title: Update 2011: leflunomide in rheumatoid arthritis - strengths and weaknesses.
abstract: OBJECTIVE
  Leflunomide is often used as a first choice disease-modifying antirheumatic drug after methotrexate. New data are available for efficacy and safety in both, monotherapy and combination with biologicals.
  
  
  RESULTS
  New data on efficacy demonstrate comparable effect sizes for leflunomide and methotrexate in the treatment of signs and symptoms in combination with tumour necrosis factor-blocking agents and rituximab. Equipotency has also been demonstrated by a recent radiographic outcome study on methotrexate and leflunomide monotherapy. Pharmacogenetic studies indicate an impact of polymorphisms on the variability in serum levels of the compound with potential relevance to effectiveness and tolerability in individual patients. Genetic factors are also likely to contribute to the significantly increased risk for leflunomide-induced pulmonary disease reported in Asia. Because pre-existing interstitial lung disease as well as methotrexate-induced pneumonitis have been identified as risk factors for leflunomide-induced pulmonary disease, the use of leflunomide as an alternative to methotrexate is limited under these conditions.
  
  
  CONCLUSIONS
  Effectiveness of leflunomide renders it a potent treatment option in rheumatoid arthritis. The known tolerability issues resulting in a less favourable adherence to therapy constitutes a weakness. However, documented data from large registries indicate that leflunomide is safe as far as the contraindications and recommendations for monitoring are regarded.
authors.affiliation: Division of Rheumatology, University Hospital Frankfurt/Main, Johann Wolfgang Goethe-University Hospital, Frankfurt/Main, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Behrens
authors.forename: Michaela
authors.initials: M
authors.lastname: Koehm
authors.forename: Harald
authors.initials: H
authors.lastname: Burkhardt
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001171:Arthritis, Juvenile / Q000188:drug therapy; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects; D007555:Isoxazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077339:Leflunomide; D008099:Liver / Q000187:drug effects; D008171:Lung Diseases / Q000139:chemically induced; D016169:Lymphocyte Function-Associated Antigen-1 / Q000187:drug effects; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use; D009369:Neoplasms / Q000209:etiology; D010597:Pharmacogenetics; D000069283:Rituximab; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D007555:Isoxazoles; D016169:Lymphocyte Function-Associated Antigen-1; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D000069283:Rituximab; D000077339:Leflunomide; D008727:Methotrexate