The Efficacy of Tocilizumab in the Treatment of Patients with Refractory Immune-Mediated Necrotizing Myopathies: An Open-Label Pilot Study

Li, Sizhao; Li, Wenli; Jiang, Wei; He, Linrong; Peng, Qinglin; Wang, Guochun; Lu, Xin

doi:10.3389/fphar.2021.635654

Cited by 21 publications

(13 citation statements)

References 23 publications

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“…Fresh muscle biopsy specimens were cut into 7-μm frozen sections using cryostat frozen sections (Thermo Cryotome E) and stained using haematoxylin-eosin, periodic acid-Schiff (PAS), oil red O (ORO), modified Gomori's trichrome, NADH-tetrazolium reductase, succinate dehydrogenase, cytochrome C oxidase, and myosin ATPase. Immunohistochemistry staining for dysferlin, dystrophin, α-sarcoglycans to δ-sarcoglycans, α-dystroglycans and β-dystroglycans, MHC-I, CD4, CD8, CD20, and CD68, and membrane attack complex (MAC) was performed using the avidin-biotin-peroxidase complex method as previously described [23]. All reagents used were purchased from Abcam (Cambridge, UK).…”

Section: Muscle Biopsymentioning

confidence: 99%

Clinical and pathological features of immune-mediated necrotising myopathies in a single-centre muscle biopsy cohort

Yang

Tian

Zhang

et al. 2022

BMC Musculoskelet Disord

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Objective Immune-mediated necrotising myopathy (IMNM) is a subset of idiopathic inflammatory myopathies (IIM) characterized by significantly elevated creatine kinase level, muscle weakness and predominant muscle fibre necrosis in muscle biopsy. This study aimed to investigate the clinical and pathological characteristics of patients with IMNM in a single-centre muscle biopsy cohort. Methods A total of 860 patients who had muscle biopsy reports in our centre from May 2008 to December 2017 were enrolled in this study. IMNM was diagnosed according to the 2018 European Neuromuscular Centre (ENMC) clinicopathological diagnostic criteria for IMNM. Results The muscle biopsy cohort consisted of 531 patients with IIM (61.7%), 253 patients with non-IIM (29.4%), and 76 undiagnosed patients (8.8%). IIM cases were classified as IMNM (68[7.9%]), dermatomyositis (346[40.2%]), anti-synthetase syndrome (82[9.5%]), polymyositis (32[3.7%]), and sporadic inclusion body myositis (3[0.3%]). Limb girdle muscular dystrophy (LGMD) 2B and lipid storage myopathy (LSM) are the two most common non-IIM disorders in our muscle biopsy cohort. IMNM patients had a higher onset age (41.57 ± 14.45 vs 21.66 ± 7.86 and 24.56 ± 10.78, p < .0001), shorter duration (21.79 ± 26.01 vs 66.69 ± 67.67 and 24.56 ± 10.78, p < .0001), and more frequent dysphagia (35.3% vs. 3.4 and 6.3%, p = .001) than LGMD 2B and LSM patients. Muscle biopsy from IMNM showed more frequent muscle fibre necrosis (95.6% vs 72.4 and 56.3%, p < .0001), overexpression of major histocompatibility complex-I on sarcolemma (83.8% vs 37.9 and 12.9%, p < .0001), and CD4+ T cell endomysia infiltration (89.7% vs 53.6 and 50%, p < .0001) compared with those from LGMD 2B and LSM patients. Conclusions It is easy to distinguish IMNM from other IIM subtypes according to clinical symptoms and myositis specific antibodies profiles. However, distinguishing IMNM from disorders clinically similar to non-IIM needs combined clinical, serological and pathological features.

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Section: Muscle Biopsymentioning

confidence: 99%

Clinical and pathological features of immune-mediated necrotising myopathies in a single-centre muscle biopsy cohort

Yang

Tian

Zhang

et al. 2022

BMC Musculoskelet Disord

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“…The definition of refractory IMNM is not explicit. When the treatment with glucocorticoids with immunosuppressants at a known effective dose is performed for at least three to twelve months, and muscle weakness is still worsening or not better, these patients can be deemed to be refractory ( 44 , 87 ). There are some risk factors associated with refractory SRP-IMNM, including being male, severe muscle weakness, concurrent ILD, quick development of muscle fatty infiltration, and more B cell activating factor receptor and B lymphocyte infiltration in muscle specimens ( 44 ).…”

Section: Treatment and Prognosismentioning

confidence: 99%

“…Rituximab may be an effective treatment strategy against refractory IMNM ( 83 , 84 ). Some patients with refractory IMNM respond well to tocilizumab ( 87 ). High-dose cyclophosphamide is effective for several refractory IMNM patients ( 88 ).…”

Section: Treatment and Prognosismentioning

confidence: 99%

Anti-SRP immune-mediated necrotizing myopathy: A critical review of current concepts

2022

Front. Immunol.

