Dose-loading with hydroxychloroquine improves the rate of response in early, active rheumatoid arthritis - A randomized, double-blind six-week trial with eighteen-week extension

Objective. To investigate the usefulness of hydroxychloroquine (HCQ) dose-l oading to increase the percentage of responders or rate of response in trea ting rheumatoid arthritis (RA), Methods. Two hundred twelve patients,vith early RA (mean duration 1.5 years ) were enrolled in a 24-week trial. Patients were stabilized with 1,000 mg naproxen/ day and then began a 6-week, double-blind trial comparing treatme nt with HCQ at 400 mg/day (n = 71), 800 mg/day (n = 71), and 1,200 mg/day ( n = 66), followed by 18 weeks of open-label HCQ treatment at 400 mg/day, Results. All patients had mild, active disease at the time of initiation of HCQ treatment (31-43% rheumatoid factor positive; no previous disease-modi fying antirheumatic drugs; mean swollen joint count 8.6-10.4). Based on the Paulus criteria, response during the 6-week double-blind portion of the st udy was 47.9%, 57.7%, and 63.6% in the 400 mg/day, 800 mg/day, and 1,200 mg /day groups, respectively (P = 0.052). Discontinuations for adverse events were dose related (3 in the 400 mg/day group, 5 in the 800 mg/day group, 6 in the 1,200 mgiday group), Most involved the gastrointestinal (GI) system, with the background naproxen treatment possibly contributing. Ocular abnor malities occurred in 17 of 212 patients (8%) but were not dose related. Conclusion. Dose-loading with HCQ increased the degree of response at 6 wee ks in this group of patients with early, predominantly seronegative RA. Adv erse GI events were dose related, while adverse ocular events were not.