Background There is a paucity of clinical trial data comparing the efficacy and safety of biologic therapies for RA.
Objectives To evaluate remission rates and safety for patients treated with SC or IV abatacept compared with the anti-TNF monoclonal antibodies, adalimumab and infliximab, in a post hoc, cross-trial comparison.
Methods In the head-to-head AMPLE study,1 patients were randomized to SC abatacept (125 mg weekly) or SC adalimumab (40 mg biweekly), plus background MTX. In the double-blind, double-dummy, placebo- and active-controlled ATTEST study,2 patients were randomized 3:3:2 to IV abatacept (~10 mg/kg every 4 weeks), infliximab (3 mg/kg every 8 weeks) or placebo, plus background MTX. Patients in both trials had active RA with inadequate response to MTX and were biologic-naïve. Remission according to DAS28 (CRP) and SDAI was evaluated post hoc over 12 months of treatment for all randomized and treated patients with data available at the visit of interest. Safety was evaluated for all patients who received at least one dose of study drug.
Results In AMPLE, 318 and 328 patients received SC abatacept and adalimumab, respectively; in ATTEST, 156 patients received IV abatacept and 165 received infliximab. Baseline DAS28 (CRP) scores (mean±SD) were 5.5±1.1 in AMPLE and 6.4±0.9 in ATTEST. Duration of RA was 1.9±1.4 and 1.7±1.4 years for SC abatacept and adalimumab in AMPLE, and 7.9±8.5 and 7.3±6.2 years for IV abatacept and infliximab in ATTEST. Remission rates over 12 months were similar for treatment groups in each trial (Table). Over 12 months, 11 (3.5%) vs 20 (6.1%) SC abatacept vs adalimumab-treated patients, and 4 (2.6%) vs 12 (7.3%) IV abatacept vs infliximab-treated patients discontinued due to AEs; 32 (10.1%) vs 30 (9.1%) and 15 (9.6%) vs 30 (18.2%) experienced SAEs; 5 (1.6%) vs 4 (1.2%) and 1 (0.6%) vs 2 (1.2%) had malignancy; 10 (3.1%) vs 4 (1.2%) and 2 (1.3%) vs 1 (0.6%) experienced autoimmune events. Serious infections were reported in 7 (2.2%) vs 9 (2.7%) and 3 (1.9%) vs 14 (8.5%) patients treated with SC abatacept vs adalimumab in AMPLE and IV abatacept vs infliximab in ATTEST, respectively, with 0/7 vs 5/9 and 0/3 vs 4/14 serious infections leading to discontinuation, and opportunistic infections for 1 (0.3%) vs 1 (0.3%) and 0 vs 5 (3.0%).
Conclusions Greater proportions of patients in the AMPLE trial achieved remission outcomes vs ATTEST; however, patients in AMPLE had shorter disease duration and lower disease activity at baseline. Both routes of abatacept administration provided similar remission rates over time to the anti-TNF therapies, regardless of disease duration. Safety outcomes were mostly balanced, with increased SAEs and serious infections for infliximab vs abatacept, and increased discontinuations due to AEs and serious infections in both anti-TNF groups vs abatacept. This analysis provides valuable comparative insight into the efficacy and safety of these biologic agents.
Weinblatt ME. Arthritis Rheum 2013;65:28-38;
Schiff M. Ann Rheum Dis 2008;67:1096-103
Disclosure of Interest: M. Schiff Consultant for: Bristol-Myers Squibb, Abbvie, Speakers bureau: Bristol-Myers Squibb, Abbvie, M. Dougados Grant/research support from: Bristol-Myers Squibb, Abbott, Pfizer, Roche, UCB, Novartis, Merck, Lilly, Consultant for: Bristol-Myers Squibb, Abbott, Pfizer, Roche, UCB, Novartis, Merck, Lilly, Paid instructor for: Bristol-Myers Squibb, Speakers bureau: Bristol-Myers Squibb, Abbott, Pfizer, Roche, UCB, Novartis, Merck, Lilly, R. Fleischmann Grant/research support from: Abvie, Amgen, Astellas, Astra Zeneca, Bristol-Myers Squibb, Celgene, Dynavax, Genzyme, J anssen, Eli Lilly, Merck, Novartis, Pfizer, Roche, sanofi aventis, UCB, X oma, Consultant for: Abvie, Amgen, Astra Zeneca, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Pfizer, Roche, sanofi aventis, UCB, J. Fay Employee of: Bristol-Myers Squibb, M. Maldonado Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb