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Minocycline in Rheumatoid Arthritis: A 48-Week, Double-Blind, Placebo-Controlled Trial

Barbara C. Tilley, PhD; Graciela S. Alarcon, MD; Stephen P. Heyse, MD, MPH; David E. Trentham, MD; Rosemarie Neuner, MD; David A. Kaplan†, MD; Daniel O. Clegg, MD; James C. C. Leisen, MD; Lenore Buckley, MD; Sheldon M. Cooper, MD; Howard Duncan, MD; Stanley R. Pillemer, MD; Marilyn Tuttleman, MS; and Sarah E. Fowler, PhD
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From the Henry Ford Health Sciences Center, Detroit, Michigan; the University of Alabama at Birmingham; National Institutes of Health, Bethesda, Maryland; Beth Israel Hospital, Boston, Massachusetts; the State University of New York at Brooklyn; the University of Utah Medical Center, Salt Lake City, Utah; and the University of Vermont, Burlington, Vermont. For the MIRA Trial Group* Requests for Reprints: The MIRA Trial Group, c/o Stephen P. Heyse, MD, Office of Disease Prevention, Epidemiology, and Clinical Applications, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Natcher Building, Room 5AS-53, 45 Center Drive, MSC 6500, Bethesda, MD 20892-6500. Acknowledgments: The authors thank the physicians who referred their patients to the clinical centers, the clinic coordinators, the patients who participated in the study, and Helene Boldarini and Ella Henderson for secretarial assistance. Grant Support: By research contracts from the National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases (contracts N01-AR-1-2202, N01-AR-1-2203, N01-AR-1-2205, N01-AR-1-2207, N01-AR-1-2206, N01-AR-2-2210, and N01-AR-2-2205). Study medication and placebo were provided by Lederle Laboratories, a Division of Cyanamid, Inc., Pearl River, New York.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1995;122(2):81-89. doi:10.7326/0003-4819-122-2-199501150-00001
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Objective: To assess the safety and efficacy of minocycline in the treatment of rheumatoid arthritis.

Design: A double-blind, randomized, multicenter, 48-week trial of oral minocycline (200 mg/d) or placebo.

Setting: 6 clinical centers in the United States.

Patients: 219 adults with active rheumatoid arthritis who had previous limited treatment with disease-modifying drugs.

Measurements: As the primary outcomes, 60 diarthrodial joints were examined for tenderness, and 58 joints were examined for swelling (hips excluded). Grip strength, evaluator's global assessment, morning stiffness, Modified Health Assessment Questionnaire, patient's global assessment, hematocrit, erythrocyte sedimentation rate, platelet count, and IgM rheumatoid factor levels were also assessed; radiographs of both hands and wrists were taken.

Results: 109 and 110 patients were randomly assigned to receive minocycline and placebo, respectively. At entry, demographic, clinical, and laboratory measurements were similar in both groups. Most patients had mild to moderate disease activity and some evidence of destructive disease. At the week 48 visit, 79% of the minocycline group and 78% of the placebo group continued to receive the study medication. At 48 weeks, more patients in the minocycline group than in the placebo group showed improvement in joint swelling (54% and 39%) and joint tenderness (56% and 41%) (P < 0.023 for both comparisons). The minocycline group also showed greater improvement in hematocrit, erythrocyte sedimentation rate, platelet count, and IgM rheumatoid factor levels (all P values < 0.001), and more patients receiving minocycline had laboratory values within normal ranges at 48 weeks. For the remaining outcomes, P values ranged from 0.04 to 0.76, all greater than the critical value of 0.005 (Bonferroni adjustment for multiple comparisons). The frequency of reported side effects was similar in both groups, and no serious toxicity occurred.

Conclusions: Minocycline was safe and effective for patients with mild to moderate rheumatoid arthritis. Its mechanisms of action remain to be determined.

For current author affiliations, see end of text.*For members of the MIRA Trial Group, see the Appendix. For current author affiliations, see end of text.†Deceased.


Grahic Jump Location
Figure 1.

Proportion of patients with 50% or greater improvement in joint swelling, by visit. Proportion of patients with 50% or greater improvement in joint tenderness, by visit.

Grahic Jump Location




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