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:
categories:
Small molecules
cell therapies
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.
2026-05-25 | Extracorporeal membrane oxygenation for idiopathic inflammatory myopathy-associated interstitial lung disease: a narrative review.
Idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD), particularly its rapidly progressive form (RP-ILD), carries a grave prognosis, with refractory respiratory failure being a leading cause of death. For patients with IIM-ILD who progress to refractory respiratory failure, extracorporeal membrane oxygenation (ECMO) can bridge patients to recovery or transplantation. This review synthesizes existing literature on the role of ECMO in managing IIM-ILD with severe respiratory failure. PubMed was systematically searched from its inception to August 31, 2025, for studies focusing on the use of ECMO in the management of IIM-ILD. Eligible studies were full-text articles published in English in peer-reviewed journals; studies were excluded if they involved patients under 18 years of age or if individual patient data could not be extracted. Current evidence, primarily from case reports and case series, indicates that for IIM-ILD patients with severe respiratory failure, the primary value of ECMO lies in serving as a bridge to lung transplantation, with a markedly higher survival rate compared to its use solely as a bridge to recovery. However, this result may be influenced by publication bias, survivor bias, and center-level variations in clinical practices. The outcomes of patients with IIM-ILD are highly heterogeneous, influenced by myositis-specific antibody subtypes, fluctuations in antibody titers, and the presence of modifiable triggering factors. The review underscores the critical challenges of early diagnosis-often delayed due to atypical presentations-and the imperative for both early, aggressive, combination immunosuppressive therapy and evaluation for lung transplantation. The future role of ECMO in IIM-ILD remains a critical question mark, depending less on technology and more on refining patient selection, optimizing immunosuppressive regimens, integrating ECMO into proactive treatment pathways, and establishing ethical frameworks to improve meaningful outcomes for this complex population. In IIM-ILD with refractory respiratory failure, ECMO primarily bridges selected patients to transplantation rather than recovery, though evidence is limited and biased. Given extreme disease heterogeneity, success hinges on patient selection and integrating ECMO into a proactive strategy combining early immunosuppression with timely transplant evaluation. Collaborative research is urgently needed.
2026-05-19 | A new hope with CAR T-cell therapy for refractory idiopathic inflammatory myopathies: a systematic review.
Treatment options for refractory idiopathic inflammatory myopathies (IIMs) remain limited, and sustained remission is frequently not achieved with conventional immunosuppression or biologic agents. Chimeric antigen receptor (CAR) T-cell therapy has been approved for multiple refractory hematologic malignancies and is increasingly being explored as an immune reset strategy for autoimmune diseases. This Review synthesizes all available clinical evidence on CAR T-cell therapy in adult and pediatric IIM, with the aim of raising awareness within the rheumatology community regarding its clinical application and providing an evidence-based framework to guide future therapeutic decision-making. Across 10 reports comprising 12 refractory IIM patients, CAR T-cell therapy was associated with rapid improvements in muscle enzymes and strength, meaningful treatment de-escalation with frequent drug-free remission. Safety was generally manageable, with predominantly grade 1-2 cytokine release syndrome, rare immune effector cell-associated neurotoxicity syndrome, and treatable infections. Pharmacokinetic and immunodynamic patterns were consistent, with early in-vivo expansion, rapid B-cell depletion, and reconstitution dominated by naïve and transitional phenotypes. Early clinical experience supports CAR T-cell therapy as a promising experimental approach for refractory IIM, but current evidence is limited by small sample sizes, heterogeneous endpoints, and short follow-up. Prospective studies with standardized outcomes, organ-specific assessments, and long-term safety monitoring are required.
2026-05-11 | Case Report: Juvenile dermatomyositis complicated by acute myeloid leukemia: achievement of sustained remission through hematopoietic stem cell transplantation.
Juvenile dermatomyositis (JDM), a pediatric subtype of idiopathic inflammatory myopathy, is a relatively rare rheumatic and immune system disease among children. Although paraneoplastic dermatomyositis (DM) has been documented in adult malignancies, its association with acute myeloid leukemia (AML) in pediatric populations remains exceptionally rare. We present a male patient diagnosed with JDM at age 6, characterized by Gottron's papules and muscle weakness. Despite receiving sequential immunosuppressive therapies and biological agents, the disease followed a relapsing-remitting course over 9 years. At age 15, he developed persistent knee arthralgia accompanied by intermittent fever lasting 8 days. Hematologic evaluation revealed thrombocytopenia (platelet count: 76 ×109/L) and leukocytosis (white blood cell count: 36.46 ×109/L), prompting bone marrow aspiration confirmed AML diagnosis (French-American-British M2 subtype). Following induction chemotherapy and two consolidation cycles, allogeneic hematopoietic stem cell transplantation (HSCT) from a matched unrelated donor was successfully performed. Notably, both JDM symptoms and AML achieved sustained remission at 1-year follow-up post-HSCT. This case suggests that HSCT may represent a potential therapeutic approach for refractory autoimmune-hematologic malignancy overlap syndromes, though further studies are required to validate its efficacy.
2026-04-27 | Benefits of adjunct plasma exchange in idiopathic inflammatory myopathy with anti-signal recognition particle antibodies: a real-world study.
The objective of this study was to compare the efficacy of adjunct plasma exchange (PE) therapy with standard therapy in idiopathic inflammatory myopathy (IIM) with anti-signal recognition particle (SRP) antibodies. Anti-SRP-positive myositis patients were consecutively enrolled and followed up. Two-way ANOVA was performed to compare the pre- and post-treatment changes in myositis disease activities between the two groups. The Kaplan-Meier method was used to compare the composite end point of all-cause death and relapse after propensity score matching (PSM) and inverse probability weighting (IPW) analyses. Cox regression analyses were performed to screen long-term prognostic factors. In total, 53 patients were included (35 received standard therapy, 18 received adjunct PE therapy). The PE therapy group tended to have severer muscle weakness (P = 0.027), higher levels of anti-SRP antibody titres (P = 0.001), and creatine kinase (P < 0.001), as well as higher doses of CS administration (P = 0.038). At the 4-week follow-up point, both groups achieved remarkable remission, as indicated by significant improvements in the six core set measures (CSMs), and the changes in the six CMSs were more prominent in the PE therapy group (all P < 0.001). During a median follow-up of 15 months, 26 patients reached the composite end point, and the PE therapy group had significantly better prognosis after IPW analysis (P = 0.029). In the multivariate Cox regression analyses, PE therapy [hazard ratio: 0.14 (0.03-0.57), P = 0.006] and interstitial lung disease [HR: 4.82 (1.22-19.12), P = 0.025] turned out to be independent predictors for long-term prognosis. Adjunct PE therapy provided quick remission and sustained benefits for IIM with anti-SRP antibodies.
small molecules
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.
2026-05-27 | Prediction of intravenous cyclophosphamide treatment efficacy in idiopathic inflammatory myopathies-associated interstitial lung disease patients: a nomogram based on radiomics and clinical factors.
Intravenous cyclophosphamide (IV-CYC) is a first-line treatment for idiopathic inflammatory myopathy (IIMs) complicated with interstitial lung disease (ILD) but has been hampered by a lack of targeted clinical trials and heterogeneous patient responses. Therefore, this study established an evaluation model for IV-CYC treatment response in IIMs-ILD patients by combining clinical characteristics and radiomics. Retrospectively included total of 62 IIMs-ILD patients were enrolled and categorized into two groups on the basis of treatment response: the Effective group (n = 18) and the Non-effective group (n = 44). Baseline clinical and imaging characteristics were analyzed, with no significant differences observed in demographic or clinical factors between the groups. Least absolute shrinkage and selection operator (LASSO) regression identified five key predictors of treatment response: ROl_Lobe2 infected rates, ROl_Segment1 infected rates, anti-MDA5 antibody, anti-Jo1 antibody, and IgA levels. A nomogram incorporating these factors was developed, with an area under the curve (AUC) of 0.876 (95% CI: 0.788-0.964), a sensitivity of 0.889 and a specificity of 0.790. The model's Youden's index was 0.639. The calibration curve indicated strong agreement between the predicted and actual outcomes. Decision curve analysis (DCA) and a clinical impact curve (CIC) confirmed the model's clinical utility, showing significant net benefits in predicting the treatment response to IV-CYC in IIMs-ILD patients. The proposed nomogram provides a reliable tool for predicting treatment response in IIMs-ILD patients receiving IV-CYC therapy, potentially guiding personalized treatment strategies.
