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 Table of Contents  
Year : 2020  |  Volume : 15  |  Issue : 6  |  Page : 153-162

Emerging therapeutics in idiopathic inflammatory myopathy

Division of Rheumatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan

Date of Submission11-May-2020
Date of Acceptance07-Jul-2020
Date of Web Publication18-Jan-2021

Correspondence Address:
Dr. Shinji Sato
Division of Rheumatology, Department of Internal Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/injr.injr_124_20

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Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of systemic autoimmune diseases characterized mainly by inflammation of muscle tissue. Although IIM traditionally encompasses polymyositis, dermatomyositis (DM), and inclusion body myositis, the disease concept has been changing in association with progress in diagnostic techniques. Thus, the new disease entities of amyopathic DM (ADM) or clinically ADM and immune-mediated necrotizing myopathy have been recognized recently. Because of the variety of symptoms or low prevalence or difficulty in correct evaluation of muscle strength and function in IIM patients, no standard treatment strategies have been established yet. Currently, glucocorticoids remain the first line of treatment of IIMs, but in addition to these, several other immunosuppressive agents or intravenous immunoglobulin have been used in a variety of different combinations. However, due to clinical heterogeneity of these conditions as well as the number of therapeutic target organs, IIM therapy remains challenging, and refractory cases are especially difficult to treat. In recent years, new therapeutic approaches using biologics or Janus kinase inhibitors, plasma exchange therapy, and other agents have been evaluated for IIMs. However, validation of the efficacy of these new treatment options remains an issue to be resolved. In this article, the author reviews current treatment strategies and new emerging therapies for IIM patients.

Keywords: Clinically amyopathic dermatomyositis, dermatomyositis, inclusion body myositis, interstitial lung disease, myositis-specific antibody, polymyositis, treatment

How to cite this article:
Sato S. Emerging therapeutics in idiopathic inflammatory myopathy. Indian J Rheumatol 2020;15:153-62

How to cite this URL:
Sato S. Emerging therapeutics in idiopathic inflammatory myopathy. Indian J Rheumatol [serial online] 2020 [cited 2022 Dec 10];15:153-62. Available from:

  Introduction Top

Idiopathic inflammatory myopathies (IIMs) are clinical entities mainly manifesting as chronic inflammation of the muscle.[1],[2] IIMs were heretofore divided into characteristic subgroups including polymyositis (PM), dermatomyositis (DM), and inclusion body myositis (IBM).[3] Recently, due to advances in diagnostic techniques, amyopathic DM (ADM) or clinically ADM (CADM) that have typical skin manifestations but no signs of muscle inflammation have been proposed as new subgroups. In addition, treatment-resistant immune-mediated necrotizing myopathy (IMNM) with severe proximal muscle weakness and necrosis and regeneration of muscle fibers with little inflammatory infiltration has been recognized. Of note, in 2018, Mariampillai et al. proposed a new classification scheme for IIMs by performing unsupervised multiple correspondence and hierarchical clustering analyses using the database of a French myositis network.[4] This scheme classified IIMs into four subgroups: DM, IBM, IMNM, and anti-synthetase syndrome.

Indeed, IIMs form a group of very heterogeneous conditions in terms of the number of affected organs and severity of the disease, each with a relatively low prevalence. Therefore, it has not been possible to perform large-scale, randomized, placebo-controlled prospective studies to evaluate the treatment efficacy of candidate agents, and no evidence-based standard treatment strategies have been established for each subgroup of IIMs.

Conventionally, glucocorticoids have been used as first-line therapeutic agents, and immunosuppressive drugs or intravenous immunoglobulin (IVIG) have been added on a case-by-case basis. In addition, multiple trials to discover new improved therapeutic agents such as biologics, or Janus kinase (JAK) inhibitors, or agents acting on degenerating pathways and other agents have been carried out or are ongoing. More recently, exciting advances in IIM phenotyping using myositis-specific autoantibodies, as well as introduction of data-driven and consensus-driven diagnostic and response criteria, are increasing the diagnostic accuracy of assessments of disease activity. Clinical trials based on such refined diagnostic schemes for rigorously evaluating novel therapeutic agents will be planned in the near future.

Here, we provide a short overview of conventional treatments and summarize recent advances regarding new therapeutic strategies for patients with IIMs.

  Idiopathic Inflammatory Myopathy (Excluding Inclusion Body Myositis) Top

Conventional therapies

Although no randomized controlled studies have been carried out, it has been established that treatment with glucocorticoids and several other immunosuppressive agents provides clear clinical benefit in IIMs, with the exception of IBM. In this section, we provide a brief overview of current treatment options for IIMs (excluding IBM).


Glucocorticoids remain first-line treatments for both the muscle symptoms and interstitial lung disease (ILD) associated with IIMs. This is despite the lack of randomized controlled clinical trials. Generally, glucocorticoid treatment is initiated at 1 mg/kg/day of prednisolone (PSL) in several discrete doses. In some hypertensive patients, methylprednisolone may be substituted for prednisone. After 2–4 weeks at the initial dose, PSL is gradually tapered at the rate of ~10% every 2 weeks until a maintenance dose of 5–10 mg/day is achieved. Intravenous methylprednisolone pulse therapy (1000 mg × 3 days) followed by high-dose prednisone is preferred when the patient has severe symptoms such as severe muscle weakness, dysphagia, rapidly progressive ILD (RP-ILD), or IMNM. On the other hand, the initial dose of PSL can be lower (0.5 mg/kg/day) if the patient has only mild symptoms (e.g., mild elevation of serum creatine kinase [CK] and weakened muscle strength without ILD), or if complications that would be worsened by PSL are present. Combinations of other immunosuppressive agents with glucocorticoids in the early treatment phase are recommended to more robustly control disease activity as well as to reduce the risk of adverse events caused by the glucocorticoids.[5]


Methotrexate (MTX), a folic acid antagonist, was one of the first candidate immunosuppressive agents for patients with IIMs instead of or in addition to PSL. The efficacy of MTX has been demonstrated on the basis of open-label studies. In general, MTX can be administrated either orally or subcutaneously in various doses. A randomized, open-label, blinded Phase III trial to evaluate the effectiveness of MTX plus glucocorticoid combination therapy versus glucocorticoid monotherapy in patients with PM/DM is still underway ( Identifier: NCT00651040).[6] Because of pulmonary toxicity (MTX pneumonitis), the administration of this agent should be avoided in cases with concomitant ILD or for the purpose of treating ILD associated with myositis.


