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To identify predictors of response to immunosuppressive therapy after 1 year, with a focus on autoantibodies, in patients newly diagnosed with idiopathic inflammatory myopathies (IIM) followed longitudinally in an electronic registry.We assessed the association between autoantibody-defined groups and improvement according to American College of Rheumatology/European Alliance of Associations for Rheumatology 2016 response criteria.We identified 156 patients; of those, 111 (71%) were positive for any autoantibody tested, 90% received glucocorticoid treatment at baseline, and 78% received immunosuppressive drugs at some follow-up point. After 1 year from the index date, the overall median improvement score was 27.5 (interquartile range 10-51). No differences were observed in the total improvement score between the autoantibody-defined groups. Overall, 62% of patients (n = 96) showed a minimal response, 38% (n = 60) achieved a moderate response, and 19% (n = 30) achieved a major response. Regarding the different levels of response, dermatomyositis-specific autoantibodies were associated with a moderate response versus the seronegative group (reference), odds ratio 4.12 (95% confidence interval 1.2-16.5). In addition, dysphagia, time from symptom onset to diagnosis, and initial glucocorticoid dose were significant predictors of response after 1 year of follow-up.Patients with DM-specific autoantibodies achieved better levels of response compared to other autoantibody-defined groups. Dysphagia, a shorter time span from symptom onset to diagnosis, and intensive initial immunosuppressive treatment were associated with a higher response rate after 1 year of pharmacologic treatment from the index date, regardless of autoantibody status.

There have been a number of advances in the clinical and translational understanding of cutaneous lupus and dermatomyositis, which both disproportionately affect women. These advances have involved ongoing collaborations between dermatology and rheumatology that highlight the importance of the skin in these disorders, with improvement in the education of trainees and clinical management of these complex multisystem diseases. In addition, a new disease classification has allowed inclusion of patients with skin-predominant dermatomyositis, frequently associated with systemic findings, in the spectrum of idiopathic inflammatory myopathies. Validated outcome measures allow translational research and facilitate progress toward better and more targeted therapeutics. Clinical trials using disease severity tools, such as the Cutaneous Lupus Erythematosus Area and Severity Index and the Cutaneous Dermatomyositis Disease Area and Severity Index, allow measurement of improvement in the skin. Recent results of phase 2 and 3 trials clearly show that patients will benefit from collaborative interactions and studies between dermatology and rheumatology.

PURPOSE OF REVIEW To summarize information on polymyositis; diagnosis, definitions, published data and opinions. RECENT FINDINGS Polymyositis originally referred to inflammatory muscle diseases presenting with muscle weakness and inflammatory cell infiltrates on muscle tissue visible by microscopy. Over time and with improved technology to immunophenotype infiltrating inflammatory cells and characterize muscle fibres, the meaning of polymyositis changed and became more specific. There is ongoing controversy over the term polymyositis, with proponents for a strict definition based on histopathological and immunohistochemical features on muscle biopsies whereas others advocate for a broader clinical and histopathological phenotype. Over the past decades, the discovery of several myositis-specific autoantibodies together with distinct histopathological features have enabled the identification of new subsets previously labelled as polymyositis notably the antisynthetase syndrome and the immune-mediated necrotizing myopathies thus reducing the number of patients classified as polymyositis. SUMMARY There are still a small number of patients among the idiopathic inflammatory myopathies that can be classified as polymyositis as discussed in this review but the entity is now considered relatively rare.

ObjectivesThe magnitude of the genetic contribution to idiopathic inflammatory myopathies (IIMs) is unknown. In this project, we aimed to investigate the familial aggregation and heritability of IIM.MethodsThis is a family-based study using nationwide healthcare register data in Sweden. We matched each patient with IIM to individuals without IIM, identified their first-degree relatives and determined the IIM status among all first-degree relatives. We estimated the adjusted ORs (aORs) of familial aggregation of IIM using conditional logistic regression. In addition, we used tetrachoric correlation to estimate the heritability of IIM.ResultsWe included 7615 first-degree relatives of 1620 patients with IIM diagnosed between 1997 and 2016 and 37 309 first-degree relatives of 7797 individuals without IIM. Compared with individuals without IIM, patients with IIM were more likely to have ≥1 first-degree relative affected by IIM (aOR=4.32, 95% CI 2.00 to 9.34). Furthermore, the aOR of familial aggregation of IIM in full siblings was 2.53 (95% CI 1.62 to 3.96). The heritability of IIM was 22% (95% CI 12% to 31%) among any first-degree relatives and 24% (95% CI 12% to 37%) among full siblings.ConclusionsIIM has a familial component with a risk of aggregation among first-degree relatives and a heritability of about 20%. This information is of importance for future aetiological studies and in clinical counselling.