2026-05-27 | Idiopathic Inflammatory Myopathies-Treatment Perspective of Highly Specialised Rheumatology Centre.
Background/Objectives: Idiopathic inflammatory myopathies (IIMs) are chronic immune-mediated disorders, causing striated muscle weakness and extramuscular symptoms. Real-world, single-centre data are needed to interpret phenotype patterns and evolving therapies. Methods: A single-centre, retrospective cohort study was conducted at the Rheumatology Clinic of the National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland from 1 January 2022 to 31 December 2025. Data included demographics, IIM subtypes, extramuscular involvement, co-existing Sjögren disease (SD), biopsy results, autoantibodies, and treatment. Due to sample size, descriptive analysis was used. Results: The study included 35 patients (31.4% men). Mean age was 50.7 years; mean body mass index (BMI) was 26.0 kg/m2. The cohort consisted of 10 dermatomyositis (DM), one polymyositis (PM), two immune-mediated necrotising myopathy (IMNM), one inclusion body myositis (IBM), 16 anti-synthetase syndrome (ASyS), four juvenile dermatomyositis (JDM), and one clinically amyopathic dermatomyositis (CADM). SD co-occurred in eight cases, including six cases of ASyS. Anti-Jo1 was observed in 13 ASyS cases and one DM. Glucocorticoids (GCSs) were administered in all patients for induction in addition to cyclophosphamide (28.6%), mycophenolate mofetil (MMF) (51.4%), and methotrexate (MTX) (17.1%). Maintenance therapy included MTX (20%), MMF (31.4%), rituximab (34.3%), azathioprine (AZA) (42.9%), and others. Two DM, two JDM, and one ASyS patient received JAK inhibitors, one DM and one JDM anifrolumab, one IBM sirolimus, and four patients with interstitial lung disease (ILD) nintedanib. Conclusions: This Polish single-centre cohort shows effective use of novel therapies for IIM. Sirolimus, JAK inhibitors, and nintedanib were effective. Co-occurrence of SD in ASyS patients requires further research.
2026-04-17 | Energy metabolism dysregulation in idiopathic inflammatory myopathies: mechanisms and therapeutic implications
Idiopathic inflammatory myopathies (IIMs) are being increasingly recognized as disorders driven by profound disturbances in cellular energy metabolism rather than inflammation alone. Recent studies have highlighted mitochondrial dysfunction, oxidative stress, and metabolic reprogramming across glucose, lipid, and amino acid pathways as central mechanisms linking energy metabolism dysregulation to sustained muscle injury. Defective mitophagy, mitochondrial DNA (mtDNA) depletion, and excessive reactive oxygen species (ROS) production create a self-amplifying loop with interferon-driven inflammation, whereas abnormal glycolysis, impaired fatty acid oxidation, and dysregulated tryptophan-kynurenine metabolism further shape the immunometabolic landscape of IIMs. These metabolic shifts not only contribute to muscle weakness and tissue degeneration but are also correlated with disease severity, autoantibody profiles, and treatment resistance. Emerging therapeutic strategies, including antioxidant approaches, mitochondrion-targeted agents, metabolic modulators, and exercise-based interventions, underscore the translational potential of targeting energy homeostasis. This review synthesizes current evidence on energy metabolism abnormalities in IIMs, integrates molecular findings with clinical implications, and highlights future directions for immunometabolic-based precision therapies.
2026-04-13 | Efficacy and safety of upadacitinib in refractory interstitial lung disease with idiopathic inflammatory myopathies: a retrospective study.
To assess the efficacy and safety of upadacitinib (UPA) in patients with refractory idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD) following conventional therapy failure. We conducted a single-centre retrospective cohort study of IIM-ILD patients initiating UPA after conventional therapy failure. Clinical characteristics, pulmonary function tests (PFTs), high-resolution CT (HRCT) Warrick scores and therapeutic regimens were collected at baseline and follow-ups. Patients receiving conventional treatment were included as the control group following propensity score matching (PSM, 1:2). Treatment responses and adverse events were analysed and compared. Among 28 UPA-treated patients (mean age 57, 87.5% female), 16 had complete paired data of PFTs and/or HRCT both at baseline and after treatment. After mean 7.4 months, lung function improved: the mean FVC increased from 1.84 to 2.13 l (P = 0.0069), FVC% from 63.5% to 76.77% (P = 0.0004). HRCT Warrick scores remained stable overall, with some patients showing radiographic improvement. Inflammatory indicators, including IL-6 (14.06-8.44 pg/ml, P = 0.039) and serum ferritin (240.30-188.15 µg/l, P = 0.018), decreased significantly after treatment. Further PSM analysis (n = 16 UPA vs 32 controls) showed notably lower post-treatment IL-6 (8.44 vs 20.60 pg/ml, P = 0.0012) and lower glucocorticoid dose (7.50 vs 12.50 mg, P = 0.017). No significant differences in PFTs or HRCT scores were found between the groups. Infections occurred in 6/28 (21.4%), all recovered well. UPA significantly improved lung function, reduced glucocorticoid dependence and suppressed systemic inflammation in refractory IIM-ILD with acceptable safety, supporting its use as a promising therapeutic option in IIM-ILD patients after conventional treatment failure.
antibodies
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.
2026-07-26 | 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.
2026-07-10 | Predictors of intravenous immunoglobulin therapy in juvenile idiopathic inflammatory myopathies
Objective: Juvenile idiopathic inflammatory myopathies (JIIM) exhibit heterogeneous presentation, and intravenous immunoglobulin (IVIG) is often required in refractory cases. This study aimed to identify the clinical characteristics associated with IVIG use. Methods: This retrospective study included patients aged 0–18 years who fulfilled the Bohan and Peter and/or 2017 EULAR/ACR criteria for JIIM and were followed between March 2009 and August 2025. Demographic, clinical, laboratory, and treatment data were recorded. Results: Thirty-eight patients were included; 29 (76.3%) had juvenile dermatomyositis. Sixteen patients received IVIG. Severe or unresponsive muscle weakness was the main indication (56.3%). IVIG-treated patients had significantly lower Childhood Myositis Assessment Scale (CMAS) scores at diagnosis and at the third month, higher AST levels, more frequent nailfold capillaroscopy abnormalities, and lower remission rates. Each one-point decrease in CMAS increased the odds of IVIG use. Additionally, the third-month CMAS score was the only independent predictor for IVIG therapy. Conclusion: In conclusion, IVIG is an effective treatment option for patients with more severe and refractory JIIM. These patients are characterized by lower CMAS scores and marked microvascular involvement. Earlier use of IVIG as a steroid-sparing strategy may help restrict adverse effects.
2026-06-17 | Successful corticosteroid-free management of anti-HMG-CoA reductase immune-mediated necrotizing myopathy with subcutaneous immunoglobulins monotherapy: a case report.
