|
1
|
Aggarwal R, Lundberg IE, Song Y, Shaibani A, Werth VP, Maldonado MA. Efficacy and Safety of Subcutaneous Abatacept Plus Standard Treatment for Active Idiopathic Inflammatory Myopathy: Phase 3 Randomized Controlled Trial. Arthritis Rheumatol 2025; 77:765-776. [PMID: 39609094 PMCID: PMC12123255 DOI: 10.1002/art.43066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Revised: 10/22/2024] [Accepted: 10/29/2024] [Indexed: 11/30/2024]
Abstract
OBJECTIVE Our objective was to evaluate the efficacy and safety of subcutaneous (SC) abatacept and standard of care (SOC) for the treatment of idiopathic inflammatory myopathy (IIM) over 52 weeks. METHODS In this randomized, double-blind, placebo-controlled phase III trial, patients with treatment-refractory IIM received SC abatacept (at 125 mg weekly) with SOC (abatacept group) or a placebo with SOC (placebo group). A 24-week double-blind period was followed by an open-label period to assess outcomes from continued therapy with abatacept and initiation with abatacept (placebo-to-abatacept switch group) from 24 to 52 weeks. The primary end point was International Myositis Assessment and Clinical Studies definition of improvement (IMACS DOI) at week 24. Secondary efficacy and safety end points were assessed. RESULTS Overall, 148 (double-blind) and 133 (open-label) patients were treated. Baseline demographics were well-balanced between treatment groups and disease subtypes. At 24 weeks, improvement per IMACS DOI was 56.0% for the abatacept group and 42.5% for the placebo group (P = 0.083); at 52 weeks, improvement was 69.8% (continued abatacept) and 69.0% (placebo-to-abatacept switch). The IMACS DOI rate at 24 weeks was greater in the nondermatomyositis (non-DM) group (abatacept: 57.1%; placebo: 32.3%; P = 0.040) than the DM group (abatacept: 55.0%; placebo: 50.0%; P = 0.679). The observed safety profile was similar in both groups. CONCLUSION The proportion of patients who met improvement criteria after 24 weeks was similar between abatacept and placebo groups. However, analysis by IIM subtype suggested there may be a sustained benefit of SC abatacept for patients with non-DM subtypes.
Collapse
Affiliation(s)
| | | | | | | | | | - Michael A. Maldonado
- Immunology and Fibrosis Research and DevelopmentBristol Myers SquibbPrincetonNew Jersey
| |
Collapse
|
|
2
|
Izuka S, Komai T, Tsuchida Y, Tsuchiya H, Okamura T, Fujio K. The role of monocytes and macrophages in idiopathic inflammatory myopathies: insights into pathogenesis and potential targets. Front Immunol 2025; 16:1567833. [PMID: 40181992 PMCID: PMC11965591 DOI: 10.3389/fimmu.2025.1567833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2025] [Accepted: 03/03/2025] [Indexed: 04/05/2025] Open
Abstract
Idiopathic inflammatory myopathies (IIMs) are heterogeneous autoimmune disorders characterized by muscle inflammation, weakness, and extramuscular manifestations such as interstitial lung disease, skin rash, arthritis, dysphagia, myocarditis and other systemic organ involvement. Although T and B cells have historically been central to the understanding of IIM immunopathology, monocytes and their differentiated progenitor cells, macrophages, are increasingly being recognized as critical mediators of both tissue damage and repair. In subtypes such as dermatomyositis, immune-mediated necrotizing myopathy and antisynthetase syndrome, macrophages infiltrate skeletal muscle and other affected tissues, contributing to inflammation via production of pro-inflammatory cytokines, chemokines, and reactive oxygen species. Dysregulated interferon signaling, mitochondrial stress, and aberrant metabolic states in these cells further perpetuate tissue injury in IIMs. Conversely, certain macrophage subsets can support muscle fiber regeneration and dampen inflammation, underscoring the dual roles these cells can play. Future research into the heterogeneity of monocytes and macrophages, including single-cell transcriptomic and metabolomic approaches, will help clarify disease mechanisms, identify biomarkers of disease activity and prognosis, and guide novel therapeutic strategies targeting these innate immune cells in IIM.
Collapse
Affiliation(s)
- Shinji Izuka
- Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Toshihiko Komai
- Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yumi Tsuchida
- Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Haruka Tsuchiya
- Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Tomohisa Okamura
- Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
- Department of Functional Genomics and Immunological Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Keishi Fujio
- Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| |
Collapse
|
|
3
|
Bassett J, Back W, Simman R. Wound management in end-stage dermatomyositis: a case report. J Wound Care 2025; 34:S24-S26. [PMID: 39928507 DOI: 10.12968/jowc.2024.0013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/12/2025]
Abstract
Little has been written about the challenges in wound healing presented by rare cases of dermatomyositis (DM) complicated by glucocorticoid use. The authors explore the clinical presentation of a 60-year-old female patient with end-stage DM, chronic steroid use and delayed wound healing, requiring surgical debridement of wounds and extensive calcification removal. Her atypical presentation-lacking some of the characteristic dermal and antibody findings-is described, while also highlighting calcification and wound trials that complicated management. The underlying pathophysiology of effects on capillary networks is discussed, as well as the effectiveness of various treatment modalities, including steroids, antimetabolites and biologics, some of which were used. The report concludes with opportunities for future study on the disease's complex mechanisms.
Collapse
Affiliation(s)
- James Bassett
- College of Medicine and Life Sciences, University of Toledo, Toledo, Ohio, US
| | - Warren Back
- College of Medicine and Life Sciences, University of Toledo, Toledo, Ohio, US
| | - Richard Simman
- Wound Care and Plastic Surgery, College of Medicine and Life Sciences, University of Toledo, Toledo, Ohio, US
- Jobst Vascular Institute, ProMedica Toledo Hospital, Toledo, Ohio, US
| |
Collapse
|
|
4
|
Neves A, Viveiros L, Venturelli V, Isenberg DA. Where are we now in biologic drugs for myositis? Rheumatology (Oxford) 2024; 63:2938-2947. [PMID: 38321569 DOI: 10.1093/rheumatology/keae096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Revised: 01/10/2024] [Accepted: 01/30/2024] [Indexed: 02/08/2024] Open
Abstract
Idiopathic inflammatory myopathies (IIMs) are a rare and heterogeneous group of chronic autoimmune disorders. Up to 40% of IIM patients have long-term sequelae and significant functional disability. Its management can be challenging and new therapies are badly needed. The small number of cases with diverse presentations and different diagnostic criteria significantly affect clinical trial results. Only IVIG has been internationally approved for IIM patients. Most clinical trials of new biologic therapies have failed to meet their primary endpoints in IIM, with only one biologic drug recommended for refractory IIM treatment (rituximab), although not approved. We review several new emerging biologic drugs, including B cell depletion therapies, abatacept, Janus kinase inhibitors, and aldesleukin. Encouragingly, some phase II randomized controlled trials have evaluated the efficacy and safety of new biologics in IIM, demonstrating an improvement in clinical and laboratory measures.
Collapse
Affiliation(s)
- Ana Neves
- Internal Medicine Department, Centro Hospitalar Universitário de São João, Oporto, Portugal
| | - Luísa Viveiros
- Internal Medicine Department, Centro Hospitalar Universitário de Santo António, Oporto, Portugal
| | - Veronica Venturelli
- Rheumatology Unit, Department of Medical Sciences, Università degli Studi di Ferrara, Azienda Ospedaliero-Universitaria S. Anna, Cona, Italy
| | - David A Isenberg
- Centre for Rheumatology, Department of Medicine, University College London, London, UK
| |
Collapse
|
|
5
|
Behrangi E, Moodi F, Jafarzadeh A, Goodarzi A. Paradoxical and bimodal immune-mediated dermatological side effects of TNF-α inhibitors: A comprehensive review. Skin Res Technol 2024; 30:e13718. [PMID: 38700458 PMCID: PMC11067872 DOI: 10.1111/srt.13718] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2024] [Accepted: 04/15/2024] [Indexed: 05/05/2024]
Abstract
INTRODUCTION Due to the increasing prevalence of immune-mediated diseases such as psoriasis, lichen planus, rheumatoid arthritis and inflammatory bowel disease, dermatologists have turned to new biologic drugs known as DMARDs (disease-modifying anti-rheumatic drugs) in recent years. AREAS COVERED In this study, we evaluate the immune-mediated dermatological side effects of DMARDS by reviewing and analyzing previous peer-reviewed research on the effects of TNF-α inhibitors in the treatment of skin diseases, as well as adverse effects of these drugs and some of the main causes of these effects. EXPERT OPINION DMARDs are very effective in improving control of the above diseases. TNF-α inhibitors are an important group of DMARDs that are widely used. The paradoxical adverse events (PAEs) associated with the use of TNF-α inhibitors are divided into three categories: true paradoxical, borderline paradoxical, and non-paradoxical. True PAEs include conditions for which TNF-α inhibitors are approved for treatment. Borderline PAEs are considered to occur with this class of drugs for which there is no definite approval but for which there is sufficient evidence. Although these events are rare, early recognition of the accused drug and appropriate decision-making may prevent progression of complications and irreversible side effects.
Collapse
Affiliation(s)
- Elham Behrangi
- Department of DermatologyRasool Akram Medical Complex Clinical Research Development Center (RCRDC)School of MedicineIran University of Medical Sciences (IUMS)TehranIran
- Skin and Stem Cell Research CenterTehran University of Medical SciencesTehranIran
| | - Farzan Moodi
- School of MedicineIran University of Medical SciencesTehranIran
| | - Alireza Jafarzadeh
- Department of DermatologyRasool Akram Medical Complex Clinical Research Development Center (RCRDC)School of MedicineIran University of Medical Sciences (IUMS)TehranIran
| | - Azadeh Goodarzi
- Department of DermatologyRasool Akram Medical Complex Clinical Research Development Center (RCRDC)School of MedicineIran University of Medical Sciences (IUMS)TehranIran
- Skin and Stem Cell Research CenterTehran University of Medical SciencesTehranIran
| |
Collapse
|
|
6
|
Sevim E, Kobrin D, Casal-Dominguez M, Pinal-Fernandez I. A comprehensive review of dermatomyositis treatments - from rediscovered classics to promising horizons. Expert Rev Clin Immunol 2024; 20:197-209. [PMID: 37842905 PMCID: PMC11611049 DOI: 10.1080/1744666x.2023.2270737] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Accepted: 10/10/2023] [Indexed: 10/17/2023]
Abstract
INTRODUCTION Dermatomyositis (DM) is a rare inflammatory disease with diverse cutaneous and systemic manifestations, often associated with myositis-specific antibodies. Managing patients with refractory DM, or individuals presenting pecific complications, like calcinosis or rapidly progressive interstitial lung disease, presents unique challenges. AREAS COVERED This review explores current and promising treatment options for DM, drawing from clinical studies, case series, and case reports that consider the underlying disease pathophysiology. EXPERT OPINION Recent advancements have improved our understanding and management of DM. The discovery of distinct DM autoantibodies and their correlation with specific clinical phenotypes has transformed patient categorization and enhanced our knowledge of the pathogenesis of the disease. Intravenous immunoglobulin, a well-established treatment in dermatomyositis, has regained prominence and a large randomized clinical trial has reaffirmed its efficacy, confirming it as an effective therapeutic option in this group of patients. Identification of the type I interferon pathway as a key pathogenic mechanism in DM has opened up new avenues for more effective treatment strategies. Blocking the JAK/STAT pathway offers potential for improved management of refractory patients and prevention of highly morbid complications. These recent advancements have significantly impacted the management and care of dermatomyositis patients, enabling tailored approaches, targeted interventions, and improved outcomes for individuals affected by this complex condition.
