Background To study the prolonged effect on disease activity by an early induction therapy with adalimumab (ADA) plus methotrexate (MTX) versus MTX alone in DMARD naïve patients (pts) with early RA (designated HIT HARD, funded by the German Ministry of Science).
Methods In a double-blind randomized controlled trial, RA pts (disease duration of ≤12 months, ≥6 swollen, ≥6 tender joints, and CRP≥10 mg/l) were randomized into two groups: placebo (PBO) plus MTX (n=85), given s.c. at 15 mg/week (w) versus MTX 15 mg/w s.c. plus 40 mg ADA s.c. eow over 24w (n=87). After w24, both groups were treated only with MTX up to w48. The primary outcome measure was the DAS28-response at w48. Secondary outcomes was the pts in remission (DAS28<2.6), ACR responses, HAQ, SF36 and radiographic progression. Statistical analysis was based on the ITT population. To improve power, analysis of covariance (ANCOVA) with baseline (BL) status as covariable was applied to compare DAS28, HAQ between groups. Non-parametric ANCOVA was used to compare van der Heijde modified Sharp (Sharp vdH) scores. Multiple imputation method was used to replace missing data.
Results Mean disease duration at BL was 1.7 years, 91 (53%) were ACPA positive and 114 (63%) IgM RF positive. DAS28 was 6.2±0.8 (ADA/MTX) and 6.3±0.9 (PBO/MTX) (p=0.60). Outcome parameters at w24 and w48 are presented in tables 1. During the induction phase, ADA/MTX reduced disease activity to a significantly greater extent than PBO/MTX (Table 1). After termination of ADA or PBO and continuation with MTX alone, the differences between both groups in clinical outcome parameters (DAS28, remission, ACR50 response, HAQ, SF36 mental score) decreased at w24/48 and did not reach statistical significance at w48. Nevertheless, combination therapy significantly reduced radiographic progression as demonstrated by the Sharp vdH erosion score (p=0.010) as compared to the combination group, joint space narrowing score (p=0.035) and Sharp vdH total score (p=0.003); Ratingen score (p=0.012) compared to MTX alone when analyzed after w48.
Conclusions Superiority in reduction of radiographic progression after initial combination therapy with ADA and MTX was seen at w 48, even after discontinuation of ADA treatment at w 24. Such a sustained effect was not found regarding the primary endpoint (DAS28 reduction).
Disclosure of Interest J. Detert Grant/Research support from: Abbott & Co GmbH, Speakers Bureau: Abbott & Co GmbH, H. Bastian Speakers Bureau: Abbott & Co GmbH, J. Listing: None Declared, A. Weiss: None Declared, S. Wassenberg: None Declared, A. Liebhaber: None Declared, K. Rockwitz: None Declared, R. Alten: None Declared, K. Krüger: None Declared, R. Rau: None Declared, C. Simon: None Declared, E. Gremmelsbacher: None Declared, T. Braun: None Declared, B. Marsmann: None Declared, V. Höhne-Zimmer: None Declared, K. Egerer: None Declared, F. Buttgereit: None Declared, G.-R. Burmester Grant/Research support from: Abbott & Co GmbH, Consultant for: Abbott & Co GmbH, Speakers Bureau: Abbott & Co GmbH
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