prostanoids. However, urinary eicosanoid levels do not appear to be predictive of the response to DMARDs therapy.

Shoulder arthroplasty trends in patients with rheumatoid arthritis receiving disease-modifying antirheumatic drug therapy

BackgroundDisease-modifying antirheumatic drugs (DMARDs) are used to treat rheumatoid arthritis (RA) and may lead to remission and decreased rates of joint arthroplasty. The rates of total shoulder arthroplasty (TSA) in RA patients since the implementation of DMARDs therapy are unknown. Furthermore, the utilization rates of TSA among various age cohorts as well as by procedure type: anatomic (ATSA) and reverse (RTSA), are not well defined in this patient population. The primary aim of this study was to assess TSA trends from 2011 to 2019 in RA patients with and without DMARD prescriptions. MethodsA retrospective trends analysis utilizing a national claims database was performed investigating the trends of TSA in RA patients with and without DMARD prescription claims from 2011 to 2019. Patients and prescriptions were identified using International Classification of Diseases codes and database-specific drug codes. Patients were divided into two cohorts: RA patients who underwent a TSA either with or without DMARD prescription claims. Patients were also stratified by age groups (≤59, 60-69, and ≥70 years) and procedure type (ATSA and RTSA) for analysis. Linear regression and compound annual growth rate were performed to compare trends of surgical utilization. Significant changes between trends were determined using an interaction term between the trend and calendar year within the regression. ResultsFrom 2011 to 2019, incidence of TSA in RA patients without DMARD prescription claims increased significantly more than in RA patients with prescription claims. Among the age groups, incidence of TSA in RA patients with and without DMARD prescription claims significantly increased among all age groups. The rate of change of TSA incidence in RA patients in all age groups was significantly higher in patients without DMARD prescription claims compared to RA patients with prescription claims. By procedure type, the incidences of RTSA were significantly increasing while incidences of ATSA were significantly decreasing in both groups. ConclusionThe incidence of TSA has increased significantly more in RA patients without DMARD prescription claims when compared to RA patients with prescription claims. Across all age groups, TSA was performed increasingly more in patients without prescription claims than in patients with prescription claims. The greater increase in TSA surgeries among patients aged 59 and younger without prescription claims suggests that DMARD therapy may play a beneficial role in preventing or delaying the need for TSA in RA patients. Examination of surgical utilization trends illustrates that RTSA is the preferred treatment over ATSA among RA patients.

Impact of pre-existing background therapy on placebo responses in randomised controlled clinical trials of rheumatoid arthritis

ObjectivesVarious hypotheses exist for the explanation of placebo response rates in randomised controlled trials (RCTs) of patients with rheumatoid arthritis with IR to methotrexate (MTX). We hypothesised that placebo responses...

Exploring Factors Influencing Medication Compliance in Saudi Rheumatoid Arthritis Patients: A Nationwide Cross-Sectional Survey - Results from the COPARA Study.

PurposeCompliance is essential to achieve treatment goals in rheumatoid arthritis (RA) patients. The current study evaluated compliance and related factors in a large and diverse population.Patients and MethodsPatients with RA who received active treatment were invited to participate in an online survey. The Arabic versions of the 5-Item Compliance Questionnaire for Rheumatology (ACQR-5) and the RA Impact of Disease (RAID) were used to measure compliance and disability, respectively. The patients were sub-grouped based on background disease-modifying anti-rheumatic drugs (DMARDs). Variables associated with high compliance were selected for the logistic regression analysis.ResultsA total of 1241 patients completed the survey and were included in the final analysis. Of those, 1055 (85%) were females with a mean (±SD) age and disease duration of 47.14 ± 13.71 and 8.77 ± 7.43 years, respectively. The mean RAID was 4.4±2.58, with 980 (79%) having an unacceptable level state. Patients with an unacceptable RAID level had a lower compliance rate (78.8% vs 85.8%, p = 0.001). Demographics associated with high compliance were female sex and increased age, with reported odds ratios of 1.018 (95% CI: 1.007–1.028) and 1.464 (95% CI: 1.016–2.108), respectively. Compliance was similar between patients on Janus kinase inhibitors or biological DMARDs (88.14% vs 80.83%, p = 0.17), between monotherapy, double therapy, or triple therapy recipients (80% vs 82.23% vs 81.32%, p = 0.665), and between patients receiving injectable and oral therapy (77.32% vs 81.14%, p = 0.246).ConclusionA high compliance level was observed in this population, with patient demographics influencing compliance rather than the medication type or route of administration. Interventional studies should focus on the of high-risk patients identified in this study.