Collapse
Affiliation(s)
- Ecem Sevim
- National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Dale Kobrin
- National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Maria Casal-Dominguez
- Muscle Disease Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Iago Pinal-Fernandez
- Muscle Disease Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| |
Collapse
|
|
7
|
Shiari R, Khalili M, Zeinali V, Shashaani N, Samami M, Moghaddamemami FH. Local injection of infliximab into calcinosis lesions in patients with juvenile dermatomyositis (JDM): a clinical trial. Pediatr Rheumatol Online J 2024; 22:2. [PMID: 38166943 PMCID: PMC10759742 DOI: 10.1186/s12969-023-00941-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Accepted: 12/08/2023] [Indexed: 01/05/2024] Open
Abstract
BACKGROUND Juvenile Dermatomyositis (JDM) is a rare autoimmune disorder that primarily affects muscles and skin. One of the severe complications associated with JDM is calcinosis, and treating this condition presents significant challenges. This study aimed to evaluate the efficacy and safety of local injection of infliximab into calcinosis lesions in patients with JDM. METHODS In this clinical trial, five patients diagnosed with JDM and calcinosis lesions were enrolled. The primary treatment consisted of weekly infliximab injections for 16 weeks, targeting all four sides of each lesion. Lesion dimensions, including length and width, were documented and monitored weekly. Before the intervention, patients underwent radiographic imaging. After the final injection in week 16, a follow-up radiographic assessment was performed. Data were analyzed using the Generalized Estimating Equation (GEE) method. RESULTS The lesions' size significantly decreased in both length and width during each visit. On average, the lesion length reduced by 2.66%, and the width shrank by 3.32% per visit. Based on radiographic findings, the average length and width of lesions at the initial visit were 12.09 ± 5.05 mm (range: 6.00-25.50 mm) and 6.35 ± 3.00 mm (range: 2.00-16.00 mm), respectively. The average length and width at the last visit were 5.59 ± 7.05 mm (range: 0-23.00 mm) and 3.41 ± 4.05 mm (range: 0-13.00 mm), respectively. No specific side effects related to the treatment were reported. CONCLUSIONS The results suggest that the direct administration of infliximab into the calcinosis lesions of patients with JDM could be a safe and effective treatment approach. TRIAL REGISTRATION Name of the registry: The effect of infliximab injection into calcinosis lesions on patients with juvenile dermatomyositis (JDM), Trial registration number: IRCT20210808052107N1, Registration date: 2022-07-22, URL of trial registry record: https://en.irct.ir/trial/58329 .
Collapse
Affiliation(s)
- Reza Shiari
- Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mitra Khalili
- Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Vahide Zeinali
- Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Niloufar Shashaani
- Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Samami
- Dental Sciences Research Center, Department of Oral and Maxillofacial Medicine, School of Dentistry, Guilan University of Medical Sciences, Rasht, Iran
| | | |
Collapse
|
|
8
|
Moon SJ, Jung SM, Baek IW, Park KS, Kim KJ. Molecular signature of neutrophil extracellular trap mediating disease module in idiopathic inflammatory myopathy. J Autoimmun 2023; 138:103063. [PMID: 37220716 DOI: 10.1016/j.jaut.2023.103063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 05/07/2023] [Accepted: 05/09/2023] [Indexed: 05/25/2023]
Abstract
The rarity and heterogeneity of idiopathic inflammatory myopathy (IIM) pose challenges for researching IIM in affected individuals. We analyzed integrated transcriptomic datasets obtained using muscle tissues from patients with five distinct IIM subtypes to investigate the shared and distinctive cellular and molecular characteristics. A transcriptomic dataset of muscle tissues from normal controls (n = 105) and patients with dermatomyositis (n = 89), polymyositis (n = 33), inclusion body myositis (n = 121), immune-mediated necrotizing myositis (n = 75), and anti-synthetase syndrome (n = 18) was used for differential gene-expression analysis, functional-enrichment analysis, gene set-enrichment analysis, disease-module identification, and kernel-based diffusion scoring. Damage-associated molecular pattern-associated pathways and neutrophil-mediated immunity were significantly enriched across different IIM subtypes, although their activities varied. Interferons-signaling pathways were differentially activated across all five IIM subtypes. In particular, neutrophil extracellular trap (NET) formation was significantly activated and correlated with Fcγ R-mediated signaling pathways. NET formation-associated genes were key for establishing disease modules, and FCGRs, C1QA, and SERPINE1 markedly perturbed the disease modules. Integrated transcriptomic analysis of muscle tissues identified NETs as key components of neutrophil-mediated immunity involved in the pathogenesis of IIM subtypes and, thus, has therapeutically targetable value.
Collapse
Affiliation(s)
- Su-Jin Moon
- Division of Rheumatology, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Seung Min Jung
- Division of Rheumatology, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - In-Woon Baek
- Division of Rheumatology, Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Republic of Korea
| | - Kyung-Su Park
- Division of Rheumatology, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Ki-Jo Kim
- Division of Rheumatology, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
| |
Collapse
|
|
9
|
Patil A, Lu J, Kassir M, Babaei M, Goldust M. Adult and juvenile dermatomyositis treatment. J Cosmet Dermatol 2023; 22:395-401. [PMID: 36065712 DOI: 10.1111/jocd.15363] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Revised: 08/17/2022] [Accepted: 09/02/2022] [Indexed: 11/29/2022]
Abstract
INTRODUCTION Dermatomyositis is a rare autoimmune inflammatory condition affecting skin and muscles. The disease can be seen in both adults and children. It can be associated with malignancy. Considering involvement of skin in the disease, many patients consult dermatologists for its treatment. Hence, knowledge about its presentation, complications, prognosis, and treatment is necessary. OBJECTIVE The objective of this review article is to provide comprehensive information about treatment of dermatomyositis. METHODS In this review article, we reviewed the published literature on adult and juvenile dermatomyositis to highlight the treatment. Articles published in peer-reviewed journals including reviews, clinical trials, case series, and case reports published in electronic database (MEDLINE/PubMed) through January 2021, cross references of respective articles and trials from clinicaltrials.gov were included for qualitative analysis of the literature. RESULTS Treatment options for dermatomyositis include traditional immunosuppressive agents and immunomodulatory therapy. High-dose corticosteroids represent the first line of treatment while other immunosuppressive agents are also used, either in combination with or as an alternative to corticosteroids, after initial treatment failure. Some biological agents have been used for the treatment of dermatomyositis with variable responses. CONCLUSION Although several treatment options are available, several questions remain unanswered about the optimal treatment of dermatomyositis.
Collapse
Affiliation(s)
- Anant Patil
- Department of Pharmacology, Dr. DY Patil Medical College, Navi Mumbai, India
| | - Jun Lu
- UConn Health Department of Dermatology, Farmington, Connecticut, USA
| | | | - Mahsa Babaei
- Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohamad Goldust
- Department of Dermatology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
| |
Collapse
|
|
10
|
Impaired muscle stem cell function and abnormal myogenesis in acquired myopathies. Biosci Rep 2023; 43:232343. [PMID: 36538023 PMCID: PMC9829652 DOI: 10.1042/bsr20220284] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 12/08/2022] [Accepted: 12/19/2022] [Indexed: 12/24/2022] Open
Abstract
Skeletal muscle possesses a high plasticity and a remarkable regenerative capacity that relies mainly on muscle stem cells (MuSCs). Molecular and cellular components of the MuSC niche, such as immune cells, play key roles to coordinate MuSC function and to orchestrate muscle regeneration. An abnormal infiltration of immune cells and/or imbalance of pro- and anti-inflammatory cytokines could lead to MuSC dysfunctions that could have long lasting effects on muscle function. Different genetic variants were shown to cause muscular dystrophies that intrinsically compromise MuSC function and/or disturb their microenvironment leading to impaired muscle regeneration that contributes to disease progression. Alternatively, many acquired myopathies caused by comorbidities (e.g., cardiopulmonary or kidney diseases), chronic inflammation/infection, or side effects of different drugs can also perturb MuSC function and their microenvironment. The goal of this review is to comprehensively summarize the current knowledge on acquired myopathies and their impact on MuSC function. We further describe potential therapeutic strategies to restore MuSC regenerative capacity.
Collapse
|
|
11
|
Abstract
The autoimmune inflammatory myopathies constitute a heterogeneous group of acquired myopathies that have in common the presence of endomysial inflammation and moderate to severe muscle weakness. Based on currently evolved distinct clinical, histologic, immunopathologic, and autoantibody features, these disorders can be best classified as dermatomyositis, necrotizing autoimmune myositis, antisynthetase syndrome-overlap myositis, and inclusion body myositis. Although polymyositis is no longer considered a distinct subset but rather an extinct entity, it is herein described because its clinicopathologic information has provided over many years fundamental information on T-cell-mediated myocytotoxicity, especially in reference to inclusion body myositis. Each inflammatory myopathy subset has distinct immunopathogenesis, prognosis, and response to immunotherapies, necessitating the need to correctly diagnose each subtype from the outset and avoid disease mimics. The paper describes the main clinical characteristics that aid in the diagnosis of each myositis subtype, highlights the distinct features on muscle morphology and immunopathology, elaborates on the potential role of autoantibodies in pathogenesis or diagnosis , and clarifies common uncertainties in reference to putative triggering factors such as statins and viruses including the 2019-coronavirus-2 pandemic. It extensively describes the main autoimmune markers related to autoinvasive myocytotoxic T-cells, activated B-cells, complement, cytokines, and the possible role of innate immunity. The concomitant myodegenerative features seen in inclusion body myositis along with their interrelationship between inflammation and degeneration are specifically emphasized. Finally, practical guidelines on the best therapeutic approaches are summarized based on up-to-date knowledge and controlled studies, highlighting the prospects of future immunotherapies and ongoing controversies.
