Background The extent to which current rheumatoid arthritis (RA) treatments modify the course of disease varies, and most patients require continued, long-term therapy. Information surrounding the effectiveness and safety of long-term treatment is limited.
Objectives This post hoc analysis evaluated data from patients (pts) completing up to 10 years (yrs) of adalimumab (ADA)+MTX therapy to determine 1) long-term efficacy and safety, and 2) whether a 1 yr delay in ADA initiation results in differences in clinical, functional, or radiographic efficacy.
Methods DE019 was a phase 3, randomized, controlled trial (RCT) in which pts with long-standing RA and an inadequate response to MTX were randomized to 1 yr of ADA 40 mg every other week (ADA-40), ADA 20 mg weekly (ADA-20), or placebo (PBO) injections; all received concomitant MTX.1 Pts completing the RCT were eligible to receive open-label (OL) ADA-40+MTX for an additional 9 yrs. This post hoc analysis included data from pts completing 10 yrs of treatment who also had radiographs available at baseline (BL) and Yr 10; results are summarized overall and by initial treatment arms. Clinical and functional outcomes were assessed by DAS28(CRP) and HAQ-DI, respectively. Radiographic damage was assessed using the modified total Sharp score (mTSS) at BL and Yrs 1, 8, and 10. Safety was assessed in terms of adverse events for all pts exposed to ADA.
Results Of the 619 pts initially randomized, 202 (32.6%; 80, 66, and 56 from the initial ADA-40+MTX, ADA-20+MTX, and PBO+MTX arms, respectively) continued on OL ADA+MTX through Yr 10. Following up to 10 yrs of ADA+MTX treatment, pts continued to demonstrate effective disease control and inhibition of radiographic progression [mean DAS28(CRP)=2.6, DAS28(CRP) <2.6=59.6%; mean HAQ-DI=0.7, HAQ-DI <0.5=42.8%; mean ΔmTSS=2.8). The significant differences in clinical and functional responses between ADA-40 or -20+MTX and PBO+MTX observed during the RCT were largely resolved following an additional 9 yrs of OL ADA+MTX treatment. Still, pts who initially received ADA-40 or -20+MTX had significantly lower mean ΔmTSS at Yr 10 compared with pts who initially received PBO+MTX [0.7 (ADA-40) and 2.6 (ADA-20) vs 6.2 (PBO); P =0.002 and 0.01, respectively], a result that was driven by ΔmTSS during the RCT (-1.3 and -0.5 vs 1.9; both P<0.001). No new safety signals arose following up to 10 yrs of ADA exposure.
Conclusions During up to 10 yrs of treatment with ADA+MTX, pts with long-standing RA experienced effective disease control. Initial treatment with ADA+MTX led to better outcomes than initial treatment with PBO+MTX, but the disparities in clinical and functional response rates observed during the RCT were largely ameliorated after treatment with OL ADA+MTX. Notably, radiographic damage remained lower in pts who initially received ADA+MTX, owing to the more extensive damage accrued during the RCT in PBO+MTX-treated pts.
Keystone, et al. Arthritis Rheum 2004;50:1400-11.
Disclosure of Interest E. Keystone Grant/Research support from: Abbott, AstraZeneca, Biotest, BMS, Centocor, Genentech, Merck, Nycomed, Pfizer, Roche, UCB, Consultant for: Abbott, Amgen, AstraZeneca, BMS, Centocor, Genzyme, Merck, Novartis, Pfizer, UCB, D. van der Heijde Consultant for: Abbott, Amgen, AstraZeneca, BMS, Centocor, Chugai, Merck, Novartis, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB, Wyeth, M. Weinblatt Grant/Research support from: Abbott, Consultant for: Abbott, A. Kavanaugh Consultant for: Abbott, H. Kupper Shareholder of: Abbott, Employee of: Abbott, S. Liu Shareholder of: Abbott, Employee of: Abbott, N. Mozaffarian Shareholder of: Abbott, Employee of: Abbott