Azathioprine (AZA), a purine analog, is another first-line immunosuppressive agent and is thought to have efficacy similar to MTX, according to previous reports.[5] A combination of oral MTX with AZA may be effective even in refractory myositis patients for whom MTX or AZA monotherapies are ineffective.[7] AZA was also reported to have benefit for the treatment of ILD and PM/DM patients.[8] The starting dose is usually 25–50 mg/day, which is gradually increased up to 1.5–2 mg/kg/day. Patients with a thiopurine methyltransferase genetic deficiency should be carefully monitored to avoid the occurrence of severe hepato-biliary adverse events.

Calcineurin inhibitor (cyclosporine A and tacrolimus)

Cyclosporine A (CyA) and tacrolimus (TAC) are classified as calcineurin inhibitors. CyA blocks interleukin (IL)-2 production and release, whereas TAC binds the FKBP-12 protein; both agents inhibit T cell activation through blocking the activity of calcineurin. However, although T cell activation is clearly involved in the pathogenesis of muscle and pulmonary inflammation in IIMs, most previous studies were focused on the improvement of ILD associated with PM/DM.[9] Regarding muscle symptoms, an improvement of myositis exacerbation and PSL-sparing effects in patients with PM/DM has been published.[10] Favorable responses regarding pulmonary manifestations of these agents are seen, especially in anti-aminoacyl-tRNA synthetase autoantibody (anti-ARS antibody)-positive patients with PM/DM.[11] Efficacy for treating patients with pulmonary involvement in anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 antibody)-positive RP-ILD with DM in combination with other immunosuppressive agents such as cyclophosphamide was also reported.[12] At present, differences in efficacy between CyA and TAC in terms of treating pulmonary involvement remain unclear. The initial dose of CyA is usually 2–4 mg/kg/day in two doses, to achieve the target of blood trough levels of 100–150 ng/mL, whereas TAC is initiated at 1 mg/day or 0.075 mg/kg once or twice a day, targeting blood trough levels of 5-10 ng/mL. For both efficacy and safety, it is recommended that serum concentrations of CyA and TAC should be carefully controlled in daily practice.

Mycophenolate mofetil

Mycophenolate mofetil (MMF) is a prodrug of mycophenolic acid that inhibits lymphocyte proliferation through the reduction of guanosine nucleotide synthesis. MMF is effective for muscle manifestations or PSL-sparing treatment in PM/DM patients, as well as for refractory skin symptoms in DM. Similarly, several studies reported the efficacy of MMF in ILD associated with myositis. Fischer et al. reported the beneficial effects of MMF in patients with ILD associated with connective tissue disease including PM/DM, both in terms of pulmonary function and PSL-sparing effects.[13] MMF is initiated from 250 to 500 mg twice a day, gradually increasing the dose up to 2–3 g/day. In general, MMF is relatively safe and well tolerated with few adverse events. These are mainly gastrointestinal manifestations such as vomiting or diarrhea. This agent is contraindicated during pregnancy.


Cyclophosphamide (CYC) is an alkylating agent that inhibits cell proliferation. Since before 2000, CYC has been applied only for cases of severe and refractory myositis or RP-ILD in myositis because of the risk of secondary malignancy and other side effects associated with its use. Its effectiveness in combination with standard therapy has been reported in case series, and it was suggested in 2007 that CyA treatment together with intermittent intravenous CYC (IVCY) in addition to PSL may be a promising treatment for RP-ILD in DM.[14] Currently, many RP-ILD and DM patients are successfully treated with multiple combination therapies including high-dose PSL together with immunosuppressants (calcineurin inhibitor and IVCY). Beneficial effects on reversing muscle weakness as well as on pulmonary involvement have been reported.[15] In general, CYC is administrated orally or intravenously in varying doses and intervals, most commonly IVCY at 0.3–0.8 g/m 2 monthly for at least 6 months. The risk of malignancy or hemorrhagic cystitis, myelosuppression, and increased susceptibility to infections requires careful monitoring.

Intravenous immunoglobulin

The efficacy of IVIG for refractory PM/DM patients was first reported in a double-blind, placebo-controlled trial.[16] Subcutaneous immunoglobulin administration every week was also effective in relieving muscle symptoms in PM/DM. However, the guidelines of the American Academy of Neurology, 2012, advocated the use of IVIG only in refractory DM but not in PM. A possible effectiveness of IVIG for ILD associated with PM/DM has been noted in several case reports.[17],[18] A retrospective study on anti-ARS-positive ILD reported improvements in forced vital capacity (FVC)% and DLCO%.[8] IVIG also resulted in the improvement of skin lesions in patients with treatment-resistant DM.[19] A double-blind, randomized, placebo-controlled, multicentric Phase III trial to evaluate the efficacy and safety of IVIG (Octagam ®) in patients with DM ( Identifier: NCT02728752) was completed in November, 2019.

Although the mechanism of action of IVIG remains unclear, several possibilities are considered to be involved in its clinical effect in controlling and maintaining reductions of inflammatory processes resulting from autoimmunity. IVIG is usually administrated at 2 g/kg on 5 consecutive days every month. However, the dose and interval may be changed according to disease severity or treatment effectiveness. IVIG is more likely to be used when intensification of additional immunosuppressive treatment is problematic due to concomitant infection.