Collapse
Affiliation(s)
- Marinos C Dalakas
- Department of Neurology, Thomas Jefferson University, Philadelphia, PA, United States; Neuroimmunology Unit National and Kapodistrian University of Athens Medical School, Athens, Greece.
| |
Collapse
|
|
12
|
Current and new targets for treating myositis. Curr Opin Pharmacol 2022; 65:102257. [PMID: 35724455 DOI: 10.1016/j.coph.2022.102257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Accepted: 05/17/2022] [Indexed: 11/17/2022]
Abstract
As treatment of refractory idiopathic inflammatory myopathies (IIM) has been challenging, there is growing interest in assessing new therapies that target various pathways implicated in the pathogenesis of IIM. In the largest clinical trial to date, rituximab was studied in adult and juvenile myositis, but the primary outcome was not met despite 83 percent of subjects with refractory myositis meeting the definition of improvement. The U.S. Food and Drug Administration (FDA) has recently granted approval to Octagam 10% immune globulin intravenous (IVIg), for the treatment of adult dermatomyositis based on impressive results from a double-blind placebo-controlled trial. Anti-tumor necrosis factor (anti-TNF) utility in IIM is not recommended and recent reports suggest this therapy may induce systemic autoimmune disease including myositis. Further, anti-IL6 therapy cannot be recommended as a recent trial of tocilizumab failed to reach its primary endpoint. Further studies are needed to assess the role of newer therapies such as abatacept (inhibition of T cell co-stimulation), sifalimumab (anti-IFNα), Janus kinase [JAK] inhibitors, apremilast (phosphodiesterase 4 inhibitor), and KZR-616 (selective inhibitor of the immunoproteasome) given their biological plausibility and encouraging recent small-case series results. The future of IIM therapy will depend on exploring biomarkers implicated in the etiopathogenesis of IIM, improvements in myositis classification based on serological and histopathological features, and well-designed controlled clinical trials using validated consensus outcome measures.
Collapse
|
|
13
|
Pathophysiological Mechanisms and Treatment of Dermatomyositis and Immune Mediated Necrotizing Myopathies: A Focused Review. Int J Mol Sci 2022; 23:ijms23084301. [PMID: 35457124 PMCID: PMC9030619 DOI: 10.3390/ijms23084301] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Revised: 03/31/2022] [Accepted: 04/05/2022] [Indexed: 12/15/2022] Open
Abstract
Idiopathic inflammatory myopathies (IIM), collectively known as myositis, are a composite group of rare autoimmune diseases affecting mostly skeletal muscle, although other organs or tissues may also be involved. The main clinical feature of myositis is subacute, progressive, symmetrical muscle weakness in the proximal arms and legs, whereas subtypes of myositis may also present with extramuscular features, such as skin involvement, arthritis or interstitial lung disease (ILD). Established subgroups of IIM include dermatomyositis (DM), immune-mediated necrotizing myopathy (IMNM), anti-synthetase syndrome (ASyS), overlap myositis (OM) and inclusion body myositis (IBM). Although these subgroups have overlapping clinical features, the widespread variation in the clinical manifestations of IIM suggests different pathophysiological mechanisms. Various components of the immune system are known to be important immunopathogenic pathways in IIM, although the exact pathophysiological mechanisms causing the muscle damage remain unknown. Current treatment, which consists of glucocorticoids and other immunosuppressive or immunomodulating agents, often fails to achieve a sustained beneficial response and is associated with various adverse effects. New therapeutic targets have been identified that may improve outcomes in patients with IIM. A better understanding of the overlapping and diverging pathophysiological mechanisms of the major subgroups of myositis is needed to optimize treatment. The aim of this review is to report on recent advancements regarding DM and IMNM.
Collapse
|
|
14
|
Zeng R, Glaubitz S, Schmidt J. Antibody Therapies in Autoimmune Inflammatory Myopathies: Promising Treatment Options. Neurotherapeutics 2022; 19:911-921. [PMID: 35394612 PMCID: PMC9294121 DOI: 10.1007/s13311-022-01220-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/10/2022] [Indexed: 12/29/2022] Open
Abstract
Inflammatory myopathies, including polymyositis (PM), dermatomyositis (DM), inclusion body myositis (IBM), necrotizing myopathy (NM), antisynthetase syndrome (ASS) and overlap myositis (OM), in short myositis, are rare diseases. All forms of myositis have progressive muscle weakness in common, with each subtype characterized by different autoantibody profiles, histological findings and extramuscular manifestations. Due to better understanding of the pathogenesis of the muscle inflammation in myositis, new molecular pathways for targeted therapy have been discovered. Current therapies aim at different components of the innate or the adaptive immune response. Additionally, non-inflammatory mechanisms in myositis have come into focus as possible treatment targets. The use of therapeutical antibodies in myositis has been examined in various clinical studies, several of them randomized controlled ones: Depletion of B-cells by rituximab has been established as treatment of refractory myositis. IVIG, an antibody therapy in the wider sense, has now been licensed for DM following a recent positive clinical trial. Negative study results were reported in randomized trials with infliximab, sifalimumab and bimagrumab. Studies on basiliximab and eculizumab are currently underway, and are expected to yield results in a couple of years. Despite some promising results of clinical studies with antibody therapy in myositis, further research is crucial to optimize the treatment for this debilitating disease and to find treatment alternatives for treatment-refractory patients.
Collapse
Affiliation(s)
- Rachel Zeng
- Muscle Immunobiology Group, Neuromuscular Center, Department of Neurology, University Medical Center Göttingen, Göttingen, Germany
| | - Stefanie Glaubitz
- Muscle Immunobiology Group, Neuromuscular Center, Department of Neurology, University Medical Center Göttingen, Göttingen, Germany
| | - Jens Schmidt
- Muscle Immunobiology Group, Neuromuscular Center, Department of Neurology, University Medical Center Göttingen, Göttingen, Germany.
- Department of Neurology and Pain Treatment, Immanuel Klinik Rüdersdorf, University Hospital of the Brandenburg Medical School Theodor Fontane, Rüdersdorf bei Berlin, Germany.
- Faculty of Health Sciences Brandenburg, Brandenburg Medical School Theodor Fontane, Rüdersdorf bei Berlin, Germany.
| |
Collapse
|
|
15
|
Kodumudi V, Bibb LA, Adalsteinsson JA, Shahriari N, Skudalski L, Santiago S, Grant-Kels JM, Lu J. Emerging Therapeutics in the Management of Connective Tissue Disease. Part II. Dermatomyositis and Scleroderma. J Am Acad Dermatol 2022; 87:21-38. [PMID: 35202777 DOI: 10.1016/j.jaad.2021.12.068] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Revised: 11/30/2021] [Accepted: 12/02/2021] [Indexed: 10/19/2022]
Abstract
The management of connective tissue diseases is dramatically evolving with the advent of biologics and novel oral systemic therapeutics. Despite involvement in the care of these complex patients, there is a knowledge gap in the field of dermatology regarding these emerging agents. The second article in this continuing medical education series discusses new and emerging therapeutics for dermatomyositis and scleroderma that target cells, intracellular signaling pathways, and cytokines.
Collapse
Affiliation(s)
- Vijay Kodumudi
- Department of Dermatology, University of Connecticut Health Center, Farmington, CT
| | - Lorin A Bibb
- Department of Dermatology, University of Connecticut Health Center, Farmington, CT
| | | | - Neda Shahriari
- Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | | | - Sueheidi Santiago
- Department of Dermatology, University of Connecticut Health Center, Farmington, CT
| | - Jane M Grant-Kels
- Department of Dermatology, University of Connecticut Health Center, Farmington, CT
| | - Jun Lu
- Department of Dermatology, University of Connecticut Health Center, Farmington, CT.
| |
Collapse
|
|
16
|
Wang K, Zhu R, Li J, Zhang Z, Wen X, Chen H, Sun L. Coexpression network analysis coupled with connectivity map database mining reveals novel genetic biomarkers and potential therapeutic drugs for polymyositis. Clin Rheumatol 2022; 41:1719-1730. [DOI: 10.1007/s10067-021-06035-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 12/20/2021] [Accepted: 12/21/2021] [Indexed: 11/30/2022]
|
|
17
|
Lundberg IE, Fujimoto M, Vencovsky J, Aggarwal R, Holmqvist M, Christopher-Stine L, Mammen AL, Miller FW. Idiopathic inflammatory myopathies. Nat Rev Dis Primers 2021; 7:87. [PMID: 34857780 PMCID: PMC10425161 DOI: 10.1038/s41572-021-00325-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Idiopathic inflammatory myopathies (IIM), also known as myositis, are a heterogeneous group of autoimmune disorders with varying clinical manifestations, treatment responses and prognoses. Muscle weakness is usually the classical clinical manifestation but other organs can be affected, including the skin, joints, lungs, heart and gastrointestinal tract, and they can even result in the predominant manifestations, supporting that these are systemic inflammatory disorders. Different myositis-specific autoantibodies have been identified and, on the basis of clinical, histopathological and serological features, IIMs can be classified into several subgroups — dermatomyositis (including amyopathic dermatomyositis), antisynthetase syndrome, immune-mediated necrotizing myopathy, inclusion body myositis, polymyositis and overlap myositis. The prognoses, treatment responses and organ manifestations vary among these groups, implicating different pathophysiological mechanisms in each subtype. A deeper understanding of the molecular pathways underlying the pathogenesis and identifying the autoantigens of the immune reactions in these subgroups is crucial to improve outcomes. New, more homogeneous subgroups defined by autoantibodies may help define disease mechanisms, and will also be important in future clinical trials to develop targeted therapies and in identifying biomarkers to guide treatment decisions for the individual patient.