Search of official nationwide database in Japan for adverse events associated with disease-modifying antirheumatic drug therapies: focus on therapies in combination with methotrexate

ABSTRACT Background Disease-modifying antirheumatic drugs (DMARDs) are essential for rheumatoid arthritis (RA) therapy. The adverse events (AEs) evaluation should focus on that methotrexate (MTX) is frequently prescribed in combination with others (combination MTX). Methods A search of the website of the official Japanese Agency for AEs, including lymphoproliferative disease (LPD), cytopenia, interstitial pneumonia, infectious pneumonia other than Pneumocystis jirovecii pneumonia (PCP) (i-Pn), and PCP, associated with MTX, tacrolimus, adalimumab, tocilizumab, and abatacept therapies reported from 2014 to 2016 was performed. Number of each AE cases and its ratio to total number of AEs cases were examined. Combination MTX was checked for RA cases. Results A total of 8874 cases were listed. In 3955 MTX cases, LPD was most frequent (36.4%). In any of the other four DMARDs cases, i-Pn was most frequent (4.2 ~ 15.3%); PCP cases showed most frequent combination MTX (94.4%). In total, including cases reported for MTX therapy, 98.2% of LPD and 97.6% of PCP cases had MTX, and less than 90% of the other AEs cases had MTX. Conclusion LPD was by far the most frequent AE associated with MTX therapy. PCP was strongly associated with combination MTX. For any of the other four DMARDs, i-Pn was most frequent.

Persistently normal blood tests in patients taking methotrexate for RA or azathioprine for IBD: a retrospective cohort study.

BackgroundDisease-modifying anti-rheumatic drugs (DMARDs), including methotrexate and azathioprine, are commonly used to treat rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). Blood-test safety monitoring is mainly undertaken in primary care. Normal blood results are common.AimTo determine the frequency and associations of persistently normal blood tests in patients with RA prescribed methotrexate, and patients with IBD prescribed azathioprine.Design and settingTwo-year retrospective study of a cohort taken from an electronic pseudonymised primary care/laboratory database covering >1.4 million patients across Hampshire, UK.MethodPatients with RA and IBD, and associated methotrexate and azathioprine prescriptions, respectively, were identified. Tests and test thresholds recommended by the National Institute for Health and Care Excellence were applied. Persistent normality was defined as no abnormalities of any tests nor alanine aminotransferase (ALT), white blood count (WBC), neutrophils, and estimated glomerular filtration rate (eGFR) individually. Logistic regression was used to identify associations with test normality.ResultsOf 702 265 adults, 7102 had RA and 8597 had IBD. In total, 3001 (42.3%) patients with RA were prescribed methotrexate and 1162 (13.5%) patients with IBD were prescribed azathioprine; persistently normal tests occurred in 1585 (52.8%) and 657 (56.5%) of the populations, respectively. In patients with RA on methotrexate, 585 (19.5%) had eGFR, 219 (7.3%) ALT, 217 (7.2%) WBC, and 202 (6.7%) neutrophil abnormalities. In patients with IBD on azathioprine, 138 (11.9%) had WBC, 88 (7.6%) eGFR, 72 (6.2%) ALT, and 65 (5.6%) neutrophil abnormalities. Those least likely to have persistent test normality were older and/or had comorbidities.ConclusionPersistent test normality is common when monitoring these DMARDs, with few hepatic or haematological abnormalities. More stratified monitoring approaches should be explored.

