title: Second-line agents in myositis: 1-year factorial trial of additional immunosuppression in patients who have partially responded to steroids.
abstract: OBJECTIVE
  Ciclosporin and MTX are used in idiopathic inflammatory myopathies (DM and PM) when patients incompletely respond to glucocorticoids. Their effectiveness is unproved in randomized controlled trials (RCTs). We evaluated their benefits in a placebo-controlled factorial RCT.
  
  
  METHODS
  A 56-week multicentre factorial-design double-blind placebo-controlled RCT compared steroids alone, MTX (15-25 mg weekly) plus steroids, ciclosporin (1-5 mg/kg/day) plus steroids and all three treatments. It enrolled adults with myositis (by Bohan and Peter criteria) with active disease receiving corticosteroids.
  
  
  RESULTS
  A total of 359 patients were screened and 58 randomized. Of the latter, 37 patients completed 12 months of treatment, 7 were lost to follow-up and 14 discontinued treatment. Patients completing 12 months of treatment showed significant improvement (P < 0.001 on paired t-tests) in manual muscle testing (14% change), walking time (22% change) and function (9% change). Intention to treat and completer analyses indicated that ciclosporin monotherapy, MTX monotherapy and ciclosporin/MTX combination therapy showed no significant treatment effects in comparison with placebo.
  
  
  CONCLUSIONS
  Neither MTX nor ciclosporin (by themselves or in combination) improved clinical features in myositis patients who had incompletely responded to glucocorticoids.
  
  
  BACKGROUND
  International Standard Randomized Controlled Trial Number Register; http://www.controlled-trials.com/; ISRCTN40085050.
authors.affiliation: Department of Rheumatology, King's College London, London, Cardiff Institute of Infection & Immunity, Cardiff University School of Medicine, Cardiff, MRC Clinical Trials Unit, Department of Rheumatology, Whipps Cross University Hospital, London, Rheumatology, Russells Hall Hospital, Dudley Group of Hospitals NHS Foundation Trust, Dudley, Department of Rheumatology, University College London Hospitals, London, Musculoskeletal Unit, Freeman Hospital, Newcastle, Department of Neurology, Walton Centre for Neurology and Neurosurgery, Liverpool, Department of Rheumatology, Queen's Hospital, Romford, Department of Neurology, The Queen Elizabeth Hospital Neuroscience Centre, Birmingham, UK, Department of Internal Medicine, Medical University of Debrecen, Debrecen, Hungary and Rheumatic Diseases Centre, Salford Royal NHS Foundation Trust, Manchester, UK fowzia.ibrahim@kcl.ac.uk.
authors.forename: Fowzia
authors.initials: F
authors.lastname: Ibrahim
authors.affiliation: Department of Rheumatology, King's College London, London, Cardiff Institute of Infection & Immunity, Cardiff University School of Medicine, Cardiff, MRC Clinical Trials Unit, Department of Rheumatology, Whipps Cross University Hospital, London, Rheumatology, Russells Hall Hospital, Dudley Group of Hospitals NHS Foundation Trust, Dudley, Department of Rheumatology, University College London Hospitals, London, Musculoskeletal Unit, Freeman Hospital, Newcastle, Department of Neurology, Walton Centre for Neurology and Neurosurgery, Liverpool, Department of Rheumatology, Queen's Hospital, Romford, Department of Neurology, The Queen Elizabeth Hospital Neuroscience Centre, Birmingham, UK, Department of Internal Medicine, Medical University of Debrecen, Debrecen, Hungary and Rheumatic Diseases Centre, Salford Royal NHS Foundation Trust, Manchester, UK.
authors.forename: Ernest
authors.initials: E
authors.lastname: Choy
authors.affiliation: Department of Rheumatology, King's College London, London, Cardiff Institute of Infection & Immunity, Cardiff University School of Medicine, Cardiff, MRC Clinical Trials Unit, Department of Rheumatology, Whipps Cross University Hospital, London, Rheumatology, Russells Hall Hospital, Dudley Group of Hospitals NHS Foundation Trust, Dudley, Department of Rheumatology, University College London Hospitals, London, Musculoskeletal Unit, Freeman Hospital, Newcastle, Department of Neurology, Walton Centre for Neurology and Neurosurgery, Liverpool, Department of Rheumatology, Queen's Hospital, Romford, Department of Neurology, The Queen Elizabeth Hospital Neuroscience Centre, Birmingham, UK, Department of Internal Medicine, Medical University of Debrecen, Debrecen, Hungary and Rheumatic Diseases Centre, Salford Royal NHS Foundation Trust, Manchester, UK.