Given the high rate of cardiovascular comorbidities in anti-HMG-CoA reductase (HMGCR)-immune-mediated necrotizing myopathy (IMNM), a glucocorticosteroids (GC)-free treatment approach remains an appealing strategy. While intravenous immunoglobulins (IVIg) represents an effective therapy in most subgroups of idiopathic inflammatory myositis (IIM), there remains limited evidence supporting the use subcutaneous immunoglobulins (SCIg), a potentially safer, more convenient and cost-effective alternative. We present a case of a 68-year-old male of European descent with a 2-year history of progressive proximal bilateral lower extremity weakness. He had been treated for his dyslipidemia with atorvastatin for 2 years, then with rosuvastatin for 2 additional years until discontinued a year before our assessment. His other comorbidities included hypertension and diabetes mellitus type II. Physical examination demonstrated proximal weakness of his bilateral hip flexors and deltoids, and no rash. His creatine kinase (CK) was elevated at 1644 IU/L. Electromyography revealed a generalized myopathic disorder with proximal predominance and muscle biopsy of the right quadriceps showed typical findings of an IMNM. Serum HMG-CoA reductase antibody was positive. Due to accumulating evidence supporting the effectiveness of IVIg in anti-HMGCR-IMNM, even without concomitant GC or other immunosuppressive agent, we opted for a GC-free approach through shared-decision making in light of patient's preference regarding potential GC side effects with his comorbidities. As he lived a considerable distance from any center, where IVIg infusions could be offered, and given the patient was unable to drive himself due to his symptoms we opted for SCIg (0.5 g/kg/week). Within 1 month, his CK decreased and weakness resolved. SCIg monotherapy was tapered over 3 years and this patient remains in remission 7 years after SCIg initiation. The patient did not have any adverse effects related to SCIg use. To our knowledge, this is the first case report describing a successful corticosteroid-free management of anti-HMGCR immune-mediated necrotizing myopathy using SCIg as monotherapy. This case highlights the potential for steroids-free induction and maintenance strategies in IMNM. Larger studies are required to confirm the effectiveness and safety of SCIg in IMNM and other subtypes of IIM, and to provide guidelines for dosing recommendations.
proteins
2025-09-03 | Recombinant human hyaluronidase-facilitated subcutaneous immunoglobulin (hf-SCIg) for inflammatory myositis: a multicenter retrospective real-world observational study.
Subcutaneous immunoglobulin (SCIg) is a promising alternative to intravenous Ig (IVIg) for the treatment of idiopathic inflammatory myositis (IIM), thanks to its more favorable safety profile, reduced costs, and lower impact on patients' quality of life. We assessed the short- and long-term effectiveness and safety of recombinant human hyaluronidase-facilitated SCIg (hf-SCIg) in patients with IIM treated at different referral centers in Italy. A multicenter, retrospective, real-life cohort study was conducted on consecutive adult patients diagnosed with IIM according to the EULAR/ACR criteria, treated with hf-SCIg for remission induction or maintenance. Hf-SCIg effectiveness was assessed in terms of variation in the Medical Research Council (MRC) score, serum creatine kinase (CK) values, clinical disease manifestations and daily prednisone dosage. Safety data were also collected. Twenty-six patients with IIM treated with hf-SCIg for remission induction (n = 5) or maintenance (n = 21) were included in the study (18 females; median age at diagnosis of 59 (IQR 42-64) years)). In most patients, hf-SCIg was started following previous IVIg treatment (23, 89 %) and was initiated in combination with oral corticosteroids (21, 81 %) and/or traditional or biologic DMARDs. Short-term use of hf-SCIg for remission induction appeared associated with a corticosteroid-sparing effect, without worsening of MRC score. Long-term hf-SCIg treatment for up to 24 months maintained clinical stability and serum CK levels with further improvement of MRC score. Hf-SCIg was well tolerated, with mild adverse events mostly related to local site reactions. Hf-SCIg seems effective and safe for induce and maintain clinical remission in patients with IIM.
2025-06-01 | POS0278 RISK FACTORS AND PROGNOSTIC OUTCOMES OF PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHY COMPLICATED WITH INFECTION
Infections cause disease exaggeration in patients with myositis, representing one of the leading causes of mortality. Patients with myositis are often treated by glucocorticoids and immunosuppressants that could increase the risk of infection, which in turn deteriorate the disease. This study investigates the incidence and risk factors of infections in patients with idiopathic inflammatory myopathy (IIM). A case-control study was conducted to assess the infection rates and associated risk factors among patients with IIM, who were treated at the Department of Rheumatology and Immunology, Peking University People's Hospital from 2000 to 2023. All the patients were diagnosed based on 2017 EULAR/ACR criteria. The occurrence of infectious complications was identified over a 12-month follow-up period, based on supportive clinical features, positive microbial cultures, and/or responses to antibiotic therapy. Demographics, clinical data at baseline, and mortality rates of patients were systematically recorded. IL-2 treatment was defined as 1×106 IU of IL-2 subcutaneously every other day for 12 weeks on top of standard care. Multivariate logistic regression analysis was employed to determine independent risk factors for significant infections. Additionally, cumulative survival rates were estimated using the Kaplan–Meier method. Of the 616 patients with IIM, 151 (24.5%) suffered from infections. The lung was the most common infection site (69.5%), The most common pathogen was bacteria (50.3%), followed by viruses (41.7%), fungi (17.2%), and mixed infections (7.2%). Multivariate analyses demonstrated that age >45 years (OR=1.79; 95% CI=1.11-2.87; p=0.017); skin ulcer (OR=2.19; 95% CI=1.01-4.74; p=0.048); fever (OR=1.71; 95% CI=1.09-2.69; p=0.019); thrombocytopenia (OR=2.44; 95% CI=1.20-4.95; p=0.014); hypoproteinemia (OR=1.86; 95% CI=1.18-2.93; p=0.008); C-ILD (OR=2.34; 95% CI=1.36-4.02; p=0.002) are independent risk factors for infection. Treatment with low-dose IL-2 (OR=0.31; 95% CI=0.14-0.65; p=0.002) was a protective factor for infection. Survival analysis demonstrated that the infection group's ten-year survival rate was lower than that of the non-infection group (54.7% vs. 90.1%, p<0.001). After the first episode of infection, survival rates of patients with IIM declined sharply to 85.7% at one year and 76.0% at three years. This study underlines the high frequency of infections in IIM, which is significantly detrimental to patient survival rates. It also provides a summary of the risk factors contributing to infection development. Encouragingly, low-dose IL-2 emerges as a potential strategy for mitigating the risk of severe infections. Figure 1Multivariate analysis: adjusted OR for risk of infection in IIM. Figure 2Survival curves for IIM patients with and without infection. NIL. This study is based on the contributions of all colleagues in our department. None declared. © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.
2025-03-31 | Successful treatment of rheumatoid arthritis complicated by anti-Jo-1 antibody-positive myopathy with abatacept: A case report.
Abatacept (ABT) is effective in the treatment of rheumatoid arthritis (RA). However, there is no consensus regarding the treatment of patients with RA and idiopathic inflammatory myopathy (IIM). Here, we describe the case of a 55-year-old Japanese female with a 5-year history of RA who developed anti-Jo1 antibody-positive IIM. She developed myalgia and dyspnea while receiving a combination therapy of methotrexate and a Janus kinase inhibitor for RA. Chest computed tomography imaging revealed bilateral middle-to-lower lung frosted shadows. Magnetic resonance imaging of the lower limbs showed a high short tau inversion recovery signal in the bilateral thigh muscle groups. Needle electromyography revealed myogenic changes in the proximal muscles of both the upper and lower extremities. Symmetric proximal muscle weakness, elevated serum muscle enzymes, and the presence of anti-Jo1 antibodies were noted. The diagnosis of IIM was made according to the European Alliance of Associations for Rheumatology diagnostic criteria. The myositis symptoms stabilized with glucocorticoids; however, RA worsened during steroid tapering. After ABT initiation, RA clinical symptoms and functional outcomes improved and myositis remained in remission. In conclusion, ABT may be an effective treatment option for patients with RA and IIM. .
2023-12-30 | Glucagon-Like Peptide-1 Receptor Agonists in the Treatment of Idiopathic Inflammatory Myopathy: From Mechanisms of Action to Clinical Applications
Idiopathic inflammatory myopathies (IIMs) result in proximal muscle weakness and other intramuscular and extramuscular manifestations. Pharmacologic treatments in use for IIMs are limited to corticosteroids and immunosuppressants in addition to supportive physical and occupational therapy. Glucagon-like peptide-1 receptor (GLP-1R) agonists are currently utilized in the treatment of type II diabetes and obesity but may play a role in the treatment of IIMs. The current scoping review of extant literature aims to synthesize findings from studies assessing the therapeutic effects of GLP-1R agonists in the management of inflammatory myopathy and muscle atrophy. A literature search was conducted through PubMed, resulting in a total of 19 research-based articles included in this review. Mice and human studies showed, with varying levels of significance, that GLP-1R agonists led to decreases in muscle atrophy, inflammation, adiposity, and weakness; improvement in muscle microvasculature and endurance; and promotion of muscle mitochondria biogenesis. The potential for GLP-1R agonists to improve muscle function and architecture underscores the need for large randomized controlled, clinically comparative trials of GLP-1R agonists in patients with IIM.
