Hotline Archive - Minocycline as Treatment for Rheumatoid Arthritis
January 1995
In the January 15, 1995 issue of the Annals of Internal Medicine, investigators in the MIRA (Minocycline in Rheumatoid Arthritis) Trial Group reported the results of a double-blind, placebo-controlled trial of minocycline in patients with rheumatoid arthritis. These data were reviewed in a November, 1993 Hotline, following presentation at the Annual Scientific Meeting of the American College of Rheumatology.
Patients in this trial were randomized to receive either minocycline (109 patients, 100 mg bid) or placebo (110 patients) for 48 weeks. Approximately one-half of the patients had previously received disease-modifying drugs, although therapy during, or 3 months prior to, the trial was not permitted. One-third were receiving low-dose corticosteroids (<10 mg of prednisone/day), and NSAIDs were permitted. Primary outcome measures included joint tenderness, joint swelling, evaluator' s global assessment, patient' s global assessment, duration of morning stiffness, Modified Health Assessment Questionnaire (MHAQ), hematocrit, erythrocyte sedimentation rate, platelet count, IgM rheumatoid factor, and radiographs. The majority of patients were classified as having mild to moderate disease with some evidence of joint destruction.
Statistically significant reductions (50% or greater improvement) in joint swelling and tenderness were noted compared to placebo-treated patients (54% versus 39% of patients; 56% versus 41% of patients, respectively). Significant changes in hematocrit, ESR, and rheumatoid factor were also observed, although no statistical differences in other parameters were appreciated.
At 48 weeks, approximately 80% of both groups continued to receive study medication. Therapy was discontinued most frequently secondary to inefficacy in the placebo group and toxicity in the minocycline group. In this regard, 6% of drug-treated patients dropped out because of possible toxicity, although only slight differences in the frequency of dizziness were reported.
Based on these results, the authors concluded that minocycline was a safe and effective medication for treating patients with mild to moderately active rheumatoid arthritis.
A similar study has been reported by Kloppenburg et al (Arthritis & Rheumatism 37:629-636, 1994). Although this Dutch study was of shorter duration (26 weeks), it included patients with more severe disease than in the MIRA trial. Again, the drug was well-tolerated, but the improvement in clinical parameters was modest.
The precise mechanisms whereby minocycline may be efficacious in RA 2re unclear. Apart from the potential anti-microbial effects of this medication and the interest in Mycoplasma as a causative or contributing agent for the development of RA, minocycline has been demonstrated to be an inhibitor of metalloproteinases, including collagenases and gelatinases. Conceivably, reduction in enzymatic activity induced by minocycline might exert a beneficial effect. Other potential mechanisms of action might include inhibition of phospholipase A2, suppression of neutrophil function, and reduction in T cell proliferation.
Although these results are clearly of interest, enthusiasm for minocycline in the treatment of RA must be tempered. The patients in the MIRA trial appeared to have moderately severe disease, and many had required remittive therapy prior to inclusion in the trial. Modest responses were noted for some, but not all, parameters. Both minocycline- and placebo-treated patients showed improvement in joint swelling and tenderness, although statistically significant changes were observed in the comparison of agents. Many patients received either NSAIDs or low-dose corticosteroids during the study which may have influenced disease activity. Furthermore, the duration of response after discontinuation of treatment is unclear. Finally, longer treatment periods and comparison with disease-modifying drugs will be necessary.
Additional trials are required before minocycline can be favorably compared with, or used instead of, current second-line agents in RA.
January 16, 1995
Prepared by Paul Katz, MD, and Robert Thoburn, MD, editors.
This Hotline is provided by the American College of Rheumatology (ACR) Communications and Marketing Group as an information service for members. This Hotline does not represent a position statement of the College
