RESEARCH - Should tetracycline treatment be used more extensively for RA?

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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

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=pubmed & dopt=Abstra\

ct & list_uids=14528503 & itool=iconabstr & query_hl=3

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