Abstract
Objective. To evaluate the longterm safety of adalimumab administered with or without methotrexate (MTX) and compare the efficacy of combination therapy initialization to adalimumab or MTX monotherapy initialization during the open-label extension (OLE) of the PREMIER trial (ClinicalTrials.gov Identifier:NCT00195663).
Methods. Patients with early rheumatoid arthritis (RA) were randomized to receive blinded adalimumab + MTX, adalimumab alone, or MTX alone for 2 years. Following the double-blinded period, patients enrolling in the OLE were given adalimumab for up to 8 additional years, beginning as monotherapy; investigators could add MTX at their discretion. Results for clinical, functional, and radiographic progression were collected for up to 10 years of treatment.
Results. During the PREMIER OLE, 250/497 patients (50.3%) completed the trial without new safety signals arising. Similar proportions of patients discontinued the trial early, although lack of efficacy was reported less often for patients initially randomized to the adalimumab + MTX arm (9.3%; 21.2%, and 23.7% for adalimumab and MTX monotherapies, respectively). Clinical and functional disease control was maintained throughout the trial. Patients initially randomized to adalimumab + MTX displayed better outcomes, particularly in prevention of radiographic progression (modified total Sharp score change = 4.0, 8.8, 11.0 at Year 10 for the initial adalimumab + MTX, adalimumab, and MTX arms, respectively).
Conclusion. Intensive therapy with adalimumab + MTX combination in patients with early RA has longterm benefits compared to patients initiating with 2-year adalimumab or MTX monotherapy that persists up to 10 years following adalimumab OLE. No new safety findings were observed following longterm adalimumab treatment.
Footnotes
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Supported by AbbVie Inc. (NCT00195663). AbbVie Inc. sponsored the study, contributed to its design, and participated in the collection, analysis, and interpretation of the data, and in the writing, reviewing, and approval of the final version. ECK has received consulting fees or other remuneration from, and served on advisory boards on behalf of AbbVie Inc., AstraZeneca, Biotest, Bristol-Myers Squibb, Genentech, Janssen Inc., Eli-Lilly, Merck, Nycomed, Pfizer, Roche, and UCB, has received research grants from AbbVie Inc., Amgen, AstraZeneca, Bristol-Myers Squibb, Eli-Lilly, Janssen Inc., Novartis, Pfizer, Roche, and UCB, and has speaker honoraria agreements with AbbVie Inc., Amgen, AstraZeneca, Bristol-Myers Squibb, Janssen Inc., Pfizer, Roche, and UCB. FCB has received consulting fees or other remuneration from Centocor, Schering-Plough, Amgen/Wyeth, and AbbVie Inc. DvdH has received consulting fees or other remuneration from AbbVie Inc., Amgen, AstraZeneca, Bristol-Myers Squibb, Centocor, Chugai, Eli-Lilly, GlaxoSmithKline, Merck, Novartis, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB, and Wyeth, and is the director of Imaging Rheumatology bv. RL has received consulting fees or other remuneration from AbbVie Inc., Amgen, Bristol-Myers Squibb, Centocor, GlaxoSmithKline, Merck, Novartis, Pfizer, Roche, Schering-Plough, UCB, and Wyeth, and is the owner of Rheumatology Consultancy bv. AK has received consulting fees or other remuneration and research grants from AbbVie Inc., Amgen, Astra-Zeneca, Bristol-Myers Squibb, Celgene, Centocor-Janssen, Pfizer, Roche, and UCB. SF, UA, SL, and HK are all fulltime employees of AbbVie Inc. and may hold stock or stock options.
- Accepted for publication September 3, 2013.
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