Rituximab (RTX) is an anti-CD20 monoclonal antibody that exerts its favorable effects in autoimmune disease by depleting B lymphocytes from the blood. Thus far, numerous case series or open trials have reported possible efficacy for treating refractory IIM patients.[20] For example, the Rituximab in Myositis study, a large randomized, double-blind, placebo-controlled trial to evaluate efficacy in refractory juvenile DM and adult PM/DM, found that RTX reduced disease activity and led to a reduction in steroid dose given (although the trial primary end point was not achieved).[21] Additional analysis of this study indicated that patients with anti-ARS-or anti-Mi-2-positive myositis had significantly better outcomes.[22] It is known that RTX can also be effective for controlling skin or pulmonary manifestations.[23] The efficacy of RTX for refractory ILD associated with anti-ARS- or anti-MDA5 antibody-positive PM/DM has been published.[23],[24],[25] RTX is usually administered twice at a dose of 1 g at an interval of 2 weeks or 37.5 mg/m 2 four times at intervals of a week, according to the protocol for the treatment of RA or vasculitis. Careful observation is needed for side effects such as bacterial or viral infection, infusion reactions, or cardiac involvement during the treatment.


For treatment of cutaneous manifestations of DM, it is essential to avoid sun exposure or photosensitive medications, and to use sunscreens. Previous data indicated that hydroxychloroquine (HCQ) in addition to glucocorticoids with or without other immunosuppressants is effective for skin manifestations.[26] HCQ is prescribed at 200–400 mg daily in clinical practice. It is important to pay attention to side effects such as vomiting, diarrhea, headache, and retinopathy. As the latter can lead to loss of vision, it is preferably recommended that patients are examined for the condition of the fundus oculi by an ophthalmologist before starting treatment, and then following up on a regular basis. It is to be noted that cutaneous manifestations might paradoxically worsen during treatment.

  Special Conditions Top

Immune-mediated necrotizing myopathy

Necrotizing myopathy (NM) due to autoimmune mechanisms has recently been recognized as a new IIM entity,[27] with the designation “immune-mediated NM” (IMNM). Two distinct autoantibodies are found associated with IMNM, with one being anti-signal recognition particle antibody (anti-SRP)[28] and the other being anti-hydroxy-methylglutaryl-CoA reductase antibody (anti-HMGCR).[29] Early on, it was thought that anti-SRP antibody was specific for PM. Anti-HMGCR antibody was first discovered in patients who were taking statins for hyperlipidemia.[27],[29] Clinical features associated with the presence of both of these antibodies share characteristics of severe proximal muscle weakness with high serum CK (>10,000 IU/L) and dysphagia.[28],[30] Treatment responses to high-dose PSL (including PSL pulse therapy) together with immunosuppressant therapy are usually poor and often recurrent. Although some patients with anti-HMGCR antibodies improve when statins are discontinued, this is not the case for some patients. Some statin-naïve patients may also be positive for anti-HMGCR antibody.[29] Extramuscular manifestations are generally rare in patients with either anti-SRP or anti-HMGCR antibodies. However, a polyarthritic syndrome similar to rheumatoid arthritis (RA), or cardiac disorders, has been reported in patients with anti-SRP antibodies. Muscle biopsy findings show pathologically distinct severe necrosis of myofibrils with a few infiltrations of inflammatory cells. Standard treatment strategy for IMNM is the initiation of intravenous PSL pulse therapy followed by high-dose PSL and immunosuppressants (MTX or AZA or CyA or TAC or MMF). In addition, monthly IVIG therapy can be initiated and continued for several cycles with the expectation of achieving favorable effects.[31] Similarly, RTX could be another treatment option if patients are refractory to this treatment or for disease recurrence.[32]

Rapidly progressive interstitial lung disease

DM, and especially CADM, is often associated with life-threatening intractable RP-ILD. It is well known that such patients frequently possess autoantibodies with distinct specificities, especially anti-MDA5 antibody in Eastern Asian populations.[33],[34],[35] Previous studies revealed that the presence of anti-MDA5 antibody is closely associated with RP-ILD and is a useful biomarker predicting a poor prognosis.[35],[36] Because randomized prospective clinical trials for this condition have not yet been conducted, evidence-based treatment strategies for anti-MDA5-positive RP-ILD associated with DM have not been established. Recently, the efficacy of intensive triple combination therapy consisting of high-dose corticosteroids together with calcineurin inhibitors for this condition has been described (e.g., CyA starting at 2–4 mg/kg/day once or twice daily aiming for a blood trough level of 150–200 ng/mL; or TAC starting at 1 mg/day or 0.075 mg/kg once or twice a day aiming for a blood trough level of 10-15 ng/mL and IVCY (generally 0.3–0.8 g/m 2 monthly, with dosage, interval, and frequency varying according to the severity of disease, response to therapy, and adverse events).[37]

Nevertheless, RP-ILD associated with DM still has a very poor prognosis despite initiation of such intensive treatment regimens. In such patients who have failed this treatment, additional options including MMF, JAK inhibitors, RTX, IVIG, polymyxin B-immobilized fiber column direct hemoperfusion, and plasma exchange therapy have all been attempted to try to improve the clinical condition. However, the efficacy of these therapies for RP-ILD associated with DM has not been determined, and establishing effective therapies for this condition remains a major challenge.

  Emerging Therapies Top

Anti-tumor necrosis factor-α agents

Infliximab and etanercept have been employed in efforts to decrease the disease activity of PM/DM. However, their efficacy and safety is extremely variable, and evaluation of their potential usefulness remains to be completed. Some studies have indicated that infliximab is well tolerated and effective,[38] whereas others have reported no effects and lack of improvement of muscle strength in patients with PM/DM.[39] Results of etanercept treatment of PM/DM are similar to infliximab.[40] Moreover, patients in whom DM was actually induced by anti-tumor necrosis factor (TNF)-α therapy have been reported.[41] Taken together, the available data suggested that anti-TNF-α therapy for PM/DM patients cannot be recommended at this time [Table 1].
Table 1: Possible emerging treatments for idiopathic inflammatory myopathies other than inclusion body myositis

Click here to view


Because previous studies had demonstrated that overexpression of IL-6 in muscle tissue and serum IL-6 concentration are significantly correlated with disease activity in myositis, the use of the humanized IL-6 receptor antibody tocilizumab was expected to improve muscle inflammation in patients with PM/DM.[42]

Two case reports from Japan describing the effect of tocilizumab are available.[43],[44] One reported that two anti-Jo-1-positive refractory PM patients were successfully treated with tocilizumab at 8 mg/kg every 4 weeks. The other indicated that a patient with DM/SSc overlap syndrome and RA refractory to other immunosuppressive agents showed improved skin, joint, and muscle symptoms. At present, an investigator-initiated, multicentric, randomized, double-blind, controlled Phase II trial is currently running to evaluate efficacy in refractory PM/DM ( Identifier: NCT02043548). Currently, whether tocilizumab will show any activity for ILD associated with PM/DM remains unknown.


