ARTHRITIS & RHEUMATISM Vol. 62, No. 3, March 2010, pp 674–682 DOI 10.1002/art.27268 © 2010, American College of Rheumatology Two-Year Clinical and Radiographic Results With Combination Etanercept–Methotrexate Therapy Versus Monotherapy in Early Rheumatoid Arthritis A Two-Year, Double-Blind, Randomized Study Paul Emery, 1 Ferdinand Breedveld, 2 De ´sire ´e van der Heijde, 2 Gianfranco Ferraccioli, 3 Maxime Dougados, 4 Deborah Robertson, 5 Ronald Pedersen, 5 Andrew S. Koenig, 5 and Bruce Freundlich, 5 for the Combination of Methotrexate and Etanercept in Early Rheumatoid Arthritis Trial Group Objective. To evaluate how continuation of and alterations to initial year 1 combination etanercept– methotrexate (MTX) therapy and MTX monotherapy regimens affect long-term remission and radiographic progression in early, active rheumatoid arthritis. Methods. Subjects were randomized at baseline for the entire 2-year period; those who completed 1 year of treatment with combination or MTX monotherapy entered year 2. The original combination group either continued combination therapy (the EM/EM group; n  111) or received etanercept monotherapy (the EM/E group; n  111) in year 2; the original MTX mono- therapy group either received combination therapy (the M/EM group; n  90) or continued monotherapy (the M/M group; n  99) in year 2. Efficacy end points included remission (a Disease Activity Score in 28 joints [DAS28] <2.6) and radiographic nonprogression (change in the modified Sharp/van der Heijde score <0.5) at year 2. A last observation carried forward analysis from the modified intention-to-treat population (n  398) and a post hoc nonresponder imputation (NRI) analysis (n  528) were performed for remission. Results. At year 2, DAS28 remission was achieved by 62/108, 54/108, 51/88, and 33/94 subjects in the EM/EM, EM/E, M/EM, and M/M groups, respectively (P < 0.01 for the EM/EM and M/EM groups versus the M/M group). This effect was corroborated by a more conservative post hoc 2-year NRI analysis, with remis- sion observed in 59/131, 50/134, 48/133, and 29/130 of the same respective groups (P < 0.05 for each of the EM/EM, EM/E, and M/EM groups versus the M/M group). The proportions of subjects achieving radio- graphic nonprogression (n  360) were 89/99, 74/99, 59/79, and 56/83 in the EM/EM (P < 0.01 versus each of ClinicalTrials.gov identifier: NCT00195494. Supported by Wyeth Pharmaceuticals, a wholly owned sub- sidiary of Pfizer Inc. Dr. Emery is an Arthritis Research Campaign Professor of Rheumatology. 1 Paul Emery, MA, MD, FRCP: University of Leeds, Leeds, UK; 2 Ferdinand Breedveld, MD, De ´sire ´e van der Heijde, MD, PhD: Leiden University Medical Center, Leiden, The Netherlands; 3 Gian- franco Ferraccioli, MD: Catholic University of the Sacred Heart–CIC, Rome, Italy; 4 Maxime Dougados, MD: Ho ˆpital Cochin, Assistance Publique Ho ˆpitaux de Paris, and Rene ´ Descartes University, Paris, France; 5 Deborah Robertson, RD, MS, Ronald Pedersen, MS, An- drew S. Koenig, DO, Bruce Freundlich, MD: Pfizer Inc., Collegeville, Pennsylvania. Dr. Emery has received consulting fees, speaking fees, and/or honoraria from Wyeth Pharmaceuticals (less than $10,000) and re- search grants from Wyeth Pharmaceuticals, and was the primary investigator in this trial. Dr. Breedveld has received consulting fees, speaking fees, and/or honoraria from Wyeth Pharmaceuticals (less than $10,000) and research grants from Wyeth Pharmaceuticals, and was an investigator in this trial. Dr. van der Heijde has received consulting fees, speaking fees, and/or honoraria from Abbott, Amgen, Centocor, Wyeth Pharmaceuticals, UCB, Roche, Pfizer, Novartis, Bristol-Myers Squibb, and Schering-Plough (less than $10,000 each) and research grants from Wyeth Pharmaceuticals. Dr. Ferraccioli has received consulting fees, speaking fees, and/or honoraria from Wyeth Pharmaceuticals (less than $10,000) and research grants from Wyeth Pharmaceuticals, and was an investigator in this trial. Dr. Dougados has received consulting fees, speaking fees, and/or honoraria from Wyeth Pharmaceuticals (less than $10,000) and research grants from Wyeth Pharmaceuticals, and was an investigator in this trial. Ms Robertson, Mr. Pedersen, and Drs. Koenig and Freundlich own stock or stock options in Pfizer Inc. Address correspondence and reprint requests to Paul Emery, MA, MD, FRCP, Leeds Institute of Molecular Medicine, Chapel Allerton Hospital, Chapeltown Road, Leeds LS4 7SA, UK. E-mail: p.emery@leeds.ac.uk. Submitted for publication June 25, 2009; accepted in revised form November 3, 2009. 674