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Meta-Analysis
. 2012 Aug 15;2012(8):CD003643.
doi: 10.1002/14651858.CD003643.pub4.

Immunosuppressant and immunomodulatory treatment for dermatomyositis and polymyositis

Patrick A Gordon  1 , John B Winer, Jessica E Hoogendijk, Ernest H S Choy
Affiliations
Meta-Analysis

Immunosuppressant and immunomodulatory treatment for dermatomyositis and polymyositis

Patrick A Gordon et al. Cochrane Database Syst Rev. .

Abstract

Background: Idiopathic inflammatory myopathies are chronic diseases with significant mortality and morbidity. Whilst immunosuppressive and immunomodulatory therapies are frequently used, the optimal therapeutic regimen remains unclear. This is an update of a review first published in 2005.

Objectives: To assess the effects of immunosuppressants and immunomodulatory treatments for dermatomyositis and polymyositis.

Search methods: We searched the Cochrane Neuromuscular Disease Group Specialized Register (August 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 3 2011), MEDLINE (January 1966 to August 2011), EMBASE (January 1980 to August 2011) and clinicaltrials.gov (August 2011). We checked the bibliographies of identified trials and wrote to disease experts.

Selection criteria: We included all randomised controlled trials (RCTs) or quasi-RCTs involving participants 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. In participants without a classical rash of dermatomyositis, inclusion body myositis should have been excluded by muscle biopsy. We considered any immunosuppressant or immunomodulatory treatment. The two primary outcomes were the change in a function or disability scale measured as the proportion of participants improving one grade, two grades etc, predefined based on the scales used in the studies after at least six months, and a 15% or greater improvement in muscle strength compared with baseline after at least six months. Other outcomes were: the International Myositis Assessment and Clinical Studies Group (IMACS) definition of improvement, number of relapses and time to relapse, remission and time-to-remission, cumulative corticosteroid dose and serious adverse effects.

Data collection and analysis: Two authors independently selected papers, extracted data and assessed risk of bias in included studies. They collected adverse event data from the included studies.

Main results: The review authors identified fourteen 14 relevant RCTs. They excluded four trials.The 10 included studies, four of which have been added in this update, included a total of 258 participants. Six studies compared an immunosuppressant or immunomodulator with placebo control, and four studies compared two immunosuppressant regimes with each other. Most of the studies were small (the largest had 62 participants) and many of the reports contained insufficient information to assess risk of bias.Amongst the six studies comparing immunosuppressant with placebo, one study, investigating intravenous immunoglobulin (IVIg), showed statistically significant improvement in scores of muscle strength in the IVIg group over three months. Another study investigating etanercept showed some evidence of a steroid sparing effect, a secondary outcome in this review, but no improvement in other assessed outcomes. The other four randomised placebo-controlled trials assessed either plasma exchange and leukapheresis, eculizumab, infliximab or azathioprine against placebo and all produced negative results.Three of the four studies comparing two immunosuppressant regimes (azathioprine with methotrexate, ciclosporin with methotrexate, and intramuscular methotrexate with oral methotrexate plus azathioprine) showed no statistically significant difference in efficacy between the treatment regimes. The fourth study comparing pulsed oral dexamethasone with daily oral prednisolone and found that the dexamethasone regime had a shorter median time to relapse but fewer side effects.Immunosuppressants were associated with significant side effects.

Authors' conclusions: This systematic review highlights the lack of high quality RCTs that assess the efficacy and toxicity of immunosuppressants in inflammatory myositis.

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Conflict of interest statement

Professor Ernest Choy has received research grants, and served as member of advisory boards and speaker bureaus of Abbott Laboratories, Allergan, AstraZeneca, Boehringer Ingelheim, Chelsea Therapeutics, Chugai Pharma, Eli Lilly, Ferring Pharmacuetical, GSK, Jazz Pharmaceuticals, MedImmune, Merrimack Pharmaceutical, MSD, Pfizer, Pierre Fabre Medicament, Roche, Schering Plough, Synovate, UCB Celltech and Wyeth.