Healthcare professionals\u2019 perceptions on barriers and facilitators to DMARD use in rheumatoid arthritis

BackgroundDisease-modifying anti-rheumatic drugs (DMARDs) are the cornerstone of rheumatoid arthritis (RA) treatment. However, the full benefits of DMARDs are often not realized because many patients are sub-optimally adherent to their medication. In order to optimize adherence, it is essential that healthcare professionals (HCPs) understand patients’ barriers and facilitators for medication use. Insight in these barriers and facilitators may foster the dialogue about adequate medication use between HCPs and patients. What HCPs perceive as barriers and facilitators has, so far, scarcely been investigated. This study aimed to identify the perceptions of HCPs on patients’ barriers and facilitators that might influence their adherence.MethodsThis qualitative study was performed using semi structured in-depth interviews with HCPs. An interview guide was used, based on an adjusted version of the Theoretical Domains Framework (TDF). Thematic analysis was conducted to identify factors that influence barriers and facilitators to DMARD use according to HCPs.ResultsFifteen HCPs (5 rheumatologists, 5 nurses and 5 pharmacists) were interviewed. They mentioned a variety of factors that, according to their perceptions, influence DMARD adherence in patients with RA. Besides therapy-related factors, such as (onset of) medication effectiveness and side-effects, most variation was found within patient-related factors and reflected patients’ beliefs, ways of coping, and (self-management) skills toward medication and their condition. In addition, factors related to the condition (e.g., level of disease activity), healthcare team and system (e.g., trust in HCP), and social and economic context (e.g. support, work shifts) were reported.ConclusionsThis study provided insights in HCPs’ perceptions of the barriers and facilitators to DMARD use patients with RA. Most factors that were mentioned were patient-related and potentially modifiable. When physicians understand patients’ perceptions on medication use, adherence to DMARDs can probably be optimized in patients with RA leading to more effectiveness of treatment outcomes.

OP0120 DURATION OF CLINICAL EFFICACY FOLLOWING TREATMENT WITH VIB4920 IN SUBJECTS WITH MODERATE TO SEVERE RHEUMATOID ARTHRITIS

Background:VIB4920 binds CD40 ligand and functionally neutralizes its engagement with CD401. We reported results through Day 85 of a Phase 1b, randomized, double-blind, placebo-controlled study (NCT02780388) in subjects with moderate to severe rheumatoid arthritis (RA) who had an inadequate response to methotrexate (MTX) or other disease modifying anti-rheumatic drugs (DMARDs) or tumor necrosis factor (TNF)-inhibitors1. We showed that at the end of the 12-week treatment period (Day 85), subjects treated with 1000 or 1500 mg VIB4920 (once every 2 weeks) had a clinically meaningful and statistically significant greater reduction in disease activity compared to placebo.Objectives:To assess the duration of clinical efficacy following the last dose of VIB4920 in subjects with moderate to severe RA.Methods:Subjects in the Phase 1b study (Ph1b) continued to have monthly safety and efficacy assessments between Days 85 and 169, the end of a 12-week follow-up. To estimate the subsequent duration of meaningful clinical improvement, we conducted an observational one-visit study (OS) (EudraCT 2019-002351-42) with the primary endpoint of time from last dose of VIB4920 to start of a new DMARD or biologic therapy or increase in dose of DMARD that was ongoing at Day 169 (ie, rescue therapy).Results:At Day 169 of the Ph1b (3 months after the last dose), clinical responses achieved at Day 85 were maintained in the 1000 and 1500 mg cohorts (Figure). Of 24 subjects, 16 (6/12 treated with 1000 mg and 10/12 with 1500 mg) participated in the OS. The median (range) time from Day 169 (last visit) in the Ph1b to the OS was 21.8 (21.2 to 23.1) months in the 1000 mg group and 33.7 (32.3 to 34.8) months in the 1500 mg group. All subjects had taken DMARDs (primarily methotrexate [MTX]) for at least part of this time (Table). Rescue therapy was started in 1/6 (16.7%) subject in the 1000 mg group and 3/10 (30.0%) subjects in the 1500 mg group (Table); median time to rescue could not be estimated due to the limited number of rescues. Two subjects were on no DMARDs at the OS. All subjects, except for 1 in the 1000 mg group, who was rescued with adalimumab, and 2 in the 1500 mg group (no rescue), had active disease (DAS28-CRP ≥ 2.6) at the OS. The median DAS28-CRP at the OS was higher than at Day 169 of the Ph1b but lower than at the Ph1b baseline visit (Table). Two subjects who received 1500 mg and met DAS28-CRP criteria for low disease activity (< 3.2) at Day 169 also met these criteria at the OS without receiving any rescue therapy after a median of nearly 37 months after last treatment. Results from the Patient and Physician Global Assessment VAS showed trends similar to the DAS28-CRP.Conclusion:Blocking CD40L with VIB4920 led to prolonged clinical benefit in patients with RA when added to stable background DMARD therapy. The exact duration of benefit could not be defined in this study, but most patients did not require rescue therapy during a prolonged follow-up period, and some patients maintained low disease activity or discontinued DMARDs, suggesting a possible long-term benefit of VIB4920. Interpretation of these data is limited because the OS did not include placebo-treated subjects from the Ph1b. The duration of clinical response needs to be confirmed in prospective, double-blind, placebo-controlled studies.

