Minocycline Treatment of Rheumatoid Arthritis

Two recent reports have created renewed interest in antibiotic treatment of rheumatoid arthritis: In this issue, Tilley and colleagues [1] report the findings of the large double-blind, placebo-controlled Minocycline in Rheumatoid Arthritis (MIRA) clinical trial; in 1994, Kloppenburg and colleagues [2] reported the results of a similar study from the Netherlands. In 1968, Sanchez [3] first reported the use of tetracycline to treat 14 patients with rheumatoid arthritis, with favorable results. McPherson-Brown and colleagues [4] also found good results in a retrospective cohort study of 98 patients with rheumatoid arthritis who were treated with antibiotics from 1978 to 1982. However, these reports were largely discounted because a 1971 double-blind study of 30 patients with rheumatoid arthritis who were randomly assigned to receive either placebo or 250 mg of tetracycline daily for 1 year failed to show any significant benefit in those receiving tetracycline therapy [5]. In two other recent open trials, patients receiving daily oral minocycline treatment showed clinical improvement [6, 7].

The findings of the Dutch study [2] and the MIRA trial [1] are remarkably similar. However, 80 patients in the Dutch study were equally randomly assigned to receive either placebo or minocycline, whereas 110 and 109 patients in the MIRA study received placebo and minocycline, respectively. Both trials used 100 mg of oral minocycline twice a day; patients were treated for 48 weeks in the MIRA study but for only 26 weeks in the Dutch study (with 4 weeks of post-withdrawal follow-up). Patients in the Dutch study had had rheumatoid arthritis for an average of 12 to 14 years compared with 8 years for those in the MIRA study. Patients in the Dutch study were also more likely to have positive test results for rheumatoid factor (89% …