A RANDOMIZED TRIAL OF HYDROXYCHLOROQUINE IN EARLY RHEUMATOID-ARTHRITIS - THE HERA STUDY

PURPOSE: Studies of the efficacy of hydroxychloroquine in rheumatoid a rthritis have had methodological flaws and have failed to produce defi nitive results. The benefits and toxicity of hydroxychloroquine sulfat e in 120 patients with rheumatoid arthritis of less than 2 years durat ion are assessed. PATIENTS AND METHODS: A 36-week randomized double-bl ind, placebo-controlled trial was conducted at two university centers and four community rheumatology private practices. Patients had to hav e had their disease for less than 2 years and to have never received a second-line drug. Patients were randomly assigned to receive hydroxyc hloroquine or an equivalent number of placebo tablets in a dose of up to 7 mg/kg per day (maximum 400 mg/day). The initial dose was half the maximum dose and, if after 2 weeks of treatment there had been no sid e effects, the full dose was prescribed. There were four a priori prim ary outcomes: (1) a joint index composed of the tender joint count, th e swollen joint count, the grip strength, and the duration of morning stiffness; (2) a pain index composed of the pain dimension of the Arth ritis Impact measurement Scales (AIMS) and the visual analog pain scal e of the Health Assessment Questionnaire (HAQ); (3) a physical functio n index composed of the HAQ, the physical disability dimension of the AIMS, and the McMaster-Toronto Arthritis Patient Performance Disabilit y Questionnaire; (4) the psychological function subscale of the AIMS. Secondary outcomes included adverse events, patient and physician glob al assessments, hematocrit, erythrocyte sedimentation rate (ESR) and c orticosteroid usage. An intent-to-treat analysis assessed improvement at 36 weeks by Student's t-test and average improvement over the cours e of the study by analysis of variance for repeated measures. RESULTS: Of 148 eligible patients, 120 were randomized. The characteristics of those randomized to hydroxychloroquine compared to placebo were simil ar at the study onset. At 36 weeks and over the course of the study th ere was statistically significant improvement in the joint index (P = 0.004, P = 0.034, respectively), the pain index (P = 0.007, P = 0.001, respectively), and the physical function index (P = 0.020, P = 0.011, respectively) in the group receiving hydroxychloroquine compared to t he placebo group. There was no improvement in psychological function f or hydroxychloroquine compared to placebo (P = 0.837 at 36 weeks, P = 0.89 over the course of the study). Among the secondary outcomes there was significant improvement only in the patient's (P = 0.01) and the outcome assessor's (P = 0.03) assessment of change and a trend towards a fewer number of intra-articular corticosteroid injections (P = 0.05 ) in the hydroxychloroquine-treated group. There were no important dif ferences in the side effects between hydroxychloroquine or placebo. CO NCLUSION: Over 36 weeks, hydroxychloroquine had a significant benefit on synovitis, pain, and physical disability of recent-onset rheumatoid arthritis, but did not benefit psychological function.