title: Risk of alanine transferase (ALT) elevation in patients with rheumatoid arthritis treated with methotrexate in a DAS-steered strategy.
abstract: OBJECTIVE
  To determine incidence of increased levels of alanine transferase (ALT) >2× upper limit of normal (ULN) in patients receiving methotrexate (MTX), treated according to a dynamic strategy, and to identify predictors of ALT of >2× ULN.
  
  
  METHODS
  Data of 508 recent-onset rheumatoid arthritis (RA) patients from the BeSt study, randomized to initial monotherapy or combination therapy, were used. Treatment was dynamic, aiming at a disease activity score = ≤ 2.4. ALT was measured every three months. With logistic regression analyses, baseline variables predictive of first ALT of >2× ULN were identified and the association between use of concomitant antirheumatic drugs, the actual and cumulative dose of MTX and ALT of >2× ULN was determined.
  
  
  RESULTS
  In total, 498 patients ever initiated MTX, with a total duration on MTX of 1,416 patient-years. In 89 patients, a first incidence of ALT of >2× ULN occurred. Incidence rate was 6.3 per 100 patient-years and cumulative incidence 18 %. ACPA positivity and baseline ALT of >1× ULN were independent predictors of later ALT of >2× ULN (OR 1.8 (95 % CI, 1.1-3.1) and OR 3.1 (95 % CI, 1.6-6.2), respectively). Smoking showed a trend (OR 1.6 (95 % CI, 0.98-2.7)). Mean MTX dosage over time was higher in patients with an ALT of >2× ULN. Patients who did not have an ALT of >2× ULN used more concomitant disease-modifying antirheumatic drugs and longer.
  
  
  CONCLUSIONS
  In RA patients treated with MTX according to a dynamic strategy resembling daily clinical practice, incidence of increased ALT of >2× ULN was lower than previously reported, and also without treatment adjustments, persistence was rare. The recommendations for ALT monitoring may be reevaluated.
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, PO Box 9600, 2300 Leiden, The Netherlands. l.dirven@lumc.nl
authors.forename: L
authors.initials: L
authors.lastname: Dirven
authors.forename: N B
authors.initials: NB
authors.lastname: Klarenbeek
authors.forename: M
authors.initials: M
authors.lastname: van den Broek
authors.forename: J H L M
authors.initials: JH
authors.lastname: van Groenendael
authors.forename: P B J
authors.initials: PB
authors.lastname: de Sonnaville
authors.forename: P J S M
authors.initials: PJ
authors.lastname: Kerstens
authors.forename: T W J
authors.initials: TW
authors.lastname: Huizinga
authors.forename: B A C
authors.initials: BA
authors.lastname: Dijkmans
authors.forename: W F
authors.initials: WF
authors.lastname: Lems
authors.forename: C F
authors.initials: CF
authors.lastname: Allaart
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D016017:Odds Ratio; D012306:Risk; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D000410:Alanine Transaminase; D008727:Methotrexate