authors.forename: Patrick
authors.initials: P
authors.lastname: Gordon
authors.affiliation: Department of Rheumatology, King's College London, London, Cardiff Institute of Infection & Immunity, Cardiff University School of Medicine, Cardiff, MRC Clinical Trials Unit, Department of Rheumatology, Whipps Cross University Hospital, London, Rheumatology, Russells Hall Hospital, Dudley Group of Hospitals NHS Foundation Trust, Dudley, Department of Rheumatology, University College London Hospitals, London, Musculoskeletal Unit, Freeman Hospital, Newcastle, Department of Neurology, Walton Centre for Neurology and Neurosurgery, Liverpool, Department of Rheumatology, Queen's Hospital, Romford, Department of Neurology, The Queen Elizabeth Hospital Neuroscience Centre, Birmingham, UK, Department of Internal Medicine, Medical University of Debrecen, Debrecen, Hungary and Rheumatic Diseases Centre, Salford Royal NHS Foundation Trust, Manchester, UK.
authors.forename: Caroline J
authors.initials: CJ
authors.lastname: Doré
authors.affiliation: Department of Rheumatology, King's College London, London, Cardiff Institute of Infection & Immunity, Cardiff University School of Medicine, Cardiff, MRC Clinical Trials Unit, Department of Rheumatology, Whipps Cross University Hospital, London, Rheumatology, Russells Hall Hospital, Dudley Group of Hospitals NHS Foundation Trust, Dudley, Department of Rheumatology, University College London Hospitals, London, Musculoskeletal Unit, Freeman Hospital, Newcastle, Department of Neurology, Walton Centre for Neurology and Neurosurgery, Liverpool, Department of Rheumatology, Queen's Hospital, Romford, Department of Neurology, The Queen Elizabeth Hospital Neuroscience Centre, Birmingham, UK, Department of Internal Medicine, Medical University of Debrecen, Debrecen, Hungary and Rheumatic Diseases Centre, Salford Royal NHS Foundation Trust, Manchester, UK.
authors.forename: Alan
authors.initials: A
authors.lastname: Hakim
authors.affiliation: Department of Rheumatology, King's College London, London, Cardiff Institute of Infection & Immunity, Cardiff University School of Medicine, Cardiff, MRC Clinical Trials Unit, Department of Rheumatology, Whipps Cross University Hospital, London, Rheumatology, Russells Hall Hospital, Dudley Group of Hospitals NHS Foundation Trust, Dudley, Department of Rheumatology, University College London Hospitals, London, Musculoskeletal Unit, Freeman Hospital, Newcastle, Department of Neurology, Walton Centre for Neurology and Neurosurgery, Liverpool, Department of Rheumatology, Queen's Hospital, Romford, Department of Neurology, The Queen Elizabeth Hospital Neuroscience Centre, Birmingham, UK, Department of Internal Medicine, Medical University of Debrecen, Debrecen, Hungary and Rheumatic Diseases Centre, Salford Royal NHS Foundation Trust, Manchester, UK.
authors.forename: George
authors.initials: G
authors.lastname: Kitas
authors.affiliation: Department of Rheumatology, King's College London, London, Cardiff Institute of Infection & Immunity, Cardiff University School of Medicine, Cardiff, MRC Clinical Trials Unit, Department of Rheumatology, Whipps Cross University Hospital, London, Rheumatology, Russells Hall Hospital, Dudley Group of Hospitals NHS Foundation Trust, Dudley, Department of Rheumatology, University College London Hospitals, London, Musculoskeletal Unit, Freeman Hospital, Newcastle, Department of Neurology, Walton Centre for Neurology and Neurosurgery, Liverpool, Department of Rheumatology, Queen's Hospital, Romford, Department of Neurology, The Queen Elizabeth Hospital Neuroscience Centre, Birmingham, UK, Department of Internal Medicine, Medical University of Debrecen, Debrecen, Hungary and Rheumatic Diseases Centre, Salford Royal NHS Foundation Trust, Manchester, UK.
