RARE DISEASE
Idiopathic inflammatory myopathy
Idiopathic inflammatory myopathy
Idiopathic inflammatory myopathy
Synonyms: IMM, Idiopathic inflammatory myositis
Synonyms: IMM, Idiopathic inflammatory myositis
Synonyms: IMM, Idiopathic inflammatory myositis
Drug discovery
9
drugs
With orphan designations
Overview
Idiopathic Inflammatory Myopathy (IIM) comprises a group of rare, heterogeneous autoimmune disorders characterized by chronic muscle inflammation and systemic involvement (e.g., skin, lungs, heart). Key subtypes include dermatomyositis, polymyositis, inclusion body myositis (IBM), antisynthetase syndrome, and immune-mediated necrotizing myopathy. Diagnosis hinges on clinical findings (progressive weakness, extramuscular manifestations), elevated muscle enzymes, serologic markers (myositis-specific autoantibodies), and imaging/biopsy. Early intervention is critical to mitigate irreversible damage and mortality from malignancy or cardiopulmonary complications [1][5][12].
Population
Incidence: 0.2–2.0 per 100,000 person-years; prevalence: 2–25 per 100,000 [6][10][16].
Demographics: Peaks in adults (45–60 years) and children (5–15 years); predominates in females (2:1 ratio), except IBM (male predominance) [9][12].
Risk factors: Ethnic disparities (higher incidence in Black and Asian populations vs. White) [2][13].
Burden
Mortality: Standardized mortality ratio 5.1 (up to 7.9 with ILD); malignancy, respiratory, and cardiovascular causes dominate [2][6][16].
Economic impact: Annual costs 3–5× higher vs. general population, driven by hospitalizations, outpatient care, and productivity loss [4].
Caregiver burden: Severe in IBM (33% report moderate-severe strain) due to chronic disability and slow progression [8][12].
Therapies
First-line: High-dose corticosteroids + steroid-sparing agents (methotrexate, azathioprine) [3][11][17].
Refractory/ILD: Biologics (rituximab), calcineurin inhibitors (tacrolimus), IV immunoglobulin, or JAK inhibitors [3][11][14].
IBM: Largely treatment-resistant; focus on physical therapy, dysphagia management, and fall prevention [7][15].
Categories: rare neurological diseases, rare systemic and rheumatological diseases
Research Papers
856 drug discovery papers about Idiopathic inflammatory myopathy, with 2 first-in-class and 5 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
856 drug discovery papers about Idiopathic inflammatory myopathy, with 2 first-in-class and 5 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-30 | [Analysis of clinical and muscle pathological features of juvenile idiopathic inflammatory myopathy].
Objective: To investigate the clinical manifestations, muscle imaging features, and muscle pathological characteristics of juvenile idiopathic inflammatory myopathies (IIM). Methods: A retrospective cohort study was conducted including 76 children with IIM admitted to Children's Medical Center, Peking University First Hospital from January 2012 to January 2024. Clinical manifestations, laboratory findings, muscle imaging features, and muscle pathological characteristics were compared between the major subtypes of dermatomyositis and immune-mediated necrotizing myopathy (IMNM). Independent sample t-test or Mann-Whitney U test, and χ2 test or Fisher's exact test were used to compare differences in characteristics between groups. Results: Among 76 children with IIM, 30 were males and 46 were females, with the age of onset at 5.0 (3.0, 8.0) years. Of these 76 children, 57 children were diagnosed with dermatomyositis, 15 children with immune-mediated necrotizing myopathy (IMNM) and 4 children with overlap myositis. The proportion of heliotrope rash, Gottron's sign, and antinuclear antibody positivity were all higher in the dermatomyositis group than those in the IMNM group (63% (36/57) vs.1/15, 47% (27/57) vs. 0/15, and 68% (32/47) vs. 5/14, respectively, all P<0.05), whereas serum creatine kinase (CK), alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase levels were all lower (all P<0.05). The proportion of myositis specific autoantibody positivity was also lower in the dermatomyositis group than in the IMNM group (52% (24/46) vs. 13/14, P=0.006). Muscle MRI showed that subcutaneous soft tissue edema was more frequently observed in the dermatomyositis group than in the IMNM group (28% (14/50) vs. 0/14, P=0.005), whereas muscle fatty infiltration was less common in the dermatomyositis group (16% (8/50) vs. 9/14, P<0.001). On muscle pathology, perifascicular muscle fiber atrophy and perivascular inflammatory cell infiltration, as well as sarcoplasmic myxovirus resistance protein A expression on perifascicular myofibers, were more common in the dermatomyositis group (78% (28/36) vs. 1/7, 89% (32/36) vs.1/7 and 10/14 vs. 0/4, respectively, all P<0.05), while muscle fiber necrosis, perimysial hyperplasia, and endomysial hyperplasia were more common in the IMNM group (7/7 vs. 33% (12/36), 2/7 vs. 0/36 and 4/7 vs. 3% (1/36), respectively, all P<0.05). Conclusions: There are differences between the 2 major juvenile IIM subtypes in terms of clinical manifestations, muscle MRI findings, and muscle pathological features. Dermatomyositis is more likely to present with characteristic skin rashes and perifascicular muscle fiber pathological changes, whereas IMNM is characterized by markedly elevated serum CK levels and prominent muscle fiber necrosis, and is more frequently associated with muscle fatty infiltration.
