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

Henry Ford Health Sciences Center, Detroit, Michigan.
Annals of internal medicine (Impact Factor: 17.81). 01/1995; 122(2):81-9.
Source: PubMed


To assess the safety and efficacy of minocycline in the treatment of rheumatoid arthritis.
A double-blind, randomized, multicenter, 48-week trial of oral minocycline (200 mg/d) or placebo.
6 clinical centers in the United States.
219 adults with active rheumatoid arthritis who had previous limited treatment with disease-modifying drugs.
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.
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.
Minocycline was safe and effective for patients with mild to moderate rheumatoid arthritis. Its mechanisms of action remain to be determined.

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    • "Minocycline, a semi-synthetic tetracycline derivative, ameliorates the severity of a number of inflammatory diseases, including rheumatoid arthritis [43] and animal models of multiple sclerosis [44], amyotrophic lateral sclerosis [45], Huntington’s disease [46], Parkinson’s disease [47], allergy/asthma [48], [49], Japanese encephalitis virus [50], and SIV-associated neurological disease [51], [52]. Minocycline’s effects have been primarily attributed to its ability to decrease activation of a variety of immune cell types, including monocytes/macrophages, microglia, and T cells [53]–[56]. "
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    ABSTRACT: HIV immune pathogenesis is postulated to involve two major mechanisms: 1) chronic innate immune responses that drive T cell activation and apoptosis and 2) induction of immune regulators that suppress T cell function and proliferation. Both arms are elevated chronically in lymphoid tissues of non-natural hosts, which ultimately develop AIDS. However, these mechanisms are not elevated chronically in natural hosts of SIV infection that avert immune pathogenesis despite similarly high viral loads. In this study we investigated whether minocycline could modulate these pathogenic antiviral responses in non-natural hosts of HIV and SIV. We found that minocycline attenuated in vitro induction of type I interferon (IFN) and the IFN-stimulated genes indoleamine 2,3-dioxygenase (IDO1) and TNF-related apoptosis inducing ligand (TRAIL) in human plasmacytoid dendritic cells and PBMCs exposed to aldrithiol-2 inactivated HIV or infectious influenza virus. Activation-induced TRAIL and expression of cytotoxic T-lymphocyte antigen 4 (CTLA-4) in isolated CD4+ T cells were also reduced by minocycline. Translation of these in vitro findings to in vivo effects, however, were mixed as minocycline significantly reduced markers of activation and activation-induced cell death (CD25, Fas, caspase-3) but did not affect expression of IFNβ or the IFN-stimulated genes IDO1, FasL, or Mx in the spleens of chronically SIV-infected pigtailed macaques. TRAIL expression, reflecting the mixed effects of minocycline on activation and type I IFN stimuli, was reduced by half, but this change was not significant. These results show that minocycline administered after infection may protect against aspects of activation-induced cell death during HIV/SIV immune disease, but that in vitro effects of minocycline on type I IFN responses are not recapitulated in a rapid progressor model in vivo.
    PLoS ONE 04/2014; 9(4):e94375. DOI:10.1371/journal.pone.0094375 · 3.23 Impact Factor
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    • "This study was carried out for 1 year and investigated 219 moderate RA patients who did not respond to one or more DMARD. The patients discontinued use of DMARDs during the study.5 The other two studies were conducted by the Rheumatoid Arthritis Investigational Network (RAIN).6,7 "
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    ABSTRACT: Antibiotic treatment for rheumatoid arthritis (RA) commenced in the 1930s with the use of sulfasalazine. Later, tetracyclines were successfully used for the treatment of RA. In double-blind and randomized studies, levofloxacin and macrolide antibiotics (including clarithromycin and roxithromycin) were also shown to be effective in the treatment of RA. There have been several reports in the literature indicating that periodontal pathogens are a possible cause of RA. Oral bacteria are one possible cause of RA. In this review, we aimed to investigate the effects of different antibiotics in RA treatment.
    International Journal of General Medicine 12/2013; 7:43-47. DOI:10.2147/IJGM.S56957
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    • "Tetracyclines inhibit most periodontopathic bacteria in vitro and in vivo,6 and minocycline is effective for the treatment of RA and PD.6,7 "
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    ABSTRACT: A statistically significant association between periodontal disease (PD) and systemic diseases has been identified. Rheumatoid arthritis (RA), which is a chronic inflammatory joint disease, exhibits similar characteristics and pathogenesis to PD. The association between RA and PD has been investigated, and numerous publications on this subject exist. Approximately 20 bacterial species have been identified as periodontal pathogens, and these organisms are linked to various types of PD. The most analyzed species of periodontopathic bacteria are Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia, and Aggregatibacter actinomycetemcomitans. Antibodies and DNA from these oral pathogens have been isolated from the sera and synovial fluids of RA patients. This rapid communication describes the role of periodontal pathogens in the etiopathogenesis of RA.
    International Journal of General Medicine 05/2013; 6:383-6. DOI:10.2147/IJGM.S45929
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