Real-world questions and concerns about disease-modifying antirheumatic drugs (DMARDs): a retrospective analysis of questions to a medicine call center

BackgroundDisease-modifying antirheumatic drugs (DMARDs) have transformed the treatment of numerous autoimmune and inflammatory diseases but their perceived risk of harm may be a barrier to use.MethodsIn a retrospective mixed-methods study, we analysed conventional (c) and biologic (b) DMARDs-related calls and compared them with rest of calls (ROC) from consumers to an Australian national medicine call center operated by clinical pharmacists from September 2002 to June 2010. This includes the period where bDMARDs became available on the Pharmaceutical Benefits Scheme, the government-subsidized prescription medicines formulary. We compared caller and patient demographics, enquiry types and motivation to information-seek for both cDMARDs and bDMARDs with ROC, using a t-test for continuous data and a chi-square test for categorical data. We explored call narratives to identify common themes.ResultsThere were 1547 calls involving at least one DMARD. The top three cDMARD enquiry types were side effects (27.2%), interactions (21.9%), and risk versus benefit (11.7%). For bDMARDs, the most common queries involved availability and subsidized access (18%), mechanism and profile (15.8%), and side effects (15.1%). The main consumer motivations to information-seek were largely independent of medicines type and included: inadequate information (44%), wanting a second opinion (23.6%), concern about a worrying symptom (18.8%), conflicting information (6.9%), or information overload (2.3%). Question themes common to conventional and biological DMARDs were caller overemphasis on medication risk and the need for reassurance. Callers seeking information about bDMARDs generally overestimated effectiveness and focused their attention on availability, cost, storage, and medicine handling.ConclusionConsumers have considerable uncertainty regarding DMARDs and may overemphasise risk. Patients cautiously assess the benefits and risks of their DMARDs but when new treatments emerge, they tend to overestimate their effectiveness.

Factors Influencing Placebo Responses in Rheumatoid Arthritis Clinical Trials: A Meta-Analysis of Randomized, Double-Blind, Placebo-Controlled Studies.

A better understanding of placebo responses and the specific factors influencing these outcomes is important for clinical trial design. We investigated the magnitude of placebo responses at 3months and the potential factors influencing these outcomes in rheumatoid arthritis (RA) clinical trials. We conducted a systematic review of randomized placebo-controlled trials of pharmacological agents for RA identified from PubMed, Embase, and Cochrane Central Register of Controlled Trials databases. The primary placebo outcome was American College of Rheumatology 20% response rate (ACR20). Data were pooled with a random-effects model. Factors influencing placebo response were assessed by meta-regression analyses. Subgroup analyses were performed for studies conducted in non-Western countries only versus in Western countries (North America and/or Europe) only or both. The meta-analysis included 88 studies comprising 8406 patients receiving a placebo. The pooled estimate of placebo ACR20 was 29.0% (range 10.0-46.2; 95% confidence interval 27.2-30.9). Placebo ACR20 was negatively associated with trials in non-Western (Asian) countries and patient populations showing an inadequate response to biological disease-modifying antirheumatic drugs (DMARDs) in the multivariable analysis, whereas it was positively associated with the year of publication. No background DMARD treatment was also a negative predictor (albeit statistically non-significant). In subgroup analyses of Western and multiregional studies, study population and publication year were significant factors. Our meta-analysis suggests that study location, patient population, and a background DMARD treatment influence placebo ACR20. These along with placebo response temporal profiles have important implications for designing and interpreting RA clinical trials.