2026-07-29 | [From CAR-T to T-cell engagers : New T-cell-based treatment in rheumatology].
Cellular forms of treatment mark a paradigm shift in the treatment of autoimmune diseases. While conventional and targeted antirheumatic treatment controls disease activity mostly by continued immunomodulation, innovative cellular approaches, especially chimeric antigen receptor (CAR) T‑cells targeting CD19, target a deep elimination of disease-relevant immune cell compartments with subsequent immunological reconstitution. This concept of an immune reset is particularly attractive for those diseases in which autoreactive B‑cells, plasmablasts, autoantibodies and misdirected lymphocyte networks are pathogenetically central. In addition, T‑cell engagers or bispecific T‑cell engagers (TCE) are now becoming of interest, which as off the shelf strategies without cellular production also enable a deep B‑cell or plasma cell depletion via T cell-mediated cytotoxicity. The most impressive clinical data so far are available for systemic lupus erythematosus (SLE), likewise accumulating indications for the efficacy in systemic sclerosis (SSc) and idiopathic inflammatory myositis (IIM). The concept is highly plausible for rheumatoid arthritis (RA) and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) but is clinically still in an early developmental stage. Initial clinical experiences are available for TCE, especially for refractory RA and for severe connective tissue diseases, including SSc and antisynthetase syndrome. The evidence for other rheumatological indications is so far much more limited. This article discusses the biological principles, production and mechanisms of action, the revolutionary potential of these strategies, current evidence in selected rheumatological indications and open questions on safety, patient selection and future perspectives.
2026-07-28 | CAR-based cellular therapies for autoimmune diseases: immune reset, clinical evidence, and translational boundaries.
CAR-based cellular therapy is emerging as a time-limited strategy for severe autoimmune disease, but its clinical value depends on more than early response. We conducted a structured narrative review with a targeted update of PubMed/MEDLINE and ClinicalTrials.gov through July 11, 2026, with study-level extraction and explicit handling of overlapping cohorts. Autologous CD19 CAR-T has the most mature evidence, particularly in systemic lupus erythematosus and other systemic rheumatic diseases, while one randomized phase 2b trial has evaluated transient mRNA BCMA-directed CAR-T in myasthenia gravis. Early studies also support disease-specific development in systemic sclerosis, idiopathic inflammatory myopathy, rheumatoid arthritis, autoimmune cytopenias, and selected neurologic disorders. However, cohorts remain small and heterogeneous, and severe cytokine release syndrome, neurotoxicity, hematotoxicity, infection, viral reactivation, hypogammaglobulinemia, and prolonged organ dysfunction have been reported. Immune reset should therefore be treated as a testable multidomain state: durable disease control after the acute treatment phase, withdrawal of conventional immunosuppression, evolution or recovery of the targeted immune compartment without immediate pathogenic recurrence, and preservation of clinically acceptable immune competence. It is not synonymous with cure, continued aplasia, complete autoantibody eradication, or reversal of fixed organ damage. Future development requires disease-specific comparative trials, biomarker-guided platform selection, standardized clinical and immune-reconstitution endpoints, transparent reporting of manufacturing attrition and cohort overlap, experienced multidisciplinary delivery, and long-term registries capturing infection, fertility, neurologic outcomes, secondary malignancy, relapse, retreatment, and patient-centered value. Until these data mature, autoimmune CAR therapy should remain investigational and restricted to highly selected patients in prospective programs.
