Dataset Information

Risk of opportunistic infections in patients with rheumatoid arthritis initiating abatacept: cumulative clinical trial data.

ABSTRACT:

Background

To evaluate incidence of opportunistic infections (OIs) in patients with rheumatoid arthritis (RA) treated with abatacept in clinical trials.

Methods

This pooled analysis of 16 randomized, double-blind/open-label trials, with ??1 abatacept (intravenous or subcutaneous) arm, and with/without placebo control covered cumulative (controlled short-term and open-label long-term) abatacept exposure periods. OIs were analyzed separately in controlled (abatacept and placebo individually) and cumulative periods. OIs were identified using a prespecified list; events were independently adjudicated. Unadjusted incidence rates (IRs; per 100 patient-years) with 95% confidence intervals (CIs) were calculated.

Results

In cumulative periods, 7044 patients received abatacept, with a mean (standard deviation) duration of exposure of 36.9 (26.2) months (21,274 patient-years of exposure). IRs (95% CIs) of OIs were 0.17 (0.05-0.43) for abatacept and 0.56 (0.22-1.15) for placebo during the controlled periods and 0.21 (0.15-0.28) for abatacept during the cumulative periods. There was 1 case of tuberculosis in both the abatacept (IR [95% CI] 0.04 [0.00-0.24]) and placebo (IR [95% CI] 0.08 [0.00-0.44]) groups during the controlled periods; 13 verified tuberculosis cases (IR [95% CI] 0.06 [0.03-0.10]) were reported in the cumulative period. Herpes zoster was reported numerically more often with abatacept (IR 1.9 [1.4-2.5]), versus placebo (1.7 [1.1-2.6]) in the controlled periods; within the cumulative period, herpes zoster IR (95% CI) was 1.53 (1.36-1.71) for abatacept-treated patients.

Conclusion

In controlled periods of the clinical trials, abatacept-treated patients had similarly low rates of OIs compared with placebo-treated patients. Overall, OI rates were similar among abatacept-treated patients in the controlled and cumulative periods and consistent with the ranges reported in the literature.

SUBMITTER: Simon TA

PROVIDER: S-EPMC7798209 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Risk of opportunistic infections in patients with rheumatoid arthritis initiating abatacept: cumulative clinical trial data.

Simon Teresa A TA Dong Lixian L Winthrop Kevin L KL

Arthritis research & therapy 20210111 1

<h4>Background</h4>To evaluate incidence of opportunistic infections (OIs) in patients with rheumatoid arthritis (RA) treated with abatacept in clinical trials.<h4>Methods</h4>This pooled analysis of 16 randomized, double-blind/open-label trials, with ≥ 1 abatacept (intravenous or subcutaneous) arm, and with/without placebo control covered cumulative (controlled short-term and open-label long-term) abatacept exposure periods. OIs were analyzed separately in controlled (abatacept and placebo indi ...[more]

PMID: 33430948

Similar Datasets

Project description:BACKGROUND:Patients with rheumatoid arthritis (RA) are at an increased risk of developing certain cancers and infections compared with the general population. Biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) are effective treatment options for RA, but limited evidence is available on the comparative risks among b/tsDMARDs. We assessed the risk of malignancies and infections in patients with RA who initiated abatacept versus other b/tsDMARDs in a real-world setting. METHODS:This retrospective, observational study used administrative data from three large US healthcare databases (MarketScan, PharMetrics, and Optum) to identify patients treated with abatacept or other b/tsDMARDs. In both groups, age-stratified incidence rates (IRs) with 95% confidence intervals (CIs) were calculated for total malignancy and hospitalized infections; propensity score matching and Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% CIs for total malignancy, lung cancer, lymphoma, breast cancer, non-melanoma skin cancer (NMSC), hospitalized infections, opportunistic infections, and tuberculosis (TB), both within individual databases and in meta-analyses across the three databases. RESULTS:A rounded total of 19.2, 13.6, and 4.2 thousand patients initiating abatacept and 55.3, 40.8, and 13.8 thousand initiating other b/tsDMARDs were identified in the MarketScan, PharMetrics, and Optum databases, respectively. The IRs for total malignancy and hospitalized infections were similar between the two groups in each age stratum. In meta-analyses, total malignancy risk (HR [95% CI] 1.09 [1.02-1.16]) of abatacept versus other b/tsDMARDs was slightly but statistically significantly increased; small, but not statistically significant, increases were seen for lung cancer (1.10 [0.62-1.96]), lymphoma (1.27 [0.94-1.72]), breast cancer (1.15 [0.92-1.45]), and NMSC (1.10 [0.93-1.30]). No significant increase in hospitalized infections (0.96 [0.84-1.09]) or opportunistic infections (1.06 [0.96-1.17]) was seen. For TB, low event counts precluded meta-analysis. CONCLUSIONS:In this real-world multi-database study, the risks for specific cancers and infections did not differ significantly between patients in the abatacept and other b/tsDMARDs groups. The slight increase in total malignancy risk associated with abatacept needs further investigation. These results are consistent with the established safety profile of abatacept.

Project description: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.

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.

Dataset Information

Risk of opportunistic infections in patients with rheumatoid arthritis initiating abatacept: cumulative clinical trial data.

Background

Methods

Results

Conclusion

Publications

Risk of opportunistic infections in patients with rheumatoid arthritis initiating abatacept: cumulative clinical trial data.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure