Immunosuppressant and immunomodulatory treatment for dermatomyositis and polymyositis

Patrick A Gordon; John B Winer; Jessica E Hoogendijk; Ernest HS Choy

doi:10.1002/14651858.CD003643.pub4

. 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 ², Jessica E Hoogendijk ³, Ernest HS Choy ⁴

Editor: Cochrane Neuromuscular Group

PMCID: PMC7144740 PMID: 22895935

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

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 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 longer median time to relapse in the etanercept group, 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.

Plain language summary

Drugs that suppress or modify the immune system for dermatomyositis and polymyositis

Dermatomyositis and polymyositis are long‐term inflammatory muscle diseases, causing muscle weakness and disability. For some reason, the body's immune system turns against its own muscles in an autoimmune response. Corticosteroids are the principal treatment but due to side effects, there is a need for additional treatment with drugs that suppress the immune system (immunosuppressants) or modify it (immunomodulatory therapies) to improve patient outcomes. For this review, an update of a review first published in 2005, we found ten randomised trials available, involving 258 participants.

Most of the studies were small (the largest had 62 participants) and many of the reports contained insufficient information to assess risk of bias. Immunosuppressants were associated with significant side effects. The small number of RCTs of immunosuppressants and immunomodulatory therapies are inadequate to decide whether these agents are beneficial in dermatomyositis and polymyositis. Two small trials, one of IVIg in dermatomyositis, the other of etanercept in dermatomyositis suggested that they are beneficial. More RCTs are needed.

Background

The inflammatory myopathies include recognised causes of muscle inflammation such as those due to infection by bacteria, viruses and parasites. Idiopathic inflammatory myopathies refer to diseases in which muscle inflammation occurs without a recognised infective cause and these include dermatomyositis and polymyositis. Such diseases are thought to result from an auto‐immune process. Dermatomyositis and polymyositis are characterised by chronic inflammation of skeletal muscle which can result in persisting muscle weakness with significant disability (Dalakas 1991; Dalakas 2001). They may both occur in association with gastrointestinal, pulmonary and cardiac dysfunction, while only dermatomyositis has skin involvement. The prevalence of idiopathic inflammatory myositis is approximately 11 per 100,000 (Ahlstrom 1993). As idiopathic inflammatory myositis is uncommon, optimal therapy has not been adequately defined (Choy 2002).

Corticosteroids are the principal treatment. Both high‐ and low‐dose corticosteroid regimes are used. In many people, long‐term high dose corticosteroids are necessary to control disease and, in a few people, myositis may be refractory to steroid treatment. Therefore, many people with an idiopathic inflammatory myopathy suffer from the side effects of corticosteroids. The mortality and morbidity of inflammatory myositis remains high despite such treatment (Carpenter 1977; Joffe 1993; Riddoch 1975). Thus, there is a frequent need to use additional treatment both to improve the disease response and to reduce the side effects of corticosteroids.

Immunosuppressive agents, especially azathioprine, methotrexate, mycophenolate mofetil and ciclosporin, are commonly used in autoimmune diseases as well as in transplant rejection and chronic inflammatory diseases. They are usually employed as second‐line therapy to corticosteroids for disease refractory to steroid treatment alone. They can also be used as adjuvants to steroid treatment to allow reduction in the dosage of corticosteroids and thereby decrease the risk of long‐term complications. While these treatments are in use for dermatomyositis and polymyositis, the optimal therapeutic regimen remains unclear (Choy 2002). Biological agents, in particular the anti‐TNF agents and the B‐cell depleting agent rituximab, are also presently being assessed as potential therapeutic agents in the inflammatory myopathies.

An alternative approach to improving the treatment of dermatomyositis and polymyositis is the use of immunomodulatory therapy. This includes interferon, intravenous immunoglobulin (IVIg) and plasma exchange which have proven efficacy in various autoimmune disorders. They are gaining attention as possible second‐line treatment for polymyositis and dermatomyositis (Choy 2002; Dalakas 2001).

This is an update of a Cochrane review first published in 2005.

Objectives

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

Methods

Criteria for considering studies for this review

Types of studies

Randomised controlled trials (RCTs) or quasi‐RCTs (trials in which allocation is not strictly random but is based, for example, on case record number or date of birth).

Types of participants

People with probable or definite dermatomyositis and polymyositis as defined by the criteria of Bohan and Peter (Bohan 1975 a; Bohan 1975 b) (Table 1) or definite, probable or mild/early by the criteria of Dalakas (Dalakas 1991) (Table 2). In participants without a classical rash of dermatomyositis, inclusion body myositis should have been excluded by muscle biopsy. If no diagnostic criteria were cited, all the assessors would have judged the quality of evidence for correct diagnosis. The study was included in the review only if the assessors agreed that the participants had probable or definite dermatomyositis or polymyositis.

1. Bohan and Peter criteria.

Features	Polymyositis	Dermatomyositis
1. Symmetrical proximal muscle weakness	Definite: all 1‐4	Definite: 5 plus any 3 of 1‐4
2. Muscle biopsy evidence of myositis	Probable: any 3 of 1‐4	Probable: 5 plus any 2 of 1‐4
3. Elevation in serum skeletal muscle enzymes	Possible: any 2 of 1‐4	Possible: 5 plus any 1 of 1‐4
4. Characteristic electromyographic pattern of myositis
5. Typical rash of dermatomyositis

Features	Definite PM	Probable PM	Definite DM	Mild/early DM
Muscle strength	Myopathic muscle weakness	Myopathic muscle weakness	Myopathic muscle weakness	Seemingly normal strength
Electromyographic findings	Myopathic	Myopathic	Myopathic	Myopathic or non‐specific
Muscle enzymes	Elevated (up to 50‐fold)	Elevated (up to 50‐fold)	Elevated (up to 50‐fold) or normal	Elevated (up to 10‐fold) or normal
Muscle‐biopsy findings	Diagnostic for this type of inflammatory myopathy	Non‐specific myopathy without signs of primary inflammation	Diagnostic	Non‐specific or diagnostic
Rash or calcinosis	Absent	Absent	Present	Present

