Factors predicting response to treatment in rheumatoid arthritis - The importance of disease duration

Objective. To use individual patient data from rheumatoid arthritis (RA) cl inical trials to identify factors that affect the response to treatment as defined by the American College of Rheumatology (ACR) criteria for improvem ent (the "ACR response"). Methods. Primary trial data from 14 diverse, randomized, controlled trials of second-line drugs or devices in RA were analyzed. The trials included 11 methotrexate (MTX) trials (5 placebo controlled and 6 comparative, of whic h 2 were unpublished), 1 combination trial of cyclosporine plus MTX, 1 indu ction trial of a combination treatment in early RA (the COBRA trial), and 1 placebo-controlled trial of a new device (Prosorba). Both patient factors and disease activity measures (primarily, items from the ACR core criteria set) were available. Results. A total of 1,435 patients (549 in placebo-controlled trials, 886 i n comparative trials) were studied. In both active treatment and placebo gr oups, disease duration had a strong effect on the likelihood of patient res ponse (e.g., with any active treatment, the response rate was 53% for patie nts with less than or equal to 1 year of disease, 43% for 1-2 years' diseas e duration, 44% for 2-5 years, 38% for 5-10 years, and 35% for >10 years; P = 0.001). Decreasing response with greater disease duration was seen durin g treatment with most of the individual active drugs, as well as with place bo. Other factors decreasing the rate of response to treatment included any prior use of a disease-modifying antirheumatic drug (DMARD), higher diseas e functional class (according to the Steinbrocker criteria), low disease ac tivity (according to patient's global assessment), and female sex. Each ACR core set variable exhibited a diminished response to treatment in patients with longstanding disease. The difference between active treatment and pla cebo response rates was not affected by disease duration nor by other facto rs associated with the ACR response. Conclusion. RA patients with longer disease duration do not respond as well to treatment compared with patients with early disease, and female sex, pr ior DMARD use, disease functional class, and disease activity also have eff ects on the likelihood of patient response to treatment. This has implicati ons for trial interpretation and for the clinical expectations of RA patien ts.