Second-line agents in myositis: 1-year factorial trial of additional immunosuppression in patients who have partially responded to steroids

Fowzia Ibrahim, Ernest Choy, Patrick Gordon, Caroline J. Doré, Alan Hakim, George Kitas, David Isenberg, Bridget Griffiths, Bryan Lecky, Kuntal Chakravarty, John Winer, K. Dankó, Robert G. Cooper, Beverley White-Alao, David L. Scott

Research output: Contribution to journalArticle

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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.

CONCLUSION: Neither MTX nor ciclosporin (by themselves or in combination) improved clinical features in myositis patients who had incompletely responded to glucocorticoids.

TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number Register; http://www.controlled-trials.com/; ISRCTN40085050.

Original languageEnglish
Pages (from-to)1050-1055
Number of pages6
JournalRheumatology (Oxford, England)
Volume54
Issue number6
DOIs
Publication statusPublished - Jun 1 2015

Fingerprint

Myositis
Immunosuppression
Cyclosporine
Steroids
Randomized Controlled Trials
Placebos
Glucocorticoids
Therapeutics
Intention to Treat Analysis
Lost to Follow-Up
Walking
Adrenal Cortex Hormones
Muscles

Keywords

  • basic and clinical sciences
  • clinical trials and methods
  • DMARDs therapies
  • immunosuppressant therapies
  • myositis and muscle disease
  • psychology and social phenomena
  • quality of life
  • rheumatic diseases

ASJC Scopus subject areas

  • Rheumatology
  • Pharmacology (medical)

Cite this

Second-line agents in myositis : 1-year factorial trial of additional immunosuppression in patients who have partially responded to steroids. / Ibrahim, Fowzia; Choy, Ernest; Gordon, Patrick; Doré, Caroline J.; Hakim, Alan; Kitas, George; Isenberg, David; Griffiths, Bridget; Lecky, Bryan; Chakravarty, Kuntal; Winer, John; Dankó, K.; Cooper, Robert G.; White-Alao, Beverley; Scott, David L.

In: Rheumatology (Oxford, England), Vol. 54, No. 6, 01.06.2015, p. 1050-1055.

Research output: Contribution to journalArticle

Ibrahim, F, Choy, E, Gordon, P, Doré, CJ, Hakim, A, Kitas, G, Isenberg, D, Griffiths, B, Lecky, B, Chakravarty, K, Winer, J, Dankó, K, Cooper, RG, White-Alao, B & Scott, DL 2015, 'Second-line agents in myositis: 1-year factorial trial of additional immunosuppression in patients who have partially responded to steroids', Rheumatology (Oxford, England), vol. 54, no. 6, pp. 1050-1055. https://doi.org/10.1093/rheumatology/keu442
Ibrahim, Fowzia ; Choy, Ernest ; Gordon, Patrick ; Doré, Caroline J. ; Hakim, Alan ; Kitas, George ; Isenberg, David ; Griffiths, Bridget ; Lecky, Bryan ; Chakravarty, Kuntal ; Winer, John ; Dankó, K. ; Cooper, Robert G. ; White-Alao, Beverley ; Scott, David L. / Second-line agents in myositis : 1-year factorial trial of additional immunosuppression in patients who have partially responded to steroids. In: Rheumatology (Oxford, England). 2015 ; Vol. 54, No. 6. pp. 1050-1055.
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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.CONCLUSION: Neither MTX nor ciclosporin (by themselves or in combination) improved clinical features in myositis patients who had incompletely responded to glucocorticoids.TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number Register; http://www.controlled-trials.com/; ISRCTN40085050.",
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AU - Ibrahim, Fowzia

AU - Choy, Ernest

AU - Gordon, Patrick

AU - Doré, Caroline J.

AU - Hakim, Alan

AU - Kitas, George

AU - Isenberg, David

AU - Griffiths, Bridget

AU - Lecky, Bryan

AU - Chakravarty, Kuntal

AU - Winer, John

AU - Dankó, K.

AU - Cooper, Robert G.

AU - White-Alao, Beverley

AU - Scott, David L.

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N2 - 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.CONCLUSION: Neither MTX nor ciclosporin (by themselves or in combination) improved clinical features in myositis patients who had incompletely responded to glucocorticoids.TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number Register; http://www.controlled-trials.com/; ISRCTN40085050.

AB - 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.CONCLUSION: Neither MTX nor ciclosporin (by themselves or in combination) improved clinical features in myositis patients who had incompletely responded to glucocorticoids.TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number Register; http://www.controlled-trials.com/; ISRCTN40085050.

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