2026-07-26 | Anti-IL-33 monoclonal antibody attenuates MAILD by suppressing the PI3K/AKT/mTOR signal pathway.
Interstitial lung disease (ILD) is a serious complication of idiopathic inflammatory myopathies (IIM) for which targeted therapies are lacking. Our previous work identified interleukin‑33 (IL‑33) as playing a key role in the pathogenesis of IIM-ILD. Using a mouse model of myositis-associated ILD (MAILD), including IL‑33 knockout (IL‑33 KO) mice, together with clinical samples, proteomics and multiple cellular reporter systems (dual luciferase, mTOR nuclear translocation reporter), we assessed the effects of IL‑33 NAb on lung injury repair, macrophage polarisation and endothelial/epithelial protection. IL‑33 NAb significantly reduced pulmonary inflammation and collagen deposition, improved body weight, and ameliorated liver and muscle biochemical parameters in MAILD mice. Notably, IL‑33 KO MAILD mice exhibited almost identical phenotypic improvements to the IL‑33 NAb‑treated group, confirming IL‑33 as a core driver of the disease. Mechanistically, IL‑33 NAb blocked aberrant NETs deposition, reduced PI3K/AKT/mTOR phosphorylation, and suppressed NF‑κB and STAT3 activation. Consequently, it inhibited both pro‑inflammatory M1 and pro‑fibrotic M2 macrophage polarisation, alleviated alveolar epithelial‑mesenchymal transition (EMT), preserved endothelial CD31 expression, and enhanced tissue repair via cytoskeletal remodelling. IL‑33 NAb exerts significant anti‑inflammatory and anti‑fibrotic effects through multi‑target interventions. Both genetic (IL‑33 KO) and pharmacological (IL‑33 NAb) evidence demonstrate that IL‑33 is a key driver of IIM-ILD, acting via PI3K/AKT/mTOR‑mediated NF‑κB/STAT3 activation. This provides a novel therapeutic strategy for IIM-ILD.
2026-07-16 | Targeting ERK1/2 attenuates neutrophil extracellular traps-mediated pro-inflammatory and pro-fibrotic effects in myositis-associated interstitial lung disease.
This study aimed to investigate the mechanism and therapeutic potential of targeting the extracellular signal-regulated kinase 1/2 (ERK1/2) signalling pathway in myositis-associated interstitial lung disease, focusing on its role in neutrophil extracellular traps (NETs)-mediated pro-inflammatory and pro-fibrotic processes. Lung tissue samples were collected from patients with idiopathic inflammatory myopathy-associated ILD (IIM-ILD) and from mice with experimental autoimmune myositis (EAM) and a myositis-associated interstitial lung disease model (MAILD). Multiple experimental techniques, including immunohistochemistry, western blotting, immunofluorescence and transcriptome sequencing were employed to analyse ERK1/2 activation, NETs infiltration and the expression of epithelial-mesenchymal transition (EMT)-related markers. The ERK1/2 inhibitor U0126 was applied both in vivo and in vitro for interventional validation. The ERK1/2 signalling pathway was activated in the lung tissues of IIM-ILD patients and in the EAM and MAILD mouse models. Substantial NETs infiltration was observed in the lung tissues of EAM and MAILD mice. NETs induced EMT and the release of pro-inflammatory factors by activating ERK1/2. Inhibiting NETs formation attenuated ERK1/2 phosphorylation and the downstream fibrotic process. Administration of the ERK1/2 inhibitor U0126 not only effectively alleviated NETs-induced EMT and inflammatory responses but also significantly reduced pulmonary inflammation infiltration and NETs formation in the MAILD model. NETs-mediated pro-inflammatory and pro-fibrotic processes contribute to the progression of myositis-associated interstitial lung disease by activating the ERK1/2 signalling pathway. Targeting ERK1/2 effectively inhibits this pathogenic cascade, providing a novel strategy for clinical treatment.
