1231 - Initial Combination Therapy with Adalimumab Plus Methotrexate Leads to Better Long-Term Outcomes Than with Either Monotherapy in Patients with Early Rheumatoid Arthritis: 8-Year Results of An Open-Label Extension of a Phase 3 Trial

Monday, November 7, 2011: 9:00 AM-6:00 PM
Hall F2 - Poster Hall (McCormick Place West)
Ferdinand C. Breedveld1, Edward Keystone2, Désirée van der Heijde3, Robert Landewe4, Josef Smolen5, Benoit Guerette6, Melissa McIlraith6, Hartmut Kupper7, Shufang Liu8, Benjamin Wolfe8 and Arthur Kavanaugh9, 1Leiden Univ Medical Ctr, Leiden, Netherlands, 2University of Toronto, Toronto, ON, 3Leiden University Medical Center, Leiden, Netherlands, 4Academic Medical Center, Amsterdam, Netherlands, 5Medical University of Vienna and Hietzing Hospital, Vienna, Austria, 6Abbott, Rungis, France, 7Abbott GmbH & Co KG, Ludwigshafen, Germany, 8Abbott, Abbott Park, IL, 9University of California San Diego, San Diego, CA
Presentation Number: 1231

Background/Purpose: PREMIER was a phase 3, randomized, controlled trial (RCT) in MTX-naïve patients (pts) with early RA who received MTX, adalimumab (ADA), or ADA+MTX for 2 years (yrs) of blinded treatment. The RCT demonstrated the radiographic, clinical, and functional superiority of initial combination therapy over the individual monotherapies1; results were extended through an additional 3 yrs of open-label (OL) treatment in a 5-yr report2. This analysis aimed to evaluate long-term radiographic, clinical, and functional outcomes in pts treated with ADA, with and without MTX, for up to 8 yrs (i.e. 6 yrs beyond the 2-yr RCT).

Method: Pts completing the RCT were eligible to receive OL ADA for a total of 10 yrs of treatment (this trial is ongoing); MTX could be added at the investigator’s discretion during the OL extension. This post hoc analysis evaluated the 8-yr completers cohort with radiographic data available at baseline (BL) and yr 8; results are summarized overall and by initial treatment arms. Radiographic damage [mTSS, representing the sum of joint (jt) erosion (JE) and jt space narrowing (JSN)] was assessed at BL and yrs 2, 6, and 8; progressors were defined as a change (Δ) in mTSS from BL >0.5. Differences in ΔmTSS were assessed using a longitudinal ANCOVA following adjustment for BL damage. Clinical outcomes were assessed using the DAS28, and swollen (66 jts assessed) and tender (68 jts assessed) jt counts. Physical function was assessed using the HAQ-DI.

Result: A total of 299 (37.4%; 103, 96, and 100 from the initial ADA+MTX, MTX, and ADA arms, respectively) of the 799 pts initially randomized received OL ADA±MTX through yr 8. Following up to 8 yrs of ADA±MTX therapy, pts continued to demonstrate inhibition of radiographic progression and effective disease control (mean ΔmTSS=8.6; mean DAS28=2.6; mean HAQ-DI=0.6). Further, approximately half of pts experienced an absence of swollen (52.5%) and tender (47.9%) jts. Pts initially randomized to ADA+MTX demonstrated lower mean ΔmTSS, ΔJE, and ΔJSN at yr 8 (3.8, 1.4, 2.4) when compared with pts initially randomized to either MTX (11.4, 6.1, 5.2) or ADA (10.8, 5.6, 5.3) monotherapy (P <.001 for both mTSS comparisons) and were associated with fewer radiographic progressors (56.3% versus 72.9% and 73.0% for MTX and ADA monotherapy, respectively). OL ADA±MTX treatment inhibited radiographic progression in pts initially randomized to MTX or ADA monotherapy to levels that were comparable with those observed during OL treatment of pts from the initial ADA+MTX arm. Initial randomization to combination therapy also was associated with greater proportions of pts achieving high levels of disease control and normal physical function at yr 8 (DAS28 <2.6: 71.3%, 58.4%, 49.5%, and HAQ-DI <0.5: 60.2%, 55.9%, 47.4%, for ADA+MTX, MTX, ADA, respectively).

Conclusion: Following up to 8 yrs of treatment with ADA±MTX, pts with early, aggressive RA maintained effective disease control. Pts who initially received combination therapy with ADA+MTX demonstrated better long-term outcomes than those initially receiving either monotherapy. 

1Breedveld et al. Arthritis & Rheum. 2006; 54(1):26-37.

2van der Heijde et al. J Rheum. 2010; 37(11):2237-46. 


Keywords: adalimumab, anti-TNF therapy, methotrexate (MTX) and rheumatoid arthritis, treatment

Disclosure: F. C. Breedveld, Centocor, Schering-Plough, Amgen/Wyeth, Abbott, 5 ; E. Keystone, Abbott Laboratories, Amgen, AstraZeneca, Bristol-Myers Squibb, Centocor, F Hoffmann-LaRoche, Genzyme, Merck, Novartis, Pfizer, UCB, 2, Abbott Laboratories, AstraZeneca, Biotest, Bristol-Myers Squibb, Centocor, F Hoffmann-LaRoche, Genentech, Merck, Nycomed, Pfizer, UCB, 5, Abbott Laboratories, Bristol-Myers Squibb, F Hoffman-LaRoche, Merck, Pfizer, UCB, 8 ; D. van der Heijde, Abbott, Amgen, AstraZeneca, BMS, Centocor, Chugai, Eli-Lilly, GSK, Merck, Novartis, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB, Wyeth, 2, Abbott, Amgen, AstraZeneca, BMS, Centocor, Chugai, Eli-Lilly, GSK, Merck, Novartis, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB, Wyeth, 5 ; R. Landewe, Abbott, Centocor, Merck, BMS, Pfizer, UCB, 2, Abbott, Centocor, Merck, BMS, Pfizer, UCB, 5, Pfizer, UCB, 8 ; J. Smolen, Abbott Laboratories, 5, Abbott Laboratories, 2 ; B. Guerette, Abbott Laboratories, 1, Abbott Laboratories, 3 ; M. McIlraith, Abbott Laboratories, 1, Abbott Laboratories, 3 ; H. Kupper, Abbott Laboratories, 1, Abbott Laboratories, 3 ; S. Liu, Abbott Laboratories, 1, Abbott Laboratories, 3 ; B. Wolfe, Abbott Laboratories, 3 ; A. Kavanaugh, Abbott Laboratories, 5 .