REVIEW - The efficacy and toxicity of MTX monotherapy versus MTX combination therapy with non-biologic DMARDs in RA

[Guest guest]

Ann Rheum Dis. Published Online First: 3 December 2008.

doi:10.1136/ard.2008.099861

--------------------------------------------------------------------------------

Extended Report

The efficacy and toxicity of Methotrexate (MTX) monotherapy vs. MTX

combination therapy with non-biologic disease-modifying anti-rheumatic

drugs in rheumatoid arthritis: A systematic review and metaanalysis

Wanruchada Katchamart 1, Judith Trudeau 2, Veerapong Phumethum 1 and

Bombardier 3*

1 University of Toronto, Canada

2 Hospital Notre-Dame, Department of Rheumatology, Canada

3 Institute for Work and Health, Canada

Abstract

Objective: To evaluate the efficacy and toxicity of Methotrexate (MTX)

monotherapy compared to MTX combination with non-biologic

disease-modifying anti-rheumatic drugs (DMARDs) in adult with

rheumatoid arthritis.

Method: We performed a systematic review of randomized trials

comparing MTX alone and in combination with other non-biologic DMARDs.

Trials were identified in MEDLINE, EMBASE, the Cochrane Library and

ACR/EULAR meeting abstracts. Primary outcomes were withdrawals for

adverse events or lack of efficacy.

Results: A total of 19 trials (2,025 patients) from 6,938 citations

were grouped by the type of patients randomized. Trials in DMARD naive

patients showed no significant advantage of the MTX combination versus

monotherapy; withdrawals for lack of efficacy or toxicity were similar

in both groups (Relative Risk: RR 1.16, 95% CI.0.70-1.93). Trials in

MTX or non MTX DMARDs inadequate responder patients, also showed no

difference in withdrawal rates between the MTX combo vs mono groups

(RR 0.86; 95% CI 0.49 to1.51 and RR 0.75; 95% CI 0.41 to 1.35) but in

one study the specific combination of MTX with sulfasalazine and

hydroxychloroquine showed better efficacy/ toxicity ratio over MTX

alone with RR of 0.3 (95%CI 0.14 to 0.65). Adding leflunomide to MTX

non-responders improved efficacy but increased the risk of

gastrointestinal side effect and liver toxicity. Withdrawals for

toxicity were most significant with cyclosporine and azathioprine

combinations.

Conclusion: In DMARD naive patients the balance of efficacy/toxicity

favours MTX monotherapy. In DMARD inadequate responders the evidence

is inconclusive. Trials are needed that compare currently used MTX

doses and combination therapies.

http://ard.bmj.com/cgi/content/abstract/ard.2008.099861v1?papetoc

Not an MD