2023-05-30 | AB0911 EFFICACY OF LOW-DOSE IL-2 IN PATIENTS WITH MYOSITIS
Idiopathic inflammatory myopathies (IIMs) are a group of rare and heterogeneous muscle inflammatory diseases characterized by disturbances of regulatory T(Treg) cells. Interleukin (IL)-2 has been rediscovered as a pivotal cell population in the control of autoimmunity, which effectively relieves idiopathic inflammatory myopathies(IIMs) such as polymyositis(PM) and dermatomyositis (DM). This study aimed to systematically evaluate the efficacy of low-dose IL-2 therapy in PM, DM, and IIMs. Systematic searches of PubMed, EMBASE, Web of Science, the Cochrane Library and Medline, CNKI, CBM, and Technology Journal Database were performed. Original case reports, case series, observational studies, and clinical trials reporting the changes in the numbers of lymphocyte subsets on PM, DM, and IIMs patients treated with IL-2 were included. A random-effects meta-analysis was performed to calculate the pooled efficacy. Inconsistency was evaluated by using the I2, and Egger tests were used for the evaluation of potential publication bias (STATA v.12.0) A total of 5 studies comprising 401 patients were identified(Table 1).The CDASI scores were significantly decreased after IL-2 treatment[SMD=-1.146, 95%CI (-1.591,-0.700), P<0.001].Besides, the number of Tregs cells was significantly increased[SMD=-1.146, 95%CI (-1.591,-0.700), P=0.007], and the subgroup analysis was performed based on the dose of IL-2(Figure 1). Low-dose IL-2 was promising in the treatment of DM, PM, and IMMs, which could promote the proliferation and functional recovery of Tregs. This work was supported by the National Natural Science Foundation of China (No. 82001740). None Declared.
other
2020-02-03 | Muscle Weakness in Myositis: MicroRNA‐Mediated Dystrophin Reduction in a Myositis Mouse Model and Human Muscle Biopsies
Objective Muscle inflammation is a feature in myositis and Duchenne muscular dystrophy ( DMD ). Autoimmune mechanisms are thought to contribute to muscle weakness in patients with myositis. However, a lack of correlation between the extent of inflammatory cell infiltration and muscle weakness indicates that nonimmune pathologic mechanisms may play a role. The present study focused on 2 micro RNA (mi RNA ) sets previously identified as being elevated in the muscle of patients with DMD —an “inflammatory” mi RNA set that is dampened with glucocorticoids, and a “dystrophin‐targeting” mi RNA set that inhibits dystrophin translation—to test the hypothesis that these mi RNA s are similarly dysregulated in the muscle of patients with myositis, and could contribute to muscle weakness and disease severity. Methods A major histocompatibility complex class I–transgenic mouse model of myositis was utilized to study gene and mi RNA expression and histologic features in the muscle tissue, with the findings validated in human muscle biopsy tissue from 6 patients with myositis. Mice were classified as having mild or severe myositis based on transgene expression, body weight, histologic disease severity, and muscle strength/weakness. Results In mice with severe myositis, muscle tissue showed mononuclear cell infiltration along with elevated expression of type I interferon and NF ‐κB–regulated genes, including Tlr7 (3.8‐fold increase, P < 0.05). Furthermore, mice with severe myositis showed elevated expression of inflammatory mi RNA s (miR‐146a, miR‐142‐3p, miR‐142‐5p, miR‐455‐3p, and miR‐455‐5p; ~3–40‐fold increase, P < 0.05) and dystrophin‐targeting mi RNA s (miR‐146a, miR‐146b, miR‐31, and miR‐223; ~3–38‐fold increase, P < 0.05). Bioinformatics analyses of chromatin immunoprecipitation sequencing (ChIP‐seq) data identified at least one NF ‐κB consensus element within the promoter/enhancer regions of these mi RNA s. Western blotting and immunofluorescence analyses of the muscle tissue from mice with severe myositis demonstrated reduced levels of dystrophin. In addition, elevated levels of NF ‐κB–regulated genes, TLR 7 , and mi RNA s along with reduced dystrophin levels were observed in muscle biopsy tissue from patients with histologically severe myositis. Conclusion These data demonstrate that an acquired dystrophin deficiency may occur through NF ‐κB–regulated mi RNA s in myositis, thereby suggesting a unifying theme in which muscle injury, inflammation, and weakness are perpetuated both in myositis and in DMD .
2015-09-23 | The role of microRNAs in the idiopathic inflammatory myopathies
Purpose of review The idiopathic inflammatory myopathies (IIMs) are a group of rare autoimmune disorders characterized by skeletal muscle weakness and inflammation. MicroRNAs (miRNAs) regulate a wide range of developmental and physiological cellular processes. New approaches to investigating the mechanisms involved in IIM, such as investigating the role of miRNAs, are vital for the development of novel therapeutics and/or better diagnostic tools. Recent findings Identification of dysregulated miRNAs has led to a greater understanding of inflammation, muscle weakness/wasting and extra-muscular organ involvement in IIM. Up-regulation of immune-related miRNAs in muscle, for example, miR-155 and miR-146, is associated with autoimmunity, whereas down-regulation of myogenic miRNAs, including miR-1 and miR-206, is associated with inhibition of muscle regeneration. Disease mechanisms have been explored by altering in-vitro conditions and monitoring miRNA levels of interest, or, alternatively, changing miRNA levels and monitoring possible targets. For example, higher levels of cytokines appear to inhibit myogenic miRNAs in muscle and artificially reducing levels of miR-223 increases protein kinase C-epsilon (PKCε) levels in keratinocytes. Summary The exciting expansion of the miRNA field adds to our understanding of IIM pathogenesis and may provide future clinical potential either as diagnostic tools or as therapeutics via use of anti-miRNAs or synthetic miRNAs.
2015-09-10 | New targets to control skeletal muscle inflammation: MicroRNAs regulated by adiponectin
Although adipocytes are the main source of circulating adiponectin (ApN), several studies have now shown that ApN may be produced by the skeletal muscle in response to cellular stress. This induction could be a protective mechanism that counteracts inflammation, oxidative stress and cellular damage occurring during skeletal muscle injury. MicroRNAs (miRNAs) are small non-coding RNAs that control gene expression by inducing target mRNA degradation or blocking translation. In this work, we characterized miRNAs that may contribute to the anti-inflammatory action of ApN on skeletal muscle. To this end, we used ApN-knockout (KO) mice: one tibialis anterior muscle was electroporated with a plasmid coding for the ApN gene while the contralateral leg received a control plasmid. Mice were next challenged by lipopolysaccharide (LPS) to induce inflammation. Muscle electrotransfer of ApN gene induced anti-inflammatory effects: expression of markers of inflammation (TNFα, IL-1β) and oxidative stress (péroxiredonine-3; PRDX3) were downregulated (~−50%) in the muscle electroporated with ApN compared to the contralateral one. miRNA expression profiling revealed that ApN increased the expression of miR-711(~+150%), data which were validated by RT-qPCR. In murine myotubes (C2C12), ApN treatment also upregulated miR-711 and reduced gene expression of TNFα and IL-1β caused by LPS. Transfection of miR-711 mimic reproduced the anti-inflammatory effects of ApN, while using miR-711 inhibitor attenuated these effects. We found that miR-711 repressed 4 genes (fadd, pi3kδ, tab1 and tollip) belonging to the toll-like receptor 4 signalling pathway, which is activated by LPS. In primary cultures of human myotubes, ApN treatment also stimulated the expression of miR-711. The anti-inflammatory effects of ApN appear to be mediated at least in part by miR-711. These data may open new therapeutic perspectives to control muscle inflammation.
cell therapies
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.