IVIg versus placebo for dermatomyositis
Patient or population: patients with dermatomyositis and polymyositis  Settings:   Intervention: IVIg versus placebo
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect  (95% CI)	No of Participants  (studies)	Quality of the evidence  (GRADE)	Comments
	Assumed risk	Corresponding risk
	Placebo	IVIg
15% or greater improvement in muscle strength compared with baseline after at least six months	See comment	See comment	Not estimable	‐	See comment	No data available, only one study of three months duration
Achieving the International Myositis Assessment and Clinical Studies Group (IMACS) definitions of improvement	See comment	See comment	Not estimable	‐	See comment	Not measured
Change in function or disability scale at six months	See comment	See comment	Not estimable	‐	See comment	Although an activities of daily living score was assessed, the results in the 2 groups were not reported systematically and statistical comparison between the 2 groups was not reported.
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).  CI: confidence interval; IVIg: intravenous immunoglobilin
GRADE Working Group grades of evidence  High quality: Further research is very unlikely to change our confidence in the estimate of effect.  Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.  Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.  Very low quality: We are very uncertain about the estimate.

Azathioprine versus placebo for dermatomyositis and polymyositis
Patient or population: patients with dermatomyositis and polymyositis  Settings:   Intervention: azathioprine
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect  (95% CI)	No of Participants  (studies)	Quality of the evidence  (GRADE)	Comments
	Assumed risk	Corresponding risk
	Placebo	Azathioprine
15% or greater improvement in muscle strength compared with baseline after at least six months. ‐ not measured	See comment	See comment	Not estimable	‐	See comment	No data as study only lasted three months
Achieving the International Myositis Assessment and Clinical Studies Group (IMACS) definitions of improvement ‐ not measured	See comment	See comment	Not estimable	‐	See comment	Not measured
Change in function or disability scale at six months ‐ not measured	See comment	See comment	Not estimable	‐	See comment	Not measured
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).  CI: confidence interval
GRADE Working Group grades of evidence  High quality: Further research is very unlikely to change our confidence in the estimate of effect.  Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.  Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.  Very low quality: We are very uncertain about the estimate.

Azathioprine plus prednisolone compared with methotrexate plus prednisolone for polymyositis or dermatomyositis
Patient or population: patients with polymyositis or dermatomyositis Settings: Intervention: prednisolone plus either azathioprine 2.5 mg per kg daily Comparison: prednisolone plus methotrexate 15 mg weekly for 1 year
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect  (95% CI)	No of Participants  (studies)	Quality of the evidence  (GRADE)	Comments
	Assumed risk	Corresponding risk
	Low dose methotrexate	Azathioprine
15% or greater improvement in muscle strength compared with baseline after at least 6 months ‐ not reported	See comment	See comment	Not estimable	‐	‐	Hand‐held myometry used but data not provided
Achieving the International Myositis Assessment and Clinical Studies Group (IMACS) definitions of improvement at 52 weeks ‐ not measured	See comment	See comment	Not estimable	‐	‐	Not measured
Change in function or disability scale at 6 months ‐ not reported	See comment	See comment	Not estimable	‐	‐	Timed walk was measured but data not available
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).  CI: confidence interval; RR: risk ratio
GRADE Working Group grades of evidence  High quality: Further research is very unlikely to change our confidence in the estimate of effect.  Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.  Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.  Very low quality: We are very uncertain about the estimate.

Plasma exchange or leukapheresis versus placebo for dermatomyositis and polymyositis
Patient or population: patients with dermatomyositis and polymyositis  Settings:   Intervention: plasma exchange or leukapheresis versus placebo
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect  (95% CI)	No of Participants  (studies)	Quality of the evidence  (GRADE)	Comments
	Assumed risk	Corresponding risk
	Placebo	Plasma exchange or leukapheresis
15% or greater improvement in muscle strength compared with baseline after at least six months ‐ not measured	See comment	See comment	Not estimable	‐	See comment	One study of only one month duration.
Achieving the International Myositis Assessment and Clinical Studies Group (IMACS) definitions of improvement ‐ not measured	See comment	See comment	Not estimable	‐	See comment	Not measured
Change in function or disability scale at six months¹ ‐ not measured	See comment	See comment	Not estimable	‐	See comment	One study of only 1 month duration.
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).  CI: confidence interval
GRADE Working Group grades of evidence  High quality: Further research is very unlikely to change our confidence in the estimate of effect.  Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.  Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.  Very low quality: We are very uncertain about the estimate.

Oral methotrexate with azathioprine versus intravenous methotrexate with leucovorin rescue for dermatomyositis and polymyositis
Patient or population: patients with dermatomyositis and polymyositis  Settings:   Intervention: oral methotrexate with azathioprine  Comparison: intravenous methotrexate with leucovorin rescue
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect  (95% CI)	No of Participants  (studies)	Quality of the evidence  (GRADE)	Comments
	Assumed risk	Corresponding risk
	Intravenous methotrexate with leucovorin rescue	Oral methotrexate with azathioprine
15% or greater improvement in muscle strength compared with baseline after at least six months ‐ not reported	See comment	See comment	Not estimable	‐	See comment	One study of 1 month's duration
Achieving the International Myositis Assessment and Clinical Studies Group (IMACS) definitions of improvement ‐ not measured	See comment	See comment	Not estimable	‐	See comment	No data
Change in function or disability scale at six months ‐ not reported	See comment	See comment	Not estimable	‐	See comment	No data available. Activities of daily living score was measured but the results were only presented in participants who improved according to the trial definition
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).  CI: confidence interval
GRADE Working Group grades of evidence  High quality: Further research is very unlikely to change our confidence in the estimate of effect.  Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.  Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.  Very low quality: We are very uncertain about the estimate.

Methotrexate versus ciclosporin for dermatomyositis and polymyositis
Patient or population: patients with dermatomyositis and polymyositis  Settings:   Intervention: methotrexate  Comparison: ciclosporin
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect  (95% CI)	No of Participants  (studies)	Quality of the evidence  (GRADE)	Comments
	Assumed risk	Corresponding risk
	Ciclosporin	Methotrexate
15% or greater improvement in muscle strength compared with baseline after at least six months ‐ not reported	See comment	See comment	Not estimable	‐	See comment	Muscle strength data not available.
Achieving the International Myositis Assessment and Clinical Studies Group (IMACS) definitions of improvement ‐ not measured	See comment	See comment	Not estimable	‐	See comment	Not an outcome in this study
Change in function or disability scale at six months ‐ not reported	See comment	See comment	Not estimable	‐	See comment	Function measured but not reported separately from composite score of 'muscle endurance with function'.
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).  CI: confidence interval
GRADE Working Group grades of evidence  High quality: Further research is very unlikely to change our confidence in the estimate of effect.  Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.  Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.  Very low quality: We are very uncertain about the estimate.