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Purpose of reviewThis review aims to describe clinical and histological features, treatment, and prognosis in patients with anti-signal recognition particle (SRP) autoantibodies positive immune-mediated necrotizing myopathy (SRP-IMNM) based on previous findings.Previous findingsAnti-SRP autoantibodies are specific in IMNM. Humoral autoimmune and inflammatory responses are the main autoimmune characteristics of SRP-IMNM. SRP-IMNM is clinically characterized by acute or subacute, moderately severe, symmetrical proximal weakness. Younger patients with SRP-IMNM tend to have more severe clinical symptoms. Patients with SRP-IMNM may be vulnerable to cardiac involvement, which ought to be regularly monitored and cardiac magnetic resonance imaging is the recommended detection method. The pathological features of SRP-IMNM are patchy or diffuse myonecrosis and myoregeneration accompanied by a paucity of inflammatory infiltrates. Endoplasmic reticulum stress-induced autophagy pathway and necroptosis are activated in skeletal muscle of SRP-IMNM. Treatment of refractory SRP-IMNM encounters resistance and warrants further investigation.SummaryAnti-SRP autoantibodies define a unique population of IMNM patients. The immune and non-immune pathophysiological mechanisms are involved in SRP-IMNM.

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“…Fresh muscle biopsy specimens were cut into 7-μm frozen sections using cryostat frozen sections (Thermo Cryotome E) and stained using haematoxylin-eosin, periodic acid-Schiff, oil red O, modi ed Gomori's trichrome, NADH-tetrazolium reductase, succinate dehydrogenase, cytochrome C oxidase, and myosin ATPase. Immunohistochemistry staining for dysferlin, dystrophin, α-sarcoglycans to δ-sarcoglycans, αdystroglycans and β-dystroglycans, MHC-I, CD4, CD8, CD20, and CD68, and major attack complex (MAC) was performed using the avidin-biotin-peroxidase complex method as previously described [11]. All reagents used were purchased from Abcam (Cambridge, UK).…”

Section: Muscle Biopsymentioning

confidence: 99%

Clinical and Pathological Features of Immune-Mediated Necrotising Myopathies in a Single-Centre Muscle Biopsy Cohort

Yang

Tian

Zhang

et al. 2022

Preprint

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Objective Immune-mediated necrotising myopathy (IMNM) is a recently entitled novel subset of idiopathic inflammatory myopathies (IIM) characterized by significant elevated creatine kinase (CK) level, muscle weakness and predominant muscle fibre necrosis in muscle biopsy. This study aimed to investigate the clinical and pathological characteristics of patients with IMNM in our single-centre muscle biopsy cohort. Methods A total of 860 patients who had muscle biopsy reports in our centre from May 2008 to December 2017 were enrolled in this study. IMNM was diagnosed in according with 2018 European Neuromuscular Centre (ENMC) clinicopathological diagnostic criteria for IMNM. Results The muscle biopsy cohort consisted of 531 patients with IIM (61.7%), 253 patients with non-IIM (29.4%), and 76 undiagnosed patients (8.8%). Among IIM patients, polymyositis (PM), dermatomyositis(DM), amyopathic dermatomyositis, juvenile DM, and inclusion body myositis were 182(21.2%), 236(27.4%), 83(9.7%), 18(2.1%) and 3(0.3%), respectively. In PM subgroup, 59 patients met serological and pathological characteristics of IMNM according to 2018 ENMC criteria including 29 anti-SRP-positive patients,10 anti-HMGCR-positive patients and 20 MSA-negative patients. Limb girdle muscular dystrophy (LGMD) 2B and lipid storage myopathy (LSM) were 29 and 16 respectively, which present similar manifestations of IMNM with elevated CK levels and muscle weakness among non-IIM group. IMNM patients had older age of onset (mean: 42.25 vs 21.66 and 24.56, p<0.0001), shorter duration of diseases (mean: 22.56 vs 66.69 and 48.94, p<0.0001) and more frequent of dysphagia (33.9% vs 3.4% and 6.3%, p<0.0001) compare to patients with LGMD 2B and LSM. Muscle biopsy from IMNM patients showed frequent muscle fibre necrosis (96.6% vs 72.4% and 56.3%, p<0.0001), overexpression of MHC-I on sarcolemma (81.4% vs 37.9% and 12.9%, p<0.0001) and CD4+ T cell endomysial infiltration (89.9% vs 53.6% and 50%, p<0.0001) compared with LGMD 2B and LSM patients. Conclusions It is easy to distinguish IMNM from other subtype of IIM according to clinical symptoms and MSAs profiles. However, distinguishing IMNM from disorders clinically similar non-IIM need to combine with clinical, serological and pathological features.

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The Efficacy of Tocilizumab in the Treatment of Patients with Refractory Immune-Mediated Necrotizing Myopathies: An Open-Label Pilot Study

Cited by 21 publications

References 23 publications

Clinical and pathological features of immune-mediated necrotising myopathies in a single-centre muscle biopsy cohort

Clinical and pathological features of immune-mediated necrotising myopathies in a single-centre muscle biopsy cohort

Anti-SRP immune-mediated necrotizing myopathy: A critical review of current concepts

Clinical and Pathological Features of Immune-Mediated Necrotising Myopathies in a Single-Centre Muscle Biopsy Cohort

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