Background The availability of multiple biologic agents to treat RA has created a need for comparative assessment. To date, there have been no randomized, controlled studies designed to directly compare the safety and efficacy of different biologic DMARDs. We present data for Year 1 from the first head-to-head study in RA.
Objectives To compare the efficacy and safety of subcutaneous (SC) abatacept (ABA) and adalimumab (ADA) both on background MTX in the treatment of RA.
Methods AMPLE (Abatacept Versus Adalimumab Comparison in Biologic-Naive RA Subjects With Background Methotrexate) is a phase IIIb randomized, investigator-blinded study of 24 months duration with a 12 month efficacy primary endpoint. Biologic-naïve patients with active RA and inadequate response to MTX were stratified by disease activity and randomized to either 125 mg SC abatacept (without an IV load) weekly or 40 mg SC adalimumab bi-weekly, in combination with a stable dose of MTX. The primary end point was non-inferiority (NI) by ACR20 response at 12 months with a NI margin of 12%. Key secondary endpoints were the frequency of injection site reactions, radiographic non-progression as assessed using the van der Heijde modified total Sharp score (mTSS) method, safety and retention.
Results Baseline characteristics of both groups were similar (mean DAS28 (CRP) of 5.5 and disease duration ∼1.8 yrs) with 72% and 28% of subjects from North and South America, respectively. Of 646 patients who were randomized and treated, 86.2% (274 of 318) ABA patients and 82% (269 of 328) ADA patients completed 12 months. At 1 year, by ITT analysis, the ACR 20 responders were 64.8% of ABA patients and 63.4% of ADA patients. The estimated difference between groups (95% CI) was 1.8 (-5.6, 9.2) supporting NI of ABA to ADA (confirmed by per protocol analysis). The ACR20 response evident at week 4 was 42.5% ABA vs 47.6% ADA and remained comparable to the end of Year 1. At 12 months, additional response rates in ABA and ADA arms were: ACR50 46.2% versus 46%, and ACR70 29.2% versus 26.2%. At 12 months, radiographic non-progression rates were comparable and the mean changes in mTSS were 0.58 versus 0.38, for ABA versus ADA. There were similar rates of AE, SAE, serious infections and malignancies. There were more subjects with autoimmune AEs (10 versus 3) in the ABA arm, none were SAEs. There were fewer discontinuations (DC) including DC due to AEs (3.5% versus 6.1%) and DC due to serious infections (0 versus 5) in the ABA arm. Injection site reactions occurred in 3.8% of ABA versus 9.1% of ADA patients (Difference (95% CI): -5.37 (-9.13, -1.62); p=0.006).
Conclusions This first head-to-head study in RA patients comparing biologic DMARD agents demonstrated that SC ABA is comparable to ADA in efficacy (by non-inferiority analysis) with similar kinetics of response and inhibition of radiographic progression at one year. The safety was generally similar with fewer discontinuations and significantly fewer injection site reactions observed with ABA.
Disclosure of Interest M. Schiff Consultant for: Bristol-Myers Squibb, Speakers Bureau: Abbott, R. Fleischmann Grant/Research support from: Bristol-Myers Squibb, Abbott, Consultant for: Bristol-Myers Squibb, Abbott, M. Weinblatt Grant/Research support from: Bristol-Myers Squibb, Abbott, Consultant for: Bristol-Myers Squibb, Abbott, R. Valente Grant/Research support from: Ucb,Pfizer,Novartis,Eli Lilly, Takeda, D. van der Heijde Grant/Research support from: Abbott, Amgen, AstraZeneca, BMS, Centocor, Chugai, Eli-Lilly, GSK, Merck, Novartis, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB, Wyeth, Consultant for: Abbott, Amgen, AstraZeneca, BMS, Centocor, Chugai, Eli-Lilly, GSK, Merck, Novartis, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB, Wyeth, G. Citera Grant/Research support from: Pfizer, Consultant for: Pfizer, Bristol-Myers Squibb, Astra Zeneca, C. Zhao Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, M. Maldonado Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb
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