RESEARCH - Elevated liver enzyme tests among RA and PsA patients treated with MTX and/or Arava

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Ann Rheum Dis. 2009 Jan 15.

Elevated liver enzyme tests among rheumatoid arthritis and psoriatic

arthritis patients treated with methotrexate and/or leflunomide.

Curtis JR, Beukelman T, Onofrei A, Cassell S, Greenberg J, Kavanaugh

A, G, Strand V, Kremer JM.

University of Alabama at Birmingham, United States.

Introduction: Potential hepatotoxicity associated with disease

modifying anti-rheumatic drugs [DMARDs] requires laboratory

monitoring. In rheumatoid and psoriatic arthritis [RA, PsA] patients,

we examined the incidence of elevated alanine/aspartate

aminotransferase (ALT/AST) enzymes associated with methotrexate (MTX),

leflunomide (LEF), and MTX+LEF vs. other DMARDs. METHODS: RA and PsA

patients enrolled in the Consortium of Rheumatology Researchers of

North America (CORRONA) initiating DMARDs were identified.

Abnormalities were identified when either was 1 or 2-fold time above

the upper limits of normal (ULN). Odds ratios [OR] between MTX/LEF

dose and elevated ALT/AST enzymes were estimated using generalized

estimating equations. Interaction terms for use of MTX+LEF quantified

the incremental risk of the combination compared to each individually.

RESULTS: Elevated ALT/AST levels (>1x ULN) occurred in 22, 17, 31, and

14% RA patients receiving MTX, LEF, MTX+LEF, or neither, respectively;

elevations were 2.76 fold (95% CI 1.84 - 4.15) more likely in PsA

patients. Elevations > 2x ULN occurred in 1-2% of patients on MTX or

LEF monotherapy compared to 5% with the combination. After

multivariable adjustment and compared with either monotherapy,

combination MTX + LEF was associated with greater risk according to

MTX dose used as part of the combination: MTX 10-17.5mg/week, OR=2.91

(95% confidence interval [CI] 1.23-6.90) and MTX >/=20 mg/week,

OR=3.98 (95% CI: 1.72-9.24). CONCLUSIONS: 14-35% of RA and PsA

patients initiating DMARD therapy developed abnormal ALT/AST levels.

Risks were incrementally greater in those with PsA and in those

receiving MTX (>/= 10mg/day) + LEF. These findings should help inform

monitoring for potential hepatotoxicity in these patient populations.

PMID: 19147616

http://www.ncbi.nlm.nih.gov/pubmed/19147616

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