Infliximab versus placebo for dermatomyositis and polymyositis
Patient or population: patients with dermatomyositis and polymyositis  Settings:   Intervention: infliximab versus placebo
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect  (95% CI)	No of Participants  (studies)	Quality of the evidence  (GRADE)	Comments
	Assumed risk	Corresponding risk
	Placebo	Infliximab
15% or greater improvement in muscle strength compared with baseline after at least six months ‐ not measured	See comment	See comment	Not estimable	‐	See comment	No data
Achieving the International Myositis Assessment and Clinical Studies Group (IMACS) definitions of improvement   Follow‐up: 16 weeks	333 per 1000	1000 per 1000   (77 to 1000)	RR 3.77   (0.23 to 63.05)	18  (1 study)	⊕⊝⊝⊝  very low¹	‐
Change in function or disability scale at six months ‐ not measured	See comment	See comment	Not estimable	‐	See comment	Not measured
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).  CI: confidence interval; RR: risk ratio;
GRADE Working Group grades of evidence  High quality: Further research is very unlikely to change our confidence in the estimate of effect.  Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.  Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.  Very low quality: We are very uncertain about the estimate.

Etanercept versus placebo
Patient or population: patients with dermatomyositis, either 1. treatment naïve (prednisolone < 2 months) or 2. refractory to therapy with prednisolone > 2 months and either methotrexate (stable dose ≥1 month or more) or intravenous immunoglobulin ≥ 3 months  Settings:   Intervention: etanercept versus placebo
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect  (95% CI)	No of Participants  (studies)	Quality of the evidence  (GRADE)	Comments
	Assumed risk	Corresponding risk
	Placebo	Etanercept
15% or greater improvement in muscle strength compared with baseline after at least 6 months ‐ not reported	See comment	See comment	Not estimable	‐	See comment	Not an outcome in this study
Achieving the International Myositis Assessment and Clinical Studies Group (IMACS) definitions of improvement at 24 weeks	400 per 1000	820 per 1000   (268 to 1000)	RR 2.05   (0.67 to 6.2)	16 (1 study)	⊕⊕⊕⊝  moderate¹	‐
Change in function or disability score   Various measures  Follow‐up: 24 weeks	See comment	See comment	Not estimable	16  (1 study)	See comment	No significant difference between control and etanercept in any measure of function or disability (final values) (see text)
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).  CI: confidence interval; RR: risk ratio
GRADE Working Group grades of evidence  High quality: Further research is very unlikely to change our confidence in the estimate of effect.  Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.  Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.  Very low quality: We are very uncertain about the estimate.

Eculizumab versus placebo for dermatomyositis and polymyositis
Patient or population: patients with dermatomyositis and polymyositis  Settings:   Intervention: eculizumab versus placebo
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect  (95% CI)	No of Participants  (studies)	Quality of the evidence  (GRADE)	Comments
	Assumed risk	Corresponding risk
	Placebo	Eculizumab
15% or greater improvement in muscle strength compared with baseline after at least six months ‐ not measured	See comment	See comment	Not estimable	‐	See comment	Single study of only 9 weeks' duration.
Achieving the International Myositis Assessment and Clinical Studies Group (IMACS) definitions of improvement ‐ not measured	See comment	See comment	Not estimable	‐	See comment	Not an outcome in this study
Change in function or disability scale at six months ‐ not measured	See comment	See comment	Not estimable	‐	See comment	Single study of only 9 weeks' duration.
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).  CI: confidence interval
GRADE Working Group grades of evidence  High quality: Further research is very unlikely to change our confidence in the estimate of effect.  Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.  Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.  Very low quality: We are very uncertain about the estimate.

Date	Event	Description
13 August 2012	Amended	Minor corrections to wording in abstract and objectives
7 March 2012	New citation required and conclusions have changed	New studies included with new interventions. Conclusions changed.
22 August 2011	New search has been performed	Searches were updated to August 2011 and four new trials were included. 'Risk of bias' and 'Summary of findings' tables were added. No new authors but change in order of listing.
29 May 2008	Amended	Converted to new review format.
10 March 2005	New citation required and conclusions have changed	Substantive amendment

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Improvement in manual muscle strength by ≧15% at 16 weeks	1	18	Risk Ratio (M‐H, Fixed, 95% CI)	3.77 [0.23, 63.05]
2 Improved by IMACS criteria at 16 weeks	1	18	Risk Ratio (M‐H, Fixed, 95% CI)	1.75 [0.51, 5.98]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Improvement in 'Muscle endurance with functional test' measurement at 6 months (maximum score 56)	1	36	Mean Difference (IV, Fixed, 95% CI)	6.80 [‐1.65, 15.25]
2 Improvement in 'Clinical Assessment' score at 6 months (maximum score 33)	1	36	Mean Difference (IV, Fixed, 95% CI)	1.90 [‐1.83, 5.63]
3 Improvement in global patient's assessment at 6 months (0 to 10)	1	36	Mean Difference (IV, Fixed, 95% CI)	0.30 [‐1.20, 1.80]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mean change in Health Assessment Questionnaire score at 52 weeks	1	16	Mean Difference (IV, Fixed, 95% CI)	‐0.02 [‐0.55, 0.51]
2 Mean change in Health Assessment Questionnaire score at 24 weeks	1	16	Mean Difference (IV, Fixed, 95% CI)	‐0.10 [‐0.78, 0.58]
3 Achieving the International Myositis Assessment and Clinical Studies Group (IMACS) definitions of improvement at 24 weeks	1	16	Risk Ratio (M‐H, Fixed, 95% CI)	2.05 [0.67, 6.20]
4 Achieving the International Myositis Assessment and Clinical Studies Group (IMACS) definitions of improvement at 52 weeks	1	16	Risk Ratio (M‐H, Fixed, 95% CI)	0.91 [0.37, 2.23]
5 Cumulative dosage of prednisone over the one‐year study period	1	16	Mean Difference (IV, Fixed, 95% CI)	‐4.01 [‐8.66, 0.64]
6 Average change in time (sec) to walk 30 feet comparing performance at baseline to week 52	1	16	Mean Difference (IV, Fixed, 95% CI)	1.10 [‐6.57, 8.77]
7 Average change in time to rise from a chair from baseline to week 52	1	14	Mean Difference (IV, Fixed, 95% CI)	1.17 [‐1.37, 3.71]
8 Treatment failure	1	16	Risk Ratio (M‐H, Fixed, 95% CI)	0.59 [0.33, 1.05]
9 Individualized Neuromuscular Quality of Life	1	16	Mean Difference (IV, Fixed, 95% CI)	‐5.4 [‐26.82, 16.02]
10 SF‐36 Physical Component Summary Score	1	16	Mean Difference (IV, Fixed, 95% CI)	6.4 [‐3.28, 16.08]

