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Outcomes related to methotrexate dose and route of administration in patients
with rheumatoid arthritis: a systematic literature review
#MMPMID25536122
Goodman SM
; Cronstein BN
; Bykerk VP
Clin Exp Rheumatol
2015[Mar]; 33
(2
): 272-8
PMID25536122
show ga
OBJECTIVES: Methotrexate (MTX) is considered the 'anchor drug' in the therapy of
rheumatoid arthritis (RA), yet many physicians do not optimise MTX regimens in
spite of high RA disease activity. The recent development of an auto-injector for
the subcutaneous (subQ) administration of MTX has prompted re-evaluation of MTX
utilisation. The purpose of this systematic literature review is to determine the
optimal dose, drug level, and route of administration for MTX in the context of
relevant pharmacokinetics and pharmacogenomics. METHODS: A systematic literature
review was performed in Medline searching specifically for randomised controlled
trials, systematic reviews, case control and cohort studies evaluating outcomes
related to MTX dose and route of administration. Articles fulfilling these
inclusion criteria were reviewed. Data on MTX dose, route of administration,
clinical response, drug levels and adverse events were evaluated. RESULTS: Our
search identified 420 articles of which 6 were eligible for inclusion using the
above criteria. These included 2 systematic reviews, 2 randomised open label
trials, one longitudinal study and one retrospective cohort study. CONCLUSIONS:
Efficacy and toxicity for MTX appear related to absorbed dose of MTX, not to
route of administration. While bioavailability is greater for parenteral MTX,
there is no evidence yet that splitting the oral dose of MTX is less
advantageous, less safe or less tolerable than administering parenteral MTX.
However, there appear to be modest benefits in beginning with higher doses of
MTX, and switching to parenteral MTX when the clinical response to an oral dose
is inadequate.
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