2026-05-25 | Extracorporeal membrane oxygenation for idiopathic inflammatory myopathy-associated interstitial lung disease: a narrative review.
Idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD), particularly its rapidly progressive form (RP-ILD), carries a grave prognosis, with refractory respiratory failure being a leading cause of death. For patients with IIM-ILD who progress to refractory respiratory failure, extracorporeal membrane oxygenation (ECMO) can bridge patients to recovery or transplantation. This review synthesizes existing literature on the role of ECMO in managing IIM-ILD with severe respiratory failure. PubMed was systematically searched from its inception to August 31, 2025, for studies focusing on the use of ECMO in the management of IIM-ILD. Eligible studies were full-text articles published in English in peer-reviewed journals; studies were excluded if they involved patients under 18 years of age or if individual patient data could not be extracted. Current evidence, primarily from case reports and case series, indicates that for IIM-ILD patients with severe respiratory failure, the primary value of ECMO lies in serving as a bridge to lung transplantation, with a markedly higher survival rate compared to its use solely as a bridge to recovery. However, this result may be influenced by publication bias, survivor bias, and center-level variations in clinical practices. The outcomes of patients with IIM-ILD are highly heterogeneous, influenced by myositis-specific antibody subtypes, fluctuations in antibody titers, and the presence of modifiable triggering factors. The review underscores the critical challenges of early diagnosis-often delayed due to atypical presentations-and the imperative for both early, aggressive, combination immunosuppressive therapy and evaluation for lung transplantation. The future role of ECMO in IIM-ILD remains a critical question mark, depending less on technology and more on refining patient selection, optimizing immunosuppressive regimens, integrating ECMO into proactive treatment pathways, and establishing ethical frameworks to improve meaningful outcomes for this complex population. In IIM-ILD with refractory respiratory failure, ECMO primarily bridges selected patients to transplantation rather than recovery, though evidence is limited and biased. Given extreme disease heterogeneity, success hinges on patient selection and integrating ECMO into a proactive strategy combining early immunosuppression with timely transplant evaluation. Collaborative research is urgently needed.
2026-05-19 | A new hope with CAR T-cell therapy for refractory idiopathic inflammatory myopathies: a systematic review.
Treatment options for refractory idiopathic inflammatory myopathies (IIMs) remain limited, and sustained remission is frequently not achieved with conventional immunosuppression or biologic agents. Chimeric antigen receptor (CAR) T-cell therapy has been approved for multiple refractory hematologic malignancies and is increasingly being explored as an immune reset strategy for autoimmune diseases. This Review synthesizes all available clinical evidence on CAR T-cell therapy in adult and pediatric IIM, with the aim of raising awareness within the rheumatology community regarding its clinical application and providing an evidence-based framework to guide future therapeutic decision-making. Across 10 reports comprising 12 refractory IIM patients, CAR T-cell therapy was associated with rapid improvements in muscle enzymes and strength, meaningful treatment de-escalation with frequent drug-free remission. Safety was generally manageable, with predominantly grade 1-2 cytokine release syndrome, rare immune effector cell-associated neurotoxicity syndrome, and treatable infections. Pharmacokinetic and immunodynamic patterns were consistent, with early in-vivo expansion, rapid B-cell depletion, and reconstitution dominated by naïve and transitional phenotypes. Early clinical experience supports CAR T-cell therapy as a promising experimental approach for refractory IIM, but current evidence is limited by small sample sizes, heterogeneous endpoints, and short follow-up. Prospective studies with standardized outcomes, organ-specific assessments, and long-term safety monitoring are required.
2026-05-11 | Case Report: Juvenile dermatomyositis complicated by acute myeloid leukemia: achievement of sustained remission through hematopoietic stem cell transplantation.
Juvenile dermatomyositis (JDM), a pediatric subtype of idiopathic inflammatory myopathy, is a relatively rare rheumatic and immune system disease among children. Although paraneoplastic dermatomyositis (DM) has been documented in adult malignancies, its association with acute myeloid leukemia (AML) in pediatric populations remains exceptionally rare. We present a male patient diagnosed with JDM at age 6, characterized by Gottron's papules and muscle weakness. Despite receiving sequential immunosuppressive therapies and biological agents, the disease followed a relapsing-remitting course over 9 years. At age 15, he developed persistent knee arthralgia accompanied by intermittent fever lasting 8 days. Hematologic evaluation revealed thrombocytopenia (platelet count: 76 ×109/L) and leukocytosis (white blood cell count: 36.46 ×109/L), prompting bone marrow aspiration confirmed AML diagnosis (French-American-British M2 subtype). Following induction chemotherapy and two consolidation cycles, allogeneic hematopoietic stem cell transplantation (HSCT) from a matched unrelated donor was successfully performed. Notably, both JDM symptoms and AML achieved sustained remission at 1-year follow-up post-HSCT. This case suggests that HSCT may represent a potential therapeutic approach for refractory autoimmune-hematologic malignancy overlap syndromes, though further studies are required to validate its efficacy.
2026-04-27 | Benefits of adjunct plasma exchange in idiopathic inflammatory myopathy with anti-signal recognition particle antibodies: a real-world study.
The objective of this study was to compare the efficacy of adjunct plasma exchange (PE) therapy with standard therapy in idiopathic inflammatory myopathy (IIM) with anti-signal recognition particle (SRP) antibodies. Anti-SRP-positive myositis patients were consecutively enrolled and followed up. Two-way ANOVA was performed to compare the pre- and post-treatment changes in myositis disease activities between the two groups. The Kaplan-Meier method was used to compare the composite end point of all-cause death and relapse after propensity score matching (PSM) and inverse probability weighting (IPW) analyses. Cox regression analyses were performed to screen long-term prognostic factors. In total, 53 patients were included (35 received standard therapy, 18 received adjunct PE therapy). The PE therapy group tended to have severer muscle weakness (P = 0.027), higher levels of anti-SRP antibody titres (P = 0.001), and creatine kinase (P < 0.001), as well as higher doses of CS administration (P = 0.038). At the 4-week follow-up point, both groups achieved remarkable remission, as indicated by significant improvements in the six core set measures (CSMs), and the changes in the six CMSs were more prominent in the PE therapy group (all P < 0.001). During a median follow-up of 15 months, 26 patients reached the composite end point, and the PE therapy group had significantly better prognosis after IPW analysis (P = 0.029). In the multivariate Cox regression analyses, PE therapy [hazard ratio: 0.14 (0.03-0.57), P = 0.006] and interstitial lung disease [HR: 4.82 (1.22-19.12), P = 0.025] turned out to be independent predictors for long-term prognosis. Adjunct PE therapy provided quick remission and sustained benefits for IIM with anti-SRP antibodies.
small molecules
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.
2026-05-27 | Prediction of intravenous cyclophosphamide treatment efficacy in idiopathic inflammatory myopathies-associated interstitial lung disease patients: a nomogram based on radiomics and clinical factors.
Intravenous cyclophosphamide (IV-CYC) is a first-line treatment for idiopathic inflammatory myopathy (IIMs) complicated with interstitial lung disease (ILD) but has been hampered by a lack of targeted clinical trials and heterogeneous patient responses. Therefore, this study established an evaluation model for IV-CYC treatment response in IIMs-ILD patients by combining clinical characteristics and radiomics. Retrospectively included total of 62 IIMs-ILD patients were enrolled and categorized into two groups on the basis of treatment response: the Effective group (n = 18) and the Non-effective group (n = 44). Baseline clinical and imaging characteristics were analyzed, with no significant differences observed in demographic or clinical factors between the groups. Least absolute shrinkage and selection operator (LASSO) regression identified five key predictors of treatment response: ROl_Lobe2 infected rates, ROl_Segment1 infected rates, anti-MDA5 antibody, anti-Jo1 antibody, and IgA levels. A nomogram incorporating these factors was developed, with an area under the curve (AUC) of 0.876 (95% CI: 0.788-0.964), a sensitivity of 0.889 and a specificity of 0.790. The model's Youden's index was 0.639. The calibration curve indicated strong agreement between the predicted and actual outcomes. Decision curve analysis (DCA) and a clinical impact curve (CIC) confirmed the model's clinical utility, showing significant net benefits in predicting the treatment response to IV-CYC in IIMs-ILD patients. The proposed nomogram provides a reliable tool for predicting treatment response in IIMs-ILD patients receiving IV-CYC therapy, potentially guiding personalized treatment strategies.