2026-07-30 | [Analysis of clinical and muscle pathological features of juvenile idiopathic inflammatory myopathy].
Objective: To investigate the clinical manifestations, muscle imaging features, and muscle pathological characteristics of juvenile idiopathic inflammatory myopathies (IIM). Methods: A retrospective cohort study was conducted including 76 children with IIM admitted to Children's Medical Center, Peking University First Hospital from January 2012 to January 2024. Clinical manifestations, laboratory findings, muscle imaging features, and muscle pathological characteristics were compared between the major subtypes of dermatomyositis and immune-mediated necrotizing myopathy (IMNM). Independent sample t-test or Mann-Whitney U test, and χ2 test or Fisher's exact test were used to compare differences in characteristics between groups. Results: Among 76 children with IIM, 30 were males and 46 were females, with the age of onset at 5.0 (3.0, 8.0) years. Of these 76 children, 57 children were diagnosed with dermatomyositis, 15 children with immune-mediated necrotizing myopathy (IMNM) and 4 children with overlap myositis. The proportion of heliotrope rash, Gottron's sign, and antinuclear antibody positivity were all higher in the dermatomyositis group than those in the IMNM group (63% (36/57) vs.1/15, 47% (27/57) vs. 0/15, and 68% (32/47) vs. 5/14, respectively, all P<0.05), whereas serum creatine kinase (CK), alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase levels were all lower (all P<0.05). The proportion of myositis specific autoantibody positivity was also lower in the dermatomyositis group than in the IMNM group (52% (24/46) vs. 13/14, P=0.006). Muscle MRI showed that subcutaneous soft tissue edema was more frequently observed in the dermatomyositis group than in the IMNM group (28% (14/50) vs. 0/14, P=0.005), whereas muscle fatty infiltration was less common in the dermatomyositis group (16% (8/50) vs. 9/14, P<0.001). On muscle pathology, perifascicular muscle fiber atrophy and perivascular inflammatory cell infiltration, as well as sarcoplasmic myxovirus resistance protein A expression on perifascicular myofibers, were more common in the dermatomyositis group (78% (28/36) vs. 1/7, 89% (32/36) vs.1/7 and 10/14 vs. 0/4, respectively, all P<0.05), while muscle fiber necrosis, perimysial hyperplasia, and endomysial hyperplasia were more common in the IMNM group (7/7 vs. 33% (12/36), 2/7 vs. 0/36 and 4/7 vs. 3% (1/36), respectively, all P<0.05). Conclusions: There are differences between the 2 major juvenile IIM subtypes in terms of clinical manifestations, muscle MRI findings, and muscle pathological features. Dermatomyositis is more likely to present with characteristic skin rashes and perifascicular muscle fiber pathological changes, whereas IMNM is characterized by markedly elevated serum CK levels and prominent muscle fiber necrosis, and is more frequently associated with muscle fatty infiltration.
2026-07-29 | [From CAR-T to T-cell engagers : New T-cell-based treatment in rheumatology].
