title: Disease-modifying antirheumatic drugs other than methotrexate in rheumatoid arthritis and seronegative arthritis.
abstract: OBJECTIVE
  To outline recent research findings with nonmethotrexate disease-modifying antirheumatic drugs in rheumatoid arthritis and seronegative arthritis spanning systematic reviews, randomized controlled trials, observational clinical practice trials and assessments of adverse effects.
  
  
  RESULTS
  Systematic reviews show no important differences between methotrexate, leflunomide and sulfasalazine monotherapies; early disease-modifying antirheumatic drug therapy reduces erosive progression. Observational studies show that nonmethotrexate disease-modifying antirheumatic drugs are widely prescribed; their usage has increased in the biologic era. A systemic review also showed patients who failed monotherapy benefited from disease-modifying antirheumatic drug combinations without excess toxicity. Randomized controlled trials of intensive initial disease-modifying antirheumatic drug combinations showed they reduce synovitis and erosive damage, especially when used with steroids. The subsequent sequence of disease-modifying antirheumatic drugs and the value of changing disease-modifying antirheumatic drug monotherapies or stepping-up to combination disease-modifying antirheumatic drugs are, however, unresolved. The adverse risks of nonmethotrexate disease-modifying antirheumatic drugs have been evaluated, including infections and lung disease; patient-related risks seem more important than drug-related risks, though several disease-modifying antirheumatic drugs increase both types of adverse reactions. Two limitations of nonmethotrexate disease-modifying antirheumatic drugs are reduced impact on comorbidities like cardiovascular disease and reduced patient and clinician preferences for these treatments.
  
  
  CONCLUSIONS
  Nonmethotrexate disease-modifying antirheumatic drugs are effective, relatively well tolerated and widely used. Their role in intensive treatment strategies in early rheumatoid arthritis appears of crucial importance.
authors.affiliation: Department of Rheumatology, Kings College Hospital, London, UK.
authors.forename: Pradip
authors.initials: P
authors.lastname: Nandi
authors.forename: Gabrielle H
authors.initials: GH
authors.lastname: Kingsley
authors.forename: David L
authors.initials: DL
authors.lastname: Scott
mesh_terms: D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015535:Arthritis, Psoriatic / Q000188:drug therapy*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy*; D002318:Cardiovascular Diseases / Q000150:complications; D004359:Drug Therapy, Combination; D006801:Humans; D016032:Randomized Controlled Trials as Topic
chemical_list: D018501:Antirheumatic Agents