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

Inclusion body myositis: therapeutic approaches.

The idiopathic inflammatory myopathies are a heterogeneous group of diseases that include dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM) and other less common myopathies. These are clinically and histopathologically distinct diseases with many shared clinical features. IBM, the most commonly acquired inflammatory muscle disease occurs in individuals aged over 50 years, and is characterized by slowly progressive muscle weakness and atrophy affecting proximal and distal muscle groups, often asymmetrically. Unlike DM and PM, IBM is typically refractory to immunotherapy. Although corticosteroids have not been tested in randomized controlled trials, the general consensus is that they are not efficacious. There is some suggestion that intravenous immunoglobulin slows disease progression, but its long-term effectiveness is unclear. The evidence for other immunosuppressive therapies has been derived mainly from case reports and open studies and the results are discouraging. Only a few clinical trials have been conducted on IBM, making it difficult to provide clear recommendations for treatment. Moreover, IBM is a slowly progressive disease so assessment of treatment efficacy is problematic due to the longer-duration trials needed to determine treatment effects. Newer therapies may be promising, but further investigation to document efficacy would be expensive given the aforementioned need for longer trials. In this review, various treatments that have been employed in IBM will be discussed even though none of the interventions has sufficient evidence to support its routine use

WSDL-S: Adding Semantics to WSDL

Web services have primarily been designed for providing inter-operability between business applications. Current technologies assume a large amount of human interaction, for integrating two applications. This is primarily due to the fact that business process integration requires understanding of data and functions of the involved entities. Semantic Web technologies, powered by description logic based languages like OWL[1], aim to add greater meaning to Web content, by annotating the data with ontologies. Ontologies provide a mechanism of providing shared conceptualizations of domains. This allows agents to get an understanding of users’ Web content and greatly reduces human interaction for meaningful Web searches. A similar approach can be used for adding greater meaning to Web service descriptions, which will in turn, allow greater automation, by reducing human involvement for understanding the data and functions of the services

34587 Efficacy of ruxolitinib cream for the treatment of atopic dermatitis by anatomic region: Pooled analysis from two randomized phase 3 studies

Atopic dermatitis (AD) is a highly pruritic inflammatory skin disease. Two phase 3 studies (TRuE-AD1/TRuE-AD2) enrolled patients aged ≥12 years with AD for ≥2 years, an Investigator’s Global Assessment (IGA) score of 2/3, and 3%–20% affected body surface area. Patients (total N = 1249; median age, 32 years) were randomized (2:2:1) to twice-daily 0.75% ruxolitinib (Janus kinase [JAK] 1/JAK2 inhibitor) cream, 1.5% ruxolitinib cream, or vehicle cream for 8 weeks of double-blind treatment, and thereafter continued in a long-term, 44-week period of the studies. In this pooled analysis, mean percentage change from baseline in Eczema Area and Severity Index (EASI) anatomic region subscores is reported up to Week 8 (n = 1208). For the head and neck region, patients applying 0.75%/1.5% ruxolitinib cream (vs vehicle) achieved mean improvements of 59.3%/55.8% (vs 13.4%), 70.4%/71.3% (vs 22.4%), and 70.0%/78.7% (vs 45.0%) at Weeks 2, 4, and 8, respectively (all P \u3c.0001). Results were similar for the upper limbs region (48.5%/54.7% [vs 13.3%], 66.6%/70.3% [vs 25.0%], and 73.5%/74.9% [vs 35.1%] all P \u3c.0001). For the trunk region, patients achieved mean improvements of 49.8%/60.0% (vs 12.1%), 67.3%/73.8% (vs 15.0%), and 72.7%/81.0% (vs 15.6%) at Weeks 2, 4, and 8, respectively (all P \u3c.0001). Similar results were observed for the lower limbs region (46.0%/48.2% [vs 16.3%], 65.9%/66.2% [vs 13.9%], and 76.3%/74.9% [vs 39.8%]; all P \u3c.0001). Ruxolitinib cream was well tolerated, with an adverse event profile similar to vehicle. In summary, ruxolitinib cream demonstrated significant improvements vs vehicle in patients with AD across anatomic regions as early as Week 2

2016 ACR-EULAR adult dermatomyositis and polymyositis and juvenile dermatomyositis response criteria-methodological aspects

Objective. The objective was to describe the methodology used to develop new response criteria for adult DM/PM and JDM. Methods. Patient profiles from prospective natural history data and clinical trials were rated by myositis specialists to develop consensus gold-standard ratings of minimal, moderate and major improvement. Experts completed a survey regarding clinically meaningful improvement in the core set measures (CSM) and a conjoint-analysis survey (using 1000Minds software) to derive relative weights of CSM and candidate definitions. Six types of candidate definitions for response criteria were derived using survey results, logistic regression, conjoint analysis, application of conjoint-analysis weights to CSM and published definitions. Sensitivity, specificity and area under the curve were defined for candidate criteria using consensus patient profile data, and selected definitions were validated using clinical trial data. Results. Myositis specialists defined the degree of clinically meaningful improvement in CSM for minimal, moderate and major improvement. The conjoint-analysis survey established the relative weights of CSM, with muscle strength and Physician Global Activity as most important. Many candidate definitions showed excellent sensitivity, specificity and area under the curve in the consensus profiles. Trial validation showed that a number of candidate criteria differentiated between treatment groups. Top candidate criteria definitions were presented at the consensus conference. Conclusion. Consensus methodology, with definitions tested on patient profiles and validated using clinical trials, led to 18 definitions for adult PM/DM and 14 for JDM as excellent candidates for consideration in the final consensus on new response criteria for myositis

