Risk factors and outcomes in inflammatory myopathies

Idiopathic inflammatory myopathies (IIM) are complex autoimmune diseases associated with high morbidity and mortality. Although knowledge about the pathogenic mechanisms underlying IIM is improving, limited data are available to inform clinical decision-making contributing to overall poor clinical outcomes in that population. The different projects in this thesis aimed to generate knowledge to help improve clinical outcomes in IIM and covered a wide range of topics related to outcome research namely risk factors, drug effectiveness, morbidity, mortality, and healthcare costs. In study I, genetic predisposition to autoantibody development in IIM was studied using a large international cross-sectional study. Based on an unsupervised cluster analysis, eight autoantibody-defined IIM subgroups were identified, and associated with distinct HLA class II and I, supporting the incorporation of autoantibody profiles in future IIM classification projects. In study II, based on a single center experience, significant improvement in physical function was found in anti-aminoacyl tRNA synthetase (ARS) positive patients but not in anti-ARS negative patients after exposure to one cycle of rituximab. Moreover, 78% of anti-ARS positive and 50% of anti-ARS negative patients achieved moderate/major ACR/EULAR improvement, supporting the effectiveness of rituximab in IIM. In study III, using Swedish administrative databases, a 2.4-fold higher risk of acute coronary syndrome (ACS) was found in patients with IIM compared to the general population. When accounting for the competing risk of death, the cumulative incidence of ACS at 5 years was estimated at 7% in IIM compared to 3% in the general population, confirming the substantial cardiovascular burden in IIM. In study IV, a modification effect of cancer on the association between dysphagia in early disease and mortality was demonstrated using an international IIM cohort. While dysphagia exposure in the absence of cancer was not associated with higher mortality risk, exposure to dysphagia in the presence of cancer was associated with a 5-fold higher mortality risk when compared to patients with IIM unexposed to dysphagia and cancer. This finding highlights the importance of stratification on cancer status when studying mortality in IIM. In study V, annual healthcare costs in IIM were estimated using Swedish administrative databases and found to be 3 to 5-fold higher than the general population in the 5-year period following diagnosis. In addition to providing the first Swedish estimates of IIM healthcare costs, this study emphasized the significant contribution of indirect costs that accounted for 40 to 60% of the overall annual costs over the five-year period after IIM diagnosis. Thus, the results generated by these studies demonstrate novel HLA associations with autoantibody-defined subgroups in IIM while supporting the effectiveness of B-cell depletion, confirming the increased cardiovascular risk, and shedding light on the relationship between dysphagia and mortality in IIM. These results, along with the comprehensive estimates of IIM healthcare costs, are valuable to define the orientation of future studies that will help bridge the therapeutic gap, reduce the cardiovascular burden, and improve cancer-associated management in IIM

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

Pain in autoimmune inflammatory myopathies: a scoping review

Background Pain is considered a priority for research by adult patients with autoimmune inflammatory myopathy (AIM) and their families. Our aim was to review the literature for studies reporting on pain in adult AIM and to summarise their findings.Methods A scoping review was conducted searching for studies in PubMed and MEDLINE including more than five adult patients with AIM and assessing pain using a patient-reported outcome measure. Study population characteristics, pain measurement and clinical correlates of pain were extracted using a standardised protocol.Results The search strategy identified 2831 studies with 33 meeting inclusion criteria. Most studies used visual analogue scales (n=14) and/or the Medical Outcomes Study 36-Item Short Form Bodily Pain Scale (n=17). Frequency of pain and/or myalgias ranged from 64% to 100%. Subjects with AIM had significantly more pain than the general population and comparable pain to other chronic rheumatic diseases. Insufficient results were available to identify significant clinical correlates of pain in AIM.Conclusion This review suggests that the burden of pain in AIM is considerable. Still, due to the heterogeneity and low quality of the evidence, significant knowledge gaps persist. Studies are needed to characterise pain trajectories of patients with AIM

Health-Related Quality of Life (HRQoL) in Idiopathic Inflammatory Myopathy: A Systematic Review

<div><p>Health-related quality of life (HRQoL) is a research priority in chronic diseases. We undertook a systematic review (registration #CRD42015024939) to identify, appraise and synthesize the evidence relating to HRQoL in idiopathic inflammatory myopathies (IIM). A comprehensive search was conducted in August 2015 using CINAHL, EMBase and Pubmed to identify studies reporting original data on HRQoL in IIM using generic HRQoL instruments. Characteristics of samples and results from selected studies were extracted and appraised using a standardized approach. Qualitative synthesis of the results was performed. Ten studies including a total of 654 IIM subjects were included in this systematic review. HRQoL was significantly impaired in all subsets of IIM compared with the general population. Disease activity, disease damage and chronic disease course were associated with poorer HRQoL. Insufficient or conflicting results were found in associations between clinical features, treatment, disease duration and mood or illness perception, and HRQoL in IIM. This study suggests that HRQoL is impaired in IIM. However, due to the paucity and heterogeneity of the evidence to date, robust estimates are lacking and significant knowledge gaps persist. There is a need for studies that systematically investigate the correlates and trajectory of HRQoL in IIM.</p></div

Health-Related Quality of Life (HRQoL) in Idiopathic Inflammatory Myopathy: A Systematic Review.

Health-related quality of life (HRQoL) is a research priority in chronic diseases. We undertook a systematic review (registration #CRD42015024939) to identify, appraise and synthesize the evidence relating to HRQoL in idiopathic inflammatory myopathies (IIM). A comprehensive search was conducted in August 2015 using CINAHL, EMBase and Pubmed to identify studies reporting original data on HRQoL in IIM using generic HRQoL instruments. Characteristics of samples and results from selected studies were extracted and appraised using a standardized approach. Qualitative synthesis of the results was performed. Ten studies including a total of 654 IIM subjects were included in this systematic review. HRQoL was significantly impaired in all subsets of IIM compared with the general population. Disease activity, disease damage and chronic disease course were associated with poorer HRQoL. Insufficient or conflicting results were found in associations between clinical features, treatment, disease duration and mood or illness perception, and HRQoL in IIM. This study suggests that HRQoL is impaired in IIM. However, due to the paucity and heterogeneity of the evidence to date, robust estimates are lacking and significant knowledge gaps persist. There is a need for studies that systematically investigate the correlates and trajectory of HRQoL in IIM

Description of the studies included in this review.

<p>Description of the studies included in this review.</p

Flow diagram of study selection.

<p>Flow diagram of study selection.</p

Summary of HRQoL results using the SF-36.

<p>Summary of HRQoL results using the SF-36.</p

Comparison of HRQoL between IIM and other chronic conditions using the SF-36.

<p>Comparison of HRQoL between IIM and other chronic conditions using the SF-36.</p