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

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Ann Rheum Dis 2010;69:43-47 doi:10.1136/ard.2008.101378

Clinical and epidemiological research

Extended report

Elevated liver enzyme tests among patients with rheumatoid arthritis

or psoriatic arthritis treated with methotrexate and/or leflunomide

J R Curtis1, T Beukelman1, A Onofrei2, S Cassell3, J D Greenberg4, A

Kavanaugh5, G 2, V Strand6, J M Kremer7

+ Author Affiliations

1Division of Clinical Immunology and Rheumatology, University of

Alabama at Birmingham, Birmingham, Alabama, USA

2University of Massachusetts Medical School, Worcester, Massachusetts, USA

3Los Alamos Medical Center, Los Alamos, New Mexico, USA

4New York University, New York, USA

5University of California, San Diego, California, USA

6Stanford University, Palo Alto, California, USA

7Albany Medical College, The Center for Rheumatology, New York, USA

Abstract

Introduction: Potential hepatotoxicity associated with

disease-modifying antirheumatic drugs (DMARDs) requires laboratory

monitoring. In patients with rheumatoid arthritis (RA) or psoriatic

arthritis (PsA), the incidence of elevated alanine

aminotransferase/aspartate aminotransferase (ALT/AST) enzymes

associated with methotrexate (MTX), leflunomide (LEF) and MTX+LEF

versus other DMARDs was examined.

Methods: Patients with RA and PsA 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 times above the upper limits of normal (ULN). Odds ratios (OR)

between MTX/LEF dose and elevated ALT/AST enzymes were estimated using

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

quantified the incremental risk of the combination compared with each

individually.

Results: Elevated ALT/AST levels (>1× ULN) occurred in 22%, 17%, 31%

and 14% of patients with RA receiving MTX, LEF, MTX+LEF or neither,

respectively; elevations were 2.76-fold (95% CI 1.84 to 4.15) more

likely in patients with PsA. Elevations >2× ULN occurred in 1–2% of

patients on MTX or LEF monotherapy compared with 5% with the

combination. After multivariable adjustment and compared with either

monotherapy, the combination of MTX and LEF was associated with a

greater risk according to MTX dose used as part of the combination:

MTX 10–17.5 mg/week, OR 2.91 (95% CI 1.23 to 6.90); MTX ≥20 mg/week,

OR 3.98 (95% CI 1.72 to 9.24).

Conclusions: Abnormal ALT/AST levels developed in 14–35% of patients

with RA or PsA initiating DMARD therapy. The risks were incrementally

greater in those with PsA and in those receiving MTX (≥10 mg/day) +

LEF. These findings should help inform monitoring for potential

hepatotoxicity in these patient populations.

http://ard.bmj.com/content/69/01/43.abstract?etoc

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