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J Rheumatol Suppl. 2012 Sep;90:62-73. doi: 10.3899/jrheum.120345.

Safety of nonsteroidal antiinflammatory drugs and/or paracetamol in people receiving methotrexate for inflammatory arthritis: a Cochrane systematic review.

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  • 1Department of Rheumatology, Southampton General Hospital, Southampton, UK.



To systematically review the literature on the safety of using nonsteroidal antiinflammatory drugs (NSAID) and/or paracetamol in people receiving methotrexate (MTX) for inflammatory arthritis (IA), as an evidence base for generating clinical practice recommendations.


A systematic literature review was performed using the Cochrane Library, Medline, Embase, and conference proceedings for the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) for 2008-2009. The search aimed to identify studies describing adverse events (AE) with the concurrent use of paracetamol and/or NSAID in people taking MTX for IA. Articles fulfilling our predefined inclusion criteria were systematically reviewed and quality appraised.


Seventeen publications out of 8681 identified studies were included in the review, all of which included people with rheumatoid arthritis (RA) using various NSAID; there were no identified studies for other forms of IA or with paracetamol. Of the studies examining concurrent use of MTX and NSAID, there were no reported adverse effects on lung, liver, or renal function, and no increase in MTX withdrawal or in major toxic reactions. However, transient thrombocytopenia was demonstrated in 1 study. Looking at specific NSAID, there were no clinically significant AE with concomitant piroxicam or etodolac, and only mild AE with celecoxib or etoricoxib. Antiinflammatory dose aspirin was demonstrated to have an adverse effect on liver and renal function.


In the management of RA, concurrent use of NSAID with MTX appears to be safe, provided appropriate monitoring is performed. The use of antiinflammatory doses of aspirin should be avoided.

[PubMed - indexed for MEDLINE]
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