Abatacept, a fusion protein of CTLA-4 and the Fc fragment of IgG, is well known to be effective for joint inflammation in RA by means of inhibiting co-stimulatory signals from antigen-presenting cells. The upregulation of CD28 and CTLA-4 has been reported in muscle tissue from PM/DM patients, and several case reports indicating the efficacy of abatacept for refractory PM/DM have appeared.[45] In 2018, Tjärnlund et al. reported the results of a randomized, Phase IIb delayed-start trial to study the efficacy of abatacept for refractory PM/DM (ARTEMIS study).[46] Twenty patients with PM/DM (PM n = 11, DM n = 9) were randomized to receive abatacept at the start of the trial or after 3 months. Eight of 19 (42%) patients achieved the International Myositis Assessment and Clinical Studies Group definition of improvement. A randomized, placebo-controlled Phase III trial is now ongoing to evaluate the efficacy and safety of intravenous abatacept together with standard therapy compared to standard therapy alone in patients with active IIMs ( identifier: NCT02971683). A randomized, controlled Phase II trial to evaluate the efficacy and safety for ILD associated with the ARS syndrome is also underway ( identifier: NCT03215927).

Janus kinase inhibitor

The JAK-signal transducer and activator of transcription (JAK-STAT) pathway plays a critical role in the regulation of immunity affecting several cytokines and interferon (IFN) activity. At present, several JAK inhibitors are available to treat RA. The JAK inhibitor, ruxolitinib, approved for myelofibrosis and polycythemia rubra vera, was the first with reported efficacy in patients with myelofibrosis and DM overlap. Subsequently, several case reports or case series were published documenting successful treatment with tofacitinib (a JAK I/III inhibitor) of skin and/or joint symptoms in DM patients.[47] A study of tofacitinib in refractory DM (STIR: Open-label, pilot Phase I study recruiting ten patients) is underway ( Identifier: NCT03002649), and interim results were presented in 2018.[48] In that report, five of nine patients (56%) exhibited moderate improvement and the remaining four (44%) had minimal improvement as evaluated by the Total Improvement Score of the Myositis Response Criteria. Kurasawa et al. reported the efficacy of tofacitinib in combination with triple therapy (high-dose glucocorticoid, CyA, and CY) for refractory anti-MDA5-positive RP-ILD and DM.[49] Although respiratory symptoms improved in three of the five patients with RP-ILD associated with DM, the remaining two patients died of their disease. However, that survival rate is significantly better than for historical controls. In that study, viral infections were encountered and care needs to be taken during treatment with tofacitinib. Another study reported the efficacy of tofacitinib in early-stage anti-MDA5-positive ILD associated with ADM.[50]


Recent studies revealed the importance of type I IFN (IFN-α/-β)-mediated innate immunity in the pathogenesis of DM. Previous reports showed that a group of type I IFN-inducible genes is overexpressed in DM patients in contrast to other myositis patients, and that levels of IFN-regulated cytokines are increased in the serum of DM patients. Guo et al. reported that sifalimumab neutralized this type I IFN gene signature, leading to sequential suppression of soluble IL-2 receptor A (IL-2RA), TNF receptor 2, and IL-18.[51] Suppression of IL-2RA correlated with muscle strength in MMT-8. A Phase Ib randomized, double-blind, controlled trial revealed the suppression of the IFN signature in both the serum and muscle tissue and its correlation with clinical manifestations.[52]


Apremilast, a phosphodiesterase-4 inhibitor, is presumed to exert its anti-inflammatory effects by increasing the concentrations of adenosine monophosphate. The effectiveness of apremilast for relieving the cutaneous symptoms of patients with psoriasis and Behçet's disease has been reported, and Bitar et al. have reported the efficacy of this agent in three cases with recalcitrant DM. In that report, both cutaneous DM activity and severity index and muscle enzyme level improved in all the three patients.[53] A Phase II clinical trial to examine the safety and efficacy of apremilast in patients with treatment-resistant DM with cutaneous manifestations is currently ongoing ( identifier: NCT03529955).


Lenabasum exerts agonistic functions through binding the type 2 cannabinoid (CB2) receptor, which is mainly expressed in immunopathologically inflamed tissues. Previous studies indicated that CB2 receptor activation has anti-inflammatory effects. Therefore, CB2 receptor may be a promising target in the treatment of chronic inflammatory disease such as RA, or PM/DM. Moreover, it is also assumed to be involved in anti-fibrotic effects. A double-blind, randomized, placebo-controlled Phase II study to evaluate the safety, tolerability, and efficacy in skin-predominant DM refractory to treatment with HCQ is ongoing ( Identifier: NCT02466243).[54] A multicentric, double-blind, randomized, placebo-controlled Phase III trial to evaluate the efficacy and safety of lenabasum in DM (DETERMINE) is also now ongoing ( Identifier: NCT03813160).

Adrenocorticotropic hormone gel

Adrenocorticotropic hormone gel (corticotropin injection) is a long-acting, full-sequence adrenocorticotropic hormone preparation that contains pro-opiomelanocortin peptides. It is expected to have anti-inflammatory and immunomodulatory effects through the activation of melanocortin receptors. Previously, a retrospective case review examined the effects of ACTH gel in five PM/DM patients who were refractory to treatment or could not be treated due to adverse events. ACTH gel was effective for both skin and muscle manifestations in all the five patients.[55] Recently, the results of an open-label clinical trial to assess the efficacy, safety, tolerability, and steroid-sparing effect of corticotropin injection in patients with refractory PM/DM were published.[56] In that study, corticotropin injection was effective in seven patients (70%) and was safe and tolerated in patients with adult PM/DM who were refractory to conventional therapy.