Collapse
Affiliation(s)
- Ingrid E. Lundberg
- Division of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, and Karolinska University Hospital. Stockholm, Sweden
| | - Manabu Fujimoto
- Department of Dermatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Jiri Vencovsky
- Institute of Rheumatology, Prague, Czech Republic
- Deptartment of Rheumatology, 1st Medical Faculty, Charles University, Prague, Czech Republic
| | - Rohit Aggarwal
- UPMC Myositis Center, Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Marie Holmqvist
- Division of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, and Karolinska University Hospital. Stockholm, Sweden
- Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
| | - Lisa Christopher-Stine
- Johns Hopkins Myositis Center, Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Andrew L. Mammen
- National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA
- Departments of Neurology and Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Frederick W. Miller
- Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA
| |
Collapse
|
|
18
|
Abstract
Idiopathic inflammatory myopathies (IIM), also known as myositis, are a heterogeneous group of autoimmune disorders with varying clinical manifestations, treatment responses and prognoses. Muscle weakness is usually the classical clinical manifestation but other organs can be affected, including the skin, joints, lungs, heart and gastrointestinal tract, and they can even result in the predominant manifestations, supporting that IIM are systemic inflammatory disorders. Different myositis-specific auto-antibodies have been identified and, on the basis of clinical, histopathological and serological features, IIM can be classified into several subgroups - dermatomyositis (including amyopathic dermatomyositis), antisynthetase syndrome, immune-mediated necrotizing myopathy, inclusion body myositis, polymyositis and overlap myositis. The prognoses, treatment responses and organ manifestations vary among these groups, implicating different pathophysiological mechanisms in each subtype. A deeper understanding of the molecular pathways underlying the pathogenesis and identifying the auto-antigens of the immune reactions in these subgroups is crucial to improving outcomes. New, more homogeneous subgroups defined by auto-antibodies may help define disease mechanisms and will also be important in future clinical trials for the development of targeted therapies and in identifying biomarkers to guide treatment decisions for the individual patient.
Collapse
|
|
19
|
Zeng R, Glaubitz S, Schmidt J. Inflammatory myopathies: shedding light on promising agents and combination therapies in clinical trials. Expert Opin Investig Drugs 2021; 30:1125-1140. [PMID: 34779311 DOI: 10.1080/13543784.2021.2003776] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
INTRODUCTION Due to new insights into the pathogenesis of inflammatory myopathies - in short myositis - and the urgent need for new treatment options in patients who are refractory to standard therapy, multiple novel drugs have been developed and studied in clinical trials. In light of this exciting development, a critical evaluation of the present data is necessary in order to identify the best pathway to future treatment of inflammatory myopathies. AREAS COVERED This review focuses on the current evidence from clinical trials in myositis and encompasses dermatomyositis, polymyositis, necrotizing myopathy, antisynthetase-syndrome, overlap myositis, and inclusion body myositis. The results of studies on new therapeutic agents are summarized, in particular larger cohort studies and randomized trials from recent years. When such data were not available, earlier and smaller representative studies were included instead. EXPERT OPINION Current studies in most myositis subtypes have shown positive effects of novel biologicals such as abatacept, sifalimumab, JAK-Inhibitors as well as known agents such as rituximab, but further studies are needed to confirm these observations. In inclusion body myositis, the eagerly awaited recent therapeutic trials have missed their primary endpoints, except for the phase 2 study with rapamycin, which has demonstrated significant improvements in secondary endpoints. Future trials will also need to focus on combination therapies of multiple immunomodulatory agents.
Collapse
Affiliation(s)
- Rachel Zeng
- Muscle Immunobiology Group, Department of Neurology, Neuromuscular Center, University Medical Center Göttingen, Göttingen, Germany
| | - Stefanie Glaubitz
- Muscle Immunobiology Group, Department of Neurology, Neuromuscular Center, University Medical Center Göttingen, Göttingen, Germany
| | - Jens Schmidt
- Muscle Immunobiology Group, Department of Neurology, Neuromuscular Center, University Medical Center Göttingen, Göttingen, Germany.,Department of Neurology and Pain Treatment, University Hospital of the Medical School Brandenburg, Immanuel Klinik Rüdersdorf, Rüdersdorf bei Berlin, Germany.,Faculty of Health Sciences Brandenburg, Brandenburg Medical School Theodor Fontane, Rüdersdorf bei Berlin, Germany
| |
Collapse
|
|
20
|
Glaubitz S, Zeng R, Rakocevic G, Schmidt J. Update on Myositis Therapy: from Today's Standards to Tomorrow's Possibilities. Curr Pharm Des 2021; 28:863-880. [PMID: 34781868 DOI: 10.2174/1381612827666211115165353] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 10/18/2021] [Indexed: 11/22/2022]
Abstract
Inflammatory myopathies, in short, myositis, are heterogeneous disorders that are characterized by inflammation of skeletal muscle and weakness of arms and legs. Research over the past few years has led to a new understanding regarding the pathogenesis of myositis. The new insights include different pathways of the innate and adaptive immune response during the pathogenesis of myositis. The importance of non-inflammatory mechanisms such as cell stress and impaired autophagy has been recently described. New target-specific drugs for myositis have been developed and are currently being tested in clinical trials. In this review, we discuss the mechanisms of action of pharmacological standards in myositis and provide an outlook of future treatment approaches.
Collapse
Affiliation(s)
- Stefanie Glaubitz
- Department of Neurology, Muscle Immunobiology Group, Neuromuscular Center, University Medical Center Göttingen, Göttingen. Germany
| | - Rachel Zeng
- Department of Neurology, Muscle Immunobiology Group, Neuromuscular Center, University Medical Center Göttingen, Göttingen. Germany
| | - Goran Rakocevic
- Department of Neurology, Neuromuscular Division, University of Virginia, Charlottesville. United States
| | - Jens Schmidt
- Department of Neurology, Muscle Immunobiology Group, Neuromuscular Center, University Medical Center Göttingen, Göttingen. Germany
| |
Collapse
|
|
21
|
Unger L. Therapieoptionen und outcome bei idiopathischen entzündlichen Muskelerkrankungen. AKTUEL RHEUMATOL 2021. [DOI: 10.1055/a-1423-7579] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
ZusammenfassungDie idiopathischen entzündlichen Muskelerkrankungen (IIM) sind eine sehr heterogene Gruppe, die sich immer besser differenzieren lässt. Damit eröffnen sich mehr Möglichkeiten für gezieltere Therapien, die zum einen auf die Veränderung pathogenetischer Faktoren gerichtet sind. Zum anderen sollen sie Krankheitsaktivität vermindern, Muskelaufbau fördern, Organschäden verhindern und Lebensqualität verbessern.Die folgende Übersichtsarbeit fasst die vorhandenen Daten zu bereits angewandten Behandlungen in der Praxis zusammen und gibt einen Ausblick auf zukünftige Alternativen.Für die Polymyositis (PM) und Dermatomyositis (DM) sind Glukokortikoide weiter unverzichtbarer Therapiebestandteil. Eine frühe Kombination mit konventionellen DMARDs hat sich durchgesetzt. Die ProDerm- Studie stellt für die Immunglobulintherapie in der Praxis eine gute Basis dar. Rituximab (RTX) löst Cyclophosphamid (CYC) bei schweren Verlaufsformen immer mehr ab.Für Abatacept, Jak-Kinase-Hemmer, Apremilast, Sifalimumab und Lenabasum müssen vielversprechende erste Ergebnisse durch weiter Studien untermauert werden. Anspruchsvoll ist die Behandlung bei extramuskulärer Beteiligung. Von großem Interesse ist der zukünftige Stellenwert von Nintedanib bei der interstitiellen Lungenerkrankung im Rahmen einer Myositis (IIM-ILD).Die Therapie der Einschlusskörperchen- Myositis (IBM) ist immer noch eine große Herausforderung. Zahlreiche Studien haben bisher nicht überzeugend zu einer Besserung der Prognose führen können. Spätestens bei therapierefraktärem Verlauf sollte an eine Malignom- assoziierte Myositis gedacht werden. Gelegentlich verbirgt sich auch eine hereditäre Myopathie hinter einer, zum Beispiel durch einen Infekt oder Überlastung getriggerten, Myositis.Komplikationen im Verlauf, wie Dysphagie, Infektionen, Myokardbeteiligung stellen keine Seltenheit dar. Häufig besteht Multimorbidität. Eine interdisziplinäre Zusammenarbeit in einem kompetenten Team, in dem erfahrene Physio-, Ergo- und Psychotherapeuten fester Bestandteil sind, ist unabdingbar für eine erfolgreiche Begleitung dieser Patienten.
Collapse
Affiliation(s)
- Leonore Unger
- Städtisches Klinikum Dresden, I. Medizinische Klinik, Dresden, Deutschland
| |
Collapse
|
|
22
|
Ge Y, Li S, Chen F, He L, Li C, Lu X, Wang G. The effects of infliximab in treating idiopathic inflammatory myopathies: A review article. Dermatol Ther 2021; 34:e14976. [PMID: 33991036 DOI: 10.1111/dth.14976] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Revised: 02/06/2021] [Accepted: 05/12/2021] [Indexed: 12/17/2022]
Abstract
Anti-TNF treatment may be useful for patients with idiopathic inflammatory myopathies (IIMs). The purpose of this study is to assess the efficacy of infliximab (IFX) in the management of IIMs. Two databases (ie, PubMed and China National Knowledge Infrastructure) were searched up to Nov 2020 for studies investigating skin lesions and muscular weakness in patients with IIMs treated with IFX. A total of 18 studies were included. One hundred and eighteen patients were identified, including 58 adult patients and 60 patients with juvenile dermatomyositis (JDM) treated with IFX. Among these patients, 110 (93%) patients with refractory cases. In addition to glucocorticoids, patients from 15/18 studies received immunosuppressant agents (ISAs) concomitantly with IFX, among which methotrexate (MTX) was most common. After treatment with IFX, skin lesions and muscle strength were improved in 67% of patients with DM and 75% of patients with JDM, respectively. Skin calcinosis was improved in 21/34 (62%) of patients with JDM. Only 55% (12/22) of patients with polymyositis exhibited improvements in muscle strength. Lastly, 40% (42/104) of patients reported adverse events. Current evidence appears to support the use of IFX in some patients with refractory IIMs, especially those with JDM. The most common adverse reaction was infection. Large, randomized-controlled studies should be carried out to confirm these findings.