Dr Patrick Gordon's institution has received grants for three of the studies in this review. One was an excluded study (Chung 2007), funded by various non‐commercial grant‐giving bodies and two are ongoing studies, one funded by Bristol Myers Squibb and the Myositis Support Group (NCT01315938) and the other by the Arthritis Research Campaign (SELAM, ISRCTN40085050). Dr John Winer is a collaborator in the SELAM trial. Bristol Myers Squibb funded Dr Gordon's attendance at EULAR 2011 and 2012 (money paid to institution).

Dr Jessica Hoogendijk is co‐author of a RCT in this review (Van de Vlekkert 2010). She has no other known conflicts of interest.

Dr John Winer's institution undertook an audit of IVIg side effects and received payment for travel and equipment from CSL Behring. He has been involved in an, as yet, unpublished trial of methotrexate and azathioprine for polymyositis and dermatomyositis (Miller 2002).

Figures

1
1
Methodological quality summary: review authors' judgments about each methodological quality item for each included study.
1.1
1.1. Analysis
Comparison 1 IVIg versus placebo, Outcome 1 Improvement in manual muscle strength by ≧15% at 12 weeks.
2.1
2.1. Analysis
Comparison 2 Azathioprine versus placebo, Outcome 1 Improvement in muscle strength.
3.1
3.1. Analysis
Comparison 3 Plasma exchange or leukapheresis versus placebo, Outcome 1 Number of patients who improved after treatment.
4.1
4.1. Analysis
Comparison 4 Infliximab versus placebo, Outcome 1 Improvement in manual muscle strength by ≧15% at 16 weeks.
4.2
4.2. Analysis
Comparison 4 Infliximab versus placebo, Outcome 2 Improved by IMACS criteria at 16 weeks.
5.1
5.1. Analysis
Comparison 5 Ciclosporin versus methotrexate, Outcome 1 Improvement in 'Muscle endurance with functional test' measurement at 6 months (maximum score 56).
5.2
5.2. Analysis
Comparison 5 Ciclosporin versus methotrexate, Outcome 2 Improvement in 'Clinical Assessment' score at 6 months (maximum score 33).
5.3
5.3. Analysis
Comparison 5 Ciclosporin versus methotrexate, Outcome 3 Improvement in global patient's assessment at 6 months (0 to 10).
6.1
6.1. Analysis
Comparison 6 Oral methotrexate with azathioprine versus intravenous methotrexate with leucovorin rescue, Outcome 1 Improvement as defined by 'combined evaluation of strength and function' tool.
7.1
7.1. Analysis
Comparison 7 Etanercept versus placebo, Outcome 1 Mean change in Health Assessment Questionnaire score at 52 weeks.
7.2
7.2. Analysis
Comparison 7 Etanercept versus placebo, Outcome 2 Mean change in Health Assessment Questionnaire score at 24 weeks.
7.3
7.3. Analysis
Comparison 7 Etanercept versus placebo, Outcome 3 Achieving the International Myositis Assessment and Clinical Studies Group (IMACS) definitions of improvement at 24 weeks.
7.4
7.4. Analysis
Comparison 7 Etanercept versus placebo, Outcome 4 Achieving the International Myositis Assessment and Clinical Studies Group (IMACS) definitions of improvement at 52 weeks.
7.5
7.5. Analysis
Comparison 7 Etanercept versus placebo, Outcome 5 Cumulative dosage of prednisone over the one‐year study period  .
7.6
7.6. Analysis
Comparison 7 Etanercept versus placebo, Outcome 6 Average change in time (sec) to walk 30 feet comparing performance at baseline to week 52.
7.7
7.7. Analysis
Comparison 7 Etanercept versus placebo, Outcome 7 Average change in time to rise from a chair from baseline to week 52  .
7.8
7.8. Analysis
Comparison 7 Etanercept versus placebo, Outcome 8 Treatment failure.
7.9
7.9. Analysis
Comparison 7 Etanercept versus placebo, Outcome 9 Individualized Neuromuscular Quality of Life.
7.10
7.10. Analysis
Comparison 7 Etanercept versus placebo, Outcome 10 SF‐36 Physical Component Summary Score.
8.1
8.1. Analysis
Comparison 8 Pulse oral dexamethasone versus daily oral prednisolone, Outcome 1 Neuromuscular Symptom Score.
8.2
8.2. Analysis
Comparison 8 Pulse oral dexamethasone versus daily oral prednisolone, Outcome 2 Remission.
8.3
8.3. Analysis
Comparison 8 Pulse oral dexamethasone versus daily oral prednisolone, Outcome 3 Relapse.
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References

