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

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Ann Rheum Dis. Published Online First: 15 January 2009.

doi:10.1136/ard.2008.101378

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Extended Report

Elevated liver enzyme tests among rheumatoid arthritis and psoriatic

arthritis patients treated with methotrexate and/or leflunomide

R Curtis 1*, Beukelman 1, Alina Onofrei 2,

Cassell 3, Greenberg 4, Arthur Kavanaugh 5, 2,

Vibeke Strand 6 and M Kremer 7

1 University of Alabama at Birmingham, United States

2 University of Massachusetts, United States

3 Los Alamos Medical Center, United States

4 NYU, United States

5 University of California, United States

6 Stanford University, United States

7 The Center for Rheumatology, Albany, United States

Abstract

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.

http://ard.bmj.com/cgi/content/abstract/ard.2008.101378v1?papetoc

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