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Long-term safety of subcutaneous abatacept in rheumatoid arthritis: integrated analysis of clinical trial data representing more than four years of treatment.

ABSTRACT: To investigate the safety of long-term subcutaneous (SC) abatacept treatment using integrated clinical trial data obtained in patients with rheumatoid arthritis refractory to traditional disease-modifying antirheumatic drugs.Data from the double-blind and open-label phases of 5 clinical trials of SC abatacept were pooled. The overall and 6-month incidence rates were calculated as events per 100 patient-years of exposure.This analysis included 1,879 patients with 4,214.6 patient-years of exposure to SC abatacept. The mean ± SD length of exposure was 27.3 ± 9.1 months. The reported incidence rate of serious infections was 1.79 (95% confidence interval [95% CI] 1.42-2.24); the most frequent infections were pneumonia (incidence rate 0.36 [95% CI 0.22-0.59]), urinary tract infection (incidence rate 0.14 [95% CI 0.06-0.32]), and gastroenteritis (incidence rate 0.10 [95% CI 0.04-0.25]). Tuberculosis occurred rarely (incidence rate 0.09 [95% CI 0.04-0.25]). The reported incidence rate of malignancies was 1.32 (95% CI 1.01-1.72), and the most common was solid organ malignancy (incidence rate 0.69 [95% CI 0.48-0.99]). The incidence rate of autoimmune events was 1.37 (95% CI 1.06-1.78), and the most frequent events were psoriasis (incidence rate 0.33 [95% CI 0.20-0.56]) and Sjögren's syndrome (incidence rate 0.24 [95% CI 0.13-0.44]). The reported incidence rate of local injection site reactions was 1.72 (95% CI 1.36-2.17); these events occurred primarily during the first 6 months of treatment, and almost all were of mild or moderate intensity. The incidence rates of serious infections, malignancies, autoimmune events, and injection site reactions did not increase over time.Long-term treatment with SC abatacept was associated with low incidence rates of serious infections, malignancies, and autoimmune events and was well tolerated, with infrequent injection site reactions. These findings are consistent with those related to treatment with intravenous abatacept. Long-term treatment with SC abatacept did not lead to new safety signals over time.

SUBMITTER: Alten R

PROVIDER: S-EPMC4309516 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Long-term safety of subcutaneous abatacept in rheumatoid arthritis: integrated analysis of clinical trial data representing more than four years of treatment.

Alten Rieke R Kaine Jeffrey J Keystone Edward E Nash Peter P Delaet Ingrid I Genovese Mark C MC

Arthritis & rheumatology (Hoboken, N.J.) 20140801 8

<h4>Objective</h4>To investigate the safety of long-term subcutaneous (SC) abatacept treatment using integrated clinical trial data obtained in patients with rheumatoid arthritis refractory to traditional disease-modifying antirheumatic drugs.<h4>Methods</h4>Data from the double-blind and open-label phases of 5 clinical trials of SC abatacept were pooled. The overall and 6-month incidence rates were calculated as events per 100 patient-years of exposure.<h4>Results</h4>This analysis included 1,8 ...[more]

PMID: 24782324

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Project description:IntroductionThe purpose of the present study was to determine whether the abatacept autoinjector can be used by the intended population without patterns of preventable use errors, and is acceptable when assessed against key user needs.MethodsTwo independently conducted simulated-use studies, with no active drug administered, quantified use errors and evaluated the abatacept autoinjector and competitor devices on key attributes (comfort, control, ease of use, confidence of dose) and overall acceptability. Autoinjector preference was also assessed. Participants were patients with rheumatoid arthritis, caregivers, and healthcare professionals (HCPs). Participants were informed that a new rheumatoid arthritis autoinjector was being tested but were blinded to the intended drug and sponsor identity.ResultsIn the formative (pre-validation) study (n = 54), two high-priority use errors occurred, both of which resulted from protocol non-compliance rather than mental confusion or physical limitations. In the summative (validation) study (n = 99), one high-priority use error occurred; this was deemed a simulated-use study artifact as participant behavior was guided by actual experience associated with the feel of drug delivery into the skin rather than by protocol, so no mitigation steps were considered necessary. Across user groups, average scores were consistently high for the pre-defined key attributes. Overall acceptability scores (7-point scale) were significantly higher for the abatacept versus competitor autoinjectors-formative study: patients 6.7 vs 5.2 (P = 0.0001), caregivers 7.0 vs 4.6 (P = 0.0093), HCPs 6.8 vs 5.1 (P = 0.0020); summative study: patients 6.5 vs 5.9 (P = 0.0404), caregivers 6.8 vs 5.8 (P = 0.0047), HCPs 6.8 vs 5.1 (P = 0.0002). The abatacept autoinjector was preferred to competitor devices: patients 85.7% vs 14.3% (P = 0.00002), caregivers 84.2% vs 15.8% (P = 0.00443), HCPs 95.0% vs 5.0% (P = 0.00004). Positive experiences with the abatacept autoinjector were attributed to the rubberized grip, device size, visualization of dose progression, button ergonomics, and ease of use.ConclusionThe abatacept autoinjector demonstrated usability without patterns of preventable use errors, and with high acceptability ratings across all key attributes assessed. Preference over competitor autoinjectors was due to device ergonomics, visualization of dose progression, confidence of dose delivery, and overall ease of use.FundingBristol-Myers Squibb.

Project description:Rheumatoid arthritis (RA) is a chronic, inflammatory disease affecting synovial joints. Patients with persistent, active disease have traditionally been treated with disease-modifying antirheumatic drugs (DMARDs) (eg, methotrexate) or biologic agents (eg, tumor necrosis factor [TNF] antagonists). However, patients may discontinue these treatments due to toxicity, infection, or lack of efficacy. Two additional biologic therapies-rituximab and abatacept-are currently available for TNF-antagonist inadequate responders. Abatacept is also indicated for inadequate responders to traditional DMARDs.The aims of this review was to provide an overview of the issues surrounding the treatment of RA patients experiencing inadequate responses to current treatment and to discuss the current and future impact of abatacept on the RA treatment armamentarium.The MEDLINE, EMBASE, and BIOSIS databases were searched (search dates: January 1, 2000-September 19, 2007) using the terms abatacept or CTLA-4 or Orencia with rheumatoid arthritis. Full text articles in English were selected for relevance, and only articles presenting primary clinical trial data from randomized, placebo-controlled, clinical trials of abatacept were included. This review focused on the Phase III trials of abatacept in methotrexate and/or TNF-antagonist inadequate responders, as these trials had the largest number of patients and the longest study durations.The literature search initially yielded 848 papers. A total of 12 articles fulfilled the inclusion criteria. Abatacept is a novel agent that has been reported to reduce the signs and symptoms of RA in patients with active RA with an inadequate response to DMARDs and/or TNF-antagonist treatment. In both of these patient populations, treatment with abatacept was found to provide clinically meaningful health-related quality-of-life benefits, such as improvements in physical function, activity limitation, sleep, and fatigue. Abatacept was reported to have a consistent safety and tolerability profile, with a low rate (3.5%-4.2%) of discontinuation due to adverse events.The efficacy and tolerability data from Phase III clinical trials suggest that abatacept is an effective and generally well tolerated treatment option for RA patients with an inadequate response to methotrexate and/or TNF antagonists.

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Long-term safety of subcutaneous abatacept in rheumatoid arthritis: integrated analysis of clinical trial data representing more than four years of treatment.

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Long-term safety of subcutaneous abatacept in rheumatoid arthritis: integrated analysis of clinical trial data representing more than four years of treatment.

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