Should tetracycline treatment be used more extensively for RA?

[Guest guest]

J Rheumatol. 2003 Oct;30(10):2112-22.

Should tetracycline treatment be used more extensively for rheumatoid

arthritis? Metaanalysis demonstrates clinical benefit with reduction in

disease activity.

Stone M, Fortin PR, Pacheco-Tena C, Inman RD.

Division of Rheumatology, Department of Medicine, Toronto Western

Hospital, 399 Bathurst Street, Toronto, Ontario M5T 2S8, Canada.

OBJECTIVE: To compare the effectiveness of tetracycline antibiotics

versus control (placebo or conventional treatment) in rheumatoid

arthritis (RA) for the reduction of disease activity as defined by

American College of Rheumatology criteria. METHODS: We searched Medline

(1966-February 2002), Embase (1980-February 2002), and the Cochrane

Controlled Trials Register (Issue 1, 2002 Cochrane Library). Reference

lists of published trials were searched by hand for further

identification of published reports and presentations at scientific

meetings. Randomized controlled trials comparing tetracyclines to

control (placebo or conventional disease modifying antirheumatic

therapy) were selected for inclusion if at least one of the following

outcomes was reported: tender joint count (TJC), swollen joint count,

patient pain score by visual analog scale, patient global assessment of

disease activity, physician global assessment of disease activity,

eosinophil sedimentation rate (ESR) and C-reactive protein (CRP), joint

space narrowing and erosions, adverse events, and quality of life as

measured by the Health Assessment Questionnaire. Subjects were required

to have RA as defined by the 1987 ARA criteria. RESULTS: Ten randomized

controlled trials including 535 individuals were reviewed. Only 3 trials

were considered high quality; elements of bias could not be excluded in

the remainder. Tetracyclines, when administered for > or = 3 months,

were associated with a significant reduction in disease activity in RA

as follows: for TJC, standardized mean difference (SMD) = -0.39, 95%

CI -0.74, -0.05; and for acute phase reactants, ESR, SMD = -8.96, 95%

CI -14.51, -3.42. The treatment effect was more marked in the subgroup

of patients with disease duration < 1 year who were seropositive. There

was no absolute increased risk of adverse events associated with

tetracyclines: absolute risk difference = 0.10, 95% confidence interval

(CI) -0.01, 0.21. No beneficial effect was seen on radiological

progression of disease: for erosions, SMD = 0.17, 95% CI -0.29, 0.64. In

addition, subgroup analysis excluding trials with doxycycline showed

that minocycline alone had a greater effect on reduction of disease

activity: for TJC, SMD = -0.69, 95% CI -0.89, -0.49; and for ESR, SMD

= -10.14, 95% CI -14.72, -5.57.

CONCLUSION: Tetracyclines, in particular minocycline, were associated

with a clinically significant improvement in disease activity in RA with

no absolute increased risk of side effects. Unfortunately, the

information available was inadequate to allow a detailed analysis of

individual side effects in the studies. Further research is warranted to

compare these agents to newer disease modifying drugs for comparable

safety, efficacy, and cost-effectiveness.

PMID: 14528503

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org