authors.forename: David
authors.initials: D
authors.lastname: Isenberg
authors.affiliation: Department of Rheumatology, King's College London, London, Cardiff Institute of Infection & Immunity, Cardiff University School of Medicine, Cardiff, MRC Clinical Trials Unit, Department of Rheumatology, Whipps Cross University Hospital, London, Rheumatology, Russells Hall Hospital, Dudley Group of Hospitals NHS Foundation Trust, Dudley, Department of Rheumatology, University College London Hospitals, London, Musculoskeletal Unit, Freeman Hospital, Newcastle, Department of Neurology, Walton Centre for Neurology and Neurosurgery, Liverpool, Department of Rheumatology, Queen's Hospital, Romford, Department of Neurology, The Queen Elizabeth Hospital Neuroscience Centre, Birmingham, UK, Department of Internal Medicine, Medical University of Debrecen, Debrecen, Hungary and Rheumatic Diseases Centre, Salford Royal NHS Foundation Trust, Manchester, UK.
authors.forename: Bridget
authors.initials: B
authors.lastname: Griffiths
authors.affiliation: Department of Rheumatology, King's College London, London, Cardiff Institute of Infection & Immunity, Cardiff University School of Medicine, Cardiff, MRC Clinical Trials Unit, Department of Rheumatology, Whipps Cross University Hospital, London, Rheumatology, Russells Hall Hospital, Dudley Group of Hospitals NHS Foundation Trust, Dudley, Department of Rheumatology, University College London Hospitals, London, Musculoskeletal Unit, Freeman Hospital, Newcastle, Department of Neurology, Walton Centre for Neurology and Neurosurgery, Liverpool, Department of Rheumatology, Queen's Hospital, Romford, Department of Neurology, The Queen Elizabeth Hospital Neuroscience Centre, Birmingham, UK, Department of Internal Medicine, Medical University of Debrecen, Debrecen, Hungary and Rheumatic Diseases Centre, Salford Royal NHS Foundation Trust, Manchester, UK.
authors.forename: Bryan
authors.initials: B
authors.lastname: Lecky
authors.affiliation: Department of Rheumatology, King's College London, London, Cardiff Institute of Infection & Immunity, Cardiff University School of Medicine, Cardiff, MRC Clinical Trials Unit, Department of Rheumatology, Whipps Cross University Hospital, London, Rheumatology, Russells Hall Hospital, Dudley Group of Hospitals NHS Foundation Trust, Dudley, Department of Rheumatology, University College London Hospitals, London, Musculoskeletal Unit, Freeman Hospital, Newcastle, Department of Neurology, Walton Centre for Neurology and Neurosurgery, Liverpool, Department of Rheumatology, Queen's Hospital, Romford, Department of Neurology, The Queen Elizabeth Hospital Neuroscience Centre, Birmingham, UK, Department of Internal Medicine, Medical University of Debrecen, Debrecen, Hungary and Rheumatic Diseases Centre, Salford Royal NHS Foundation Trust, Manchester, UK.
authors.forename: Kuntal
authors.initials: K
authors.lastname: Chakravarty
authors.affiliation: Department of Rheumatology, King's College London, London, Cardiff Institute of Infection & Immunity, Cardiff University School of Medicine, Cardiff, MRC Clinical Trials Unit, Department of Rheumatology, Whipps Cross University Hospital, London, Rheumatology, Russells Hall Hospital, Dudley Group of Hospitals NHS Foundation Trust, Dudley, Department of Rheumatology, University College London Hospitals, London, Musculoskeletal Unit, Freeman Hospital, Newcastle, Department of Neurology, Walton Centre for Neurology and Neurosurgery, Liverpool, Department of Rheumatology, Queen's Hospital, Romford, Department of Neurology, The Queen Elizabeth Hospital Neuroscience Centre, Birmingham, UK, Department of Internal Medicine, Medical University of Debrecen, Debrecen, Hungary and Rheumatic Diseases Centre, Salford Royal NHS Foundation Trust, Manchester, UK.
