New insights into the treatment of myositis

Glaubitz, Stefanie; Zeng, Rachel; Schmidt, Jens

doi:10.1177/1759720x19886494

Cited by 36 publications

(33 citation statements)

References 104 publications

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“…Given that passive transfer experiments in mice showed that the antibodies are directly pathogenic ( 7 ), removal of the antibodies with plasma exchange may also be considered to produce a transient improvement. While rare patients may experience spontaneous remissions, most patients require some immunotherapy to maintain remission, and relapses upon discontinuation are not uncommon ( 2 , 8 ).…”

Section: Discussionmentioning

confidence: 99%

Case Report: Immune Mediated Necrotizing Myopathy With IgG Antibodies to 3-Hydroxy-3-Methylglutaryl-Coenzyme a Reductase (HMGCR) May Present With Acute Systolic Heart Failure

Ghannam

Manousakis

2020

Front. Neurol.

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Involvement of cardiac muscle is felt to be very uncommon in anti-HMGCR myopathy, and therefore early cardiac evaluation is not considered a high priority for this condition. We herein present the case of a 72 year-old woman admitted due to dyspnea and orthopnea, who, in retrospect, suffered from proximal more than distal muscle weakness for 3 months prior to admission. She was found to have acute systolic heart failure. Serologic testing showed positive 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) IgG antibodies, and muscle biopsy showed necrotizing myopathy. No alternative explanation for heart failure was found. Despite immunotherapy and symptomatic treatment, she died from multiorgan failure. Our study suggests that heart failure in anti HMGCR myopathy may not be as rare as previously thought, and therefore early cardiac evaluation should be considered in patients with this diagnosis, to minimize morbidity and mortality.

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Section: Discussionmentioning

confidence: 99%

Case Report: Immune Mediated Necrotizing Myopathy With IgG Antibodies to 3-Hydroxy-3-Methylglutaryl-Coenzyme a Reductase (HMGCR) May Present With Acute Systolic Heart Failure

Ghannam

Manousakis

2020

Front. Neurol.

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“…These observations, although suggestive of involvement of the classical pathway, are not NAM-specific and they do not indicate that anti-SRP or anti-HMGCR are complement-fixing antibodies because complement activation is inherently associated with muscle fibre necrosis from any cause, including muscular dystrophies 77 . Open-label studies have shown that NAM responds to IVIg or rituximab, but whether this benefit is related to complement inhibition or other immunomodulatory effects is unclear 87 – 89 .…”

Section: Complement In Neurological Diseasesmentioning

confidence: 99%

Complement in neurological disorders and emerging complement-targeted therapeutics

2020

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The human complement system is an effector of innate and adaptive humoral immunity. The system comprises soluble membrane-bound proteins (opsonins) that act collectively to recognize pathogens and non-self material and subsequently initiate opsonization and phagocytosis or lysis of pathogens. The proteolytic fragments that derive from complement activation can be targeted by white blood cells and endothelial cells, leading to extravasation and migration of immune cells at the sites of inflammation. Other physiological functions of complement include timely removal of altered and senescent self, tissue remodelling, cell lysis, chemotaxis, opsonization, inflammation and immune cell stimulation 1-4. Complement activation products link the innate and adaptive immune systems by acting directly on receptors on T cells and B cells or by modulating dendritic cell functions 5-8. Disruption of the delicate coordination required for complement activation and control is fundamental in the pathogenic mechanism of several autoimmune neurological disorders, and is even emerging as a contributor in some neurodegenerative diseases. As a result, interest is increasing in targeting complement as a therapeutic approach to prevent ongoing tissue destruction in several difficult-to-treat neurological diseases. In this Review, we provide an overview of the main components of the initial complement activation pathways, the lytic pathway and the factors associated with inappropriate complement activation or control in disease initiation and progression. We consider the role of complement in the tissue destruction that is responsible for the genesis of the most common autoimmune neurological diseases, including complement-mediated myopathies, myasthenia gravis, neuropathies and CNS disorders. We also discuss the role of complement in some neurodegenerative disorders, including Alzheimer disease (AD), amyotrophic lateral sclerosis (ALS), Huntington disease, traumatic brain injury and even schizophrenia. Finally, we discuss emerging complement-targeted therapies, such as monoclonal antibodies, fusion proteins and cyclic peptides, that inhibit the functions of individual complement proteins, especially therapies that disrupt the lytic pathway. Some of these therapeutic agents have been approved or are being tested in phase I-III clinical trials and promise to change the therapeutic armamentarium for treatment of neurological conditions that respond poorly to existing immunotherapies.

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“…In 2017, 1 of 8 patients received rituximab and a further increase in more specific and effective therapies can be expected in future. Besides rituximab, baricitinib, triple regimens and other new treatment options bear the potential to improve the situation of patients with IIM [19]. Immunosuppressive treatment was less frequently used compared to the European registry [8].…”

Section: Discussionmentioning

confidence: 99%

Trends in idiopathic inflammatory myopathies: cross-sectional data from the German National Database

et al. 2020

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Objective To describe trends in outcomes among patients with idiopathic inflammatory myopathies (IIM) over two decades. Methods From 1997 to 2017, a total of 1079 IIM patients were documented in the National Database of the German Collaborative Arthritis Centers. Annual cross-sectional data on treatment, disease activity, patient-reported outcomes, hospitalization and employment were compared across the years. Information on phenotypes, organ manifestations and autoantibodies was collected for a subset to compare the assessment of global health, pain, fatigue and sleeping disorders. Results In 2017, significantly more IIM patients were assessed to be in low disease activity (94%) than in 1997 (59%), p < 0.01. Pain (p = 0.001), global health (p = 0.049), fatigue (p = 0.03) and sleeping disorders (p = 0.01) also improved since recording. Glucocorticoid use decreased from 84 to 58% (p < 0.01). Employment in patients < 65 years remained unchanged (53%), while early retirement (23-9%), hospitalization/year (34-18%) and sick leave (52-24%) decreased. A total of 186 patients with information on subtypes were classified as polymyositis (44%), dermatomyositis (33%), anti-synthetase syndrome (10%), overlapping-myositis (8%), inclusion body myositis (2%), necrotizing myositis (0.5%) and unspecific (3%). The most frequently reported symptoms were limitations in global health (60%), fatigue (57%) and sleeping disorders (51%), and all of them were most frequent in overlap-myositis. Pulmonary hypertension and cardiomyopathy were associated with poor outcomes regarding global health, daily activities and fatigue. Conclusion IIM patients report better outcomes than 20 years ago, along with good physician-reported disease control. Global health, fatigue and sleeping disorders are relevant patient-reported domains in IIM.

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New insights into the treatment of myositis

Cited by 36 publications

References 104 publications

Case Report: Immune Mediated Necrotizing Myopathy With IgG Antibodies to 3-Hydroxy-3-Methylglutaryl-Coenzyme a Reductase (HMGCR) May Present With Acute Systolic Heart Failure

Case Report: Immune Mediated Necrotizing Myopathy With IgG Antibodies to 3-Hydroxy-3-Methylglutaryl-Coenzyme a Reductase (HMGCR) May Present With Acute Systolic Heart Failure

Complement in neurological disorders and emerging complement-targeted therapeutics

Trends in idiopathic inflammatory myopathies: cross-sectional data from the German National Database

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