Cellular forms of treatment mark a paradigm shift in the treatment of autoimmune diseases. While conventional and targeted antirheumatic treatment controls disease activity mostly by continued immunomodulation, innovative cellular approaches, especially chimeric antigen receptor (CAR) T‑cells targeting CD19, target a deep elimination of disease-relevant immune cell compartments with subsequent immunological reconstitution. This concept of an immune reset is particularly attractive for those diseases in which autoreactive B‑cells, plasmablasts, autoantibodies and misdirected lymphocyte networks are pathogenetically central. In addition, T‑cell engagers or bispecific T‑cell engagers (TCE) are now becoming of interest, which as off the shelf strategies without cellular production also enable a deep B‑cell or plasma cell depletion via T cell-mediated cytotoxicity. The most impressive clinical data so far are available for systemic lupus erythematosus (SLE), likewise accumulating indications for the efficacy in systemic sclerosis (SSc) and idiopathic inflammatory myositis (IIM). The concept is highly plausible for rheumatoid arthritis (RA) and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) but is clinically still in an early developmental stage. Initial clinical experiences are available for TCE, especially for refractory RA and for severe connective tissue diseases, including SSc and antisynthetase syndrome. The evidence for other rheumatological indications is so far much more limited. This article discusses the biological principles, production and mechanisms of action, the revolutionary potential of these strategies, current evidence in selected rheumatological indications and open questions on safety, patient selection and future perspectives.
2026-07-28 | CAR-based cellular therapies for autoimmune diseases: immune reset, clinical evidence, and translational boundaries.
CAR-based cellular therapy is emerging as a time-limited strategy for severe autoimmune disease, but its clinical value depends on more than early response. We conducted a structured narrative review with a targeted update of PubMed/MEDLINE and ClinicalTrials.gov through July 11, 2026, with study-level extraction and explicit handling of overlapping cohorts. Autologous CD19 CAR-T has the most mature evidence, particularly in systemic lupus erythematosus and other systemic rheumatic diseases, while one randomized phase 2b trial has evaluated transient mRNA BCMA-directed CAR-T in myasthenia gravis. Early studies also support disease-specific development in systemic sclerosis, idiopathic inflammatory myopathy, rheumatoid arthritis, autoimmune cytopenias, and selected neurologic disorders. However, cohorts remain small and heterogeneous, and severe cytokine release syndrome, neurotoxicity, hematotoxicity, infection, viral reactivation, hypogammaglobulinemia, and prolonged organ dysfunction have been reported. Immune reset should therefore be treated as a testable multidomain state: durable disease control after the acute treatment phase, withdrawal of conventional immunosuppression, evolution or recovery of the targeted immune compartment without immediate pathogenic recurrence, and preservation of clinically acceptable immune competence. It is not synonymous with cure, continued aplasia, complete autoantibody eradication, or reversal of fixed organ damage. Future development requires disease-specific comparative trials, biomarker-guided platform selection, standardized clinical and immune-reconstitution endpoints, transparent reporting of manufacturing attrition and cohort overlap, experienced multidisciplinary delivery, and long-term registries capturing infection, fertility, neurologic outcomes, secondary malignancy, relapse, retreatment, and patient-centered value. Until these data mature, autoimmune CAR therapy should remain investigational and restricted to highly selected patients in prospective programs.
2026-07-26 | Anti-IL-33 monoclonal antibody attenuates MAILD by suppressing the PI3K/AKT/mTOR signal pathway.
Interstitial lung disease (ILD) is a serious complication of idiopathic inflammatory myopathies (IIM) for which targeted therapies are lacking. Our previous work identified interleukin‑33 (IL‑33) as playing a key role in the pathogenesis of IIM-ILD. Using a mouse model of myositis-associated ILD (MAILD), including IL‑33 knockout (IL‑33 KO) mice, together with clinical samples, proteomics and multiple cellular reporter systems (dual luciferase, mTOR nuclear translocation reporter), we assessed the effects of IL‑33 NAb on lung injury repair, macrophage polarisation and endothelial/epithelial protection. IL‑33 NAb significantly reduced pulmonary inflammation and collagen deposition, improved body weight, and ameliorated liver and muscle biochemical parameters in MAILD mice. Notably, IL‑33 KO MAILD mice exhibited almost identical phenotypic improvements to the IL‑33 NAb‑treated group, confirming IL‑33 as a core driver of the disease. Mechanistically, IL‑33 NAb blocked aberrant NETs deposition, reduced PI3K/AKT/mTOR phosphorylation, and suppressed NF‑κB and STAT3 activation. Consequently, it inhibited both pro‑inflammatory M1 and pro‑fibrotic M2 macrophage polarisation, alleviated alveolar epithelial‑mesenchymal transition (EMT), preserved endothelial CD31 expression, and enhanced tissue repair via cytoskeletal remodelling. IL‑33 NAb exerts significant anti‑inflammatory and anti‑fibrotic effects through multi‑target interventions. Both genetic (IL‑33 KO) and pharmacological (IL‑33 NAb) evidence demonstrate that IL‑33 is a key driver of IIM-ILD, acting via PI3K/AKT/mTOR‑mediated NF‑κB/STAT3 activation. This provides a novel therapeutic strategy for IIM-ILD.
