title: Liver toxicity is rare in rheumatoid arthritis patients using combination therapy with leflunomide and methotrexate.
abstract: OBJECTIVE
  Some studies have reported that adding leflunomide (LEF) to the treatment of rheumatoid arthritis (RA) in patients who do not respond to methotrexate (MTX) improved efficacy but increased the risk of liver toxicity. This study aimed at assessing the incidence of liver toxicity in patients with active RA using the LEF and MTX combination therapy in comparison with that of patients on MTX monotherapy.
  
  
  METHODS
  Between February and September 2009, 97 consecutive patients followed up at the University Hospital of the Universidade Federal de Santa Catarina, Brazil, were enrolled. RA patients on MTX alone or using the LEF and MTX combination had their medical records systematically reviewed. The alanine/aspartate aminotransferase enzymes were retrospectively analyzed since the beginning of treatment with MTX or MTX plus LEF. Hepatotoxicity was defined as an increase of at least two-fold the upper limits of normal of the liver enzymes.
  
  
  RESULTS
  71 RA patients were included in the study: 36.6% were using 20-25 mg/week of MTX alone and 63.4% were using 20-25 mg/week of MTX plus 20 mg/day of LEF. Of the patients on the combination therapy, 11.1% had abnormal levels of liver enzymes versus 11.5% of the patients on monotherapy (P = 1.0). Abnormal aminotransferase levels have been seen with both MTX and LEF monotherapies in patients with RA. In our study, no difference was found between the percentages of aminotransferase elevations of patients being treated with MTX alone or in combination with LEF.
  
  
  CONCLUSIONS
  The combination of MTX and LEF in RA patients is generally safe and well tolerated.
authors.affiliation: Universidade Federal de Santa Catarina, Brazil.
authors.forename: Jorge Augusto Nunes Rodrigues
authors.initials: JA
authors.lastname: Alves
authors.forename: Sonia Cristina de Magalhães Souza
authors.initials: SC
authors.lastname: Fialho
authors.forename: Edelton Flávio
authors.initials: EF
authors.lastname: Morato
authors.forename: Gláucio RicardoWerner de
authors.initials: GR
authors.lastname: Castro
authors.forename: Adriana Fontes
authors.initials: AF
authors.lastname: Zimmermann
authors.forename: Giovana Gomes
authors.initials: GG
authors.lastname: Ribeiro
authors.forename: Fabrício Souza
authors.initials: FS
authors.lastname: Neves
authors.forename: Ivânio Alves
authors.initials: IA
authors.lastname: Pereira
mesh_terms: D018501:Antirheumatic Agents / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology* / Q000209:etiology*; D003430:Cross-Sectional Studies; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D015994:Incidence; D007555:Isoxazoles / Q000627:therapeutic use*; D000077339:Leflunomide; D008297:Male; D008727:Methotrexate / Q000009:adverse effects*; D008875:Middle Aged
chemical_list: D018501:Antirheumatic Agents; D007555:Isoxazoles; D000077339:Leflunomide; D008727:Methotrexate