Background Biologic therapies for RA can increase the risk of safety events such as infections, malignancies and autoimmune events; SC biologics may also cause injection site reactions (ISRs).1 Periodic re-assessment of safety data via incidence rates (IRs) allows a standardized assessment of safety that, over time, can detect any cumulative or new signals.
Objectives To investigate the safety of SC abatacept (ABA) using integrated clinical trial data with 4214.6 patient-years (pt-yrs) of exposure.
Methods Data from 5 SC ABA RA clinical trials (randomized clinical trials: 1 Phase IIb, 2 Phase IIIb; open-label studies: 2 Phase IIIb) were pooled over the short and long term.Safety events, including serious infections, malignancies, autoimmune events, and ISRs were assessed for pts who received ≥1 dose of SC ABA (125 mg/wk fixed dose). Overall and 6-monthly (up to month 30) IRs with 95% CIs were calculated as number of pts with events per 100 pt-yrs of exposure.
Results 1879 pts were evaluated with 4214.6 pt-yrs of exposure to SC ABA; mean (range) exposure was 27.3 (2–57) months. Overall, serious infections occurred at an IR (95% CI) of 1.79 (1.42, 2.24) in 74 (3.9%) pts; the most frequent (IR≥0.10) were pneumonia (0.36 [0.22, 0.59]), urinary tract infection (0.14 [0.06, 0.32]) and gastroenteritis (0.10 [0.04, 0.25]). Tuberculosis occurred rarely (IR 0.09 [0.04, 0.25] in 4 pts [2 pulmonary, 1 peritoneal, 1 not otherwise specified]). Overall, malignancies occurred at an IR of 1.32 (1.01, 1.72); the most frequent were basal cell carcinoma (0.43 [0.27, 0.68]), breast cancer (0.17 [0.08, 0.35]) and squamous cell carcinoma of skin (0.12 [0.05, 0.29]). Autoimmune disorders occurred at an IR of 1.37 (1.06, 1.78); the most frequent were psoriasis (0.33 [0.20, 0.56]), Sjögren’s syndrome (0.24 [0.13, 0.44]) and erythema nodosum (0.12 [0.05, 0.29]). ISRs occurred at an IR of 1.72 (1.36, 2.17), mainly during the first 6 months (Table). Over time, IRs for serious infections, malignancies, autoimmune disorders and ISRs, by 6-month intervals, did not increase with increasing exposure (Table).
Conclusions These pooled safety data, in over 4200 pt-yrs of exposure, demonstrate that long-term treatment with SC abatacept is well tolerated and does not lead to increases in serious infections, malignancies or autoimmune events over time. ISRs were mild and infrequent. No new safety signals were identified.
Curtis JR, et al. Curr Med Res Opin 2011;27:71–8.
Disclosure of Interest R. Alten Grant/Research support from: BMS, Merck Pharma GmbH, Wyeth Pharmaceuticals, Pfizer, Consultant for: Abbott Laboratories, Horizon Pharma, Merck Pharma GmbH, Nitec Pharma GmbH, Novartis Pharmaceuticals Corporation, Roche, Speakers Bureau: bbott Laboratories, BMS, Horizon Pharma, Merck Pharma GmbH, Novartis Pharmaceuticals Corporation, Roche, J. Kaine Grant/Research support from: Bristol-Myers Squibb, Speakers Bureau: Bristol-Myers Squibb, E. Keystone Grant/Research support from: Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb, Speakers Bureau: Bristol-Myers Squibb, P. Nash Grant/Research support from: Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb, Speakers Bureau: Bristol-Myers Squibb, I. Delaet Employee of: Bristol-Myers Squibb, K. Qi Employee of: Bristol-Myers Squibb, M. Genovese Consultant for: Bristol-Myers Squibb