Collapse
Affiliation(s)
- Yongpeng Ge
- Department of Rheumatology, China-Japan Friendship Hospital, Beijing, China
| | - Sizhao Li
- Department of Rheumatology, China-Japan Friendship Hospital, Beijing, China
| | - Fang Chen
- Department of Rheumatology, China-Japan Friendship Hospital, Beijing, China
| | - Linrong He
- Department of Rheumatology, China-Japan Friendship Hospital, Beijing, China
| | - Chunjia Li
- Department of Rheumatology, China-Japan Friendship Hospital, Beijing, China
| | - Xin Lu
- Department of Rheumatology, China-Japan Friendship Hospital, Beijing, China
| | - Guochun Wang
- Department of Rheumatology, China-Japan Friendship Hospital, Beijing, China
| |
Collapse
|
|
23
|
Clinical Trials in Myositis: Where Do We Stand? CURRENT TREATMENT OPTIONS IN RHEUMATOLOGY 2021. [DOI: 10.1007/s40674-021-00180-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
|
|
24
|
Patwardhan A, Spencer CH. Biologics in refractory idiopathic inflammatory myositis (IIM): What experience in juvenile vs adult myositis tells us about the use of biologics in pediatric IIM. Mod Rheumatol 2021; 31:933-948. [PMID: 33499694 DOI: 10.1080/14397595.2021.1881027] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
Juvenile dermatomyositis (JDM) is an extremely heterogeneous orphan disease with limited amount of dedicated research on the subject matter. Recent research suggests that JDM may not just be the classic antibody driven complements mediated microangiopathy as was thought to be in the past. The etiopathogenesis of JDM also involves inappropriate stimulation of innate immune system followed by dysregulation of the adaptive immune response through dendritic cells. Many variable immune factors such as genetics, major histocompatibility complex expressions, immunohistochemical variabilities, and diversity in specific and associated autoantibodies may make individual IIM and JDM cases unique. The diversity in IIM and JDM also explains individual variability in response to specific therapies. Classifying and matching the right patients to the right treatment is crucial to the successful treatment of these patients with better outcomes. Sub-type specific biologic therapy may be the best current treatment that can match the patient to the best treatment options. A PubMed search was performed to find all the available cases of refractory myositis patients treated with biologics up to July 2020. Using this search this article reviews all the current biologic treatment options and experiences for both adults and children in the context of recent basic science to assist pediatric rheumatologists in choosing the optimal biologic therapy for a child with recalcitrant JDM.
Collapse
Affiliation(s)
| | - Charles H Spencer
- University of Mississippi Medical Center, Batson Children's Hospital, Jackson, MS, USA
| |
Collapse
|
|
25
|
Bax CE, Maddukuri S, Ravishankar A, Pappas-Taffer L, Werth VP. Environmental triggers of dermatomyositis: a narrative review. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:434. [PMID: 33842655 PMCID: PMC8033368 DOI: 10.21037/atm-20-3719] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/02/2022]
Abstract
Dermatomyositis (DM) is an autoimmune disease that affects the skin, lungs, and muscle. Although the pathogenesis of DM is not completely understood, several environmental triggers have been linked to DM onset or flare. This article specifically examines the effects of herbal supplements, drugs, infections, ultraviolet (UV) radiation, and environmental pollutants on the onset or exacerbation of DM. Herbal supplements such as Spirulina platensis, Aphanizomenon flos-aquae, Chlorella, Echinacea, and Alfalfa have been implicated and are frequently used in health foods. Medications such as hydroxyurea, TNF-α inhibitors, immune checkpoint inhibitors (ICI), and penicillamine, as well as certain viral infections, such as parvovirus B19, coxsackie virus, polyomavirus, Epstein-Barr virus (EBV), hepatitis, influenza, and human immunodeficiency viruses (HIV) have been associated with DM onset. Bacterial infections and vaccinations have also been linked to the development of DM. Additional environmental factors, including UV radiation and air pollutants, such as silica, biological/mineral dust, and particulate air matter from vehicle and industrial emissions, may also play a role in DM pathogenesis. Overall, there is general agreement that an autoimmune attack of the skin, muscle, and lungs in DM can be triggered by various environmental factors and warrants further investigation.
Collapse
Affiliation(s)
- Christina E Bax
- Corporal Michael J. Crescenz VAMC, Philadelphia, PA, USA.,Department of Dermatology, University of Pennsylvania, Philadelphia, PA, USA
| | - Spandana Maddukuri
- Corporal Michael J. Crescenz VAMC, Philadelphia, PA, USA.,Department of Dermatology, University of Pennsylvania, Philadelphia, PA, USA
| | - Adarsh Ravishankar
- Corporal Michael J. Crescenz VAMC, Philadelphia, PA, USA.,Department of Dermatology, University of Pennsylvania, Philadelphia, PA, USA
| | - Lisa Pappas-Taffer
- Corporal Michael J. Crescenz VAMC, Philadelphia, PA, USA.,Department of Dermatology, University of Pennsylvania, Philadelphia, PA, USA
| | - Victoria P Werth
- Corporal Michael J. Crescenz VAMC, Philadelphia, PA, USA.,Department of Dermatology, University of Pennsylvania, Philadelphia, PA, USA
| |
Collapse
|
|
26
|
Liang J, Cao H, Yang Y, Ke Y, Yu Y, Sun C, Yue L, Lin J. Efficacy and Tolerability of Nintedanib in Idiopathic-Inflammatory-Myopathy-Related Interstitial Lung Disease: A Pilot Study. Front Med (Lausanne) 2021; 8:626953. [PMID: 33614683 PMCID: PMC7886679 DOI: 10.3389/fmed.2021.626953] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Accepted: 01/13/2021] [Indexed: 11/17/2022] Open
Abstract
Objectives: To initially clarify the efficacy and tolerability of nintedanib in patients with idiopathic-inflammatory-myopathy-related interstitial lung disease (IIM-ILD). Methods: A retrospective, real-world analysis was conducted in IIM-ILD patients who regularly received outpatient visit or hospitalization from January 2018 to March 2020 in three centers. And the patients were divided into two groups depending on presence or absence of nintedanib therapy. Comparisons, Kaplan-Meier survival analysis and propensity score matching were made to identify difference in time to death from any cause, incidence of rapidly progressive interstitial lung disease (RP-ILD) and comorbidity of pulmonary infection between the two groups. The following logistic regression analyses and Cox proportional-hazard regression analyses were used to verify the therapeutic value of nintedanib as well as clinical significance of other factors. Adverse events were descriptively recorded. Results: Thirty-six patients receiving nintedanib therapy and 115 patients without use of nintedanib were included. Before and after propensity score matching, the primary comparisons revealed better survival (P = 0.015, P = 0016, respectively) and lower incidence of RP-ILD (P = 0.017, P = 0.014, respectively) in patients with nintedanib therapy. Logistic regression analysis identified that disease activity (P < 0.001), percent-predicted diffusing capacity of the lung for carbon monoxide (DLCO%, P = 0.036), nintedanib therapy (P = 0.004, OR value = 0.072) and amyopathic dermatomyositis (ADM, P = 0.012) were significantly correlated with RP-ILD. Cox proportional hazards regression analysis suggested that disease activity (P < 0.001), anti-MDA5 antibody (P < 0.001) and nintedanib therapy (P = 0.013, HR value=0.268) were significantly associated with survival of IIM-ILD patients. Similar results can also be seen in analyses after propensity score matching. In the 36 patients with nintedanib therapy, diarrhea was the most common adverse event (44.4%) and hepatic insufficiency contributed to most dosage reduction (44.4% of nine patients) or therapy discontinuation (60.0% of five patients). Conclusions: Nintedanib was found to reduce incidence of RP-ILD and improve survival in IIM-ILD patients in a real-world setting. Anti-MDA5 antibody could be taken as a risk factor for unfavorable outcome. ADM was significantly correlated with occurrence of RP-ILD. In addition to the most frequent diarrhea, hepatic insufficiency was closely related to dosage reduction or therapy discontinuation.
Collapse
Affiliation(s)
- Junyu Liang
- Department of Rheumatology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Heng Cao
- Department of Rheumatology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yang Yang
- Department of Rheumatology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yini Ke
- Department of Rheumatology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Ye Yu
- Department of Rheumatology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Chuanyin Sun
- Department of Rheumatology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Lihuan Yue
- Department of Rheumatology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jin Lin
- Department of Rheumatology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| |
Collapse
|
|
27
|
Gklinos P, Papadopoulou M, Stanulovic V, Mitsikostas DD, Papadopoulos D. Monoclonal Antibodies as Neurological Therapeutics. Pharmaceuticals (Basel) 2021; 14:ph14020092. [PMID: 33530460 PMCID: PMC7912592 DOI: 10.3390/ph14020092] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2020] [Revised: 01/20/2021] [Accepted: 01/22/2021] [Indexed: 02/08/2023] Open
Abstract
Over the last 30 years the role of monoclonal antibodies in therapeutics has increased enormously, revolutionizing treatment in most medical specialties, including neurology. Monoclonal antibodies are key therapeutic agents for several neurological conditions with diverse pathophysiological mechanisms, including multiple sclerosis, migraines and neuromuscular disease. In addition, a great number of monoclonal antibodies against several targets are being investigated for many more neurological diseases, which reflects our advances in understanding the pathogenesis of these diseases. Untangling the molecular mechanisms of disease allows monoclonal antibodies to block disease pathways accurately and efficiently with exceptional target specificity, minimizing non-specific effects. On the other hand, accumulating experience shows that monoclonal antibodies may carry class-specific and target-associated risks. This article provides an overview of different types of monoclonal antibodies and their characteristics and reviews monoclonal antibodies currently in use or under development for neurological disease.
Collapse
Affiliation(s)
- Panagiotis Gklinos
- Department of Neurology, KAT General Hospital of Attica, 14561 Athens, Greece;
| | - Miranta Papadopoulou
- Center for Clinical, Experimental Surgery & Translational Research, Biomedical Research Foundation of the Academy of Athens (BRFAA), 11527 Athens, Greece;
| | - Vid Stanulovic
- Global Pharmacovigilance, R&D Sanofi, 91385 Chilly-Mazarin, France;
| | - Dimos D. Mitsikostas
- 1st Neurology Department, Aeginition Hospital, National and Kapodistrian University of Athens, 11521 Athens, Greece;
| | - Dimitrios Papadopoulos
- Laboratory of Molecular Genetics, Hellenic Pasteur Institute, 129 Vasilissis Sophias Avenue, 11521 Athens, Greece
- Salpetriere Neuropsychiatric Clinic, 149 Papandreou Street, Metamorphosi, 14452 Athens, Greece
- Correspondence:
| |
Collapse
|
|
28
|
Huang BB, Han LC, Liu GF, Lv XD, Gu GL, Li SQ, Chen L, Wang HQ, Zhan LL, Lv XP. Infliximab is effective in the treatment of ulcerative colitis with dermatomyositis: A case report. World J Gastroenterol 2020; 26:7425-7435. [PMID: 33362394 PMCID: PMC7739156 DOI: 10.3748/wjg.v26.i46.7425] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Revised: 10/11/2020] [Accepted: 11/04/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Joint, skin, oral cavity, and eye lesions are the most common extraintestinal manifestations of ulcerative colitis that can occur before or after its onset. The cases of ulcerative colitis with dermatomyositis (DM) are rare. In this study, we report a rare case of ulcerative colitis with DM that was effectively treated with infliximab.