Usability and Patient Preference Phase 3 Study of the Sarilumab Pen in Patients with Active Moderate-to-Severe Rheumatoid Arthritis.

Sarilumab is a human monoclonal antibody that blocks the interleukin-6 receptor alpha (IL-6Rα). The phase 3 SARIL-RA-EASY study (EASY) assessed the robustness of an autoinjector (pen) for administering sarilumab when used by adults with active moderate-to-severe rheumatoid arthritis (RA) who are candidates for anti-IL-6R therapy in an unsupervised real-world setting. EASY was a 12-week, multicenter, randomized, open-label, parallel-group usability study of the sarilumab pen and prefilled syringe. Patients were randomized 1:1:1:1 to sarilumab 150 or 200mg every 2weeks (q2w) administered via pen or syringe, plus background disease-modifying antirheumatic drugs. Patients reported their ability to remove the pen cap and initiate and complete injections; negative responses were defined as product technical complaints (PTCs). The primary endpoint was the number of validated product technical failures (PTFs; PTC with a validated technical cause). This study was not powered to demonstrate bioequivalence or differences in efficacy among groups. A total of 217 patients were randomized. There were 600 successful injections with the sarilumab pen in 108 patients and no pen-associated PTFs. One PTC was observed (the pen was mistakenly activated before injection). At week 12, 88% of patients indicated the pen was "easy" to use, and 98% reported they were "satisfied" with the pen. Proportions of patients achieving an American College of Rheumatology 20/50/70 response and a 28-joint disease activity score by C-reactive protein <2.6 were similar at each dose between the pen and syringe groups, as were the pharmacokinetics. There were no clinically meaningful differences in adverse events (AEs), serious AEs, and AEs leading to discontinuation in the pen and syringe groups. The most common treatment-emergent AEs were infections and neutropenia. This study demonstrated the ease of use and robustness of the sarilumab pen when used by patients with RA in an unsupervised setting. Pharmacokinetics, safety, and efficacy were generally similar for the pen and syringe groups (NCT02057250). Sanofi Genzyme and Regeneron Pharmaceuticals, Inc. Clinicaltrials.gov identifier, NCT02057250.

Efficacy and safety of tabalumab, an anti-BAFF monoclonal antibody, in patients with moderate-to-severe rheumatoid arthritis and inadequate response to TNF inhibitors: results of a randomised, double-blind, placebo-controlled, phase 3 study

BackgroundTabalumab is a human monoclonal antibody that neutralises B-cell activating factor.ObjectivesTo evaluate tabalumab efficacy and safety in patients with rheumatoid arthritis (RA).MethodsThis phase 3, randomised, double-blind, placebo-controlled study evaluated 456...

OP0154 Integrated Safety Analysis of Tofacitinib in RA Clinical Trials with A Cumulative Exposure of 12,664 Patient-Years

BackgroundTofacitinib is an oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA). Phase (P) 2, P3, and open-label long-term extension (LTE) studies described the safety profile of...

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Anti-TWEAK Monoclonal Antibody in Patients With Rheumatoid Arthritis

