OP0145

INDUCTION THERAPY WITH ADALIMUMAB PLUS METHOTREXATE VERSUS METHOTREXATE MONOTHERAPY IN RECENT ONSET RHEUMATOID ARTHRITIS (RA) – AN INVESTIGATOR INITIATED RANDOMIZED CONTROLLED TRIAL

J. Detert ¹H. Bastian ¹J. Listing ²A. Weiss ²S. Wassenberg ³A. Liebhaber ⁴K. Rockwitz ⁵R. Alten ⁶K. Krüger ⁷R. Rau ⁸C. Simon ⁹E. Gremmelsbacher ¹T. Braun ¹B. Marsmann ¹V. Höhne-Zimmer ¹K. Egerer ¹F. Buttgereit ¹G.-R. Burmester ^1,*

¹Department Of Rheumatology And Clinical Immunology, Charité - Universitätsmedizin Berlin, ²German Rheumatism Research Center, DRFZ, Berlin, ³Rheumatology Clinic, Evangelisches Fachkrankenhaus, Ratingen, ⁴Rheumatologic Practice, Halle, ⁵Rheumatologic Practice, Goslar, ⁶Dep. Internal Medicine II, Rheumatology, Clinical Immunology, Osteology, Schlosspark-Klinik, Berlin, ⁷Rheumatologic Office, Munich, ⁸Specialist of Radiology, Düsseldorf, ⁹Rheumatology Clinic, Charité - Universitätsmedizin Berlin, Berlin, Germany

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 (tab.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 GmbHH. Bastian Speakers Bureau: Abbott & Co GmbHJ. Listing: None DeclaredA. Weiss: None DeclaredS. Wassenberg: None DeclaredA. Liebhaber: None DeclaredK. Rockwitz: None DeclaredR. Alten: None DeclaredK. Krüger: None DeclaredR. Rau: None DeclaredC. Simon: None DeclaredE. Gremmelsbacher: None DeclaredT. Braun: None DeclaredB. Marsmann: None DeclaredV. Höhne-Zimmer: None DeclaredK. Egerer: None DeclaredF. Buttgereit: None DeclaredG.-R. Burmester Grant / Research support from: Abbott & Co GmbH Consultant for: Abbott & Co GmbH Speakers Bureau: Abbott & Co GmbH