References to studies included in this review

Bunch 1980 {published data only}
    1. Bunch TW, Worthington JW, Combs JJ, Ilstrup MS, Engel AG. Azathioprine with prednisone for polymyositis. Annals of Internal Medicine 1980;92(3):365‐9. [PUBMED: 6986827] - PubMed
Coyle 2008 {published data only}
    1. Coyle K, Pokrovnichka A, French K, Joe G, Shrader J, Swan L, et al. A randomized, double‐blind, placebo‐controlled trial of infliximab in patients with polymyositis and dermatomyositis. Arthritis and Rheumatism 2008;58(Suppl):Abstract No: 2058.
Dalakas 1993 {published data only}
    1. Dalakas MC, Illa I, Dambrosia JM, Soueidan SA, Stein DP, Otero C, et al. A controlled trial of high‐dose intravenous immune globulin infusions as treatment for dermatomyositis. New England Journal of Medicine 1993;329(27):1993‐2000. [PUBMED: 8247075] - PubMed
Miller 1992 {published data only}
    1. Miller FW, Leitman SF, Cronin ME, Hicks JE, Leff RL, Wesley R, et al. Controlled trial of plasma exchange and leukapheresis in polymyositis and dermatomyositis. New England Journal of Medicine 1992;326(21):1380‐4. [PUBMED: 1472183] - PubMed
Miller 2002 {published and unpublished data}
    1. Miller J, Walsh Y, Saminaden S, Lecky BRF, Winer JB. Randomised double blind controlled trial of methotrexate and steroids compared with azathioprine and steroids in the treatment of idiopathic inflammatory myopathy. Journal of the Neurological Sciences 2002;199(Suppl 1):S53.
Muscle Study Group 2011 {published data only}
    1. Muscle Study Group. A randomized, pilot trial of etanercept in dermatomyositis. Annals of Neurology 2011;70(3):427‐36. [PUBMED: 21688301] - PMC - PubMed
    1. NCT00112385. A pilot study of etanercept in dermatomyositis. http://clinicaltrials.gov/ct2/show/results/NCT00112385 (accessed 5 July 2012).
Takada 2002 {published data only}
    1. Takada K, Bookbinder S, Furie R, Oddis C, Mojcik C, Bombara M, et al. A pilot study of eculizumab in patients with dermatomyositis. Arthritis and Rheumatism 2002;46 (Suppl):S489.
Van de Vlekkert 2010 {published data only}
    1. Vlekkert J, Hoogendijk JE, Haan RJ, Algra A, Tweel I, Pol WL, et al. Oral dexamethasone pulse therapy versus daily prednisolone in sub‐acute onset myositis, a randomised clinical trial. Neuromuscular Disorders 2010;20(6):382‐9. [PUBMED: 20423755] - PubMed
Vencovsky 2000 {published data only}
    1. Vencovský J, Jarosová K, Machácek S, Studýnková J, Kafková J, Bartůnková J, et al. Cyclosporine A versus methotrexate in the treatment of polymyositis and dermatomyositis. Scandinavian Journal of Rheumatology 2000;29(2):95‐102. [PUBMED: 10777122] - PubMed
Villalba 1998 {published data only}
    1. Villalba L, Hicks JE, Adams EM, Sherman JB, Gourley MF, Leff RL, et al. Treatment of refractory myositis: a randomized crossover study of two new cytotoxic regimens. Arthritis and Rheumatism 1998;41(3):392‐9. - PubMed