Persistent upregulation of signaling by cytokine tumor necrosis factor-like weak inducer of apoptosis (TWEAK) through its receptor fibroblast growth factor-inducible molecule-14 (Fn14) promotes chronic inflammation and tissue destruction. The aim of this study was to explore the safety and tolerability of the TWEAK-blocking monoclonal antibody BIIB023 and determine its pharmacokinetics and effects on TWEAK pathway pharmacodynamic markers in rheumatoid arthritis (RA). Phase I, first-in-human, 2-part, multicenter, double-blind, dose-escalation study. Patients were randomized to a single dose of BIIB023 (0.03-20 mg/kg) (n = 38) or placebo (n = 15) as an add-on to methotrexate. Three open-label cohorts of RA patients taking background disease-modifying antirheumatic drugs and stable tumor necrosis factor (TNF) inhibitor therapy (n = 12) received a single-dose of BIIB023 of 2, 10, or 20 mg/kg and were assessed over 70 days. The incidence of treatment-emergent adverse events for the BIIB023 monotherapy cohorts and open-label cohorts of BIIB023 as add-on therapy to TNF inhibitors compared with placebo were 47% and 50% versus 33%, respectively. Serum exposure to BIIB023 increased in a dose-dependent manner from 0.03 to 20 mg/kg, but not in direct proportion to dose level. After administration, the time course of BIIB023 serum concentration was multiphasic and showed expedited elimination when levels decreased to < 10 µg/mL. Serum-soluble TWEAK levels were suppressed at all dose levels by 6 hours post-dose and recovered to baseline between days 7 and 28. A trend toward downward modulation of serum biomarkers of inflammatory response was suggested in monocyte chemoattractant protein 1, inducible protein 10, macrophage inflammatory protein 1β, and tissue inhibitor of metalloproteinase 1 in the BIIB023 group versus placebo. Single-dose BIIB023 showed a favorable safety and tolerability profile in RA. Suppression of serum-soluble TWEAK for ≤ 28 days was observed and downward trends in serum biomarkers suggested.

FRI0066 Meta-analysis of joint structural deterioration over time in minimally treated rheumatoid arthritis patients

BackgroundThe goals of treatment for rheumatoid arthritis (RA) are to reduce disease activity, reduce or arrest the rate of joint damage, and, if possible, achieve remission. The majority of the...

AB0335 Tocilizumab is effective for the treatment of anti-tnf- and rituximab-refractory rheumatoid arthritis

BackgroundA significant proportion of patients with rheumatoid arthritis continue to have active disease and accrue joint damage despite the use of disease modifying anti-rheumatic drugs (DMARDs) and biologicals including anti-TNF...

Efficacy of tocilizumab in patients with moderate to severe active rheumatoid arthritis and a previous inadequate response to disease-modifying antirheumatic drugs: the ROSE study

ObjectiveTo evaluate efficacy of tocilizumab in US patients with moderate to severe active rheumatoid arthritis (RA) and inadequate clinical response to disease-modifying antirheumatic drugs (DMARD). Safety-related outcomes were also analysed.MethodsThe...

Impact of concomitant use of DMARDs on the persistence with anti-TNF therapies in patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register

ObjectiveTo evaluate the effect of different concomitant disease modifying antirheumatic drugs (DMARDs) on the persistence with antitumour necrosis factor (anti-TNF) therapies in patients with rheumatoid arthritis (RA).MethodThis analysis included 10...

Abatacept

Abatacept (Orencia) is the first in a new class of biologics known as selective costimulation modulators. It inhibits full activation of T cells and interacts with other cell types to affect additional mediators of the inflammatory cascade. The clinical efficacy of abatacept in patients with active rheumatoid arthritis, despite prior treatment with methotrexate or anti-tumor necrosis factor-alpha (anti-TNFalpha) therapies, has been investigated in two randomized, double-blind, placebo-controlled, multicenter, phase III trials of 6 or 12 months' duration. In these trials, patients received intravenous abatacept (fixed-dose regimen based on bodyweight) or placebo in addition to background disease-modifying anti-rheumatic drugs (DMARDs) other than anti-TNFalpha therapies. Relative to placebo, abatacept significantly improved signs and symptoms of disease assessed using American College of Rheumatology (ACR) 20, 50, and 70 criteria and specific improvement in physical function as measured by the Health Assessment Questionnaire Disability Index at 6 months and significantly slowed structural damage progression in joints at 12 months. Improvements in ACR 20, 50, and 70 response rates were maintained at the final assessment in the 12-month trial. Abatacept infusions were generally well tolerated. Acute infusion-related reactions occurred in 9% of abatacept and 6% of placebo recipients in phase III trials. Integrated safety data from five clinical trials showed that serious adverse events were reported in 13.6% of abatacept and 12.3% of placebo recipients and the incidence of serious infections was 3.0% and 1.9%. Abatacept administered with background biologic DMARDs appears to be less well tolerated than abatacept plus background nonbiologic DMARDs.