Proceedings of the 2019 Canadian Inflammatory Myopathy Study Symposium: Clinical Trial Readiness in Myositis.

The Canadian Inflammatory Myopathy Study (CIMS) is a multicenter prospective cohort recruiting in 8 centers across Canada. One of the aims of CIMS is to conduct and participate in clinical trials in autoimmune inflammatory myopathies (AIM). Conducting clinical trials in rare diseases such as AIM presents challenges. During this symposium, experts in the field presented different solutions to successfully conduct clinical trials in AIM, including the importance of collaboration and careful trial design, as well as training and mentoring of young investigators

Scleromyositis: A distinct novel entity within the systemic sclerosis and autoimmune myositis spectrum. Implications for care and pathogenesis

Systemic sclerosis and autoimmune myositis are both associated with decreased quality of life and increased mortality. Their prognosis and management largely depend on the disease subgroups. Indeed, systemic sclerosis is a heterogeneous disease, the two predominant forms of the disease being limited and diffuse scleroderma. Autoimmune myositis is also a heterogeneous group of myopathies that classically encompass necrotizing myopathy, antisynthetase syndrome, dermatomyositis and inclusion body myositis. Recent data revealed that an additional disease subset, denominated “scleromyositis”, should be recognized within both the systemic sclerosis and the autoimmune myositis spectrum. We performed an in-depth review of the literature with the aim of better delineating scleromyositis. Our review highlights that this concept is supported by recent clinical, serological and histopathological findings that have important implications for patient management and understanding of the disease pathophysiology. As compared with other subsets of systemic sclerosis and autoimmune myositis, scleromyositis patients can present with a characteristic pattern of muscle involvement (i.e. distribution of muscle weakness) along with multisystemic involvement, and some of these extra-muscular complications are associated with poor prognosis. Several autoantibodies have been specifically associated with scleromyositis, but they are not currently integrated in diagnostic and classification criteria for systemic sclerosis and autoimmune myositis. Finally, striking vasculopathic lesions at muscle biopsy have been shown to be hallmarks of scleromyositis, providing a strong anatomopathological substratum for the concept of scleromyositis. These findings bring new insights into the pathogenesis of scleromyositis and help to diagnose this condition, in patients with subtle SSc features and/or no autoantibodies (i.e. “seronegative” scleromyositis). No guidelines are available for the management of these patients, but recent data are showing the way towards a new therapeutic approach dedicated to these patients

Reply: A child with severe juvenile dermatomyositis treated with ruxolitinib

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Methods for scoping review: Protocol and methods

This scoping review was conducted using the Joanna Briggs Institute framework (1) and responds to PRISMA-ScR checklist (2). Methods were registered on HAL on the 24rth of July 2021. The review included the following six key phases: 1) identifying the research question, 2) identifying relevant studies, 3) study selection, 4) charting the data, 5) collating, summarizing, and reporting the results. 2.2 Research question This scoping review was guided by the following question: What is the spectrum of myositis associated with polyarthritis? 2.3 Screening for relevant studies : eligibility criteria Articles were included if they considered the association of polyarthritis and IIM. For practical reason, articles in other languages than English or French were excluded. Duplicate

Physical activity monitoring: A promising outcome measure in idiopathic inflammatory myopathies

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The role of interferons type I, II and III in myositis: A review

International audienceThe classification of idiopathic inflammatory myopathies (IIM) is based on clinical, serological and histological criteria. The identification of myositis-specific antibodies has helped to define more homogeneous groups of myositis into four dominant subsets: dermatomyositis (DM), antisynthetase syndrome (ASyS), sporadic inclusion body myositis (sIBM) and immune-mediated necrotising myopathy (IMNM). sIBM and IMNM patients present predominantly with muscle involvement, whereas DM and ASyS patients present additionally with other extramuscular features, such as skin, lung and joints manifestations. Moreover, the pathophysiological mechanisms are distinct between each myositis subsets. Recently, interferon (IFN) pathways have been identified as key players implicated in the pathophysiology of myositis. In DM, the key role of IFN, especially type I IFN, has been supported by the identification of an IFN signature in muscle, blood and skin of DM patients. In addition, DM-specific antibodies are targeting antigens involved in the IFN signalling pathways. The pathogenicity of type I IFN has been demonstrated by the identification of mutations in the IFN pathways leading to genetic diseases, the monogenic interferonopathies. This constitutive activation of IFN signalling pathways induces systemic manifestations such as interstitial lung disease, myositis and skin rashes. Since DM patients share similar features in the context of an acquired activation of the IFN signalling pathways, we may extend underlying concepts of monogenic diseases to acquired interferonopathy such as DM. Conversely, in ASyS, available data suggest a role of type II IFN in blood, muscle and lung. Indeed, transcriptomic analyses highlighted a type II IFN gene expression in ASyS muscle tissue. In sIBM, type II IFN appears to be an important cytokine involved in muscle inflammation mechanisms and potentially linked to myodegenerative features. For IMNM, currently published data are scarce, suggesting a minor implication of type II IFN. This review highlights the involvement of different IFN subtypes and their specific molecular mechanisms in each myositis subset

Response to: Comment on “Systematic retrospective study on 64 patients anti-Mi2 dermatomyositis: A classic skin rash with a necrotizing myositis and high risk of malignancy”

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JAK Inhibitors: A Promising Molecular- targeted Therapy in Dermatomyositis

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Physical Activity Monitoring Using Wrist-Worn Accelerometer in theAssessment and Follow-up of Patients with Myositis

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Rituximab and Cyclophosphamide in Antisynthetase Syndrome–related Interstitial Lung Disease: An Observational Retrospective Study

International audienceObjective Antisynthetase syndrome (AS)-related interstitial lung disease (ILD) has a poor prognosis. Intravenous cyclophosphamide (IV CYC) and rituximab (RTX) are the main treatments currently used for moderate to severe ILD. Here, we compare the efficacy of CYC followed by standard immunosuppressive treatment (IST) versus RTX in AS-related ILD. Methods This observational retrospective study was conducted between 2003 and 2016 in 3 tertiary care centers. All patients with AS-related ILD and treated with CYC or RTX with at least 6 months of follow-up were included. Pulmonary progression-free survival (PFS), defined according to the American Thoracic Society guidelines, was assessed at 6 months and 2 years. All severe adverse events (AE) were recorded. Results Sixty-two patients were included. Thirty-four patients received 2–12 monthly IV CYC pulses, followed by standard IST in 30 cases (88%). The RTX group included 28 patients. Following the initial Day 1 to Day 15 infusions, RTX was repeated every 6 months in 26 cases (93%) and 15 patients (54%) concomitantly received another IST. The median steroid dose was similar between both groups. Although RTX and CYC demonstrated similar PFS at 6 months (92% vs 85%, respectively), RTX was superior at 2 years (HR 0.263, 95% CI 0.094–0.732, P = 0.011). Interestingly, lower diffusing lung capacity for carbon monoxide (DLCO) at baseline was independently predictive of poor 2-year PFS [0.965 (0.936–0.995), P = 0.023]. Forced vital capacity and DLCO improved in both groups without significant differences. Serious AE were similar in both groups. Conclusion Despite similar PFS at 6 months, RTX was associated with a better 2-year PFS compared to CYC in patients with AS-related ILD