2026-07-16 | Targeting ERK1/2 attenuates neutrophil extracellular traps-mediated pro-inflammatory and pro-fibrotic effects in myositis-associated interstitial lung disease.
This study aimed to investigate the mechanism and therapeutic potential of targeting the extracellular signal-regulated kinase 1/2 (ERK1/2) signalling pathway in myositis-associated interstitial lung disease, focusing on its role in neutrophil extracellular traps (NETs)-mediated pro-inflammatory and pro-fibrotic processes. Lung tissue samples were collected from patients with idiopathic inflammatory myopathy-associated ILD (IIM-ILD) and from mice with experimental autoimmune myositis (EAM) and a myositis-associated interstitial lung disease model (MAILD). Multiple experimental techniques, including immunohistochemistry, western blotting, immunofluorescence and transcriptome sequencing were employed to analyse ERK1/2 activation, NETs infiltration and the expression of epithelial-mesenchymal transition (EMT)-related markers. The ERK1/2 inhibitor U0126 was applied both in vivo and in vitro for interventional validation. The ERK1/2 signalling pathway was activated in the lung tissues of IIM-ILD patients and in the EAM and MAILD mouse models. Substantial NETs infiltration was observed in the lung tissues of EAM and MAILD mice. NETs induced EMT and the release of pro-inflammatory factors by activating ERK1/2. Inhibiting NETs formation attenuated ERK1/2 phosphorylation and the downstream fibrotic process. Administration of the ERK1/2 inhibitor U0126 not only effectively alleviated NETs-induced EMT and inflammatory responses but also significantly reduced pulmonary inflammation infiltration and NETs formation in the MAILD model. NETs-mediated pro-inflammatory and pro-fibrotic processes contribute to the progression of myositis-associated interstitial lung disease by activating the ERK1/2 signalling pathway. Targeting ERK1/2 effectively inhibits this pathogenic cascade, providing a novel strategy for clinical treatment.
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Drug Discovery Landscape
9 orphan drug designations for Idiopathic inflammatory myopathy.
9 orphan drug designations for Idiopathic inflammatory myopathy.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Brepocitinib | small molecules | EMA | 2025-08-22 | — | Scendea (NL) B.V. |
efgartigimod coformulated with recombinant human hyaluronidase PH20 | antibodies | FDA | 2025-08-20 | — | argenx BV |
Resecabtagene autoleucel | cell therapies | EMA | 2025-07-18 | — | Cabaletta Bio (Germany) GmbH |
rituximab | antibodies | FDA | 2025-06-03 | — | ODDIFACT SAS |
umbilical cord lining stem cell (ULSC) | cell therapies | FDA | 2024-10-17 | — | Restem LLC |
autologous anti-CD19 chimeric antibody receptor T cells designed to deplete CD19+ B cells | cell therapies | FDA | 2024-01-31 | — | Cabaletta Bio, Inc |
anifrolumab | antibodies | FDA | 2022-12-14 | — | AstraZeneca Pharmaceuticals LP |
abatacept | proteins | FDA | 2017-02-22 | — | Bristol-Myers Squibb Research & Development |
human gammaglobulin | antibodies | FDA | 2003-11-14 | — | Latona Life Sciences, Inc. |
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