Approach

The objectives of treatment are to improve muscle strength to enhance quality of life for patients with idiopathic inflammatory myopathies (IIMs) by inducing and maintaining remission of skeletal muscle inflammation and extramuscular symptoms. Few randomised controlled trials have been performed due to the rarity of the IIMs and their clinical heterogeneity.[4][77]​​​[93]​ Recommended treatment regimens, with the exception of intravenous immune globulin (IVIG) and rituximab, are based on observational studies.[4][93]

Corticosteroids, immunosuppressants/conventional synthetic disease-modifying antirheumatic drugs (DMARDs; used as corticosteroid-sparing agents), and IVIG are the mainstay of treatment for patients with IIMs. Conventional synthetic DMARDs include methotrexate, azathioprine, mycophenolate, ciclosporin, and tacrolimus. Interventions such as rituximab, abatacept, and cyclophosphamide are reserved for the treatment of refractory disease.[93]

To date, there are no effective available treatments for inclusion body myositis, for which, treatment with corticosteroids or immunosuppressants is usually not recommended.​[57][72]​​​ Physical activity is the only intervention which has evidence of benefit for inclusion body myositis; the optimal exercise programme has not yet been determined.[4]

Induction of remission: severe IIM

Severe disease refers to patients with severe muscle weakness (e.g., global weakness with strength worse than 4 on Medical Research Council scale), respiratory failure from interstitial lung disease (ILD), myocarditis, or severe dysphagia, or other life-threatening complications.

First-line treatments - severe IIM

First-line treatment for patients with severe IIM include corticosteroids, immunosuppressants/conventional synthetic DMARDs, and IVIG.

Corticosteroids

For patients with severe forms of myositis, or extramuscular manifestations, such as ILD, an initial course of pulse dosing of intravenous corticosteroids should be considered to allow for increased therapeutic effect and less toxicity compared with oral corticosteroids.[4][72]​​[93]​ Following intravenous corticosteroid treatment, patients should be converted to a high-dose oral corticosteroid, which is then tapered over several months according to clinical response.[72][93]

Immunosuppressants

Immunosuppressants (used as corticosteroid-sparing agents) should be initiated early to reduce muscle inflammation, achieve clinical remission, and reduce corticosteroid burden.[4][72][93]​ Conventional synthetic DMARDs, such as methotrexate, azathioprine, and mycophenolate, are recommended in addition to corticosteroid treatment. The British Society of Rheumatology guideline suggests that there is no evidence to determine which conventional synthetic DMARD should be first line. They state that DMARDs should be prescribed and monitored according to existing age appropriate guidelines.[93] Other evidence suggests that methotrexate or azathioprine should be first-line treatment.[4] Mycophenolate may be considered a first-line treatment for patients with severe IIM with associated ILD.[4][94]​​ Retrospective and prospective studies have demonstrated the efficacy of mycophenolate for the treatment of patients with IIM, particularly for patients with IIM-associated ILD and refractory dermatomyositis rashes. 

Potential adverse effects of methotrexate include leukopenia, elevated liver enzymes, interstitial pneumonitis, and pulmonary fibrosis. Folic acid supplementation is recommended. Potential adverse effects of azathioprine include leukopenia, liver damage, and a range of gastrointestinal symptoms.[72]

IVIG

IVIG is recommended for the treatment of severe muscle inflammation concomitantly with other immunosuppressants. It may also be used as monotherapy in the settings of pregnancy, infection, or malignancy.[4][93][95]​ The efficacy of IVIG has been demonstrated as a rescue treatment in patients with ILD relapse, or in combination with early use of an intravenous corticosteroid.[57][95][96][97]​​​[98]​​ Adverse effects include renal toxicity and thrombosis.

Second-line treatments - severe IIM

If first-line treatment with a corticosteroid plus an immunosuppressant is not tolerated or is ineffective, alternative second-line immunosuppressant options should be considered. These may include ciclosporin, tacrolimus, mycophenolate, and/or IVIG.

Ciclosporin or tacrolimus

Oral ciclosporin and tacrolimus are effective immunosuppressants that can be used either as a replacement for, or in combination with, other immunosuppressants in patients with refractory myositis with either muscle weakness or associated ILD.[4][72]​ Nephrotoxicity, gastrointestinal symptoms, hypertension, and rarely reversible posterior encephalopathy syndrome are potential adverse effects.[72][99]​ Regular monitoring of serum drug trough levels, full blood count, renal function, and liver function should be performed.[100][101]

Mycophenolate

Mycophenolate can be considered as a second-line treatment for patients with severe IIM who are refractory or intolerant to first-line immunosuppressants.[4]

IVIG

IVIG is a well-established alternative corticosteroid-sparing agent or adjunct treatment for patients with severe or refractory IIM and should be considered in combination with, or following failure of, corticosteroids and/or other immunosuppressants.[4][93]

Third-line treatments - severe IIM

Third-line treatments for patients with severe IIM may include cyclophosphamide or rituximab.[4][93] Escalation to third-line treatment should be considered for patients who are refractory to, or intolerant of, corticosteroids and other immunosuppressants.[72]