authors.forename: John
authors.initials: J
authors.lastname: Winer
authors.affiliation: Department of Rheumatology, King's College London, London, Cardiff Institute of Infection & Immunity, Cardiff University School of Medicine, Cardiff, MRC Clinical Trials Unit, Department of Rheumatology, Whipps Cross University Hospital, London, Rheumatology, Russells Hall Hospital, Dudley Group of Hospitals NHS Foundation Trust, Dudley, Department of Rheumatology, University College London Hospitals, London, Musculoskeletal Unit, Freeman Hospital, Newcastle, Department of Neurology, Walton Centre for Neurology and Neurosurgery, Liverpool, Department of Rheumatology, Queen's Hospital, Romford, Department of Neurology, The Queen Elizabeth Hospital Neuroscience Centre, Birmingham, UK, Department of Internal Medicine, Medical University of Debrecen, Debrecen, Hungary and Rheumatic Diseases Centre, Salford Royal NHS Foundation Trust, Manchester, UK.
authors.forename: Katalin
authors.initials: K
authors.lastname: Danko
authors.affiliation: Department of Rheumatology, King's College London, London, Cardiff Institute of Infection & Immunity, Cardiff University School of Medicine, Cardiff, MRC Clinical Trials Unit, Department of Rheumatology, Whipps Cross University Hospital, London, Rheumatology, Russells Hall Hospital, Dudley Group of Hospitals NHS Foundation Trust, Dudley, Department of Rheumatology, University College London Hospitals, London, Musculoskeletal Unit, Freeman Hospital, Newcastle, Department of Neurology, Walton Centre for Neurology and Neurosurgery, Liverpool, Department of Rheumatology, Queen's Hospital, Romford, Department of Neurology, The Queen Elizabeth Hospital Neuroscience Centre, Birmingham, UK, Department of Internal Medicine, Medical University of Debrecen, Debrecen, Hungary and Rheumatic Diseases Centre, Salford Royal NHS Foundation Trust, Manchester, UK.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Cooper
authors.affiliation: Department of Rheumatology, King's College London, London, Cardiff Institute of Infection & Immunity, Cardiff University School of Medicine, Cardiff, MRC Clinical Trials Unit, Department of Rheumatology, Whipps Cross University Hospital, London, Rheumatology, Russells Hall Hospital, Dudley Group of Hospitals NHS Foundation Trust, Dudley, Department of Rheumatology, University College London Hospitals, London, Musculoskeletal Unit, Freeman Hospital, Newcastle, Department of Neurology, Walton Centre for Neurology and Neurosurgery, Liverpool, Department of Rheumatology, Queen's Hospital, Romford, Department of Neurology, The Queen Elizabeth Hospital Neuroscience Centre, Birmingham, UK, Department of Internal Medicine, Medical University of Debrecen, Debrecen, Hungary and Rheumatic Diseases Centre, Salford Royal NHS Foundation Trust, Manchester, UK.
authors.forename: Beverley
authors.initials: B
authors.lastname: White-Alao
authors.affiliation: Department of Rheumatology, King's College London, London, Cardiff Institute of Infection & Immunity, Cardiff University School of Medicine, Cardiff, MRC Clinical Trials Unit, Department of Rheumatology, Whipps Cross University Hospital, London, Rheumatology, Russells Hall Hospital, Dudley Group of Hospitals NHS Foundation Trust, Dudley, Department of Rheumatology, University College London Hospitals, London, Musculoskeletal Unit, Freeman Hospital, Newcastle, Department of Neurology, Walton Centre for Neurology and Neurosurgery, Liverpool, Department of Rheumatology, Queen's Hospital, Romford, Department of Neurology, The Queen Elizabeth Hospital Neuroscience Centre, Birmingham, UK, Department of Internal Medicine, Medical University of Debrecen, Debrecen, Hungary and Rheumatic Diseases Centre, Salford Royal NHS Foundation Trust, Manchester, UK.
authors.forename: David L
authors.initials: DL
authors.lastname: Scott
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D016572:Cyclosporine / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D009220:Myositis / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D008727:Methotrexate
keywords: DMARDs therapies; basic and clinical sciences; clinical trials and methods; immunosuppressant therapies; myositis and muscle disease; psychology and social phenomena; quality of life; rheumatic diseases