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Treatment of early seropositive rheumatoid arthritis: doxycycline plus methotrexate versus methotrexate alone.
Arthritis Rheum. 2006 Feb; 54(2):621-7.AR

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the high-dose doxycycline group, 2 patients in the low-dose doxycycline group, and 2 patients in the placebo group were withdrawn because of toxic reactions.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.

Authors+Show Affiliations

University of Nebraska Medical Center, Omaha, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial

Language

eng

PubMed ID

16447240

Citation

O'Dell, James R., et al. "Treatment of Early Seropositive Rheumatoid Arthritis: Doxycycline Plus Methotrexate Versus Methotrexate Alone." Arthritis and Rheumatism, vol. 54, no. 2, 2006, pp. 621-7.
O'Dell JR, Elliott JR, Mallek JA, et al. Treatment of early seropositive rheumatoid arthritis: doxycycline plus methotrexate versus methotrexate alone. Arthritis Rheum. 2006;54(2):621-7.
O'Dell, J. R., Elliott, J. R., Mallek, J. A., Mikuls, T. R., Weaver, C. A., Glickstein, S., Blakely, K. M., Hausch, R., & Leff, R. D. (2006). Treatment of early seropositive rheumatoid arthritis: doxycycline plus methotrexate versus methotrexate alone. Arthritis and Rheumatism, 54(2), 621-7.
O'Dell JR, et al. Treatment of Early Seropositive Rheumatoid Arthritis: Doxycycline Plus Methotrexate Versus Methotrexate Alone. Arthritis Rheum. 2006;54(2):621-7. PubMed PMID: 16447240.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Treatment of early seropositive rheumatoid arthritis: doxycycline plus methotrexate versus methotrexate alone. AU - O'Dell,James R, AU - Elliott,Jennifer R, AU - Mallek,Jack A, AU - Mikuls,Ted R, AU - Weaver,Cynthia A, AU - Glickstein,Scott, AU - Blakely,Kent M, AU - Hausch,Raymond, AU - Leff,Rob D, PY - 2006/2/1/pubmed PY - 2006/3/18/medline PY - 2006/2/1/entrez SP - 621 EP - 7 JF - Arthritis and rheumatism JO - Arthritis Rheum VL - 54 IS - 2 N2 - 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. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/16447240/Treatment_of_early_seropositive_rheumatoid_arthritis:_doxycycline_plus_methotrexate_versus_methotrexate_alone_ L2 - https://doi.org/10.1002/art.21620 DB - PRIME DP - Unbound Medicine ER -