  Inclusion Body Myositis Top

IBM is one of a subgroup of IIMs that is mainly characterized by insidiously slowly progressive muscle weakness. In contrast to PM/DM, IBM preferentially affects men over 50 years of age.[57] The most characteristic features are finger flexor and quadriceps muscles weakness.[58] Although the pathogenesis of IBM remains unknown, the involvement of both autoimmune and protein and myonuclear degeneration has been suggested. Previous studies showed that exercise and orthoses might be safe and useful for maintaining muscle strength and function and stabilize the lower limbs, although the sample sizes in these studies were small.[59]

  Conventional Therapies Top

Glucocorticoids and immunosuppressants

The efficacy of pharmacological treatments such as glucocorticoids and immunosuppressants such as MTX, AZA, or MMF has not been validated in large-scale, randomized controlled trials. Reports of trends toward mild and temporary improvement in small cases series are all that is available in the literature. Currently, the use of these agents is not recommended for IBM. Other than these, β-interferon-1α, anti-T-lymphocyte globulin, TNF-α blockade (etanercept), anti-CD52 monoclonal antibody (alemtuzumab), anti-IL-1R antagonist (Anakinra), anti-CD20 antibody (RTX), lithium, and simvastatin have all been tried in IBM patients, but without any reports of significant improvements.

Intravenous immunoglobulin

IVIG is a treatment option that was suggested to possibly improve the symptoms of IBM, especially dysphagia.[60] However, longer observation of larger patient groups has not indicated a consistent or significant effect to stop the progression of IBM symptoms [Table 2].[61]
Table 2: Possible treatments for inclusion body myositis

Click here to view

  Emerging Therapies Top

Because most therapies that target inflammatory pathways have been found to be inactive in IBM, recent studies have tended to focus on agents other than anti-inflammatories, as outlined below.


Arimoclomol is an inducer of heat shock protein (HSP) production through the activation of HSP factor 1. Augmentation of HSP function is thought to potentially normalize protein folding and thus prevent degenerative muscle damage in IBM. A double-blind, randomized, placebo-controlled Phase IIa trial recruiting 24 IBM patients demonstrated that arimoclomol was safe and well tolerated, and also suggested possible efficacy (but statistical significance was not achieved).[62] Currently, a large-scale Phase II/III trial is ongoing ( identifier: NCT02753530).[63]


Bimagrumab is an activin receptor II-specific monoclonal antibody postulated to improve the symptoms of IBM through the inhibition of the transforming growth factor-β (TGF-β) family member myostatin, and thus to facilitate muscle hypertrophy and increase muscle strength. In a pilot study, thigh muscle volume and lean body mass were significantly increased in bimagrumab-treated patients, who also had improved 6-min walk distance (6MWD).[64] However, a follow-up Phase IIb/III multicentric, double-blind, placebo-controlled study (RESILIENT) showed that bimagrumab was safe but failed to show any significant differences in changes of 6MWD relative to the placebo group. Hence, any benefit of bimagrumab remains unproven.[65]


Rapamycin is a potentially effective agent for IBM because of its mechanism of action. It seems both to regulate abnormal autophagic phenomena and to control autoimmune conditions. A double-blind, randomized, placebo-controlled Phase IIb trial was conducted by a French group to evaluate the effect of rapamycin to IBM. In that study, 6MWD, FVC, and fatty replacement of quadriceps were found to be improved, whereas there were no differences between the rapamycin group and control group in the decrease of maximal voluntary quadriceps isometric strength, which was the primary end point.[66]


Follistatin is thought to induce increased muscle mass via inhibition of myostatin function. Follistatin gene therapy by intramuscular injection of an isoform of follistatin (FS344) into the quadriceps muscle in six IBM patients has been reported.[67] In that study, the primary end point (6MWD) was improved in four of six patients. However, the effectiveness of follistatin for IBM remains controversial because the IBM patients tested in the study received additional treatment and exercise therapy that the control group did not.[67],[68] Further trials are required to elucidate the efficacy of follistatin gene therapy.


Previously used as an anabolic steroid, the efficacy of oxandrolone has been examined in IBM patients.[69] A randomized placebo-controlled trial indicated some improvement of whole body strength, especially the upper extremities. However, no trials repeating this result of oxandrolone use were reported thereafter.

  Conclusions Top

Although large-scaled, placebo-controlled prospective studies have not been performed to validate the efficacy of glucocorticoid therapy, steroids remain first-line agents to improve muscle and/or respiratory symptoms of IIMs, except in IBM patients. Several immunosuppressive agents and IVIG have been used concomitantly or sequentially for the purpose of steroid sparing or supplemental or to enhance the effect of corticosteroids. Moreover, several new biologics or JAK inhibitors or other anti-inflammatory/anti-degenerative agents that inhibit pathways thought to be involved in the pathogenesis of IIMs have been trialed for symptomatic relief. Thus, although treatment strategies for IIMs have markedly improved recently, only limited effects on more severe and refractory conditions as represented by IMNM or RP-ILD or IBM have been achieved [Figure 1]. Further investigations are still needed to establish the most effective therapeutic options for IIMs and associated symptoms such as ILD or cutaneous manifestations. These must be accomplished through the planning preferably of large-scale, double-blind, placebo-controlled prospective studies.
Figure 1: Approach to managing the various subgroups of idiopathic inflammatory myopathies

