RESEARCH - Treatment of early seropositive RA: doxycycline plus MTX vs. MTX alone

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Arthritis Rheum. 2006 Feb;54(2):621-7.

Treatment of early seropositive rheumatoid arthritis: Doxycycline plus

methotrexate versus methotrexate alone.

O'dell JR, Elliott JR, Mallek JA, Mikuls TR, Weaver CA, Glickstein S,

Blakely KM, Hausch R, Leff RD.

University of Nebraska Medical Center, Omaha.

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group were withdrawn because of toxic reactions.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.

PMID: 16447240

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

6447240 & dopt=Abstract

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