Pulse oral dexamethasone versus daily oral prednisolone for dermatomyositis and polymyositis
Patient or population: patients with dermatomyositis and polymyositis, non‐specific myositis, myositis with a co‐existing connective tissue disease or with cancer within 2 years before onset of myositis, disease of less than one year duration. On no more than 20 mg prednisolone and no other immunosuppressant or immunomodulatory therapy  Settings:   Intervention: pulse oral dexamethasone versus daily oral prednisolone
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect  (95% CI)	No of Participants  (studies)	Quality of the evidence  (GRADE)	Comments
	Assumed risk	Corresponding risk
	Daily oral prednisolone	Pulse oral dexamethasone
15% or greater improvement in muscle strength compared with baseline after at least 6 months ‐ not reported	See comment	See comment	Not estimable	‐	See comment	Not an outcome in this study
Achieving the International Myositis Assessment and Clinical Studies Group (IMACS) definitions of improvement at 52 weeks ‐ not reported	See comment	See comment	Not estimable	‐	See comment	Not an outcome in this study
Change in function or disability scale   Neuromuscular Symptom Score Scale from: 0 to 60 Follow‐up: 18 months	The mean function or disability scale score in the control group was 46¹	The mean function or disability scale score in the intervention groups was  5 lower   (11.48 lower to 1.48 higher)	‐	62  (1 study)	⊕⊕⊕⊝  moderate²	‐
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).  CI: confidence interval
GRADE Working Group grades of evidence  High quality: Further research is very unlikely to change our confidence in the estimate of effect.  Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.  Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.  Very low quality: We are very uncertain about the estimate.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Neuromuscular Symptom Score	1	62	Mean Difference (IV, Fixed, 95% CI)	‐5.0 [‐11.48, 1.48]
2 Remission	1	62	Risk Ratio (M‐H, Fixed, 95% CI)	0.59 [0.22, 1.57]
3 Relapse	1	62	Risk Ratio (M‐H, Fixed, 95% CI)	1.24 [0.69, 2.24]

Methods	Double‐blind placebo‐controlled trial
Participants	23 participants with previously untreated polymyositis, but only the 16 participants completing the study were included in final analysis Age in years (SD) of 16 completers: azathioprine group, 38.3 (11.8); placebo group, 40.9 (10.6)  Sex of 16 completers: azathioprine group, 5 females, 3 males; placebo group, 2 males, 6 females  Mean disease duration (SD) of completers: azathioprine group, 8.6 (6) months, placebo group, 9.6 (9) months Established criteria not quoted but inclusion criteria should satisfy the Bowan and Peter criteria for definitive polymyositis
Interventions	60 mg of prednisolone per day plus either azathioprine (2 mg/kg/day) or placebo for 3 months
Outcomes	MMT, CK, muscle biopsy after 3 months
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Methodology for producing random sequence not reported
Allocation concealment (selection bias)	Unclear risk	Methods for concealing allocation sequence not described beyond the study being double‐blind, placebo‐controlled
Blinding (performance bias and detection bias)   All outcomes	Low risk	Double‐blinded study with placebo medication for control group
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	Significant attrition: 7 participants, of whom 3 were lost to follow up, 4 withdrew due to due side‐effects, failure of therapy or intercurrent illness
Selective reporting (reporting bias)	High risk	7 participants who failed to complete the study were excluded from the final analysis
Other bias	Unclear risk	Not clear

Methods	16‐week randomised, double‐blind, placebo‐controlled trial with subsequent open label cross‐over of placebo participants to active arm and active participants to dose escalation
Participants	11 participants with polymyositis and 1 with dermatomyositis  Age in years (SD): 45.4 (10.9)  Sex: 11 female and 1 male  Mean disease duration (SD): 5.6 (4.0) years Probable or definite refractory dermatomyositis or polymyositis by Bohan and Peter criteria Previously failed or had intolerance to immunosuppressive therapy. Baseline MMT score 80 to 120 (normal 160). Stable prednisolone (≤ 0.5 mg/kg/day) and immunosuppressive dose for at least 4 weeks
Interventions	Active arm: infliximab 5 mg/kg at weeks 0, 2, 6 and 14. Non‐responders based on IMACS criteria then increased to open label infliximab 7.5 mg/kg at weeks 22, 30 and 38 Placebo arm: placebo at weeks 0, 2, 6 and 14. Non‐responders based on IMACS criteria then given infliximab 5 mg/kg at weeks 16, 18, 22, 30 and 38
Outcomes	≥15% MMT improvement from baseline Improvement as defined by IMACS
Notes	Data from the open label and double‐blind sections of the study presented together
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Methodology for producing random sequence not reported in abstract
Allocation concealment (selection bias)	Unclear risk	Insufficient detail reported
Blinding (performance bias and detection bias)   All outcomes	Low risk	Blinded period lasted 16 weeks, then open follow‐up
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	Attritions and exclusions not reported in abstract
Selective reporting (reporting bias)	Low risk	No evidence of selective reporting
Other bias	Low risk	No evidence to suggest other bias

