Treatment of early seropositive rheumatoid arthritis: Doxycycline plus methotrexate versus methotrexate alone

Abstract

Objective. To compare the efficacy of doxycycline plus methotrexate (MTX) versus MTX alone in the treatment of early seropositive rheumatoid arthritis (RA), and to attempt to differentiate the antibacterial and antimetalloproteinase effects of doxycycline.Methods. Sixty-six patients with seropositive RA of <1 year's duration who had not been previously treated with disease-modifying antirheumatic drugs were randomized to receive 100 mg of doxycycline twice daily with MTX (high-dose doxycycline group), 20 mg of doxycycline twice daily with MTX (low-dose doxycycline group), or placebo with MTX (placebo group), in a 2-year double-blind study. Treatment was started with an MTX dosage of 7.5 mg/week, which was titrated every 3 months until remission was reached (maximum dosage of 17.5 mg/week). The primary end point was an American College of Rheumatology 50% improvement (ACR50) response at 2 years.Results. ACR50 responses were observed in 41.6%of patients in the high-dose doxycycline group, 38.9% of those in the low-dose doxycycline group, and 12.5% of patients in the placebo group. Results of chi-square analysis of the ACR50 response in the high-dose doxycycline group versus that in the placebo group were significantly different (P ‫؍‬ 0.02). Trend analysis revealed that the ACR20 response and the ACR50 response were significantly different between groups (P ‫؍‬ 0.04 and P ‫؍‬ 0.03, respectively). MTX doses at 2 years were not different among groups. Four patients in the high-dose doxycycline group, 2 patients in the low-dose doxycycline group, and 2 patients in the placebo group were withdrawn because of toxic reactions. Conclusion. In patients with early seropositive RA, initial therapy with MTX plus doxycycline was superior (based on an ACR50 response) to treatment with MTX alone. The therapeutic responses to low-dose and high-dose doxycycline were similar, suggesting that the antimetalloproteinase effects were more important than the antibacterial effects. Further studies to evaluate the mechanism of action of tetracyclines in RA are indicated.

Prevalence and Severity of Periodontitis in Indonesian Patients With Rheumatoid Arthritis

“…tissue inhibitor of MMPs (TIMPs) reduces the severity of periodontitis. Also in human studies, such a possible beneficial effect of TIMPs is shown 33,34 . E.g., O'Dell et al 33 showed that systemically administration of a TIMP (subantimicrobial-dose doxycycline), FDA-approved for periodontitis, reduced the severity of RA in these patients.…”

Resistance of rheumatoid arthritis patients to changing therapy: Discordance between disease activity and patients' treatment choices

“…This advance in effective, dose-dependent therapy was followed by the general availability of biologic therapy and the later demonstration that combinations of methotrexate and biologic agents are more effective than either treatment alone in relieving symptoms, improving function, and retarding radiographic erosion (2)(3)(4)(5)(6). Studies have also shown that simultaneous use of multiple DMARDs leads to improved outcomes (7,8), and, in some studies, treatment has resulted in profound improvement, even remission, in many users of biologic agents or combinations of biologic agents and DMARDs (2,6,9). Taken as a whole, these data imply that aggressive, high-dose, multiple-drug therapy, often including biologic agents, should be used to optimize treatment of RA.…”

The Gut Microbiota and Inflammation in Rheumatoid Arthritis

“…Certain antibiotics like tetracycline have proven eicacy in the treatment of early seropositive RA which led to the approval of minocycline, as a DMARD [22,23]. Clarithromycin is another example that gave observable beneicial efects in some refractory cases [24].…”