Hydroxychloroquine

Antimalarial agents have been used in the treatment of rheumatoid arthritis for decades, but studies of the usefulness of these drugs have been methodologically flawed. The Hydroxychloroquine in Early Rheumatoid Arthritis Study Group conducted a randomized, double-blind, placebo-controlled trial to study the efficacy of hydroxychloroquine for the treatment of rheumatoid arthritis.

The study included patients with rheumatoid arthritis of less than two years' duration. Also, patients were over 18 years of age, had persistent synovitis for at least six weeks, even after adequate therapy with nonsteroidal anti-inflammatory drugs (NSAIDs), and had at least six inflamed joints and morning stiffness or an erythrocyte sedimentation rate of at least 25 mm per hr.

Patients were randomly assigned to receive treatment with hydroxychloroquine or placebo, and they were allowed to continue therapy with aspirin or other NSAIDs, physiotherapy and use of orthotics. Patients were assessed every four weeks for 24 weeks, then again at 36 weeks. At each visit, the patient provided an assessment of his or her improvement, and an investigator evaluated the presence and severity of any adverse effects of the medication. Blood was also drawn at each visit to obtain a complete blood count and erythrocyte sedimentation rate. Ophthalmologic testing was performed to determine whether retinal toxicity had occurred.

Initially, 170 patients were evaluated for inclusion in the study; of these, 50 were excluded. The remaining 120 patients were randomized to the two groups, although one patient was later withdrawn from the study. The average age of the patients was 53 years, and most were women (76 percent). The average duration of symptoms was nine months. The two groups did not differ in terms of demographics or use of NSAIDs or analgesics.

Both groups showed improvement, but at 36 weeks, the hydroxychloroquine-treated group showed less joint involvement, less pain and improved physical functioning, compared with the placebo group. Psychologic function was not affected by treatment with hydroxychloroquine. Joint improvement was noted at 24 weeks in the treatment group, whereas scores of pain and physical function showed improvement by 12 weeks. The global assessment of benefit given by patients and physicians showed a significant improvement with the use of hydroxychloroquine. The patients perceived this benefit as occurring eight weeks into the study, whereas the physicians assessed the benefit as being significant at the end of the study.

Adverse events in the treatment group and the placebo group were generally mild (23 events and 19 events, respectively) or moderate (14 events and 19 events, respectively), and in only two instances were the investigators certain as to the cause of the adverse event. No cases of ocular toxicity occurred that necessitated withdrawal from the study, and no significant change in hematocrit or other laboratory values occurred.

The authors conclude that hydroxychloroquine is useful in limiting the pain, symptomatic joint involvement and physical limitations in patients with early rheumatoid arthritis. (American Journal of Medicine, February 1995, vol. 98, p. 156.)

COPYRIGHT 1995 American Academy of Family Physicians
COPYRIGHT 2004 Gale Group