References to studies excluded from this review

Bunch 1981 {published data only}
    1. Bunch TW. Prednisone and azathioprine for polymyositis: long‐term follow up. Arthritis and Rheumatism 1981;24(1):45‐8. - PubMed
Chung 2007 {published data only}
    1. Chung Y, Alexanderson H, Pipitone N, Morrison C, Dastmalchi M, Ståhl‐Hallengren C, et al. Creatine supplements in patients with idiopathic inflammatory myopathies who are clinically weak after conventional pharmacologic treatment: Six‐month, double‐blind, randomized, placebo‐controlled trial. Arthritis and Rheumatism 2007;57:694‐702. - PubMed
Donov 1995 {published data only}
    1. Donov G, Kartasheva V, Fomenko T. Experimental use of plasmapheresis in juvenile dermatomyositis therapy. Clinical & Experimental Rheumatology 1995;13 Suppl 13:561.
Fries 1973 {published data only}
    1. Fries JF, Sharp GC, McDevitt HO, Holman HR. Cyclophosphamide therapy in systemic lupus erythematosus and polymyositis. Arthritis and Rheumatism 1973;16(2):154‐62. [PUBMED: 4716431] - PubMed

References to ongoing studies

ISRCTN40085050 {unpublished data only}
    1. ISRCTN40085050. Second line agents in myositis. http://www.controlled‐trials.com/ISRCTN40085050 (accessed 16 March 2012).
NCT00001261 {published data only}
    1. NCT00001261. Intravenousimmunoglobulin (IVIg) for the treatment of inflammatory myopathies. http://clinicaltrials.gov/ct2/show/NCT00001261 (accessed 16 March 2012).
NCT00035958 {published data only}
    1. NCT00035958. Understanding the pathogenesis and treatment of childhood onset dermatomyositis. http://clinicaltrials.gov/ct2/show/NCT00035958 (accessed 16 March 2012).
NCT00106184 {published data only}
    1. NCT00106184. Rituximab for the treatment of refractory adult and juvenile dermatomyositis (DM) and adult polymyositis (PM). http://clinicaltrials.gov/ct2/show/NCT00106184 (accessed 16 March 2012).
NCT00323960 {published data only}
    1. NCT00323960. Five‐year actively controlled clinical trial in new onset juvenile dermatomyositis (PRINTOJDMTR). http://clinicaltrials.gov/ct2/show/NCT00323960 (accessed 16 March 2012).
NCT00335985 {published data only}
    1. NCT00335985. Efficacy and safety study of GB‐0998 for treatment of steroid‐resistant polymyositis and dermatomyositis (PM/DM). http://clinicaltrials.gov/ct2/show/NCT00335985 (accessed 16 March 2012).
NCT00533091 {published data only}
    1. NCT00533091. A study to evaluate safety of multi‐dose MEDI‐545 in adult patients with dermatomyositis or polymyositis. http://clinicaltrials.gov/ct2/show/NCT00533091 (accessed 16 March 2012).
NCT00651040 {published data only}
    1. NCT00651040. Combined treatment of methotrexate + glucocorticoids versus glucocorticoids alone in patients with polymyositis and dermatomyositis (Prometheus). http://clinicaltrials.gov/ct2/show/NCT00651040 (accessed 16 March 2012).
NCT01148810 {published data only}
    1. NCT01148810. Efficacy and tolerability of BAF312 in patients with polymyositis and dermatomyositis. http://clinicaltrials.gov/ct2/show/NCT01148810 (accessed 16 March 2012).
NCT01315938 {published data only}
    1. NCT01315938. Abatacept treatment in polymyositis and dermatomyositis (ARTEMIS). http://clinicaltrials.gov/ct2/show/NCT01315938 (accessed 16 March 2012).

