5-YEAR CLINICAL AND RADIOGRAPHIC EFFICACY WITH ADALIMUMAB OR ADALIMUMAB PLUS METHOTREXATE AFTER 2 YEARS OF COMBINATION THERAPY IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS (RA)

Background: In PREMIER, the combination of adalimumab (ADA) and methotrexate (MTX) led to significantly better clinical responses and radiographic inhibition at 2 years (yrs) than either monotherapy in early RA. It is unclear whether combination must be continued indefinitely, or if ADA monotherapy could maintain the improvements, once established. Objectives: To compare, in an open-label extension (OLE), the clinical and radiological 5-year results of treatment with ADA monotherapy versus ADA+MTX in patients (pts) who achieved clinical remission after 2 yrs of combination ADA+MTX. Methods: 799 pts with active early RA (<3 yrs) received ADA (40 mg every other week [eow])+MTX, ADA alone, or MTX alone for 2 yrs. All pts remaining on blinded therapy were permitted to enroll in an OLE and receive monotherapy ADA 40 mg eow. Blinded MTX and oral placebo were discontinued. During the OLE, MTX could be added at the investigators' discretion. Pts included in this analysis were those from the original ADA+MTX arm who 1) achieved 28-joint Disease Activity Score (DAS28) clinical remission (<2.6) at the end of the 2-yr blinded period and 2) had available American College of Rheumatology (ACR) scores and radiographic data at Yr 5. Pts who either received ADA monotherapy (no MTX use or ≤12 weeks MTX from Yrs 3 to 5) or ADA+MTX (on MTX ≥50% of the time from Yrs 3 to 5) during OLE were compared at Yr 5 on clinical responses and radiographic progression (modified total Sharp score [mTSS]). Results: Of 124 pts from the original ADA+MTX group with available Yr-5 ACR responses and X-ray images, 80 (65%) were in DAS28 clinical remission at Yr 2. Forty-nine continued on ADA monotherapy and 24 on ADA+MTX during the OLE. Baseline characteristics for ADA and ADA+MTX, respectively, were: tender joint count, 27 and 32; swollen joint count, 18 and 23; DAS28, 6.1 and 6.4; and mTSS, 14 and 22. The 24 pts restarting MTX during the OLE had a mean DAS28 of 2.3 (range 1.5–4.8) before restarting MTX. At Yr 5, similar percentages of pts from both groups achieved ACR20, 50, 70, 90 responses and DAS28 clinical remission (table). Similar mean changes (Δs) from baseline in mTSS, joint erosion (JE), and joint space narrowing (JSN) scores were observed. 5-Yr Clinical Response and Radiographic Progression, Observed Data ADA* (n=49)ADA+MTX (n=24) ACR20, %9492 ACR50, %8483 ACR70, %7880 ACR90, %4354 DAS28 <2.6, %7081 HAQ, mean (95% CI)0.3 (0.2, 0.5)0.5 (0.3, 0.7) CRP, mean (95% CI)0.7 (0.4, 0.9)0.5 (0.3, 0.7) Δ mTSS, mean (95% CI)2.4 (–0.2, 5.1)3.2 (0.8, 5.6) Δ JE, mean (95% CI)0.8 (–0.6, 2.2)0.7 (–0.4, 1.8) Δ JSN, mean (95% CI)1.6 (0.2, 3.1)2.5 (0.7, 4.3) *No MTX or ≤12 weeks' MTX, Yrs 3–5; MTX ≥50% of the time, Yrs 3–5. Conclusion: Early RA pts who had achieved clinical remission after 2 yrs of ADA+MTX therapy also had similar ACR response rates, DAS28 remission scores, and radiographic efficacy at Yr 5, following 3 years of OL ADA (with or without MTX use, per physicians' clinical judgments). References: 1. Breedveld FC, et al. Arthritis Rheum. 2006;54(1):26-37. Disclosure of Interest: R. van Vollenhoven, Abbott, Bristol Myers Squibb, Centocor, Roche, Wyeth, Shering-Plough, Research Grants and Consulting Fees R. Landewe, Abbott, Amgen, Centocor, Schering, UCB, Wyeth - Research Grants J. Perez, Abbott, Employee K. Patra, Abbott, Employee A.L. Pangan, Abbott, EmployeeCitation: Annals of the Rheumatic Diseases, volume 68, supplement 3, year 2009, page 136Session: Abstract Session: RA Can we predict treatment response? (Oral Presentations )