title: Comparative effectiveness of tumour necrosis factor alpha inhibitors in combination with either methotrexate or leflunomide.
abstract: OBJECTIVE
  The objective of this study was to compare the effectiveness of a combination of tumour necrosis factor alpha (TNFalpha) inhibitors with either methotrexate or leflunomide in the treatment of patients with rheumatoid arthritis in a real-world setting.
  
  
  METHODS
  Data from 1769 outpatients enrolled in the German biologics register RABBIT who were treated with one of the TNFalpha inhibitors adalimumab, etanercept, or infliximab in combination with either methotrexate (n = 1375) or leflunomide (n = 394) were included in the analysis. Clinical status including disease activity as well as treatment data were documented by the treating rheumatologist at baseline and at 3, 6, 12, 18, 24, 30 and 36 months of follow-up.
  
  
  RESULTS
  Patients treated with a combination of biologics with leflunomide had significantly higher baseline disease activity than those treated with methotrexate. The highest disease activity was found for patients treated with the combination infliximab/leflunomide. After 36 months, the discontinuation rates were 46.3%, 51.3% and 61.5% for combinations of etanercept, adalimumab and infliximab with methotrexate and 53.4%, 63.1% and 67.1% for combinations with leflunomide, respectively. European League Against Rheumatism response rates after 24 months ranged from 74% to 81% for combinations with methotrexate and 72% to 81% for combinations with leflunomide.
  
  
  CONCLUSIONS
  The current clinical practice is to use methotrexate as a first choice for the combination with TNFalpha antagonists. In a number of patients methotrexate has to be replaced by another disease-modifying antirheumatic drug. Our data support the view that leflunomide is a useful alternative if methotrexate is contraindicated.
authors.affiliation: German Rheumatism Research Centre, Epidemiology Unit, 10117 Berlin, Germany. Strangfeld@drfz.de
authors.forename: A
authors.initials: A
authors.lastname: Strangfeld
authors.forename: F
authors.initials: F
authors.lastname: Hierse
authors.forename: J
authors.initials: J
authors.lastname: Kekow
authors.forename: U
authors.initials: U
authors.lastname: von Hinueber
authors.forename: H-P
authors.initials: HP
authors.lastname: Tony
authors.forename: R
authors.initials: R
authors.lastname: Dockhorn
authors.forename: J
authors.initials: J
authors.lastname: Listing
authors.forename: A
authors.initials: A
authors.lastname: Zink
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D004812:Epidemiologic Methods; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D000069285:Infliximab; D007555:Isoxazoles / Q000009:adverse effects / Q000627:therapeutic use*; D000077339:Leflunomide; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D011358:Product Surveillance, Postmarketing / Q000379:methods; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D007555:Isoxazoles; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000077339:Leflunomide; D000068800:Etanercept; D008727:Methotrexate