CASE SUMMARY The patient was a 57-year-old female with a 2-year history of DM. The patient was admitted to hospital with abdominal pain, diarrhea, and blood in stool lasting for more than 2 mo. Colonoscopy revealed multiple erosions and ulcers in the entire colon and rectum. Pathological sections showed chronic inflammatory cell infiltration, especially neutrophil infiltration, in the colonic mucosa; therefore, the patient was diagnosed with ulcerative colitis. Preparations of 5-aminosalicylic acid was added to her treatment based on the original treatment for DM, but its effect was unsatisfactory. The patient’s discomfort was relieved after infliximab treatment.
CONCLUSION Infliximab can improve DM in the treatment of ulcerative colitis. Specialists need to raise awareness about patients with inflammatory bowel disease who have rare extraintestinal manifestations.
Collapse
Affiliation(s)
- Bin-Bin Huang
- Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Li-Chun Han
- Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Geng-Feng Liu
- Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Xiao-Dan Lv
- Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Guang-Li Gu
- Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Shi-Quan Li
- Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Lan Chen
- Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Hui-Qin Wang
- Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Ling-Ling Zhan
- Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Xiao-Ping Lv
- Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| |
Collapse
|
|
29
|
Hassan N, Davies EJ, Faber BG, Gunawardena H. Infliximab in a patient with treatment-resistant anti-SAE dermatomyositis. Rheumatology (Oxford) 2020; 60:e156-e158. [DOI: 10.1093/rheumatology/keaa698] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Revised: 09/03/2020] [Accepted: 09/24/2020] [Indexed: 11/12/2022] Open
Affiliation(s)
- Neelam Hassan
- Department of Rheumatology, North Bristol NHS Trust, Bristol, UK
| | - Emma Jane Davies
- Department of Rheumatology, North Bristol NHS Trust, Bristol, UK
| | | | | |
Collapse
|
|
30
|
Gaboriau L, Davion JB, Combret S, Lebrun-Vignes B, Rocher F, Rouby F, Renaud F, Morell-Dubois S, Gautier S. Adalimumab and myositis: A case report and review of the French and international Pharmacovigilance Databases. Neuromuscul Disord 2020; 30:915-920. [PMID: 33071068 DOI: 10.1016/j.nmd.2020.09.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Revised: 09/03/2020] [Accepted: 09/11/2020] [Indexed: 10/23/2022]
Abstract
TNFα inhibitors, including adalimumab, are widely used in inflammatory rheumatologic and bowel diseases. Well-known adverse effects include: opportunistic infections, immunogenicity and new inflammatory manifestations. Myositis is an inflammatory disease, which manifests with muscle symptoms and can be life-threatening. Little is known about drug-induced myositis. We aimed to describe a case of myositis induced by adalimumab and reviewed national and international pharmacovigilance databases for other cases until 01/02/2019. This was a 63 years old woman with Crohn's disease, who developed muscle weakness, and rhabdomyolysis 3 months after starting adalimumab. Diagnosis of myositis was suspected and confirmed with electromyography and muscle biopsy. Improvement in muscle symptoms was observed after stopping adalimumab and starting corticosteroids. Muscular adverse effects are well-known and usually benign with adalimumab. However, five cases of myositis during treatment with adalimumab were registered in French PharmacoVigilance Database (FPVD) with muscle symptoms observed 3 months to 7 years after starting adalimumab. In VigiBaseⓇ, 90 cases of myositis associated with adalimumab with some similar characteristics were registered. When a patient treated with adalimumab complains of muscular symptoms, inflammatory myopathies should be considered. This adverse effect should be mentioned in a 'Summary of Product Characteristics' to alert healthcare professionals.
Collapse
Affiliation(s)
- Louise Gaboriau
- Centre régional de PharmacoVigilance, service de pharmacologie médicale, CHU Lille, 1, place de Verdun, F-59000 Lille, France.
| | - Jean-Baptiste Davion
- Centre de référence des Maladies Neuromusculaires, CHU Lille, F-59000 Lille, France
| | - Sandrine Combret
- Centre régional de pharmacovigilance, Vigilances - qualité - risques, CHU Dijon Bourgogne, F-21000 Dijon, France
| | - Bénédicte Lebrun-Vignes
- Centre régional de pharmacovigilance, Pharmacologie, Groupe Hospitalier Pitié-Salpêtrière, APHP, F-75000 Paris, France; EA 7379 EpidermE, Université Paris-Est Créteil, UPEC, F-94010 Créteil, France
| | - Fanny Rocher
- Centre régional de pharmacovigilance, CHU Nice, F-06000 Nice, France
| | - Franck Rouby
- Centre régional de pharmacovigilance de Marseille Provence Corse, Assistance Publique, Hôpitaux de Marseille, F-13000 Marseille, France
| | - Florence Renaud
- Centre de biologie pathologie, CHU Lille, F-59000 Lille, France
| | | | - Sophie Gautier
- Centre régional de PharmacoVigilance, service de pharmacologie médicale, CHU Lille, 1, place de Verdun, F-59000 Lille, France
| |
Collapse
|
|
31
|
Li R, Zhu WJ, Wang F, Tang X, Luo F. AST/ALT ratio as a predictor of mortality and exacerbations of PM/DM-ILD in 1 year-a retrospective cohort study with 522 cases. Arthritis Res Ther 2020; 22:202. [PMID: 32950060 PMCID: PMC7502203 DOI: 10.1186/s13075-020-02286-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Accepted: 08/05/2020] [Indexed: 02/07/2023] Open
Abstract
OBJECTIVE To assess the associations between aspartate transaminase/alanine transaminase ratio (DRR) and mortality in patients with polymyositis/dermatomyositis-associated interstitial lung disease (PM/DM-ILD). PATIENTS AND METHODS This was a retrospective cohort study, which included 522 patients with PM/DM-ILD whose DRR on admission were tested at West China Hospital of Sichuan University during the period from January 1, 2008, to December 31, 2018. Cox regression models were used to estimate hazard ratios for mortality in four predefined DRR strata (≤ 0.91, 0.91-1.26, 1.26-1.73, and > 1.73), after adjusting for age, sex, DRR stratum, diagnosis, overlap syndrome, hemoglobin, platelet count, white blood cell count, the percentage of neutrophils, neutrophil/lymphocyte ratio, albumin, creatine kinase, uric acid/creatinine ratio, triglycerides, or low-density lipoprotein. RESULTS Higher DRR (> 1.73) was an independent predictor of 1-year mortality in multivariate Cox regression analysis (hazard ratio 3.423, 95% CI 1.481-7.911, p = .004). Patients with higher DRR more often required the use of mechanical ventilation and readmission for acute exacerbation of PM/DM-ILD at 1-year follow-up. CONCLUSION Higher DRR on admission for PM/DM-ILD patients are associated with increased mortality, risk of mechanical ventilation, and hospitalization in 1-year follow-up. This low-cost, easy-to-obtain, rapidly measured biomarker may be useful in the identification of high-risk PM/DM-ILD patients that could benefit from intensive management.
Collapse
Affiliation(s)
- Renjiao Li
- Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, 37 Guoxue Street, Chengdu, 610041, Sichuan, China
| | - Wen-Jun Zhu
- Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, 37 Guoxue Street, Chengdu, 610041, Sichuan, China
| | - Faping Wang
- Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, 37 Guoxue Street, Chengdu, 610041, Sichuan, China
| | - Xiaoju Tang
- Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, 37 Guoxue Street, Chengdu, 610041, Sichuan, China
| | - Fengming Luo
- Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, 37 Guoxue Street, Chengdu, 610041, Sichuan, China.
| |
Collapse
|
|
32
|
van den Hoogen LL, van Laar JM. Targeted therapies in systemic sclerosis, myositis, antiphospholipid syndrome, and Sjögren's syndrome. Best Pract Res Clin Rheumatol 2020; 34:101485. [PMID: 32067925 DOI: 10.1016/j.berh.2020.101485] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Targeted therapies using biological disease-modifying antirheumatic drugs (bDMARDs) and small molecule synthetic drugs have revolutionized rheumatological practice. Initially developed for the treatment of immune arthritis (rheumatoid arthritis, psoriatic arthritis, and spondylarthritis), both bDMARDs and small molecule synthetic drugs are now increasingly entering the space of connective tissue disease (CTD) treatment. Recent clinical trial data in systemic sclerosis (SSc) have been particularly encouraging with positive effects on outcomes having been observed with nintedanib preventing the decline of lung function in patients with SSc-related interstitial lung disease. Randomized trials targeting B-cells by rituximab in primary Sjogren's syndrome have led to mixed results. Novel strategies to target B-cells in primary Sjögren's syndrome including ianalumab and belimumab are underway and will hopefully result in clear treatment effects. Inflammatory idiopathic myositis (polymyositis (PM) and dermatomyositis (DM)) and antiphospholid syndrome are proving to be more difficult to tackle but are nonetheless the subject of ongoing studies. To what extent new compounds can replace more traditional immunosuppressive drugs remains to be determined, but if the experience in immune arthritis has taught us anything it is that combination therapy may be the way to go.
Collapse
Affiliation(s)
- Lucas L van den Hoogen
- Dept of Rheumatology and Clinical Immunology, University Medical Centre Utrecht, Utrecht University, the Netherlands.
| | - Jacob M van Laar
- Dept of Rheumatology and Clinical Immunology, University Medical Centre Utrecht, Utrecht University, the Netherlands.
| |
Collapse
|
|
33
|
Wu JQ, Lu MP, Reed AM. Juvenile dermatomyositis: advances in clinical presentation, myositis-specific antibodies and treatment. World J Pediatr 2020; 16:31-43. [PMID: 31556011 DOI: 10.1007/s12519-019-00313-8] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Accepted: 08/29/2019] [Indexed: 12/21/2022]
Abstract
BACKGROUND Juvenile dermatomyositis (JDM) is a chronic autoimmune disease characteristic by inflammation of small vessels within the skin, muscle and vital organs. But the clinical features and treatment of JDM have not been fully clarified. DATA SOURCES Databases underwent through PubMed for articles about the clinical features, myositis-specific antibodies of JDM and its treatment, and we selected publications written in English which were relevant to the topic of this review. RESULTS Clinical features and myositis-specific antibodies may predict the severity and prognosis of disease. Although the mortality rate has been lower with traditional treatments, such as corticosteroid, intravenous immunoglobulin, and disease-modifying anti-rheumatic drugs such as methotrexate, their usages are variable. Novel biological therapies seem to be effective for refractory JDM patients, but more clinical trials are necessary. CONCLUSIONS JDM is a sever disease of childhood. We need to better understand recent advances of JDM in the context of clinical features including skin manifestations, muscle weakness and organ damage, myositis-specific antibodies and their associated outcomes and the treatment of disease.
