Background Novel therapies have made remission and low disease activity (LDA) achievable goals in rheumatoid arthritis (RA). We report here, the impact of treatment with subcutaneous abatacept (ABA) or adalimumab (ADA) on these goals in AMPLE (Abatacept Versus Adalimumab Comparison in Biologic Naive RA Subjects with Background Methotrexate), the first head-to-head trial of biologics in RA patients with inadequate response to methotrexate (MTX).
Objectives To assess the differences in the rates of remission and LDA; and to evaluate their relationship to functional and radiographic outcomes.
Methods AMPLE is a phase IIIb, randomized, investigator-blinded study of 2 year duration. Biologic-naïve RA patients with an inadequate response to MTX were randomized to receive either 125 mg ABA weekly or 40 mg ADA bi-weekly, in combination with a stable dose of MTX.1Proportion of patients achieving remission (defined as DAS28-CRP<2.6, CDAI≤2.8, SDAI≤3.3, RAPID3<3, Boolean score ≤1) or LDA (defined as DAS28-CRP≤3.2, CDAI≤10, SDAI≤11, RAPID3≤6) were assessed. Physical function (assessed with the health assessment questionnaire disability index [HAQ-DI-responders defined as an improvement ≥0.3U]) and radiographic non-progression (defined as change in modified Total Sharp Score of ≤2.8) were analyzed in patients achieving or not achieving remission or LDA at Day 85 or Day 169.
Results The baseline clinical characteristics of ABA (n = 318) and ADA (n = 328) treatment groups were balanced, as was clinical, functional and radiographic efficacy and safety at Day 365.1 The proportions of patients meeting each of the remission criteria or LDA at Day 365 were generally equal for both groups, but significantly more patients achieved DAS28-CRP remission compared to CDAI, SDAI or RAPID3 remission, and the smallest proportion achieved Boolean remission (Table). Compared to remission, a higher proportion of patients achieved LDA. Across all definitions of remission or LDA, more than 60% of the patients that achieved remission at Day 85 and Day 169 were HAQ responders at Day 365. More than 80% of patients that achieved remission or LDA at Day 85 and Day 169 were radiographic non-progressors at Day 365. Improvement in physical function and radiographic outcomes were consistent between the two treatment groups in both remission and LDA populations.
Conclusions Through 1 year, patients treated with SC abatacept or adalimumab in the AMPLE trial achieved comparable rates of remission and LDA. Similar improvements in physical function and radiographic outcomes were observed. Data reported here help to illustrate the relationship between remission, LDA and functional and radiographic outcomes independent of treatment with SC abatacept or adalimumab.
References Weinblatt et al. Arthritis Rheum. January, 2013; 65(1): 28-38
Disclosure of Interest R. Fleischmann Grant/research support from: Genentech Inc, Roche, Abbott, Amgen, UCB, Pfizer, Bristol-Myers Squibb, Lilly, Sanofi Aventis, MSD, Novartis, BiogenIdec, Astellas, Astra-Zeneca, Jansen, Consultant for: Roche, Abbott, Amgen, UCB, Pfizer, Bristol-Myers Squibb, Lilly, Sanofi Aventis, Astra-Zeneca, Jansen, M. Schiff Consultant for: Bristol-Myers Squibb, Abbott, Speakers bureau: Bristol-Myers Squibb, Abbott, M. Weinblatt Grant/research support from: Bristol-Myers Squibb, Abbott, Consultant for: Bristol-Myers Squibb, Abbott, M. Maldonado Employee of: Bristol-Myers Squibb, E. Massarotti Grant/research support from: Bristol-Myers Squibb, Consultant for: UCB, Y. Yazici Grant/research support from: Bristol-Myers Squibb, Genentech Inc., Celgene, Janssen, Consultant for: Bristol-Myers Squibb, Abbott, Genentech Inc., UCB, Pfizer, Merck, Speakers bureau: Bristol-Myers Squibb, Abbott