Methods	Double‐blind RCT
Participants	15 participants with dermatomyositis: 8 in IVIg group, 7 in placebo group  Age in years: mean 36, range 18 to 55 years  Sex: 10 females, 5 males  Mean disease duration: IVIg group 3.9 years, placebo group 3.8 years No classification criteria used but participants quoted to have all had a diagnostic muscle biopsy, rash and progressive muscle weakness Participants had dermatomyositis that "had become unresponsive or poorly responsive to high‐dose prednisolone or therapeutic doses of another immunosuppressant (methotrexate, azathioprine or cyclophosphamide) given for at least four to six months." Nine participants were taking concomitant immunosuppressive agents (azathioprine (5), methotrexate (3) or cyclophosphamide (1)) during the study
Interventions	IVIg (2 g/kg) or placebo per month for 3 months
Outcomes	MMT, NSS, ADL Score (based on Barthel index), CK, photographs of rashes, muscle biopsy after 3 months of treatment
Notes	IVIg was beneficial
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Block‐randomisation used but further methodology on randomisation not provided
Allocation concealment (selection bias)	Low risk	Randomisation in pharmacy, code not broken until completion of the study
Blinding (performance bias and detection bias)   All outcomes	Low risk	Medication covered by opaque plastic to hide medication from participants and investigators. Stated that no inadvertent disclosure of randomisation but that all but 1 participant correctly identified the therapy they were on
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Results for all recruited participants reported, although no clear statement on attrition or exclusions made
Selective reporting (reporting bias)	Unclear risk	One of the secondary outcomes, ADL score was not reported systematically and statistical comparison between the two groups was not reported
Other bias	Low risk	No evidence to suggest other bias

Methods	Randomised, double‐blind, placebo‐controlled trial
Participants	16 participants with adult dermatomyositis.  Mean age in years (range): 43.63 (21 to 61)  Sex:10 female and 6 male  Definite dermatomyositis by Bohan and Peter criteria In active arm 3 newly diagnosed, treatment‐naïve patients and 8 refractory patients with a mean baseline prednisone dosage of 45 mg/day. Mean disease duration 1.1 years, SD 0.8 In placebo arm, 2 newly diagnosed, treatment naïve patients and 3 refractory patients with a mean baseline prednisone dosage of 39 mg/day. Mean disease duration 2.2 years, SD 3.4
Interventions	New patients were started on prednisone 60 mg daily. Refractory patients remained their maintenance prednisolone dosage for 2 months or had the dose increased to 60 mg at the discretion of their treating physician After treatment with prednisolone for 2 months, participants received etanercept 50 mg/week or placebo for 52 weeks. This was followed in all participants by tapering of the prednisolone over 24 weeks starting after first treatment with etanercept or placebo
Outcomes	Outcome Measures in clinicaltrials.gov summarised   Primary   Occurrence of at least one adverse event (at each visit during the 12 month study)  Tolerability (at any point between baseline (week 0) and the end of the study (week 52)  Average change in each of the following from baseline to week 52 (at baseline (week 0) and week 52): oral temperature, respiration rate, systolic BP, diastolic BP, pulse, body weight in kg  Frequency of subjects with treatment emergent, clinically significant, abnormal laboratory values from baseline to week 52 (at screening, baseline (week 0), weeks 4, 8, 12, 16, 20, 24, 32, 40, and 52) in the following: CK, alanine aminotransferase, gamma‐glutamyl transpeptidase, aldolase, glucose, potassium, white blood cell count, haemoglobin, haematocrit, platelet counts, urine leukocyte values, urine protein laboratory values, urine glucose, urine ketone  Frequency of subjects with treatment emergent, clinically significant, abnormal serum 25‐hydroxyvitamin D laboratory values from the screening visit to week 52 (screening visit and week 52)  Frequency of subjects with treatment emergent, clinically significant, abnormal antinuclear antibody test (ANA) values from the screening visit to week 52 (at screening, weeks 12, 24, 40, and 52)  Frequency of subjects with treatment emergent, clinically significant, abnormal monoclonal protein detection by serum protein electrophoresis from the screening visit to week 52 (screening visit, weeks 12, 24, 40, and 52)  Average cumulative dosage of prednisone over the 1 year study period (baseline until week 52)  Secondary   Average prednisone dosage after week 24 (from week 24 to 52)  Average daily dose of prednisone from baseline to week 52 (baseline through week 52)  ‘Other Pre‐specified’   The number of participants who were classified as treatment failures (at any point during the 52 week study)  From baseline to week 52 (at baseline (week 0) and week 52):  •change in the average MMT Score  •average change in time to rise from a chair  •average change in time (s) to walk 30 feet  •average change in Z‐score for DEXA of the femur  •average change in Z‐score for DEXA of the lumbar spine  •average change in physician global activity assessment  •average change in patient global activity assessment score  •average change in Cutaneous Disease Activity and Severity Index (CDASI) score  •change in pruritis rating  •change in HAQ score  •forced vital capacity (FVC) average change in percent predicted  •average change in percent predicted forced expiratory volume in 1 s (FEV1)  •average change in percent predicted diffusion capacity (DLCO) Serious adverse events  Other adverse events    Outcome measures in published paper   Primary   Adverse events  "Time from randomization to treatment failure"  "Average prednisolone dosage after week 24"  Secondary   Cumulative and average MMT scores  Composite maximum voluntary isometric contraction testing (MVICT) scores  Myositis Intention to Treat Activity Index (MITAX)  Myositis Disease Activity Assessment Visual Analogue Scales (MYOACT)  "Subject and physician assessments of global disease activity utilizing Likert and visual analogue scales (VAS)"  "Time to arise from a chair and walk 30 feet"  HAQ  "A modified cutaneous disease activity score index"  Patient VAS for pruritis  "Relevant components of the MYOACT and MITAX"  SF‐36  Individualized Neuromuscular Quality of Life Questionnaire  IMACS‐recommended definitions of improvement
Notes	Initially designed to enrol 40 newly diagnosed patients. Some slight but not significant differences in results data between published study and results section on clinicaltrials.gov. Modified form of the IMACS DOI used
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information about the sequence generation process
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding (performance bias and detection bias)   All outcomes	Unclear risk	Insufficient information
Incomplete outcome data (attrition bias)   All outcomes	Low risk	Only 2 participants withdrew from the study, one lost to follow up in the etanercept group, 1 due to lack of perceived effect in the placebo group
Selective reporting (reporting bias)	Unclear risk	Many of the numerous prespecified outcomes on the clinicaltrials.gov website are not reported in the paper. However, these results are readily available on the clinicaltrials.gov website. Notably average prednisone dosage after week 24, a secondary outcome on the clinicaltrial.gov website, is reported in the paper but the primary outcome, average cumulative dosage of prednisone over the 1 year study period, is not. Several of the outcomes reported in the published paper were not amongst the primary or secondary outcomes published on clinicaltrials.gov website. Some of these are reported in the results section of clinicaltrials.gov as pre‐specified outcomes. Notably, the missing outcomes would be not be possible to measure retrospectively
Other bias	Low risk	The study appears to be free of other sources of bias

