Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Efficacy of An Induction Therapy with Adalimumab Plus Methotrexate Versus Methotrexate Monotherapy in Recent Onset Rheumatoid ArthritisAn Investigator Initiated Randomized Controlled Trial.
Detert1, Jacqueline, Bastian1, Hans, Listing2, Joachim, Weiss2, Anja, Wassenberg3, Siegfried, Liebhaber4, Anke, Rockwitz5, Karin
Charité-Universitätsmedizin Berlin, Berlin, Germany
German Rheumatism Research Centre, Berlin, Germany
Evangelisches Fachkrankenhaus, Ratingen, Germany
Rheumatologic Practice, Halle, Germany
Rheumatologic Practice, Goslar, Germany
Rheumatology Schlossparkklinik, Berlin, Germany
Practice Center, München, Germany
The effectiveness of an early induction therapy within the window of opportunity in patients with early rheumatoid arthritis (RA) is unclear. The present study (designated HIT HARD, funded by the German Ministry of Science) investigated whether disease activity of DMARD naïve patients with early RA benefits long term from induction therapy with adalimumab (ADA) plus methotrexate (MTX).
In a double-blinded, controlled multicenter trial, DMARD naïve RA patients (active disease >=6 swollen, >=6 tender joints, CRP>=10mg/l, disease duration of <=12 months) were randomized into two groups. During the first 24 weeks (w), group A (n=87): MTX s.c. plus 40mg ADA eow; group B (n=85) 15 mg/w MTX s.c. plus placebo. After w24, both groups were treated only with MTX. Primary outcome was the DAS28 at w48. Secondary outcomes were the proportions of patients in remission (DAS28<2.6), ACR50 response, HAQ, and radiographic progression. Statistical analysis was based on the intention-to-treat population. To improve power, analysis of covariance (ANCOVA) with baseline status as covariable was applied to compare DAS28, HAQ scores 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.
Tables 1 and 2 show the baseline characteristics of patients, the outcome parameters at the end of the induction phase (w24) and at the end of follow-up (w48) in both treatment groups. 87% had disease duration of <=3 months.
Table 1. Baseline characteristics
|Age||47.2 ± 12.1||52.5 ± 14.3|
|Disease duration (months)||1.8 ± 2.1||1.6 ± 1.7|
|Rheumatoid factor positive||68 %||69 %|
|ACPA positive||54 %||52 %|
|DAS28||6.2 ± 0.8||6.3 ± 0.9|
|HAQ||1.4 ± 0.6||1.3 ± 0.6|
|Sharp vdH total score||2.3||4.6|
Table 2. Outcome parameters at the end of the induction phase (w24) and at the end of follow-up (w48)
|ADA/MTX||Placebo/MTX||p||MTX mono (ADA-group)||MTX mono (Placebo-group)||p|
|DAS28||3.0 (1.2)||3.5 (1.4)||0.013||3.2 (1.4)||3.4 (1.6)||0.49|
|ACR50 response (%)||65.5||49.4||0.033||54.0||48.2||0.45|
|ACR70 response (%)||47.1||35.3||0.007||41.4||35.3||0.41|
|HAQ||0.49 (0.6)||0.72 (0.6)||0.001||0.60 (0.6)||0.65 (0.6)||0.28|
|Sharp vdH total score||6.3 (5.0)||11.4 (14.8)||0.03|
During the induction phase, combination therapy of ADA plus MTX reduced disease activity to a significantly greater extent than MTX plus placebo (tab. 2). After termination of ADA or placebo treatment and continuation with MTX alone, the differences between both groups in clinical outcome parameters (DAS28, remission, ACR50 response HAQ) decreased and did not reach statistical significance at w48. Nevertheless, combination therapy significantly reduced radiographic progression compared to MTX alone when analyzed after w48 (implying w24 after discontinuation) of ADA.
Combination therapy with ADA and MTX was significantly superior to MTX alone during the initial treatment phase of w24. A reduction of radiographic progression was observed at w48 indicating a sustained effect of combination treatment that was not found regarding for the primary endpoint, which was the reduction in disease activity. The numerical increase in the clinical outcome parameters of the ADA/MTX group from w40 onwards may reflect the loss of response after removal of ADA.
To cite this abstract, please use the following information:
Detert, Jacqueline, Bastian, Hans, Listing, Joachim, Weiss, Anja, Wassenberg, Siegfried, Liebhaber, Anke, et al; Efficacy of An Induction Therapy with Adalimumab Plus Methotrexate Versus Methotrexate Monotherapy in Recent Onset Rheumatoid ArthritisAn Investigator Initiated Randomized Controlled Trial. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1697