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 (>1x 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 >2x 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 > or =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 (> or =10 mg/day) + LEF. These findings should help inform monitoring for potential hepatotoxicity in these patient populations.
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 (>1x 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 >2x 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 > or =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 (> or =10 mg/day) + LEF. These findings should help inform monitoring for potential hepatotoxicity in these patient populations.
Authors: Joel M Kremer; Mark C Genovese; Grant W Cannon; Jacques R Caldwell; John J Cush; Daniel E Furst; Michael E Luggen; Ed Keystone; Michael H Weisman; William M Bensen; Jeffrey L Kaine; Eric M Ruderman; Patricia Coleman; David L Curtis; Elliot J Kopp; Seth M Kantor; Jonathan Waltuck; Herbert B Lindsley; Joseph A Markenson; Vibeke Strand; Bruce Crawford; Indra Fernando; Karen Simpson; Joan M Bathon Journal: Ann Intern Med Date: 2002-11-05 Impact factor: 25.391
Authors: V Strand; S Cohen; M Schiff; A Weaver; R Fleischmann; G Cannon; R Fox; L Moreland; N Olsen; D Furst; J Caldwell; J Kaine; J Sharp; F Hurley; I Loew-Friedrich Journal: Arch Intern Med Date: 1999-11-22
Authors: S Cohen; G W Cannon; M Schiff; A Weaver; R Fox; N Olsen; D Furst; J Sharp; L Moreland; J Caldwell; J Kaine; V Strand Journal: Arthritis Rheum Date: 2001-09
Authors: P Emery; F C Breedveld; E M Lemmel; J P Kaltwasser; P T Dawes; B Gömör; F Van Den Bosch; D Nordström; O Bjorneboe; R Dahl; K Horslev-Petersen; A Rodriguez De La Serna; M Molloy; M Tikly; C Oed; R Rosenburg; I Loew-Friedrich Journal: Rheumatology (Oxford) Date: 2000-06 Impact factor: 7.580
Authors: J Peter Kaltwasser; Peter Nash; Dafna Gladman; Cheryl F Rosen; Frank Behrens; Peter Jones; Jürgen Wollenhaupt; Franziska G Falk; Philip Mease Journal: Arthritis Rheum Date: 2004-06
Authors: Joel Kremer; Mark Genovese; Grant W Cannon; Jacques Caldwell; John Cush; Daniel E Furst; Michael Luggen; Ed Keystone; Joan Bathon; Arthur Kavanaugh; Eric Ruderman; Patricia Coleman; David Curtis; Elliott Kopp; Seth Kantor; Michael Weisman; Jonathan Waltuck; Herbert B Lindsley; Joseph Markenson; Bruce Crawford; Indra Fernando; Karen Simpson; Vibeke Strand Journal: J Rheumatol Date: 2004-08 Impact factor: 4.666
Authors: L Dirven; N B Klarenbeek; M van den Broek; J H L M van Groenendael; P B J de Sonnaville; P J S M Kerstens; T W J Huizinga; B A C Dijkmans; W F Lems; C F Allaart Journal: Clin Rheumatol Date: 2012-12-09 Impact factor: 2.980