Cyclophosphamide

Cyclophosphamide can be considered for patients with severe muscle weakness, and ILD or rapidly progressive ILD associated with IIM, or refractory disease as remission induction therapy.[4][93]​ It may be associated with a high risk of opportunistic infections and its potential for liver, bladder, and bone marrow toxicity should be noted.[100][102]

Rituximab

Rituximab (an anti-CD20 monoclonal antibody biological agent) should be considered for patients with refractory myositis, and may be particularly effective for:[93] 

  • Patients with a positive myositis autoantibody profile

  • Patients with lower burden of disease damage

One randomised trial of rituximab in patients refractory to corticosteroids and at least one other immunosuppressant reported that although the primary end point (time to clinical improvement between two trial arms) was not met, 83% of the study population did met the definition of improvement during the trial period.[103]​ One review that included this trial found that rituximab may be an effective treatment for refractory IIM patients, but patients with autoantibodies anti-Jo-1 (anti-histidyl-tRNA synthetase) and anti-Mi-2 are more likely to respond to rituximab.[104]​ Several open-label studies have reported safety and efficacy in patients with severe and refractory myositis, including the subset of anti-SRP positive immune-mediated necrotising myopathy patients.[105][106]​​ Rituximab also may be an effective option in anti-MDA5 dermatomyositis with severe lung involvement.​[79][107]​​

Adverse effects include infusion reactions, severe mucocutaneous reactions, hepatitis B reactivation, and progressive multifocal leukoencephalopathy.

IVIG

IVIG is a well-established alternative corticosteroid-sparing agent or adjunct treatment for patients with severe or refractory IIM and should be considered in combination with, or following failure of, corticosteroids and/or other immunosuppressants.[4][93]

Induction of remission - non-severe IIM

Non-severe IIM Iincludes patients with mild to moderate muscle weakness without any life-threatening complications. Treatment options for non-severe IIM include oral corticosteroids, immunosuppressants/conventional synthetic DMARDs, IVIG, rituximab, and abatacept.

First-line treatments - non-severe IIM

Oral corticosteroids

Oral corticosteroids are the recommended first-line treatment for patients with non-severe IIM.[4]​​[72][93][108]​​ Corticosteroids should be tapered according to clinical response once a corticosteroid-sparing agent is started.[4][93]

Immunosuppressants

In addition to an oral corticosteroid, a conventional synthetic DMARD such as methotrexate or azathioprine should be introduced early (as a corticosteroid-sparing agent) to reduce muscle inflammation and corticosteroid burden.[4][93] The BSR states that there is insufficient evidence to determine which drug is preferred first line. However, subsequent evidence suggests that methotrexate or azathioprine should be considered first line.[4][93]

IVIG

IVIG is a well-established alternative corticosteroid-sparing agent or adjunct treatment for patients with severe or refractory IIM and should be considered in combination with, or following failure of, corticosteroids and/or other immunosuppressants.[4][93]

Second-line treatments - non-severe IIM

Treatment for patients with non-severe IIM who are refractory or intolerant to first-line immunosuppression may include ciclosporin, tacrolimus, mycophenolate, or IVIG.[4]

IVIG is a well-established alternative corticosteroid-sparing agent or adjunct treatment for patients with severe or refractory IIM and should be considered in combination with, or following failure of, corticosteroids and/or other immunosuppressants.[4][93]

Third-line treatments - non-severe IIM

Rituximab, cyclophosphamide, abatacept, or IVIG can be considered third-line treatments in patients with persistent active disease.[93]

Rituximab may be particularly effective for IIM patients with a positive MSA, and with lower burden of disease damage.[93]

Abatacept, a fully human recombinant fusion protein that blocks T-cell activation, has been demonstrated to reduce disease activity in patients with dermatomyositis or polymyositis in a phase 2b randomised study.[109]

IVIG is a well-established alternative corticosteroid-sparing agent or adjunct treatment for patients with severe or refractory IIM and should be considered in combination with, or following failure of, corticosteroids and/or other immunosuppressants.

Mycophenolate, tacrolimus, or ciclosporin should be considered where ILD is a predominant feature.[4][93]

Maintenance of remission - any severity

Immunosuppressants should be used to maintain IIM remission and allow the dose reduction or withdrawal of corticosteroid treatment.[77]​ IVIG is a well-established alternative corticosteroid-sparing agent or adjunct treatment for patients with severe or refractory IIM and should be considered in combination with, or following failure of, corticosteroids and/or other immunosuppressants.

Mycophenolate, tacrolimus, or ciclosporin should be considered where ILD is a predominant feature.[4][93] 

First-line maintenance treatment

Methotrexate, azathioprine, and mycophenolate are effective maintenance treatments for most patients.[77]

Mycophenolate, tacrolimus, or ciclosporin should be considered where ILD is a predominant feature.[4] 

Second-line maintenance treatment

For refractory patients, treatment escalation to combination therapy with ciclosporin plus methotrexate, or methotrexate or azathioprine plus mycophenolate, can be considered.[77]

Third-line maintenance treatment

For patients with more resistant disease treatment with tacrolimus, cyclophosphamide, rituximab, tocilizumab, abatacept, or IVIG can be considered.[4][77][93]

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