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

[Guest guest]

ACR/ARHP 2008 Scientific Meeting

Session: RA Treatment: Small Molecules and Cell-Directed Biological Therapy

Sunday, Oct 26, 2008, 9:00 AM - 6:00 PM

Presentation: 384 - Optimal Dosage and Route of Administration of

Methotrexate in Rheumatoid Arthritis: a Systematic Review of the

Literature

Author(s): Visser, Désirée van der Heijde. Leiden University

Medical Center, Leiden, Netherlands

Abstract:

Purpose:

To perform a systematic review of the available literature on the

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

patients with rheumatoid arthritis (RA), as part of an evidence-based

approach for generating recommendations for the use of MTX in clinical

practice.

Methods:

A systematic literature search was performed in Medline, Embase,

Cochrane, and ACR/EULAR abstracts, searching for randomized controlled

trials directly comparing different dosages or routes of

administration of MTX in RA, or comparing MTX with placebo, other

disease modifying anti-rheumatic drugs (DMARDs) or biologicals. The

identified references were screened using predefined inclusion and

exclusion criteria. Included articles were systematically reviewed and

the quality was appraised according to the Oxford Levels of Evidence.

Cohen's effects sizes (ES) and odds ratios (OR) for clinical,

radiological and toxicity outcomes were calculated and directly or

indirectly compared between treatment groups using different dosages

or routes of MTX.

Results:

Of 1748 identified references, 39 original articles were selected and

included in the systematic review. Six studies were useful for direct

comparisons of MTX dosages or routes. Results from these studies show

a dose-effect relation in clinical ES and toxicity OR for treatment

with oral MTX 5-10mg/wk, 12.5-20mg/wk or 25-35mg/wk in MTX-naïve

patients with longstanding RA. Similar patients who started with

25mg/wk oral MTX showed more gastrointestinal events, but not more

withdrawal than patients starting with 15mg/wk. Of the patients who

started with 15mg/wk, 27% increased the dose for inefficacy, while 35%

of the patients who started with 25mg/wk the dose was decreased due to

toxicity or improvement, resulting in a mean effective dose of

17-20mg/wk. In early DMARD-naïve RA, starting with oral MTX 7.5mg and

increasing the dose with 5mg/month to a maximum of 25mg/wk, according

to the response, resulted in higher clinical efficacy than escalation

with 5mg/3 months. However, fast dose escalation also resulted in more

adverse events and withdrawal. Intramuscular (im) MTX escalated from

15 to 45mg/wk was not superior to im placebo escalation in patients

receiving im 15mg/wk after failure on oral 15-20mg/wk. In contrast,

subcutaneous (sc) versus oral MTX 15mg/wk in early MTX-naïve RA

patients, was associated with higher clinical efficacy, without more

toxicity. The findings result in level 1b to 2b evidence for various

dosages or routes of administration of MTX.

Conclusions:

The available evidence indicates that doses of MTX 25mg/wk result in

better clinical efficacy associated with more toxicity. Starting on

15mg/wk orally, escalating with 5mg/month until the highest tolerable

effective dose, with a subsequent switch to sc/im in case of an

insufficient response seems to be the optimal evidence-based dosing

and routing recommendation.

http://www.abstractsonline.com/plan/start.aspx?mkey={5880E483-F47E-4EFF-A557-2EF\

143592815}

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