title: WITHDRAWN: Immunosuppressant and immunomodulatory treatment for dermatomyositis and polymyositis.
abstract: BACKGROUND
  Idiopathic inflammatory myopathies are chronic skeletal diseases with significant mortality and morbidity despite treatment by corticosteroids. Immunosuppressive agents and immunomodulatory therapy are used to improve disease control and reduce the long-term side effects of corticosteroids. While these treatments are used commonly in routine clinical practice, the optimal therapeutic regimen remains unclear.
  
  
  OBJECTIVE
  To systematically review the evidence for the effectiveness of immunosuppressants and immunomodulatory treatments for dermatomyositis and polymyositis.
  
  
  METHODS
  We searched the Cochrane Neuromuscular Disease Group trials register (searched February 2002 and updated in November 2003) and MEDLINE (January 1966 to December 2002). We checked bibliographies of identified trials and wrote to disease experts.
  
  
  METHODS
  Randomised or quasi-randomised controlled trials including patients with probable or definite dermatomyositis and polymyositis as defined by the criteria of Bohan and Peter or definite, probable or mild/early by the criteria of Dalakas. Patients with inclusion body myositis should have been excluded by muscle biopsies. Any immunosuppressant or immunomodulatory treatment including corticosteroids, azathioprine, methotrexate, ciclosporin, chlorambucil, cyclophosphamide, intravenous immunoglobulin, interferon and plasma exchange was considered. Primary outcome was assessment of muscle strength after at least six months. Other outcomes were: change in disability, number of relapses and time to relapse, number of patients in remission and time-to-remission, cumulative corticosteroid dose and serious adverse effects.
  
  
  METHODS
  Two authors (EC and JH) independently selected trials for inclusion in the review. Four authors independently assessed each study. Methodological criteria and the results of each study were recorded on data extraction forms.
  
  
  RESULTS
  Seven potentially relevant randomised controlled trials were identified. One trial was excluded. Three studies compared immunosuppressant with placebo control, one trial compared one immunosuppressant (methotrexate) with another (azathioprine), another trial compared ciclosporin A with methotrexate and the final trial compared intramuscular methotrexate with oral methotrexate plus azathioprine. The study comparing intravenous immunoglobulin with placebo concluded that the former was superior. Two randomised placebo-controlled trials assessing plasma exchange, leukapheresis and azathioprine produced negative results. The fourth study compared azathioprine with methotrexate and found azathioprine and methotrexate equally effective but methotrexate had a better side effect profile. The fifth study comparing ciclosporin A with methotrexate and the sixth study comparing intramuscular methotrexate with oral methotrexate plus azathioprine found no statistically significant differences between the treatment groups. Immunosuppressants are associated with significant side effects.
  
  
  CONCLUSIONS
  This systematic review highlights the lack of high quality randomised controlled trials that assess the efficacy and toxicity of immunosuppressants in inflammatory myositis.
authors.affiliation: Academic Department of Rheumatology, GKT School of Medicine, Weston Education Centre, Cutcombe Road, London, UK, SE5 9PJ.
authors.forename: Ernest Hs
authors.initials: EH
authors.lastname: Choy
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Hoogendijk
authors.forename: Bryan
authors.initials: B
authors.lastname: Lecky
authors.forename: John B
authors.initials: JB
authors.lastname: Winer
authors.forename: Patrick
authors.initials: P
authors.lastname: Gordon
mesh_terms: D001379:Azathioprine / Q000627:therapeutic use; D001781:Blood Component Removal; D016572:Cyclosporine / Q000627:therapeutic use; D003882:Dermatomyositis / Q000188:drug therapy / Q000628:therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008727:Methotrexate / Q000627:therapeutic use; D010951:Plasma Exchange; D017285:Polymyositis / Q000188:drug therapy / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D001379:Azathioprine; D008727:Methotrexate