2026-05-27 | Idiopathic Inflammatory Myopathies-Treatment Perspective of Highly Specialised Rheumatology Centre.
Background/Objectives: Idiopathic inflammatory myopathies (IIMs) are chronic immune-mediated disorders, causing striated muscle weakness and extramuscular symptoms. Real-world, single-centre data are needed to interpret phenotype patterns and evolving therapies. Methods: A single-centre, retrospective cohort study was conducted at the Rheumatology Clinic of the National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland from 1 January 2022 to 31 December 2025. Data included demographics, IIM subtypes, extramuscular involvement, co-existing Sjögren disease (SD), biopsy results, autoantibodies, and treatment. Due to sample size, descriptive analysis was used. Results: The study included 35 patients (31.4% men). Mean age was 50.7 years; mean body mass index (BMI) was 26.0 kg/m2. The cohort consisted of 10 dermatomyositis (DM), one polymyositis (PM), two immune-mediated necrotising myopathy (IMNM), one inclusion body myositis (IBM), 16 anti-synthetase syndrome (ASyS), four juvenile dermatomyositis (JDM), and one clinically amyopathic dermatomyositis (CADM). SD co-occurred in eight cases, including six cases of ASyS. Anti-Jo1 was observed in 13 ASyS cases and one DM. Glucocorticoids (GCSs) were administered in all patients for induction in addition to cyclophosphamide (28.6%), mycophenolate mofetil (MMF) (51.4%), and methotrexate (MTX) (17.1%). Maintenance therapy included MTX (20%), MMF (31.4%), rituximab (34.3%), azathioprine (AZA) (42.9%), and others. Two DM, two JDM, and one ASyS patient received JAK inhibitors, one DM and one JDM anifrolumab, one IBM sirolimus, and four patients with interstitial lung disease (ILD) nintedanib. Conclusions: This Polish single-centre cohort shows effective use of novel therapies for IIM. Sirolimus, JAK inhibitors, and nintedanib were effective. Co-occurrence of SD in ASyS patients requires further research.
2026-04-17 | Energy metabolism dysregulation in idiopathic inflammatory myopathies: mechanisms and therapeutic implications
Idiopathic inflammatory myopathies (IIMs) are being increasingly recognized as disorders driven by profound disturbances in cellular energy metabolism rather than inflammation alone. Recent studies have highlighted mitochondrial dysfunction, oxidative stress, and metabolic reprogramming across glucose, lipid, and amino acid pathways as central mechanisms linking energy metabolism dysregulation to sustained muscle injury. Defective mitophagy, mitochondrial DNA (mtDNA) depletion, and excessive reactive oxygen species (ROS) production create a self-amplifying loop with interferon-driven inflammation, whereas abnormal glycolysis, impaired fatty acid oxidation, and dysregulated tryptophan-kynurenine metabolism further shape the immunometabolic landscape of IIMs. These metabolic shifts not only contribute to muscle weakness and tissue degeneration but are also correlated with disease severity, autoantibody profiles, and treatment resistance. Emerging therapeutic strategies, including antioxidant approaches, mitochondrion-targeted agents, metabolic modulators, and exercise-based interventions, underscore the translational potential of targeting energy homeostasis. This review synthesizes current evidence on energy metabolism abnormalities in IIMs, integrates molecular findings with clinical implications, and highlights future directions for immunometabolic-based precision therapies.
2026-04-13 | Efficacy and safety of upadacitinib in refractory interstitial lung disease with idiopathic inflammatory myopathies: a retrospective study.
To assess the efficacy and safety of upadacitinib (UPA) in patients with refractory idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD) following conventional therapy failure. We conducted a single-centre retrospective cohort study of IIM-ILD patients initiating UPA after conventional therapy failure. Clinical characteristics, pulmonary function tests (PFTs), high-resolution CT (HRCT) Warrick scores and therapeutic regimens were collected at baseline and follow-ups. Patients receiving conventional treatment were included as the control group following propensity score matching (PSM, 1:2). Treatment responses and adverse events were analysed and compared. Among 28 UPA-treated patients (mean age 57, 87.5% female), 16 had complete paired data of PFTs and/or HRCT both at baseline and after treatment. After mean 7.4 months, lung function improved: the mean FVC increased from 1.84 to 2.13 l (P = 0.0069), FVC% from 63.5% to 76.77% (P = 0.0004). HRCT Warrick scores remained stable overall, with some patients showing radiographic improvement. Inflammatory indicators, including IL-6 (14.06-8.44 pg/ml, P = 0.039) and serum ferritin (240.30-188.15 µg/l, P = 0.018), decreased significantly after treatment. Further PSM analysis (n = 16 UPA vs 32 controls) showed notably lower post-treatment IL-6 (8.44 vs 20.60 pg/ml, P = 0.0012) and lower glucocorticoid dose (7.50 vs 12.50 mg, P = 0.017). No significant differences in PFTs or HRCT scores were found between the groups. Infections occurred in 6/28 (21.4%), all recovered well. UPA significantly improved lung function, reduced glucocorticoid dependence and suppressed systemic inflammation in refractory IIM-ILD with acceptable safety, supporting its use as a promising therapeutic option in IIM-ILD patients after conventional treatment failure.
antibodies
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.
2026-07-26 | 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.
2026-07-10 | Predictors of intravenous immunoglobulin therapy in juvenile idiopathic inflammatory myopathies
Objective: Juvenile idiopathic inflammatory myopathies (JIIM) exhibit heterogeneous presentation, and intravenous immunoglobulin (IVIG) is often required in refractory cases. This study aimed to identify the clinical characteristics associated with IVIG use. Methods: This retrospective study included patients aged 0–18 years who fulfilled the Bohan and Peter and/or 2017 EULAR/ACR criteria for JIIM and were followed between March 2009 and August 2025. Demographic, clinical, laboratory, and treatment data were recorded. Results: Thirty-eight patients were included; 29 (76.3%) had juvenile dermatomyositis. Sixteen patients received IVIG. Severe or unresponsive muscle weakness was the main indication (56.3%). IVIG-treated patients had significantly lower Childhood Myositis Assessment Scale (CMAS) scores at diagnosis and at the third month, higher AST levels, more frequent nailfold capillaroscopy abnormalities, and lower remission rates. Each one-point decrease in CMAS increased the odds of IVIG use. Additionally, the third-month CMAS score was the only independent predictor for IVIG therapy. Conclusion: In conclusion, IVIG is an effective treatment option for patients with more severe and refractory JIIM. These patients are characterized by lower CMAS scores and marked microvascular involvement. Earlier use of IVIG as a steroid-sparing strategy may help restrict adverse effects.
2026-06-17 | Successful corticosteroid-free management of anti-HMG-CoA reductase immune-mediated necrotizing myopathy with subcutaneous immunoglobulins monotherapy: a case report.
