RESEARCH - Treatment of early RF+ RA: doxycycline plus MTX versus MTX alone

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Arthritis & Rheumatism

Volume 54, Issue 2 , Pages 621 - 627

Published Online: 30 Jan 2006

Copyright © 2006 by the American College of Rheumatology

Research Article

Treatment of early seropositive rheumatoid arthritis:

Doxycycline plus methotrexate versus methotrexate alone

R. O'Dell 1, R. Elliott 2 *, Jack A. Mallek 3,

Ted R. Mikuls 1, A. Weaver 4, Glickstein 5, Kent M. Blakely 6,

Hausch 7, Rob D. Leff 7

1University of Nebraska Medical Center, Omaha

2University of Pittsburgh Medical Center, Pittsburgh,

Pennsylvania

3Central Plains Clinic, Sioux Falls, South Dakota

4Black Hills Neurology and Rheumatology, Rapid City, South

Dakota

5Park Nicollet Clinic, Minneapolis, Minnesota

6Platte Valley Medical Group, Kearney, Nebraska

7St. 's Duluth Clinic Health System, Duluth, Minnesota

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.

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Received: 13 January 2005; Accepted: 31 October 2005

http://www3.interscience.wiley.com/cgi-bin/abstract/112391543/ABSTRACT?CRETRY=1 & \

SRETRY=0

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