Collapse
Affiliation(s)
- Jian-Qiang Wu
- Department of Rheumatology Immunology and Allergy, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310052, China
| | - Mei-Ping Lu
- Department of Rheumatology Immunology and Allergy, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310052, China
| | - Ann M Reed
- Department of Pediatrics, Division of Pediatric Rheumatology, Duke University School of Medicine, Durham, 27710, USA.
| |
Collapse
|
|
34
|
Glaubitz S, Zeng R, Schmidt J. New insights into the treatment of myositis. Ther Adv Musculoskelet Dis 2020; 12:1759720X19886494. [PMID: 31949477 PMCID: PMC6950531 DOI: 10.1177/1759720x19886494] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2019] [Accepted: 10/10/2019] [Indexed: 12/17/2022] Open
Abstract
The myositis syndromes include polymyositis, dermatomyositis (DM), necrotizing myopathy, inclusion body myositis (IBM), antisynthetase syndrome and overlap syndromes with myositis. These syndromes mostly occur in middle-aged patients, while juvenile DM occurs in children and adolescents. Patients mostly show a subacute weakness and myalgia in the upper and lower limbs, the diagnosis is based upon these clinical findings in combination with muscle biopsy results and specific serum autoantibodies. In recent years, research achieved a better understanding about the molecular mechanism underlying the myositis syndromes, as well as disease progress and extramuscular organ manifestations, such as interstitial lung disease and association with neoplasias. Treatment mainly consists of glucocorticosteroids and immunosuppressants. IBM is usually refractory to treatments. This review provides an overview of the current standards of treatment and new treatment options like monoclonal antibodies and new molecular therapies and their first results from clinical trials.
Collapse
Affiliation(s)
- Stefanie Glaubitz
- Department of Neurology, Muscle Immunobiology Group, Neuromuscular Center, University Medical Center Göttingen, Göttingen, Germany
| | - Rachel Zeng
- Department of Neurology, Muscle Immunobiology Group, Neuromuscular Center, University Medical Center Göttingen, Göttingen, Germany
| | - Jens Schmidt
- Department of Neurology, Muscle Immunobiology Group, Neuromuscular Center, University Medical Center Göttingen, Robert-Koch-Sr. 40, 37075 Göttingen, Germany
| |
Collapse
|
|
35
|
Khoo T, Limaye V. Biologic therapy in the idiopathic inflammatory myopathies. Rheumatol Int 2019; 40:191-205. [PMID: 31680207 DOI: 10.1007/s00296-019-04467-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Accepted: 10/24/2019] [Indexed: 11/29/2022]
Abstract
The idiopathic inflammatory myopathies (IIM) are a group of autoimmune diseases resulting from inflammation of muscle and manifesting as weakness, though a range of extra-muscular manifestations are observed. These are often correlated closely with disease subtype and the presence of myositis-specific/myositis-associated antibodies. IIM are notoriously difficult to treat and often refractory to glucocorticoid therapy and synthetic immunosuppressants. Both the innate and adaptive immune systems are implicated in the pathogenesis of IIM. A growing understanding of the key cytokines as well as the cell-mediated and antibody effectors of disease has identified multiple potential targets for biologic therapy. The most widely used of these is B-cell depletion via rituximab though the tumour necrosis factor inhibitors and other biologic therapies used in diseases such as rheumatoid arthritis, systemic lupus erythematosus and multiple sclerosis have also been trialled. This review summarises the literature thus far on biologic therapy in IIM, highlighting both the significant trials that influence current treatment regimens and also the continuing need for further research to inform more effective therapies.
Collapse
Affiliation(s)
- Thomas Khoo
- Central Adelaide Local Health Network, Adelaide, Australia
| | - Vidya Limaye
- Rheumatology Unit, Royal Adelaide Hospital, Adelaide, Australia. .,Discipline of Medicine, School of Medicine, University of Adelaide, Adelaide, Australia.
| |
Collapse
|
|
36
|
Yang SH, Chang C, Lian ZX. Polymyositis and dermatomyositis - challenges in diagnosis and management. J Transl Autoimmun 2019; 2:100018. [PMID: 32743506 PMCID: PMC7388349 DOI: 10.1016/j.jtauto.2019.100018] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2019] [Accepted: 10/04/2019] [Indexed: 02/06/2023] Open
Abstract
Polymyositis (PM) and dermatomyositis (DM) are different disease subtypes of idiopathic inflammatory myopathies (IIMs). The main clinical features of PM and DM include progressive symmetric, predominantly proximal muscle weakness. Laboratory findings include elevated creatine kinase (CK), autoantibodies in serum, and inflammatory infiltrates in muscle biopsy. Dermatomyositis can also involve a characteristic skin rash. Both polymyositis and dermatomyositis can present with extramuscular involvement. The causative factor is agnogenic activation of immune system, leading to immunologic attacks on muscle fibers and endomysial capillaries. The treatment of choice is immunosuppression. PM and DM can be distinguished from other IIMs and myopathies by thorough history, physical examinations and laboratory evaluation and adherence to specific and up-to-date diagnosis criteria and classification standards. Treatment is based on correct diagnosis of these conditions.
Challenges of diagnosis and management influences the clinical research and practice of Polymyositis and dermatomyositis. Diagnostic criteria have been updated and novel therapies have been developed in PM/DM. Pathogenesis investigation and diagnosis precision improvement may help to guide future treatment strategies.
Collapse
Key Words
- APC, antigen presenting cell
- AZA, Azathioprine
- CAM, cancer associated myositis
- CK, creatine kinase
- DM, dermatomyositis
- Dermatomyositis
- Diagnosis criteria
- EMG, electromyography
- HLA, human leukocyte antigen
- IIM, idiopathic inflammatory myopathies
- ILD, interstitial lung disease
- IV, intravenous
- Idiopathic inflammatory myopathy
- JDM, juvenile dermatomyositis
- MAA, myositis associated antibody
- MAC, membrane attack complex
- MHC, major histocompatibility complex
- MMF, mycophenolate mofetil
- MRI, magnetic resonance imaging
- MSA, myositis specific antibody
- MTX, methotrexate
- MUAP, motor unit action potential
- NAM, necrotizing autoimmune myopathy
- PM, polymyositis
- Polymyositis
- TNF, tumor necrosis factor
- Treatment
- Treg, regulatory T cell
- UVR, ultraviolet radiation
- sIBM, sporadic inclusion body myositis
Collapse
Affiliation(s)
- Shu-Han Yang
- Chronic Disease Laboratory, Institutes for Life Sciences and School of Medicine, South China University of Technology, Guangzhou, 510006, China
| | - Christopher Chang
- Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, Davis, CA, USA.,Division of Pediatric Immunology and Allergy, Joe DiMaggio Children's Hospital, Hollywood, FL, USA
| | - Zhe-Xiong Lian
- Chronic Disease Laboratory, Institutes for Life Sciences and School of Medicine, South China University of Technology, Guangzhou, 510006, China
| |
Collapse
|
|
37
|
Abstract
PURPOSE OF THE REVIEW Dermatomyositis (DM) is an uncommon autoimmune disease that primarily affects the skin, muscle, and/or lungs, and remains a therapeutic challenge. We discuss recent studies evaluating efficacy of conventional treatments for clinically amyopathic DM (CADM), DM-associated interstitial lung (ILD) disease, and classic DM (CDM). We highlight several emerging new therapies with a focus on clinical trials, systematic reviews, and case series in the last 5 years. RECENT FINDINGS Recent studies report a significant number of patients remain refractory to antimalarials and require second- and third-line agents. Effective treatment for DM-associated ILD can vary based on patient specific antibodies. CDM requires oral glucocorticoids; recent studies have evaluated the benefits of adjunctive therapies including methotrexate and calcineurin inhibitors. New therapies target cell populations or cytokines thought to drive disease pathogenesis. Dermatomyositis is an autoimmune disease that remains challenging to treat. Many patients are refractory to conventional therapies, warranting the development and evaluation of new treatments.
Collapse
|
|
38
|
Speeckaert R, Lambert J, van Geel N. Learning From Success and Failure: Biologics for Non-approved Skin Diseases. Front Immunol 2019; 10:1918. [PMID: 31440261 PMCID: PMC6694799 DOI: 10.3389/fimmu.2019.01918] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Accepted: 07/29/2019] [Indexed: 12/14/2022] Open
Abstract
The impressive potential of biologics has been demonstrated in psoriasis, hidradenitis suppurativa, and urticaria. Numerous biologicals are entering the field for a restricted number of skin disorders. Off-label use of biologics in other recalcitrant skin diseases has increased. Mounting data point to the potential of already existing biologics acting on the IL-17/IL-23 pathway in skin disorders with epidermal hyperkeratosis (e.g., pityriasis rubra pilaris), acneiform inflammation (e.g., hidradenitis suppurativa), and loss of mucosal integrity (e.g., aphthosis). TNF-α blockers are also effective in the latter conditions but seem of particular value in granulomatous (e.g., granuloma annulare) and neutrophilic disorders (e.g., pyoderma gangrenosum). Failure of IL-17 blockade in skin diseases resulting from immune-mediated cell destruction (e.g., alopecia areata and vitiligo) illustrates its limited involvement in Th1-dependent skin immunology. Overall, disappointing results of TNF-α blockers in alopecia areata and vitiligo point to the same conclusion although promising results in toxic epidermal necrolysis suggest TNF-α exerts at least some in vivo Th1-related activities. Acting on both the Th1 and Th17 pathway, ustekinumab has a rather broad potential with interesting results in lupus and alopecia areata. The efficacy of omalizumab in bullous pemphigoid has revealed an IgE-mediated recruitment of eosinophils leading to bullae formation. Reconsidering reimbursement criteria for less common but severe diseases seems appropriate if substantial evidence is available (e.g., pityriasis rubra pilaris). For other disorders, investigator- and industry-initiated randomized clinical trials should be stimulated. They are likely to improve patient outcome and advance our understanding of challenging skin disorders.
