REVIEW - Optimal dosage and route of administration of MTX in RA

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Ann Rheum Dis. 2008 Nov 25.

Optimal dosage and route of administration of methotrexate in

rheumatoid arthritis: a systematic review of the literature.

Visser K, van der Heijde D.

Leiden University Medical Center, Netherlands.

OBJECTIVES: To systematically review the available literature on the

optimal dosage and route of administration of methotrexate (MTX) in

patients with rheumatoid arthritis (RA), as an evidence base for

generating clinical practice recommendations.

METHODS: A systematic literature search was carried out in MEDLINE,

EMBASE, Cochrane Library and ACR/EULAR meeting abstracts, searching

for randomized controlled trials evaluating various dosages or routes

of administration of MTX in RA. Articles that fulfilled predefined

inclusion criteria were systematically reviewed and the quality was

appraised. Effect sizes (ES) and odds ratios (OR) for clinical,

radiological and toxicity outcomes were calculated and directly or

indirectly compared between study groups using MTX in different

dosages or via different routes.

RESULTS: A total of 38 publications out of 1748 identified references

were included in the review. Start doses of 25mg/wk or fast escalation

with 5mg/month to 25-30mg/wk were associated with higher clinical ES

and more (gastrointestinal) adverse events in comparison with doses of

5-15mg/wk or slow escalation. Starting with 15mg/wk subcutaneous

versus oral MTX was associated with higher clinical efficacy, but more

withdrawal due to toxicity in early RA. In longstanding RA, however,

after failure on 15-20mg/wk orally, a switch to 15mg/wk intramuscular

with subsequent dose escalation did not result in increased efficacy.

CONCLUSIONS: /B> Starting on MTX 15mg/wk orally, escalating with

5mg/month to 25-30mg/wk, or the highest tolerable dose, with a

subsequent switch to subcutaneous in case of an insufficient response,

seems to be the optimal evidence-based dosing and routing

recommendation for MTX in RA.

PMID: 19033290

http://www.ncbi.nlm.nih.gov/pubmed/19033290

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