Head‐to‐head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: Findings of a phase IIIb, multinational, prospective, randomized study

Abstract

ObjectiveThere is a need for comparative studies to provide evidence-based treatment guidance for biologic agents in rheumatoid arthritis (RA). Therefore, this study was undertaken as the first head-to-head comparison of subcutaneous (SC) abatacept and SC adalimumab, both administered along with background methotrexate (MTX), for the treatment of RA.MethodsPatients with active RA who were naive to treatment with biologic agents and had an inadequate response to MTX were randomly assigned to receive 125 mg SC abatacept weekly or 40 mg SC adalimumab biweekly, both given in combination with MTX, in a 2-year study. The primary end point was treatment noninferiority, assessed according to the American College of Rheumatology 20% improvement response (ACR20) at 1 year.ResultsOf the 646 patients who were randomized and treated, 86.2% receiving SC abatacept and 82% receiving SC adalimumab completed 12 months of treatment. At 1 year, 64.8% of patients in the SC abatacept group and 63.4% in the SC adalimumab group demonstrated an ACR20 response; the estimated difference between groups was 1.8% (95% confidence interval −5.6%, 9.2%), thus demonstrating the noninferiority of abatacept compared to adalimumab. All efficacy measures showed similar results and kinetics of response between treatments. The rate of radiographic nonprogression (defined as a total modified Sharp/van der Heijde score [SHS] less than or equal to the smallest detectable change) was 84.8% for SC abatacept–treated patients and 88.6% for SC adalimumab–treated patients, while the mean change from baseline in the total SHS was 0.58 and 0.38, respectively. In the SC abatacept and SC adalimumab groups, the incidence of serious adverse events (SAEs) was 10.1% and 9.1%, respectively, and the rate of serious infections was 2.2% and 2.7%, respectively. In patients treated with SC abatacept, the frequency of discontinuations due to AEs was 3.5% and discontinuations due to SAEs was 1.3%, while in patients treated with SC adalimumab, the frequencies were 6.1% and 3%, respectively. Injection site reactions occurred in 3.8% of patients receiving SC abatacept compared to 9.1% of patients receiving SC adalimumab (P = 0.006).ConclusionThe results demonstrate that SC abatacept and SC adalimumab have comparable efficacy in patients with RA, as shown by similar kinetics of response and comparable inhibition of radiographic progression over 1 year of treatment. The safety was generally similar, other than the occurrence of significantly more local injection site reactions in patients treated with SC adalimumab.

Patient‐Reported Outcomes From a Two‐Year Head‐to‐Head Comparison of Subcutaneous Abatacept and Adalimumab for Rheumatoid Arthritis

“…Comparable improvements from baseline to year 1 were seen in fatigue with SC abatacept and adalimumab (−23.2% SC abatacept versus −21.4% adalimumab; adjusted treatment difference −1.8% [95% CI −5.8, 2.2]) 12. Results for pain over 1 and 2 years have also been presented previously 14.…”

“…Abatacept is a T‐cell costimulation modulator that has shown efficacy in patients with RA in a wide range of disease and treatment durations 4, 5, 6, 7, 8, 9, 10, 11. The AMPLE (Abatacept versus Adalimumab Comparison in Biologic‐Naive RA Subjects with Background MTX) trial, the first head‐to‐head trial comparing biologic DMARDs in patients with RA receiving MTX, demonstrated noninferiority for abatacept versus adalimumab by the ACR 20% improvement response (ACR20) at year 1 (64.8% subcutaneous [SC] abatacept versus 63.4% adalimumab; estimated difference between treatments 1.8% [95% confidence interval (95% CI) −5.6, 9.2] in an intent‐to‐treat analysis) 12. In AMPLE, there was a similar time of onset of ACR20 response in both treatment groups, with the response maintained up to year 2 13.…”

Reanalysis of the Multi‐Biomarker Disease Activity Score for Assessing Disease Activity in the Abatacept Versus Adalimumab Comparison in Biologic‐Naive Rheumatoid Arthritis Subjects with Background Methotrexate Study: Comment on the Article by Fleischmann et al

“…We also note that 31% of patients had missing MBDA data at year 2 compared with year 1, which exceeds the 8.5% decline in total patient numbers from the end of year 1 to the end of year 2 in the overall AMPLE trial (2,22).…”

“…We read with great interest the report by Fleischmann et al (1), which presents post hoc analyses of multi-biomarker disease activity (MBDA) scores measured using serum samples from AMPLE (Abatacept versus Adalimumab Comparison in Biologic-Naive Rheumatoid Arthritis Subjects with Background Methotrexate), a study sponsored by Bristol-Myers Squibb that compared abatacept versus adalimumab in rheumatoid arthritis (RA) patients with inadequate response to methotrexate (2). The article reported 3 main results: 1) in the first year, mean MBDA scores decreased significantly less with abatacept treatment than with adalimumab, yet clinical responses by Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) (3) were similar between the 2 treatment groups; 2) RA disease activity category (i.e., low, moderate, or high) as classified by the MBDA score was often discordant with the classification according to the DAS28-CRP, Clinical Disease Activity Index (CDAI) (4), Simplified Disease Activity Index (SDAI) (5), or Routine Assessment of Patient Index Data 3 (6); and 3) radiographic data were interpreted as demonstrating that MBDA scores were not associated with radiographic progression.…”

Combination Therapy With and Without Tumor Necrosis Factor Inhibitors in Rheumatoid Arthritis: A Meta‐Analysis of Randomized Trials

“…Consequently, the present analysis is the first to integrate all available evidence directly comparing a combination of DMARDs versus a biologic treatment plus methotrexate, and is also the first to estimate the effect at consecutive time points during a period of 2 years. Although only TNF inhibitors were investigated, it is likely that the present results could be extended to other biologic agents, as the biologic agents in general have been shown to be equally efficacious (2,22,24).…”