Click here to view

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Bohan A, Peter JB. Polymyositis and dermatomyositis. N Engl J Med 1975;292:344-7.  Back to cited text no. 1
Bohan A, Peter JB. Polymyositis and dermatomyositis. N Engl J Med 1975;292:403-7.  Back to cited text no. 2
Dalakas MC. Polymyositis, dermatomyositis and inclusion-body myositis. N Engl J Med 1991;325:1487-98.  Back to cited text no. 3
Mariampillai K, Granger B, Amelin D, Guiguet M, Hachulla E, Maurier F, et al. Development of a new classification system for idiopathic inflammatory myopathies based on clinical manifestations and myositis-specific autoantibodies. JAMA Neurol 2018;75:1528-37.  Back to cited text no. 4
Joffe MM, Love LA, 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. Am J Med 1993;94:379-87.  Back to cited text no. 5
Combined Treatment of Methotrexate+Glucocorticoids Versus Glucocorticoids Alone in Patients with PM and DM. Available from: [Last accessed on 2016 May 12].  Back to cited text no. 6
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 Rheum 1998;41:392-9.  Back to cited text no. 7
Marie I, Hachulla E, Chérin P, Dominique S, Hatron PY, Hellot MF, et al. Interstitial lung disease in polymyositis and dermatomyositis. Arthritis Rheum 2002;47:614-22.  Back to cited text no. 8
Kurita T, Yasuda S, Oba K, Odani T, Kono M, Otomo K, et al. The efficacy of tacrolimus in patients with interstitial lung diseases complicated with polymyositis or dermatomyositis. Rheumatology (Oxford) 2015;54:39-44.  Back to cited text no. 9
Mitsui T, Kuroda Y, Ueno S, Kaji R. The effects of FK506 on refractory inflammatory myopathies. Acta Neurol Belg 2011;111:188-94.  Back to cited text no. 10
Wilkes MR, Sereika SM, Fertig N, Lucas MR, Oddis CV. Treatment of antisynthetase-associated interstitial lung disease with tacrolimus. Arthritis Rheum 2005;52:2439-46.  Back to cited text no. 11
Huang K, Vinik O, Shojania K, Yeung J, Shupak R, Nimmo M, et al. Clinical spectrum and therapeutics in Canadian patients with anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis: A case-based review. Rheumatol Int 2019;39:1971-81.  Back to cited text no. 12
Fischer A, Brown KK, Du Bois RM, Frankel SK, Cosgrove GP, Fernandez-Perez ER, et al. Mycophenolate mofetil improves lung function in connective tissue disease-associated interstitial lung disease. J Rheumatol 2013;40:640-6.  Back to cited text no. 13
Yamasaki Y, Yamada H, Yamasaki M, Ohkubo M, Azuma K, Matsuoka S, et al. Intravenous cyclophosphamide therapy for progressive interstitial pneumonia in patients with polymyositis/dermatomyositis. Rheumatology (Oxford) 2007;46:124-30.  Back to cited text no. 14
Ge Y, Peng Q, Zhang S, Zhou H, Lu X, Wang G. Cyclophosphamide treatment for idiopathic inflammatory myopathies and related interstitial lung disease: A systematic review. Clin Rheumatol 2015;34:99-105.  Back to cited text no. 15
Miyasaka N, Hara M, Koike T, Saito E, Yamada M, Tanaka Y, et al. Effects of intravenous immunoglobulin therapy in Japanese patients with polymyositis and dermatomyositis resistant to corticosteroids: A randomized double-blind placebo-controlled trial. Mod Rheumatol 2012;22:382-93.  Back to cited text no. 16
Diot E, Carmier D, Marquette D, Marchand-Adam S, Diot P, Lesire V. IV immunoglobulin might be considered as a first-line treatment of severe interstitial lung disease associated with polymyositis. Chest 2011;140:562-3.  Back to cited text no. 17
Koguchi-Yoshioka H, Okiyama N, Iwamoto K, Matsumura Y, Ogawa T, Inoue S, et al. Intravenous immunoglobulin contributes to the control of antimelanoma differentiation-associated protein 5 antibody-associated dermatomyositis with palmar violaceous macules/papules. Br J Dermatol 2017;177:1442-6.  Back to cited text no. 18
Huapaya JA, Hallowell R, Silhan L, Pinal-Fernandez I, Casal-Dominguez M, Johnson C, et al. Long-term treatment with human immunoglobulin for antisynthetase syndrome-associated interstitial lung disease. Respir Med 2019;154:6-11.  Back to cited text no. 19
Fasano S, Gordon P, Hajji R, Loyo E, Isenberg DA. Rituximab in the treatment of inflammatory myopathies: A review. Rheumatology (Oxford) 2017;56:26-36.  Back to cited text no. 20
Oddis CV, Reed AM, Aggarwal R, Rider LG, Ascherman DP, Levesque MC, et al. Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: A randomized, placebo-phase trial. Arthritis Rheum 2013;65:314-24.  Back to cited text no. 21
Aggarwal R, Bandos A, Reed AM, Ascherman DP, Barohn RJ, Feldman BM, et al. Predictors of clinical improvement in rituximab-treated refractory adult and juvenile dermatomyositis and adult polymyositis. Arthritis Rheumatol 2014;66:740-9.  Back to cited text no. 22
Ogawa Y, Kishida D, Shimojima Y, Hayashi K, Sekijima Y. Effective administration of rituximab in anti-MDA5 antibody-positive dermatomyositis with rapidly progressive interstitial lung disease and refractory cutaneous involvement: A case report and literature review. Case Rep Rheumatol 2017;2017:5386797.  Back to cited text no. 23
Andersson H, Sem M, Lund MB, Aaløkken TM, Günther A, Walle-Hansen R, et al. Long-term experience with rituximab in anti-synthetase syndrome-related interstitial lung disease. Rheumatology (Oxford) 2015;54:1420-8.  Back to cited text no. 24