Methods	RCT
Participants	20 participants with dermatomyositis and 16 with polymyositis  Ciclosporin (n = 17); methotrexate (n = 19)  Age in years (SD): ciclosporin group 42.6 (12), methotrexate group 38.4 (22.2)  Sex: 23 females and 13 males  Disease duration (SD): ciclosporin group 28 (35) months, methotrexate group 30 (72) months All participants fulfilled Bohan and Peter's definite criteria 30 participants had newly diagnosed disease, 6 participants relapse of previously controlled disease. All participants had weakness on MMT of at least degree 3 in at least 2 muscle groups and "severe and active" disease as judged by a physician
Interventions	Ciclosporin 3.0 to 3.5 mg/kg/day versus oral methotrexate 7.5 to 15 mg/weekly for 6 months. All participants were treated with prednisone at a dose 0.5 to 1.0 mg/kg/day
Outcomes	Muscle endurance and functional test. Maximum score 56. Improvement defined as an increase of at least 6 compared to baseline, or if original score < 36, an increase to 42 Clinical assessment: clinical composite score. Maximum score 33. Improvement defined as an increase of at least 40% compared to baseline Global patient’s assessment, VAS 0 to 10. Improvement defined as an increase of 2 points or more compared to baseline Muscle MRI as study entry and 3 months Laboratory features including: CK, myoglobin, serum interleukin‐1 receptor antagonist and c‐reactive protein
Notes	No statistically significant difference between the two groups
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation using a sequence of numbers generated by a computer program
Allocation concealment (selection bias)	High risk	Open label trial design
Blinding (performance bias and detection bias)   All outcomes	High risk	Open label trial design
Incomplete outcome data (attrition bias)   All outcomes	Low risk	7 participants, 4 in the methotrexate group and 3 in the ciclosporin group, discontinued the study due to side effects. Those who discontinued after the 12 week evaluation were included in the semiquantitative evaluation
Selective reporting (reporting bias)	Low risk	Assessments described in the methods were all reported in the results
Other bias	Low risk	No evidence to suggest other bias

Methods	Randomised, cross‐over, open‐label trial
Participants	30 participants, 11 with dermatomyositis, 18 with polymyositis and 1 overlap with systemic lupus erythematosus IV methotrexate group:  Age in years (SD): 40.1 (9.5)  Sex: 12 females, 3 males  Disease duration (SD): 34.9 (12.3) months Oral methotrexate and azathioprine group:  Age in years (SD): 41.5 (15.4)  Sex: 12 females and 3 males  Disease duration (SD): 45.1 (45.9) Diagnosis of definite polymyositis or dermatomyositis as defined by Bohan and Peter Inclusion required weakness on MMT of at least 3/5 in at least two muscle groups, a functional deficit of at least 1 level in at least 1 area of ADL, refractory disease (persistent disease despite 1 mg/kg/day prednisone, inability to taper prednisone below 0.25 mg/kg/day or unacceptable side effects) and active disease requiring further immunosuppression as judged by the evaluating physician 25 participants had had failed previous trials of methotrexate and/or azathioprine
Interventions	IV methotrexate 500 mg/m² every 2 weeks for 12 treatments followed by leucovorin rescue (50 mg/m² every 6 hours for 4 doses) versus oral methotrexate plus azathioprine (up to 25 mg/week and 150 mg/day) for 6 months
Outcomes	Primary oucome was 'improvement' as defined by a combine evaluation of strength assessed by MMT (maximum score 80) and function assessed by ADL score (maximum 91) Improvement if net increase of a least 1 grade of muscle strength in at least 2 muscle groups on MMT and an increase in at least 1 functional level in one or more areas of function Assessed at 3 and 6 months
Notes	No statistically significant difference between the 2 treatments but trend favours combination therapy
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not reported
Allocation concealment (selection bias)	High risk	No allocation concealment
Blinding (performance bias and detection bias)   All outcomes	High risk	No blinding performed
Incomplete outcome data (attrition bias)   All outcomes	Low risk	2 participants withdrawn from the study in each arm. One due to worsening respiratory symptoms and one at own request
Selective reporting (reporting bias)	Low risk	Outcomes reported as outlined in methods section
Other bias	Unclear risk	Not clear

Study	Reason for exclusion
Bunch 1981	Follow‐up study of RCT by Bunch et al. (Bunch 1980). Participants and observer not blinded to treatment
Chung 2007	Assessing creatine supplementation as a therapy for dermatomyositis and polymyositis. This supplement is not known to be immunosuppressive or immunomodulatory
Donov 1995	No evidence of randomisation or blinding
Fries 1973	Participants could not be confirmed to have polymyositis on the basis of the inclusion criteria

Trial name or title	Second line agents in myositis (SELAM trial)
Methods	Randomised, double‐blind, placebo‐controlled trial
Participants	90 participants with inflammatory myositis fulfilling the Bohan and Peter criteria, on corticosteroids with active disease
Interventions	Participants will be randomised into 4 therapy arms: ciclosporin (1 to 10 mg/kg/day) and placebo ciclosporin (1 to 10 mg/kg/day) and methotrexate (7.5 to 25 mg/week) placebo and methotrexate (7.5 to 25mg/week) placebo and placebo Treatments given for 56 weeks
Outcomes	Primary outcome measures MMT by standard MMT (modified MRC) of 16 muscle groups Timed 30 m walk Secondary outcome measures Modified Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) Generic health status measured by the SF‐36 The acute phase response measured by Westergren erythrocyte sedimentation rate Continuing muscle damage measured by plasma CK The cumulative and change in oral steroid dosage Adverse events
Starting date	2001
Contact information	Academic department of Rheumatology, GKT School of Medicine, London, UK
Notes	Study completed but not published. Preliminary data presented at the British Society for Rheumatology 2010 Annual Conference. ISRCTN40085050

