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

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Figure 1

Infections and serious infections in 1,879 patients treated with subcutaneous (SC) abatacept and 4,149 patients previously treated with intravenous (IV) abatacept. Top, Incidence rates (95% confidence intervals) at 6-month intervals in patients treated with SC abatacept, and overall incidence rates in patients treated with SC abatacept and those treated with IV abatacept. Bottom, Numbers of patients with infections and serious infections and total patient-years of exposure at 6-month intervals. Serious infections are a subset of serious adverse events and infections.

Figure 2

Malignancies (excluding nonmelanoma skin cancer [NMSC]) and autoimmune events in 1,879 patients treated with subcutaneous (SC) abatacept and 4,149 patients previously treated with intravenous (IV) abatacept. Top, Incidence rates (95% confidence intervals) at 6-month intervals in patients treated with SC abatacept, and overall incidence rates in patients treated with SC abatacept and those treated with IV abatacept. Bottom, Numbers of patients with malignancies and autoimmune events and total patient-years of exposure at 6-month intervals. Autoimmune events are prespecified (Medical Dictionary for Regulatory Activities preferred terms).

Figure 3

Injection site reactions (ISRs) in 1,879 patients treated with subcutaneous abatacept. Top, Incidence rates (95% confidence intervals) at 6-month intervals. Bottom, Numbers of patients with injection site reactions and total patient-years of exposure at 6-month intervals. Injection site reactions are prespecified (Medical Dictionary for Regulatory Activities preferred terms).