Pain in individuals with idiopathic inflammatory myopathies, other systemic autoimmune rheumatic diseases, and without rheumatic diseases: A report from the COVAD study

Myositis; Pain; Rheumatic diseasesMiositis; Dolor; Enfermedades reumáticasMiositis; Dolor; Malalties reumàtiquesObjectives To compare pain intensity among individuals with idiopathic inflammatory myopathies (IIMs), other systemic autoimmune rheumatic diseases (AIRDs), and without rheumatic disease (wAIDs). Methods Data were collected from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study, an international cross-sectional online survey, from December 2020 to August 2021. Pain experienced in the preceding week was assessed using numeral rating scale (NRS). We performed a negative binomial regression analysis to assess pain in IIMs subtypes and whether demographics, disease activity, general health status, and physical function had an impact on pain scores. Results Of 6988 participants included, 15.1% had IIMs, 27.9% had other AIRDs, and 57.0% were wAIDs. The median pain NRS in patients with IIMs, other AIRDs, and wAIDs were 2.0 (interquartile range [IQR] = 1.0–5.0), 3.0 (IQR = 1.0–6.0), and 1.0 (IQR = 0–2.0), respectively (P < 0.001). Regression analysis adjusted for gender, age, and ethnicity revealed that overlap myositis and antisynthetase syndrome had the highest pain (NRS = 4.0, 95% CI = 3.5–4.5, and NRS = 3.6, 95% CI = 3.1–4.1, respectively). An additional association between pain and poor functional status was observed in all groups. Female gender was associated with higher pain scores in almost all scenarios. Increasing age was associated with higher pain NRS scores in some scenarios of disease activity, and Asian and Hispanic ethnicities had reduced pain scores in some functional status scenarios. Conclusion Patients with IIMs reported higher pain levels than wAIDs, but less than patients with other AIRDs. Pain is a disabling manifestation of IIMs and is associated with a poor functional status.HC is supported by the National Institution for Health Research Manchester Biomedical Research Centre Funding Scheme

Pain in individuals with idiopathic inflammatory myopathies, other systemic autoimmune rheumatic diseases, and without rheumatic diseases: A report from the COVAD study

OBJECTIVES: To compare pain intensity among individuals with idiopathic inflammatory myopathies (IIMs), other systemic autoimmune rheumatic diseases (AIRDs), and without rheumatic disease (wAIDs). METHODS: Data were collected from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study, an international cross-sectional online survey, from December 2020 to August 2021. Pain experienced in the preceding week was assessed using numeral rating scale (NRS). We performed a negative binomial regression analysis to assess pain in IIMs subtypes and whether demographics, disease activity, general health status, and physical function had an impact on pain scores. RESULTS: Of 6988 participants included, 15.1% had IIMs, 27.9% had other AIRDs, and 57.0% were wAIDs. The median pain NRS in patients with IIMs, other AIRDs, and wAIDs were 2.0 (interquartile range [IQR] = 1.0-5.0), 3.0 (IQR = 1.0-6.0), and 1.0 (IQR = 0-2.0), respectively (P < 0.001). Regression analysis adjusted for gender, age, and ethnicity revealed that overlap myositis and antisynthetase syndrome had the highest pain (NRS = 4.0, 95% CI = 3.5-4.5, and NRS = 3.6, 95% CI = 3.1-4.1, respectively). An additional association between pain and poor functional status was observed in all groups. Female gender was associated with higher pain scores in almost all scenarios. Increasing age was associated with higher pain NRS scores in some scenarios of disease activity, and Asian and Hispanic ethnicities had reduced pain scores in some functional status scenarios. CONCLUSION: Patients with IIMs reported higher pain levels than wAIDs, but less than patients with other AIRDs. Pain is a disabling manifestation of IIMs and is associated with a poor functional status

A Systematic Review and Meta-Analysis to Inform Cancer Screening Guidelines in Idiopathic Inflammatory Myopathies

OBJECTIVES: To identify clinical factors associated with cancer risk in the idiopathic inflammatory myopathies (IIMs) and to systematically review the existing evidence related to cancer screening. METHODS: A systematic literature search was carried out on Medline, Embase and Scopus. Cancer risk within the IIM population (i.e. not compared to the general population) was expressed as risk ratios (RR) for binary variables and weighted mean differences (WMD) for continuous variables. Evidence relating to cancer screening practices in the IIMs were synthesised via narrative review. RESULTS: Sixty nine studies were included in the meta-analysis. Dermatomyositis subtype (RR 2.21), older age (WMD 11.19), male gender (RR 1.53), dysphagia (RR 2.09), cutaneous ulceration (RR 2.73), and anti-transcriptional intermediary factor-1 gamma positivity (RR 4.66) were identified as being associated with significantly increased risk of cancer. Polymyositis (RR 0.49) and clinically amyopathic dermatomyositis (RR 0.44) subtypes, Raynaud's phenomenon (RR 0.61), interstitial lung disease (RR 0.49), very high serum creatine kinase (WMD -1189.96) or lactate dehydrogenase (WMD -336.52) levels, and anti-Jo1 (RR 0.45) or anti-EJ (RR 0.17) positivity were identified as being associated with significantly reduced risk of cancer. Nine studies relating to IIM-specific cancer screening were included. Computed tomography (CT) scanning of the thorax, abdomen and pelvis appeared to be effective in identifying underlying asymptomatic cancers. DISCUSSION: Cancer risk factors should be evaluated in patients with IIM for risk stratification. Screening evidence is limited but CT scanning could be useful. Prospective studies and consensus guidelines are needed to establish cancer screening strategies in IIM patients