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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