Collapse
Affiliation(s)
| | - Jo Lambert
- Department of Dermatology, Ghent University Hospital, Ghent, Belgium
| | - Nanja van Geel
- Department of Dermatology, Ghent University Hospital, Ghent, Belgium
| |
Collapse
|
|
39
|
Melsheimer R, Geldhof A, Apaolaza I, Schaible T. Remicade ® (infliximab): 20 years of contributions to science and medicine. Biologics 2019; 13:139-178. [PMID: 31440029 PMCID: PMC6679695 DOI: 10.2147/btt.s207246] [Citation(s) in RCA: 70] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2019] [Accepted: 05/16/2019] [Indexed: 12/17/2022]
Abstract
On August 24, 1998, Remicade® (infliximab), the first tumor necrosis factor-α (TNF) inhibitor, received its initial marketing approval from the US Food and Drug Administration for the treatment of Crohn’s disease. Subsequently, Remicade was approved in another five adult and two pediatric indications both in the USA and across the globe. In the 20 years since this first approval, Remicade has made several important contributions to the advancement of science and medicine: 1) clinical trials with Remicade established the proof of concept that targeted therapy can be effective in immune-mediated inflammatory diseases; 2) as the first monoclonal antibody approved for use in a chronic condition, Remicade helped in identifying methods of administering large, foreign proteins repeatedly while limiting the body’s immune response to them; 3) the need to establish Remicade’s safety profile required developing new methods and setting new standards for postmarketing safety studies, specifically in the real-world setting, in terms of approach, size, and duration of follow-up; 4) the study of Remicade has improved our understanding of TNF’s role in the immune system, as well as our understanding of the pathophysiology of a range of diseases characterized by chronic inflammation; and 5) Remicade and other TNF inhibitors have transformed treatment practices in these chronic inflammatory diseases: remission has become a realistic goal of therapy and long-term disability resulting from structural damage can be prevented. This paper reviews how, over the course of its development and 20 years of use in clinical practice, Remicade was able to make these contributions.
Collapse
Affiliation(s)
| | - Anja Geldhof
- Medical Affairs, Janssen Biologics BV, Leiden, the Netherlands
| | - Isabel Apaolaza
- Medical Affairs, Janssen Biologics BV, Leiden, the Netherlands
| | | |
Collapse
|
|
40
|
Waldman R, DeWane ME, Lu J. Dermatomyositis: Diagnosis and treatment. J Am Acad Dermatol 2019; 82:283-296. [PMID: 31279813 DOI: 10.1016/j.jaad.2019.05.105] [Citation(s) in RCA: 82] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2019] [Revised: 05/09/2019] [Accepted: 05/11/2019] [Indexed: 12/13/2022]
Abstract
The second article in this continuing medical education series reviews the initial evaluation of patients with suspected dermatomyositis (DM), the relevant work-up for malignancy and interstitial lung disease once a diagnosis of DM is made, and treatment recommendations for patients with DM based on disease severity, the presence of systemic symptoms, and myositis-specific antibody (MSA) profiles. This review emphasizes the emerging role of MSAs in the diagnosis of DM and highlights how MSAs can be used to guide the appropriate work-up for malignancy and interstitial lung disease. The treatment approach proposed by this continuing medical education series discusses both established and novel therapies for DM and highlights the importance of considering lesion type, degree of muscle involvement, presence of systemic symptoms, presence of MSAs, and patient age when determining the best treatment approach for a patient with DM.
Collapse
Affiliation(s)
- Reid Waldman
- Department of Dermatology, University of Connecticut, Farmington, Connecticut
| | - Madeline E DeWane
- University of Connecticut, School of Medicine, Farmington, Connecticut
| | - Jun Lu
- Department of Dermatology, University of Connecticut, Farmington, Connecticut.
| |
Collapse
|
|
41
|
Yamada‐Kanazawa S, Kajihara I, Kobayashi A, Watanabe C, Ihn H. Infliximab improved the refractory cutaneous involvement in a patient with dermatomyositis. Dermatol Ther 2019; 32:e12859. [DOI: 10.1111/dth.12859] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Revised: 01/08/2019] [Accepted: 02/10/2019] [Indexed: 12/31/2022]
Affiliation(s)
- Saori Yamada‐Kanazawa
- Department of Dermatology and Plastic Surgery, Faculty of Life SciencesKumamoto University Kumamoto Japan
| | - Ikko Kajihara
- Department of Dermatology and Plastic Surgery, Faculty of Life SciencesKumamoto University Kumamoto Japan
| | - Atsuko Kobayashi
- Department of Dermatology and Plastic Surgery, Faculty of Life SciencesKumamoto University Kumamoto Japan
| | - Chinatsu Watanabe
- Department of Dermatology and Plastic Surgery, Faculty of Life SciencesKumamoto University Kumamoto Japan
| | - Hironobu Ihn
- Department of Dermatology and Plastic Surgery, Faculty of Life SciencesKumamoto University Kumamoto Japan
| |
Collapse
|
|
42
|
|
|
43
|
Abstract
INTRODUCTION Juvenile dermatomyositis (JDM) is a rare, chronic autoimmune illness with primary features of symmetric, proximal muscle weakness and involvement of the skin with a number of identifiable rashes. Evidence to support treatment decisions is limited, given the paucity of clinical trials. Consensus based methods, informed by available data, play an important role in treatment recommendations. Areas covered: This review focuses on evidence and consensus opinion regarding therapeutic options in JDM and identifies gaps where future research is needed. Expert commentary: The combination of trial evidence (as limited as it is) and consensus opinion support standard initial management for children with JDM to consist of high-dose corticosteroids, either intravenous or oral, and methotrexate. Several other agents have preliminary support, either through clinical trials or case series for their use in patients who either fail to respond adequately, have severe disease or have contraindications to standard initial therapy. One of the important goals of management in JDM will be to reduce the corticosteroid exposure experienced by patients. To meet this goal, progress in a number of key areas is needed: increased international collaboration, advances in study design and increased translational research.
Collapse
Affiliation(s)
- Adam M Huber
- a Division of Pediatric Rheumatology , Dalhousie University , Halifax , Nova Scotia , Canada
| |
Collapse
|
|
44
|
Abstract
PURPOSE OF REVIEW The purpose of this review was to give an update on treatment modalities for patients with idiopathic inflammatory myopathies, or shortly myositis, excluding the subgroup inclusion body myositis, based on a literature survey on therapies used in myositis. Few controlled trials have been performed in patients with myositis; therefore, we also included a summary of open-label trials, case series, and case reports. RECENT FINDINGS Glucocorticoid (GC) in high doses is still the first-line treatment of patients with myositis. There is a general recommendation to combine GCs with another immunosuppressive agent in the early phase of disease to better control disease activity and possibly to reduce the risk for GC-related side effects. Furthermore, combining pharmacological treatment with individualized and supervised exercise can be recommended based on evidence. There is some evidence for the effect of rituximab in patients with certain myositis-specific autoantibodies, whereas other biologic agents are currently being tested in clinical trials. SUMMARY Immunosuppressive treatment in combination with exercise is recommended for patients with myositis to reduce disease activity and improve muscle performance. Subgrouping of patients into clinical and serological subtypes may be a way to identify biomarkers for response to specific immunosuppressive and biological agents and should be considered in future trials.
Collapse
Affiliation(s)
- Simone Barsotti
- Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
- Department of Medical Biotechnology, University of Siena, Siena, Italy
| | - Ingrid E. Lundberg
- Division of Rheumatology, Department of Medicine, Karolinska Institutet and Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden
| |
Collapse
|
|
45
|
Selva-O'Callaghan A, Pinal-Fernandez I, Trallero-Araguás E, Milisenda JC, Grau-Junyent JM, Mammen AL. Classification and management of adult inflammatory myopathies. Lancet Neurol 2018; 17:816-828. [PMID: 30129477 PMCID: PMC11646336 DOI: 10.1016/s1474-4422(18)30254-0] [Citation(s) in RCA: 251] [Impact Index Per Article: 35.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2018] [Revised: 06/19/2018] [Accepted: 06/27/2018] [Indexed: 12/16/2022]
Abstract
Inflammatory myopathies, collectively known as myositis, are heterogeneous disorders characterised by muscle inflammation, and frequently accompanied by extramuscular manifestations that affect the skin, lung, and joints. Patients with inflammatory myopathies were previously classified as having dermatomyositis if characteristic rashes accompanied the muscle involvement, and as having polymyositis if no rashes were present. Five main types of inflammatory myopathies are now widely recognised: dermatomyositis, immune-mediated necrotising myopathy, sporadic inclusion-body myositis, overlap myositis (including antisynthetase syndrome), and polymyositis. The discovery of autoantibodies that are specifically associated with characteristic clinical phenotypes has been instrumental to the understanding of inflammatory myopathies. Treatment is still largely based on expert opinion, but several studies have shown effectiveness of different therapies in various subsets of inflammatory myopathies. These advances will undoubtedly improve the outcomes of patients with inflammatory myopathies.
Collapse
Affiliation(s)
- Albert Selva-O'Callaghan
- Systemic Autoimmune Diseases Unit, Vall d'Hebron General Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.
| | - Iago Pinal-Fernandez
- Muscle Disease Unit, Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Ernesto Trallero-Araguás
- Rheumatology Unit, Vall d'Hebron General Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - José César Milisenda
- Internal Medicine Department, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain; Centro de Investigación Médica en Red Enfermedades Raras
| | - Josep Maria Grau-Junyent
- Internal Medicine Department, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain; Centro de Investigación Médica en Red Enfermedades Raras
| | - Andrew L Mammen
- Muscle Disease Unit, Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| |
Collapse
|
|
46
|
Abstract
INTRODUCTION The idiopathic inflammatory myopathies (IIM) dermatomyositis (DM) and polymyositis (PM) are chronic diseases affecting the striated muscles with variable involvement of other organs. Glucocorticoids are considered the cornerstone of treatment, but some patients require adjunctive immunosuppressive agents because of insufficient response to glucocorticoids, flares upon glucocorticoid tapering, or glucocorticoid-related adverse events. Areas covered: The aim of this article was to review (PubMed search until February 2018) the evidence on established and new therapies derived from randomized controlled trials (RCTs) on adult DM and PM. In addition, key data from open-label trials, case reports, and abstracts were included where data from RCT were lacking. Expert commentary: Numerous synthetic and biological immunosuppressive agents are currently available to treat the IIM, sometimes in combination. The choice of the specific medication in the individual patient depends upon the disease phenotype and patient's characteristics. Exercise improves muscle performance without causing disease flares and should be an integral part of the treatment of the IIM. Prompt diagnosis and treatment can lead to better outcome.
Collapse
Affiliation(s)
- Nicolò Pipitone
- a SC di Reumatologia, Dipartimento Medicina Interna e Specialità Mediche, Azienda Unità Sanitaria Locale di Reggio Emilia - Istituto di Ricerca e Cura a Carattere Scientifico , Reggio , Emilia-Romagna , Italy
| | - Carlo Salvarani
- a SC di Reumatologia, Dipartimento Medicina Interna e Specialità Mediche, Azienda Unità Sanitaria Locale di Reggio Emilia - Istituto di Ricerca e Cura a Carattere Scientifico , Reggio , Emilia-Romagna , Italy.,b Rheumatology Department , University of Modena and Reggio Emilia , Italy
| |
Collapse
|
|
47
|
|