Additional references

Ahlstrom 1993
    1. Ahlstrom G, Gunnarsson LG, Leissner P, Sjoden PO. Epidemiology of neuromuscular diseases, including the postpolio sequelae, in a Swedish county. Neuroepidemiology 1993;12(5):262‐9. - PubMed
Bohan 1975 a
    1. Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). New England Journal of Medicine 1975;292(7):344‐7. - PubMed
Bohan 1975 b
    1. Bohan A, Peter JB. Polymyositis and dermatomyositis (second of two parts). New England Journal of Medicine 1975;292(8):403‐7. - PubMed
Carpenter 1977
    1. Carpenter JR, Bunch TW, Engel AG, O'Brien PC. Survival in polymyositis: corticosteroids and risk factors. Journal of Rheumatology 1977;4(2):207‐14. - PubMed
Choy 2002
    1. Choy EH, Isenberg DA. Treatment of dermatomyositis and polymyositis. Rheumatology 2002;41(1):7‐13. - PubMed
Dalakas 1991
    1. Dalakas MC. Polymyositis, dermatomyositis, and inclusion‐body myositis. New England Journal of Medicine 1991;325(21):1487‐98. - PubMed
Dalakas 2001
    1. Dalakas MC. Progress in inflammatory myopathies: good but not good enough. Journal of Neurology, Neurosurgery and Psychiatry 2001;70(5):569‐73. - PMC - PubMed
Higgins 2011
    1. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Hoogendijk 2004
    1. Hoogendijk JE, Amato AA, Lecky BR, Choy EH, Lundberg IE, Rose MR, et al. 119th ENMC international workshop: trial design in adult idiopathic inflammatory myopathies, with the exception of inclusion body myositis, 10‐12 October 2003, Naarden, The Netherlands. Neuromuscular Disorders 2004;14(5):337‐45. - PubMed
Isenberg 2004
    1. Isenberg D A, Allen E, Farewell V, Ehrenstein MR, Hanna M G, Lundberg IE, et al for the International Myositis and Clinical Studies Group (IMACS). International consensus outcome measures for patients with idiopathic inflammatory myopathies. Development and initial validation of myositis activity and damage indices in patients with adult onset disease. Rheumatology 2004;43(1):49‐54. - PubMed
Joffe 1993
    1. Joffe MM, Love L, Leff RL, Fraser DD, Targoff IN, Hicks JE, et al. Drug therapy of the idiopathic inflammatory myopathies: predictors of response to prednisone, azathioprine and methotrexate and a comparison of their efficacy. American Journal of Medicine 1993;94(4):379‐87. - PubMed
Oddis 2005
    1. Oddis CV, Rider LG, Reed AM, Ruperto N, Brunner HI, Koneru B, et al. International Myositis Assessment and Clinical Studies Group. International consensus guidelines for trials of therapies in the idiopathic inflammatory myopathies. Arthritis and Rheumatism 2005;52(9):2607‐15. - PubMed
RevMan 2011 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.1. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2011.
Riddoch 1975
    1. Riddoch D, Morgan‐Hughes JA. Prognosis in adult polymyositis. Journal of the Neurological Sciences 1975;26(1):71‐80. - PubMed
Rider 2004
    1. Rider LG, Giannini EH, Brunner HI, Ruperto N, James‐Newton L, Reed AM, et al. International Myositis Assessment and Clinical Studies Group. International consensus on preliminary definitions of improvement in adult and juvenile myositis. Arthritis and Rheumatism 2004;50(7):2281‐90. - PubMed
Van de Vlekkert 2004
    1. Vlekkert J, Tjin‐A‐Ton ML, Hoogendijk JE. Quality of myositis case reports open to improvement. Arthritis and Rheumatism 2004;51(1):148‐50. - PubMed
Van Swieten 1988
    1. Swieten JC, Koudstaal PJ, Visser MC, Schouten HJ, Gijn J. Interobserver agreement for the assessment of handicap in stroke patients. Stroke 1988;19(5):604‐7. - PubMed

References to other published versions of this review

Choy 2005
    1. Choy EHS, Winer J, Lecky B, Hoogendik J. Immunosuppressant and immunomodulatory treatment for dermatomyositis and polymyositis. Cochrane Database of Systematic Reviews 2005, Issue 2. [DOI: 10.1002/14651858.CD003643] - DOI - PubMed
Choy 2005b
    1. Choy EHS, Hoogendijk JE, Lecky B, Winer JB. Immunosuppressant and immunomodulatory treatment for dermatomyositis and polymyositis. Cochrane Database of Systematic Reviews 2005, Issue 3. [DOI: 10.1002/14651858.CD003643.pub2] - DOI - PubMed
Choy 2009
    1. Choy EHS, Hoogendijk JE, Lecky B, Winer JB, Gordon P. Immunosuppressant and immunomodulatory treatment for dermatomyositis and polymyositis. Cochrane Database of Systematic Reviews 2009, Issue 4. [DOI: 10.1002/14651858.CD003643.pub3] - DOI - PubMed

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