title: The SMILE study -- safety of methotrexate in combination with leflunomide in rheumatoid arthritis.
abstract: OBJECTIVE
  To assess the safety of treating patients with rheumatoid arthritis with a combination of methotrexate (MTX) and leflunomide (LEF) in comparison to MTX monotherapy, in clinical practice.
  
  
  METHODS
  The Safety of Methotrexate in Combination with Leflunomide in Rheumatoid Arthritis (SMILE) study was a multicenter, observational, cross-sectional, retrospective safety study. The study was conducted by the Optimising Patient Outcomes in Australian Rheumatology-Quality Use of Medicines Initiative (OPAL QUMI). Data were deidentified for patient, clinic, and clinician prior to collection from 13 participating rheumatology practices (25 rheumatologists). Comparative analysis of safety for the different treatments, primarily with regard to neutropenia and liver abnormalities, was performed.
  
  
  RESULTS
  In total, 2975 patients were included in the study: 74% female, 26% male, mean age 62 years (SD 13.6). Distribution of therapy: MTX monotherapy 52.2%, LEF monotherapy 7.3%, MTX plus LEF 13.9%, and neither MTX nor LEF 26.6%. Comorbid liver disease was reported in 8.1% of patients. Liver function abnormalities were reported in 12% of the MTX monotherapy group, 16% of the LEF monotherapy group, 19% of the MTX-LEF combination group, and 14% of the group not taking either drug. Neutropenia was reported in 2.3% of the MTX monotherapy group, 5.5% of the LEF monotherapy group, 3.9% of the MTX-LEF combination group, and 4.2% of the group not taking either drug.
  
  
  CONCLUSIONS
  The combination of MTX and LEF was well tolerated, with adverse events comparable to those of monotherapy and the other nonbiologic disease-modifying antirheumatic drug treatment group.
authors: Combined Rheumatology Practice, Sydney, New South Wales (NSW), Australia. pbird@optimusresearch.com.au
authors: Paul
authors: P
authors: Bird
authors: Hedley
authors: H
authors: Griffiths
authors: Kathleen
authors: K
authors: Tymms
authors: Dave
authors: D
authors: Nicholls
authors: Lynden
authors: L
authors: Roberts
authors: Mark
authors: M
authors: Arnold
authors: Simon
authors: S
authors: Burnet
authors: Julien
authors: J
authors: de Jager
authors: James
authors: J
authors: Scott
authors: Jane
authors: J
authors: Zochling
authors: Geoff
authors: G
authors: Littlejohn
mesh_terms: D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001315:Australia; D003430:Cross-Sectional Studies; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000077339:Leflunomide; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D007555:Isoxazoles; D000077339:Leflunomide; D008727:Methotrexate