So H, Wong VT, Lao VW, Pang HT, Yip RM. Rituximab for refractory rapidly progressive interstitial lung disease related to anti-MDA5 antibody-positive amyopathic dermatomyositis. Clin Rheumatol 2018;37:1983-9.  Back to cited text no. 25
Woo TY, Callen JP, Voorhees JJ, Bickers DR, Hanno R, Hawkins C. Cutaneous lesions of dermatomyositis are improved by hydroxychloroquine. J Am Acad Dermatol 1984;10:592-600.  Back to cited text no. 26
Christopher-Stine L, Casciola-Rosen LA, Hong G, Chung T, Corse AM, Mammen AL. A novel autoantibody recognizing 200-kd and 100-kd proteins is associated with an immune-mediated necrotizing myopathy. Arthritis Rheum 2010;62:2757-66.  Back to cited text no. 27
Pinal-Fernandez I, Parks C, Werner JL, Albayda J, Paik J, Danoff SK, et al. Longitudinal course of disease in a large cohort of myositis patients with autoantibodies recognizing the signal recognition particle. Arthritis Care Res (Hoboken) 2017;69:263-70.  Back to cited text no. 28
Mammen AL, Chung T, Christopher-Stine L, Rosen P, Rosen A, Doering KR, et al. Autoantibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase in patients with statin-associated autoimmune myopathy. Arthritis Rheum 2011;63:713-21.  Back to cited text no. 29
Limaye V, Bundell C, Hollingsworth P, Rojana-Udomsart A, Mastaglia F, Blumbergs P, et al. Clinical and genetic associations of autoantibodies to 3-hydroxy-3-methyl-glutaryl-coenzyme a reductase in patients with immune-mediated myositis and necrotizing myopathy. Muscle Nerve 2015;52:196-203.  Back to cited text no. 30
Mammen AL, Tiniakou E. Intravenous immune globulin for statin-triggered autoimmune myopathy. N Engl J Med 2015;373:1680-2.  Back to cited text no. 31
Valiyil R, Casciola-Rosen L, Hong G, Mammen A, Christopher-Stine L. Rituximab therapy for myopathy associated with anti-signal recognition particle antibodies: A case series. Arthritis Care Res (Hoboken) 2010;62:1328-34.  Back to cited text no. 32
Sato S, Hoshino K, Satoh T, Fujita T, Kawakami Y, Fujita T, et al. RNA helicase encoded by melanoma differentiation-associated gene 5 is a major autoantigen in patients with clinically amyopathic dermatomyositis: Association with rapidly progressive interstitial lung disease. Arthritis Rheum 2009;60:2193-200.  Back to cited text no. 33
Nakashima R, Imura Y, Kobayashi S, Yukawa N, Yoshifuji H, Nojima T, et al. The RIG-I-like receptor IFIH1/MDA5 is a dermatomyositis-specific autoantigen identified by the anti-CADM-140 antibody. Rheumatology (Oxford) 2010;49:433-40.  Back to cited text no. 34
Chen Z, Cao M, Plana MN, Liang J, Cai H, Kuwana M, et al. Utility of anti-melanoma differentiation-associated gene 5 antibody measurement in identifying patients with dermatomyositis and a high risk for developing rapidly progressive interstitial lung disease: A review of the literature and a meta-analysis. Arthritis Care Res (Hoboken) 2013;65:1316-24.  Back to cited text no. 35
Sato S, Masui K, Nishina N, Kawaguchi Y, Kawakami A, Tamura M, et al. Initial predictors of poor survival in myositis-associated interstitial lung disease: A multicentre cohort of 497 patients. Rheumatology (Oxford) 2018;57:1212-21.  Back to cited text no. 36
Tsuji H, Nakashima R, Hosono Y, Imura Y, Yagita M, Yoshifuji H, et al. Multicenter prospective study of the efficacy and safety of combined immunosuppressive therapy with high-dose glucocorticoid, tacrolimus, and cyclophosphamide in interstitial lung diseases accompanied by anti-melanoma differentiation-associated gene 5-positive dermatomyositis. Arthritis Rheumatol 2020;72:488-98.  Back to cited text no. 37
Schiffenbauer A, Garg M, Castro C, Pokrovnichka A, Joe G, Shrader J, et al. A randomized, double-blind, placebo-controlled trial of infliximab in refractory polymyositis and dermatomyositis. Semin Arthritis Rheum 2018;47:858-64.  Back to cited text no. 38
Dastmalchi M, Grundtman C, Alexanderson H, Mavragani CP, Einarsdottir H, Helmers SB, et al. A high incidence of disease flares in an open pilot study of infliximab in patients with refractory inflammatory myopathies. Ann Rheum Dis 2008;67:1670-7.  Back to cited text no. 39
Muscle Study Group. A randomized, pilot trial of etanercept in dermatomyositis. Ann Neurol 2011;70:427-36.  Back to cited text no. 40
Takata M, Yamasaki A, Yamada N, Hagino H, Funaki Y, Harada T, et al. A case of clinically amyopathic dermatomyositis that developed during anti-TNF-α therapy for rheumatoid arthritis. Allergol Int 2018;67:286-8.  Back to cited text no. 41
Bilgic H, Ytterberg SR, Amin S, McNallan KT, Wilson JC, Koeuth T, et al. Interleukin-6 and type I interferon-regulated genes and chemokines mark disease activity in dermatomyositis. Arthritis Rheum 2009;60:3436-46.  Back to cited text no. 42
Narazaki M, Hagihara K, Shima Y, Ogata A, Kishimoto T, Tanaka T. Therapeutic effect of tocilizumab on two patients with polymyositis. Rheumatology (Oxford) 2011;50:1344-6.  Back to cited text no. 43
Kondo M, Murakawa Y, Matsumura T, Matsumoto O, Taira M, Moriyama M, et al. A case of overlap syndrome successfully treated with tocilizumab: A hopeful treatment strategy for refractory dermatomyositis? Rheumatology (Oxford) 2014;53:1907-8.  Back to cited text no. 44
Kerola AM, Kauppi MJ. Abatacept as a successful therapy for myositis – A case-based review. Clin Rheumatol 2015;34:609-12.  Back to cited text no. 45
