Elevated liver enzyme tests among rheumatoid arthritis and psoriatic arthritis patients treated with methotrexate and/or leflunomide
- Jeffrey R Curtis ( )
- Alina Onofrei ( )
- George Reed ( )
- Joel M Kremer ( )
- Published Online First 15 January 2009
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.