PERMALINK

Immunosuppressant and immunomodulatory treatment for dermatomyositis and polymyositis

Patrick A Gordon

John B Winer

Jessica E Hoogendijk

Ernest HS Choy

Abstract

Background

Objectives

Search methods

Selection criteria

Data collection and analysis

Main results

Authors' conclusions

Plain language summary

Background

Objectives

Methods

Criteria for considering studies for this review

Types of studies

Types of participants

1. Bohan and Peter criteria.

2. Dalakas criteria (PM: polymyositis; DM: dermatomyositis).

Types of interventions

Types of outcome measures

Primary outcomes

Secondary outcomes

Search methods for identification of studies

Electronic database strategies

Data collection and analysis

Selection of studies

Assessment of risk of bias in included studies

Data synthesis

Subgroup analysis and investigation of heterogeneity

Sensitivity analysis

Results

Description of studies

Study designs

Participants

Interventions

Outcomes

Risk of bias in included studies

1.

Effects of interventions

Primary outcome measure

Change in function or disability scale at six months

IVIg

Azathioprine

Plasma exchange or apheresis

Methotrexate

5.1. Analysis.

5.2. Analysis.

5.3. Analysis.

Ciclosporin

Infliximab

7.6. Analysis.

7.7. Analysis.

7.1. Analysis.

7.9. Analysis.

7.10. Analysis.

Eculizumab

8.1. Analysis.

15% or greater improvement in muscle strength at six months

IVIg

1.1. Analysis.

Azathioprine

2.1. Analysis.

Plasma exchange or leukapheresis

3.1. Analysis.

Methotrexate

Ciclosporin

4.1. Analysis.

Secondary outcome measures

Achieving the International Myositis Assessment and Clinical Studies Group (IMACS) definitions of improvement

4.2. Analysis.

7.3. Analysis.

7.4. Analysis.

Number of relapses and time to relapse

8.3. Analysis.

7.8. Analysis.

Trial name or title	Intravenous immunoglobulin (IVIg) for the treatment of inflammatory myopathies
Methods	Double‐blind, randomised, placebo‐controlled cross‐over study in which participants will receive IVIg (2 gm/kg over two days each month) or placebo for 3 months and then will cross over to the alternate therapy for another period of 3 months
Participants	30 participants with dermatomyositis, polymyositis or inclusion body myositis, active disease and previous unsuccessful therapy with prednisolone and one immunosuppressive drug
Interventions	IVIg or placebo
Outcomes	Greater than 15% improvement in baseline muscle strength
Starting date	1999
Contact information	National Institutes of Health Clinical Center (CC)
Notes	Study completed according to clinicaltrials.gov website, last updated March 2008

Trial name or title	Understanding the pathogenesis and treatment of childhood onset dermatomyositis
Methods	Randomised, open‐label, multicentered trial comparing 3 treatments: oral prednisone, oral prednisone and methotrexate, and oral prednisone and etanercept. Treament duration 24 months
Participants	75 participants with definite juvenile dermatomyositis
Interventions	Oral prednisone, oral prednisone and methotrexate, or oral prednisone and etanercept
Outcomes	Primary outcome measure Mean duration of steroid therapy and manual muscle strength Secondary outcome measures Disability in daily function and height and weight growth velocity (steroid toxicity measures)
Starting date	2002
Contact information	Daniel J. Lovell, MD, MPH Children's Hospital Medical Center, Cincinnati
Notes	Study terminated 'Incorporating the recommendations of the NIH‐formed DSMB in the study procedures would make the project budget over the limit for this funding mechanism.'

Trial name or title	Rituximab for the treatment of refractory adult and juvenile dermatomyositis (DM) and adult polymyositis (PM)
Methods	A randomised, double‐blind, placebo‐controlled delayed therapy trial Group A will receive rituximab 750 mg/m² body surface area up to a maximum dose of 1 g at weeks 0 and 1 and placebo at weeks 8 and 9 Group B will receive placebo at weeks 0 and 1 and rituximab 750 mg/m² body surface area up to a maximum dose of 1 g at weeks 8 and 9
Participants	Participants with dermatomyositis, polymyositis or juvenile dermatomyositis (> 5 years old) and refractory disease Intolerance or inadequate response to therapy with corticosteroids plus at least 1 other immunosuppressive agent
Interventions	Rituximab 750 mg/m² body surface area up to a maximum dose of 1 g given at weeks 0 and 1 or weeks 8 and 9 Placebo infusions given at weeks 0 and 1 or weeks 8 and 9
Outcomes	Primary outcome measure Comparison between the 2 groups of participants in their time to achieve improvement Secondary Outcome Measures Response rates (proportion of improved participants) between Groups A (rituximab‐treated) and B (placebo‐treated) at week 8 20% improvement in MMT over baseline on 2 consecutive time points
Starting date	March 2006
Contact information	National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Notes	Study completed but not published. Preliminary data presented at the American college of Rheumatology 2010 Annual Conference.