Tjärnlund A, Tang Q, Wick C, Dastmalchi M, Mann H, Tomasová Studýnková J, et al. Abatacept in the treatment of adult dermatomyositis and polymyositis: A randomised, phase IIb treatment delayed-start trial. Ann Rheum Dis 2018;77:55-62.  Back to cited text no. 46
Moghadam-Kia S, Charlton D, Aggarwal R, Oddis CV. Management of refractory cutaneous dermatomyositis: Potential role of Janus kinase inhibition with tofacitinib. Rheumatology (Oxford) 2019;58:1011-5.  Back to cited text no. 47
Paik JJ, Albayda J, Tiniakou E, Koenig A, Christopher-Stine L. Study of tofacitinib in refractory dermatomyositis (STIR): An open label pilot study in refractory dermatomyositis. Arthritis Rheumatol 2018;70 Suppl 10:L02.  Back to cited text no. 48
Kurasawa K, Arai S, Namiki Y, Tanaka A, Takamura Y, Owada T, et al. Tofacitinib for refractory interstitial lung diseases in anti-melanoma differentiation-associated 5 gene antibody-positive dermatomyositis. Rheumatology (Oxford) 2018;57:2114-9.  Back to cited text no. 49
Chen Z, Wang X, Ye S. Tofacitinib in amyopathic dermatomyositis-associated interstitial lung disease. N Engl J Med 2019;381:291-3.  Back to cited text no. 50
Guo X, Higgs BW, Rebelatto M, Zhu W, Greth W, Yao Y, et al. Suppression of soluble T cell-associated proteins by an anti-interferon-α monoclonal antibody in adult patients with dermatomyositis or polymyositis. Rheumatology (Oxford) 2014;53:686-95.  Back to cited text no. 51
Higgs BW, Zhu W, Morehouse C, White WI, Brohawn P, Guo X, et al. A phase 1b clinical trial evaluating sifalimumab, an anti-IFN-α monoclonal antibody, shows target neutralization of a type I IFN signature in blood of dermatomyositis and polymyositis patients. Ann Rheum Dis 2014;73:256-62.  Back to cited text no. 52
Bitar C, Maghfour J, Ho-Pham H, Stumpf B, Boh E. Apremilast as a potential treatment for moderate to severe dermatomyositis: A retrospective study of 3 patients. JAAD Case Rep 2019;5:191-4.  Back to cited text no. 53
Werth VP, Hejazi E, Pena SM, Haber JS, Okawa J, Feng R, et al. A phase 2 study of safety and efficacy of anabasum (JBT-101), a cannabinoid receptor type 2 agonist, in refractory skin- predominant dermatomyositis. Arthritis Rheumatol 2017;69 Suppl 10:7L.  Back to cited text no. 54
Levine T. Treating refractory dermatomyositis or polymyositis with adrenocorticotropic hormone gel: A retrospective case series. Drug Des Devel Ther 2012;6:133-9.  Back to cited text no. 55
Aggarwal R, Marder G, Koontz DC, Nandkumar P, Qi Z, Oddis CV. Efficacy and safety of adrenocorticotropic hormone gel in refractory dermatomyositis and polymyositis. Ann Rheum Dis 2018;77:720-7.  Back to cited text no. 56
Cortese A, Machado P, Morrow J, Dewar L, Hiscock A, Miller A, et al. Longitudinal observational study of sporadic inclusion body myositis: Implications for clinical trials. Neuromuscul Disord 2013;23:404-12.  Back to cited text no. 57
Rose MR; ENMC IBM Working Group. 188th ENMC International Workshop: Inclusion Body Myositis, 2–4 December 2011, Naarden, The Netherlands. Neuromuscul Disord 2013;23:1044-55.  Back to cited text no. 58
Ko EH, Rubin AD. Dysphagia due to inclusion body myositis: Case presentation and review of the literature. Ann Otol Rhinol Laryngol 2014;123:605-8.  Back to cited text no. 59
Cherin P, Pelletier S, Teixeira A, Laforet P, Simon A, Herson S, et al. Intravenous immunoglobulin for dysphagia of inclusion body myositis. Neurology 2002;58:326.  Back to cited text no. 60
Patwa HS, Chaudhry V, Katzberg H, Rae-Grant AD, So YT. Evidence-based guideline: Intravenous immunoglobulin in the treatment of neuromuscular disorders: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2012;78:1009-15.  Back to cited text no. 61
Ahmed M, Machado PM, Miller A, Spicer C, Herbelin L, He J, et al. Targeting protein homeostasis in sporadic inclusion body myositis. Sci Transl Med 2016;8:331ra41.  Back to cited text no. 62
Machado P, Barohn R, McDermott M, Blaetter T, Lloyd T, Shaibani A, et al. Phase 2/3 study of Arimoclomol in sporadic inclusion body myositis: Study design. Neuromuscular Disord 2019;29 Suppl 1:S41-2.  Back to cited text no. 63
Amato AA, Sivakumar K, Goyal N, David WS, Salajegheh M, Praestgaard J, et al. Treatment of sporadic inclusion body myositis with bimagrumab. Neurology 2014;83:2239-46.  Back to cited text no. 64
Hanna MG, Badrising UA, Benveniste O, Lloyd TE, Needham M, Chinoy H, et al. Safety and efficacy of intravenous bimagrumab in inclusion body myositis (RESILIENT): A randomised, double-blind, placebo-controlled phase 2b trial. Lancet Neurol 2019;18:834-44.  Back to cited text no. 65
Lilleker JB, Bukhari M, Chinoy H. Rapamycin for inclusion body myositis: Targeting non-inflammatory mechanisms. Rheumatology (Oxford) 2019;58:375-6.  Back to cited text no. 66
Mendell JR, Sahenk Z, Al-Zaidy S, Rodino-Klapac LR, Lowes LP, Alfano LN, et al. Follistatin Gene Therapy for Sporadic Inclusion Body Myositis Improves Functional Outcomes. Mol Ther 2017;25:870-9.  Back to cited text no. 67
Greenberg SA. Unfounded claims of improved functional outcomes attributed to follistatin gene therapy in inclusion body myositis. Mol Ther 2017;25:2235-7.  Back to cited text no. 68
Rutkove SB, Parker RA, Nardin RA, Connolly CE, Felice KJ, Raynor EM, et al. A pilot randomized trail of oxandrolone in inclusion body myositis. Neurology. 2002;58:1081-7.  Back to cited text no. 69


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