Background/Purpose: AMPLE (Abatacept Versus Adalimumab Comparison in Biologic-Naive RA Subjects with Background Methotrexate) is the first 2 year, active comparator study in RA patients utilizing biologic agents on a background of MTX. At Year 1, SC abatacept (ABA) and adalimumab (ADA) demonstrated comparable efficacy, including radiographic outcomes, with similar safety.[1] Here we report 2 year study results including radiographic outcomes.

Methods: AMPLE is a phase IIIb randomized, investigator-blinded study of 2 years duration with a primary efficacy endpoint at Day 365. Biologic-naïve patients with active RA and an inadequate response to MTX were randomized 1:1 to receive 125 mg ABA weekly (without an IV load) or 40 mg ADA bi-weekly, with a stable dose of MTX.¹ Study conduct continued unchanged from Year 1, including investigator blinding; all clinical efficacy endpoints were captured through Day 729 including radiographs assessed using the van der Heijde modified Total Sharp score (mTSS). All efficacy analyses were done using the intent-to-treat population with non-responder imputation where appropriate. All radiographs were read through Day 729, including re-reading Year 1 images, by readers blinded to treatment allocation and sequence.

Results: Baseline characteristics of the 646 patients, equally randomized to each group, were similar as previously reported.¹ 79.2% (252 of 318) ABA patients and 74.7% (245 of 328) ADA patients completed Day 729. At Year 1, 64.8% ABA and 63.4% ADA patients were ACR20 responders. Consistent with Year 1, clinical efficacy measures and inhibition of radiographic progression were comparable between groups at Year 2 (Table). There were similar rates of AEs, SAEs (13.8% vs. 16.5%), and malignancies (2.2% vs. 2.1%). More autoimmune AEs occurred in the ABA arm (3.8% vs. 1.8%); none were SAEs. Fewer infections (3.8% vs 5.8%) and opportunistic infections (in 3 vs. 5 patients) occurred with ABA including 2 cases of tuberculosis in the ADA arm that led to discontinuation (DC). There were fewer DC due to AEs (3.8% vs. 9.5%), SAEs (1.6% vs. 4.9%), and serious infections (in 0/12 vs. 9/19 patients) in the ABA arm.  Injection site reactions (ISR) occurred less frequently in the ABA arm (4.1% vs. 10.4%).

Conclusion: Through 2 years of treatment, in this first active comparator study between biologic agents in RA patients with an inadequate response to MTX, this robust data set demonstrates that SC abatacept and adalimumab were equally efficacious in clinical, functional and radiographic outcomes. Overall, the frequency of AEs was similar in both groups but there were less discontinuations due to AEs, SAEs, serious infections, and fewer local ISR in patients treated with SC abatacept.

*LOCF **As-observed