Trial name or title	Five‐year actively controlled clinical trial in new onset juvenile dermatomyositis
Methods	Randomised, open label, active control, parallel assignment study
Participants	Newly diagnosed and untreated children with probable or definite diagnosis of JDM according to the Bohan and Peter criteria, aged between 1 and 18 years
Interventions	Prednisolone, prednisolone plus ciclosporin (5 mg/kg in 2 oral doses daily) or prednisolone plus methotrexate (15 to 20 mg/m² once per week)
Outcomes	Primary outcome measure 20% improvement in at least 3 core set variables with no more than 1 of the remaining variables (muscle strength excluded) worsened by > 30%.    Secondary outcome measures Change over time in the individual components of the JDM core set of variables: a) time to muscle enzymes normalisation; b) frequency of drop‐out of suggested steroids use; c) frequency of drop‐out for inefficacy of treatment.
Starting date	May 2006
Contact information	Nicolino Ruperto, MD, MPH 0039‐010‐382854 nicolaruperto@ospedale‐gaslini.ge.it  Simona Angioloni, B.A. 0039‐010‐393425 simonaangioloni@ospedale‐gaslini.ge.it
Notes	Study currently recruiting according to clinicaltrials.gov website, last updated February 2011

Trial name or title	Efficacy and safety study of GB‐0998 for treatment of steroid‐resistant polymyositis and dermatomyositis (PM/DM)
Methods	Randomised, double‐blind, placebo‐controlled study
Participants	Steroid‐resistant polymyositis and dermatomyositis
Interventions	High‐dose IVIg (400 mg of GB‐0998/kg per day) or placebo daily for 5 successive days
Outcomes	Primary outcome measure Change in MMT scores Secondary outcome measures Change in CK and total activity of daily living scores. Adverse events and laboratory tests 'Time frame 8 weeks'
Starting date	2006
Contact information	Professor Nobuyuki Miyasaka, Tokyo Medical and Dental University
Notes	Study completed according to clinicaltrials.gov website, last updated July 2009

Trial name or title	A phase 1B, randomised, double‐blind, placebo‐controlled, multicenter study to evaluate safety of multiple‐dose, intravenously administered MEDI‐545, a fully human anti interferon‐alpha monoclonal antibody, in adult patients with dermatomyositis or polymyositis
Methods	Randomised, double‐blind, placebo‐controlled study 40 participants with a positive gene signature randomised in a 3:1 ratio to initially receive MEDI‐545 (0.3, 1.0, 3.0, or 10.0 mg/kg) 2‐weekly for 12 weeks or placebo. In each dose cohort, 6 participants to receive MEDI‐545 and 2 participants placebo In addition, 8 participants with negative gene signature randomised in a 3:1 ratio to receive MEDI‐545 (3.0 mg/kg) or placebo every 2 weeks for 12 weeks. Thereafter, participants initially randomised to MEDI‐545 to receive the same dose of MEDI‐545 every 2 weeks for 12 weeks and participants initially randomised to placebo to receive MEDI‐545 every 2 weeks.
Participants	40 adult participants with dermatomyositis or polymyositis and a positive gene signature 8 adult participants with dermatomyositis or polymyositis and a negative gene signature
Interventions	MEDI‐545 (0.3, 1.0, 3.0, or 10.0 mg/kg) via infusion 2‐weekly, or placebo.
Outcomes	Primary outcome measures The primary endpoints of the study are safety and tolerability of multiple IV doses of MEDI‐545 in adult participants with dermatomyositis or polymyositis Secondary outcome measures The secondary endpoints of the study are the PK and IM of multiple IV doses of MEDI‐545 The third endpoint of the study are the evaluations of disease activities
Starting date	April 2007
Contact information	Mick G. Ribeiro 301‐398‐4202 ribeirom@medimmune.com Lisa Farace 301‐398‐4991 faracel@medimunne.com
Notes	Study completed according to clinicaltrials.gov website, last updated May 2011

Trial name or title	Combined treatment of methotrexate + glucocorticoids versus glucocorticoids alone in patients with polymyositis and dermatomyositis (Prometheus)
Methods	Randomised, open‐label, assessor‐blind trial
Participants	50 participants with previously untreated polymyositis or dermatomyositis
Interventions	Prednisolone at an initial dose of 1.0 mg/kg/day either alone or with methotrexate Methotrexate arm to receive methotrexate at an initial dose of 10 mg/wk escalating up to 20 to 25 mg/week according to clinical need with folic acid 10 mg given 24 hours after each methotrexate dose Treatment duration of 12 months with a further 12 month follow‐up
Outcomes	Primary outcome measure Total dose of glucocorticoids administered between baseline and the end of treatment    Secondary outcome measures Assessment of disease activity and damage, muscle strength and endurance, enzyme levels, glucocorticoid side‐effects, dose, HAQ, SF‐36, treatment failures
Starting date	May 2008
Contact information	Jiri Vencovsky, prof. MD. +420234075340 venc@revma.cz Jana Tomasova, MD. PhD. +420234075340 jtomasova@yahoo.com
Notes	Study currently recruiting according to clinicaltrials.gov website, last verified July 2011

Trial name or title	Efficacy and tolerability of BAF312 in patients with polymyositis and dermatomyositis
Methods	Randomised, double‐blind, placebo‐controlled trial of BAF312 or placebo for 12 weeks followed by a further 12 weeks where all participants recieve BAF312
Participants	Polymyositis or dermatomyositis unresponsive to at least 3 months of therapy with corticosteroids with or without disease modifying antirheumatic drugs
Interventions	BAF312
Outcomes	IMACS core set measures
Starting date	2010
Contact information	Novartis Pharmaceuticals +41‐61‐324‐1111
Notes	Study currently recruiting according to clinicaltrials.gov website, last verified April 2011

Trial name or title	Abatacept treatment in polymyositis and dermatomyositis (ARTEMIS)
Methods	Randomised, single‐blind (outcome assessor blinded), delayed treatment study
Participants	20 participants with active dermatomyositis (10) or polmyositis (10) despite therapy with steroids and either methotrexate or azathioprine for at least 3 months
Interventions	Participants will be randomised to receive abatacept at time 0 then after 2, 4, 8, 12, 16 and 20 weeks, or to have this treatment delayed for 3 months
Outcomes	Primary outcome: The number of responders, defined as improved according to the IMACs criteria, after treatment with abatacept for 6 months Secondary outcomes: The change in the individual components of the IMACS core set measures for disease activity at 3 and 6 months
Starting date	January 2011
Contact information	Ingrid E Lundberg, MD, PhD +46851770000 ext 6087 Ingrid.Lundberg@ki.se Jiri Vencovsky, MD, PhD +420224914469 venc@revma.cz Patrick Gordon, MBBS, PhD +44203 299 1735 patrick.gordon2@nhs.net
Notes	Study currently recruiting