Given the high rate of cardiovascular comorbidities in anti-HMG-CoA reductase (HMGCR)-immune-mediated necrotizing myopathy (IMNM), a glucocorticosteroids (GC)-free treatment approach remains an appealing strategy. While intravenous immunoglobulins (IVIg) represents an effective therapy in most subgroups of idiopathic inflammatory myositis (IIM), there remains limited evidence supporting the use subcutaneous immunoglobulins (SCIg), a potentially safer, more convenient and cost-effective alternative. We present a case of a 68-year-old male of European descent with a 2-year history of progressive proximal bilateral lower extremity weakness. He had been treated for his dyslipidemia with atorvastatin for 2 years, then with rosuvastatin for 2 additional years until discontinued a year before our assessment. His other comorbidities included hypertension and diabetes mellitus type II. Physical examination demonstrated proximal weakness of his bilateral hip flexors and deltoids, and no rash. His creatine kinase (CK) was elevated at 1644 IU/L. Electromyography revealed a generalized myopathic disorder with proximal predominance and muscle biopsy of the right quadriceps showed typical findings of an IMNM. Serum HMG-CoA reductase antibody was positive. Due to accumulating evidence supporting the effectiveness of IVIg in anti-HMGCR-IMNM, even without concomitant GC or other immunosuppressive agent, we opted for a GC-free approach through shared-decision making in light of patient's preference regarding potential GC side effects with his comorbidities. As he lived a considerable distance from any center, where IVIg infusions could be offered, and given the patient was unable to drive himself due to his symptoms we opted for SCIg (0.5 g/kg/week). Within 1 month, his CK decreased and weakness resolved. SCIg monotherapy was tapered over 3 years and this patient remains in remission 7 years after SCIg initiation. The patient did not have any adverse effects related to SCIg use. To our knowledge, this is the first case report describing a successful corticosteroid-free management of anti-HMGCR immune-mediated necrotizing myopathy using SCIg as monotherapy. This case highlights the potential for steroids-free induction and maintenance strategies in IMNM. Larger studies are required to confirm the effectiveness and safety of SCIg in IMNM and other subtypes of IIM, and to provide guidelines for dosing recommendations.
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2025-09-03 | Recombinant human hyaluronidase-facilitated subcutaneous immunoglobulin (hf-SCIg) for inflammatory myositis: a multicenter retrospective real-world observational study.
Subcutaneous immunoglobulin (SCIg) is a promising alternative to intravenous Ig (IVIg) for the treatment of idiopathic inflammatory myositis (IIM), thanks to its more favorable safety profile, reduced costs, and lower impact on patients' quality of life. We assessed the short- and long-term effectiveness and safety of recombinant human hyaluronidase-facilitated SCIg (hf-SCIg) in patients with IIM treated at different referral centers in Italy. A multicenter, retrospective, real-life cohort study was conducted on consecutive adult patients diagnosed with IIM according to the EULAR/ACR criteria, treated with hf-SCIg for remission induction or maintenance. Hf-SCIg effectiveness was assessed in terms of variation in the Medical Research Council (MRC) score, serum creatine kinase (CK) values, clinical disease manifestations and daily prednisone dosage. Safety data were also collected. Twenty-six patients with IIM treated with hf-SCIg for remission induction (n = 5) or maintenance (n = 21) were included in the study (18 females; median age at diagnosis of 59 (IQR 42-64) years)). In most patients, hf-SCIg was started following previous IVIg treatment (23, 89 %) and was initiated in combination with oral corticosteroids (21, 81 %) and/or traditional or biologic DMARDs. Short-term use of hf-SCIg for remission induction appeared associated with a corticosteroid-sparing effect, without worsening of MRC score. Long-term hf-SCIg treatment for up to 24 months maintained clinical stability and serum CK levels with further improvement of MRC score. Hf-SCIg was well tolerated, with mild adverse events mostly related to local site reactions. Hf-SCIg seems effective and safe for induce and maintain clinical remission in patients with IIM.
2025-06-01 | POS0278 RISK FACTORS AND PROGNOSTIC OUTCOMES OF PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHY COMPLICATED WITH INFECTION
Infections cause disease exaggeration in patients with myositis, representing one of the leading causes of mortality. Patients with myositis are often treated by glucocorticoids and immunosuppressants that could increase the risk of infection, which in turn deteriorate the disease. This study investigates the incidence and risk factors of infections in patients with idiopathic inflammatory myopathy (IIM). A case-control study was conducted to assess the infection rates and associated risk factors among patients with IIM, who were treated at the Department of Rheumatology and Immunology, Peking University People's Hospital from 2000 to 2023. All the patients were diagnosed based on 2017 EULAR/ACR criteria. The occurrence of infectious complications was identified over a 12-month follow-up period, based on supportive clinical features, positive microbial cultures, and/or responses to antibiotic therapy. Demographics, clinical data at baseline, and mortality rates of patients were systematically recorded. IL-2 treatment was defined as 1×106 IU of IL-2 subcutaneously every other day for 12 weeks on top of standard care. Multivariate logistic regression analysis was employed to determine independent risk factors for significant infections. Additionally, cumulative survival rates were estimated using the Kaplan–Meier method. Of the 616 patients with IIM, 151 (24.5%) suffered from infections. The lung was the most common infection site (69.5%), The most common pathogen was bacteria (50.3%), followed by viruses (41.7%), fungi (17.2%), and mixed infections (7.2%). Multivariate analyses demonstrated that age >45 years (OR=1.79; 95% CI=1.11-2.87; p=0.017); skin ulcer (OR=2.19; 95% CI=1.01-4.74; p=0.048); fever (OR=1.71; 95% CI=1.09-2.69; p=0.019); thrombocytopenia (OR=2.44; 95% CI=1.20-4.95; p=0.014); hypoproteinemia (OR=1.86; 95% CI=1.18-2.93; p=0.008); C-ILD (OR=2.34; 95% CI=1.36-4.02; p=0.002) are independent risk factors for infection. Treatment with low-dose IL-2 (OR=0.31; 95% CI=0.14-0.65; p=0.002) was a protective factor for infection. Survival analysis demonstrated that the infection group's ten-year survival rate was lower than that of the non-infection group (54.7% vs. 90.1%, p<0.001). After the first episode of infection, survival rates of patients with IIM declined sharply to 85.7% at one year and 76.0% at three years. This study underlines the high frequency of infections in IIM, which is significantly detrimental to patient survival rates. It also provides a summary of the risk factors contributing to infection development. Encouragingly, low-dose IL-2 emerges as a potential strategy for mitigating the risk of severe infections. Figure 1Multivariate analysis: adjusted OR for risk of infection in IIM. Figure 2Survival curves for IIM patients with and without infection. NIL. This study is based on the contributions of all colleagues in our department. None declared. © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.
2025-03-31 | Successful treatment of rheumatoid arthritis complicated by anti-Jo-1 antibody-positive myopathy with abatacept: A case report.
Abatacept (ABT) is effective in the treatment of rheumatoid arthritis (RA). However, there is no consensus regarding the treatment of patients with RA and idiopathic inflammatory myopathy (IIM). Here, we describe the case of a 55-year-old Japanese female with a 5-year history of RA who developed anti-Jo1 antibody-positive IIM. She developed myalgia and dyspnea while receiving a combination therapy of methotrexate and a Janus kinase inhibitor for RA. Chest computed tomography imaging revealed bilateral middle-to-lower lung frosted shadows. Magnetic resonance imaging of the lower limbs showed a high short tau inversion recovery signal in the bilateral thigh muscle groups. Needle electromyography revealed myogenic changes in the proximal muscles of both the upper and lower extremities. Symmetric proximal muscle weakness, elevated serum muscle enzymes, and the presence of anti-Jo1 antibodies were noted. The diagnosis of IIM was made according to the European Alliance of Associations for Rheumatology diagnostic criteria. The myositis symptoms stabilized with glucocorticoids; however, RA worsened during steroid tapering. After ABT initiation, RA clinical symptoms and functional outcomes improved and myositis remained in remission. In conclusion, ABT may be an effective treatment option for patients with RA and IIM. .
2023-12-30 | Glucagon-Like Peptide-1 Receptor Agonists in the Treatment of Idiopathic Inflammatory Myopathy: From Mechanisms of Action to Clinical Applications
Idiopathic inflammatory myopathies (IIMs) result in proximal muscle weakness and other intramuscular and extramuscular manifestations. Pharmacologic treatments in use for IIMs are limited to corticosteroids and immunosuppressants in addition to supportive physical and occupational therapy. Glucagon-like peptide-1 receptor (GLP-1R) agonists are currently utilized in the treatment of type II diabetes and obesity but may play a role in the treatment of IIMs. The current scoping review of extant literature aims to synthesize findings from studies assessing the therapeutic effects of GLP-1R agonists in the management of inflammatory myopathy and muscle atrophy. A literature search was conducted through PubMed, resulting in a total of 19 research-based articles included in this review. Mice and human studies showed, with varying levels of significance, that GLP-1R agonists led to decreases in muscle atrophy, inflammation, adiposity, and weakness; improvement in muscle microvasculature and endurance; and promotion of muscle mitochondria biogenesis. The potential for GLP-1R agonists to improve muscle function and architecture underscores the need for large randomized controlled, clinically comparative trials of GLP-1R agonists in patients with IIM.
2023-05-30 | AB0911 EFFICACY OF LOW-DOSE IL-2 IN PATIENTS WITH MYOSITIS
Idiopathic inflammatory myopathies (IIMs) are a group of rare and heterogeneous muscle inflammatory diseases characterized by disturbances of regulatory T(Treg) cells. Interleukin (IL)-2 has been rediscovered as a pivotal cell population in the control of autoimmunity, which effectively relieves idiopathic inflammatory myopathies(IIMs) such as polymyositis(PM) and dermatomyositis (DM). This study aimed to systematically evaluate the efficacy of low-dose IL-2 therapy in PM, DM, and IIMs. Systematic searches of PubMed, EMBASE, Web of Science, the Cochrane Library and Medline, CNKI, CBM, and Technology Journal Database were performed. Original case reports, case series, observational studies, and clinical trials reporting the changes in the numbers of lymphocyte subsets on PM, DM, and IIMs patients treated with IL-2 were included. A random-effects meta-analysis was performed to calculate the pooled efficacy. Inconsistency was evaluated by using the I2, and Egger tests were used for the evaluation of potential publication bias (STATA v.12.0) A total of 5 studies comprising 401 patients were identified(Table 1).The CDASI scores were significantly decreased after IL-2 treatment[SMD=-1.146, 95%CI (-1.591,-0.700), P<0.001].Besides, the number of Tregs cells was significantly increased[SMD=-1.146, 95%CI (-1.591,-0.700), P=0.007], and the subgroup analysis was performed based on the dose of IL-2(Figure 1). Low-dose IL-2 was promising in the treatment of DM, PM, and IMMs, which could promote the proliferation and functional recovery of Tregs. This work was supported by the National Natural Science Foundation of China (No. 82001740). None Declared.
other
2020-02-03 | Muscle Weakness in Myositis: MicroRNA‐Mediated Dystrophin Reduction in a Myositis Mouse Model and Human Muscle Biopsies
Objective Muscle inflammation is a feature in myositis and Duchenne muscular dystrophy ( DMD ). Autoimmune mechanisms are thought to contribute to muscle weakness in patients with myositis. However, a lack of correlation between the extent of inflammatory cell infiltration and muscle weakness indicates that nonimmune pathologic mechanisms may play a role. The present study focused on 2 micro RNA (mi RNA ) sets previously identified as being elevated in the muscle of patients with DMD —an “inflammatory” mi RNA set that is dampened with glucocorticoids, and a “dystrophin‐targeting” mi RNA set that inhibits dystrophin translation—to test the hypothesis that these mi RNA s are similarly dysregulated in the muscle of patients with myositis, and could contribute to muscle weakness and disease severity. Methods A major histocompatibility complex class I–transgenic mouse model of myositis was utilized to study gene and mi RNA expression and histologic features in the muscle tissue, with the findings validated in human muscle biopsy tissue from 6 patients with myositis. Mice were classified as having mild or severe myositis based on transgene expression, body weight, histologic disease severity, and muscle strength/weakness. Results In mice with severe myositis, muscle tissue showed mononuclear cell infiltration along with elevated expression of type I interferon and NF ‐κB–regulated genes, including Tlr7 (3.8‐fold increase, P < 0.05). Furthermore, mice with severe myositis showed elevated expression of inflammatory mi RNA s (miR‐146a, miR‐142‐3p, miR‐142‐5p, miR‐455‐3p, and miR‐455‐5p; ~3–40‐fold increase, P < 0.05) and dystrophin‐targeting mi RNA s (miR‐146a, miR‐146b, miR‐31, and miR‐223; ~3–38‐fold increase, P < 0.05). Bioinformatics analyses of chromatin immunoprecipitation sequencing (ChIP‐seq) data identified at least one NF ‐κB consensus element within the promoter/enhancer regions of these mi RNA s. Western blotting and immunofluorescence analyses of the muscle tissue from mice with severe myositis demonstrated reduced levels of dystrophin. In addition, elevated levels of NF ‐κB–regulated genes, TLR 7 , and mi RNA s along with reduced dystrophin levels were observed in muscle biopsy tissue from patients with histologically severe myositis. Conclusion These data demonstrate that an acquired dystrophin deficiency may occur through NF ‐κB–regulated mi RNA s in myositis, thereby suggesting a unifying theme in which muscle injury, inflammation, and weakness are perpetuated both in myositis and in DMD .
2015-09-23 | The role of microRNAs in the idiopathic inflammatory myopathies
Purpose of review The idiopathic inflammatory myopathies (IIMs) are a group of rare autoimmune disorders characterized by skeletal muscle weakness and inflammation. MicroRNAs (miRNAs) regulate a wide range of developmental and physiological cellular processes. New approaches to investigating the mechanisms involved in IIM, such as investigating the role of miRNAs, are vital for the development of novel therapeutics and/or better diagnostic tools. Recent findings Identification of dysregulated miRNAs has led to a greater understanding of inflammation, muscle weakness/wasting and extra-muscular organ involvement in IIM. Up-regulation of immune-related miRNAs in muscle, for example, miR-155 and miR-146, is associated with autoimmunity, whereas down-regulation of myogenic miRNAs, including miR-1 and miR-206, is associated with inhibition of muscle regeneration. Disease mechanisms have been explored by altering in-vitro conditions and monitoring miRNA levels of interest, or, alternatively, changing miRNA levels and monitoring possible targets. For example, higher levels of cytokines appear to inhibit myogenic miRNAs in muscle and artificially reducing levels of miR-223 increases protein kinase C-epsilon (PKCε) levels in keratinocytes. Summary The exciting expansion of the miRNA field adds to our understanding of IIM pathogenesis and may provide future clinical potential either as diagnostic tools or as therapeutics via use of anti-miRNAs or synthetic miRNAs.
2015-09-10 | New targets to control skeletal muscle inflammation: MicroRNAs regulated by adiponectin
Although adipocytes are the main source of circulating adiponectin (ApN), several studies have now shown that ApN may be produced by the skeletal muscle in response to cellular stress. This induction could be a protective mechanism that counteracts inflammation, oxidative stress and cellular damage occurring during skeletal muscle injury. MicroRNAs (miRNAs) are small non-coding RNAs that control gene expression by inducing target mRNA degradation or blocking translation. In this work, we characterized miRNAs that may contribute to the anti-inflammatory action of ApN on skeletal muscle. To this end, we used ApN-knockout (KO) mice: one tibialis anterior muscle was electroporated with a plasmid coding for the ApN gene while the contralateral leg received a control plasmid. Mice were next challenged by lipopolysaccharide (LPS) to induce inflammation. Muscle electrotransfer of ApN gene induced anti-inflammatory effects: expression of markers of inflammation (TNFα, IL-1β) and oxidative stress (péroxiredonine-3; PRDX3) were downregulated (~−50%) in the muscle electroporated with ApN compared to the contralateral one. miRNA expression profiling revealed that ApN increased the expression of miR-711(~+150%), data which were validated by RT-qPCR. In murine myotubes (C2C12), ApN treatment also upregulated miR-711 and reduced gene expression of TNFα and IL-1β caused by LPS. Transfection of miR-711 mimic reproduced the anti-inflammatory effects of ApN, while using miR-711 inhibitor attenuated these effects. We found that miR-711 repressed 4 genes (fadd, pi3kδ, tab1 and tollip) belonging to the toll-like receptor 4 signalling pathway, which is activated by LPS. In primary cultures of human myotubes, ApN treatment also stimulated the expression of miR-711. The anti-inflammatory effects of ApN appear to be mediated at least in part by miR-711. These data may open new therapeutic perspectives to control muscle inflammation.
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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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