Background In 2017, the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) published new classification criteria for idiopathic inflammatory myopathies (IIM). Objectives To [1] assess the performance of the EULAR/ACR criteria in a monocentric cohort of consecutive patients with IIM, compare them with the Bohan and Peter (BP) criteria, and with the physician's diagnosis; and [2] evaluate the effect of including the presence of interstitial lung disease (ILD) as variable in the criteria. Methods 439 consecutive patients with a diagnosis of IIM followed at the Rheumatology Clinic, Karolinska University Hospital, Sweden were enrolled. The patients were diagnosed as IIM and subclassified by expert physicians. Clinical, laboratory, serological and histopathological data were collected from existing databases (Euromyositis registry and Swedish Rheumatology quality registry) and clinical charts of the patients. The sensitivity of the EULAR/ACR and the BP criteria was calculated. Results The EULAR/ACR criteria had a higher sensitivity (87.7%) compared to the BP criteria (80.4%). The concordance between the two sets of criteria was low (k = 0.253 p 98%) for the major IIM subgroups polymyositis, dermatomyositis, and inclusion body myositis. The sensitivity was variable and was high in inclusion body myositis (98%), dermatomyositis (90%) and lower in polymyositis (73%). When including ILD in the variables of the criteria, six more patients were classified as IIM cases (1.3%). Conclusion The EULAR/ACR criteria for IIM are applicable with high sensitivity and specificity using data available from existing databases and clinical charts and represent a major step forward from the previous criteria for IIM and its subgroups. Their application will improve the quality of clinical trials and research studies with IIM patients.

Objectives To examine pregnancy outcomes among births to women with idiopathic inflammatory myopathy (IIM) in relation to time of IIM diagnosis using population-based data. Methods This study used Swedish nationwide registers to identify all singleton births that occurred between 1973 and 2016 among women diagnosed with IIM between 1998 and 2016 and among women unexposed to IIM. We classified births according to the IIM status of the mother at time of delivery: post-IIM (n = 68), 1–3 years pre-IIM (n = 23), >3 years pre-IIM (n = 710) and unexposed to IIM (n = 4101). Multivariate regression models were used to estimate relative risks of adverse pregnancy outcomes in post-IIM births and pre-IIM births separately, in comparison with their non-IIM comparators. Results We found that post-IIM births had increased risks of caesarean section [adjusted relative risk (aRR) = 1.98; 95% CI: 1.08, 3.64], preterm birth (aRR = 3.35; 95% CI: 1.28, 8.73) and low birth weight (aRR = 5.69; 95% CI: 1.84, 17.55) compared with non-IIM comparators. We also noticed higher frequencies of caesarean section and instrumental delivery in 1–3 years pre-IIM births than in the non-IIM comparators. Conclusion Women who gave birth after IIM diagnosis had higher risks of caesarean section, preterm birth and low birth weight. These results further underline the importance of special care and close monitoring of women with IIM. Higher frequencies of caesarean section and instrumental delivery in pre-IIM births highlight the need for future research on the influence of subclinical features of IIM on pregnancy outcomes.

Objective.Evidence suggests an increased risk of cardiovascular (CV) diseases, including acute coronary syndrome (ACS), in idiopathic inflammatory myopathies (IIM). The aim of this study was to investigate the risk of ACS in an incident IIM cohort compared to the general Swedish population.Methods.A cohort of 655 individuals with incident IIM and 6813 general population comparators were identified from national registries. IIM subjects were diagnosed from 2002 to 2011. Followup started at IIM diagnosis and corresponding date in the general population. ACS, CV comorbidities, and CV risk factors were defined using International Classification of Diseases codes. Incidence rates including 95% CI were calculated. Cox proportional hazards models were used to compare the risk of ACS in patients with IIM and the general population. The competing risk of death was accounted for using competing risk regression models.Results.The incidence rate of ACS in IIM was higher than in the general population, particularly within the first year of diagnosis and in older individuals. The overall ACS incidence rate in IIM was 15.6 (95% CI 11.7–20.4) per 1000 person-years, with an HR of 2.4 (95% CI 1.8–3.2) compared with the general population. When accounting for the competing risk of death, the risk of ACS in IIM remained increased with a cumulative incidence of 7% at 5 years compared to 3.3% in the general population.Conclusion.IIM individuals are at higher risk of ACS, particularly within the first year after diagnosis.

Objective.To present and vote on a myositis modified patient-reported outcome core domain set in the life impact area at the Outcome Measures in Rheumatology (OMERACT) 2018.Methods.Based on results from international focus groups and Delphi surveys, a draft core set was developed.Results.Domains muscle symptoms, fatigue, level of physical activity, and pain reached ≥ 70% consensus and were mandatory to assess in all trials. Domains lung, joint, and skin symptoms were mandatory in specific circumstances. This core set was endorsed by > 85% at OMERACT 2018.Conclusion.We propose a life impact core set for patients with idiopathic inflammatory myopathies and will proceed with instrument selections.

Objective Post-hoc analyses of the Rituximab in Myositis trial indicate that specific autoantibodies profiles may influence treatment response. We compared the efficacy and safety of rituximab in anti-synthetase antibody (ARS-ab) positive and negative patients. Methods Adult idiopathic inflammatory myopathy (IIM) subjects in the Swedish Rheumatology Quality Register who received ⩾ 1 cycle of rituximab were enrolled. Efficacy assessment was based on the International Myositis Assessment and Clinical Studies (IMACS) core set measures and the 2016 ACR/EULAR definition of improvement for PM and DM. Safety assessment included drug-related adverse event and death during study period. Comparisons were done within and between the ARS-ab defined groups before and after first and last cycles. Associations between selected clinical features and improvement after one rituximab cycle were assessed using logistic regression. Results Sixty-five subjects were included and 43 had a follow-up visit within 5-10 months. Seventy-eight percent of ARS-ab positive subjects had moderate/major ACR/EULAR improvement after one cycle compared with 50% in the ARS-ab negative group. After several cycles, 79% of the ARS-ab positive and 67% of the ARS-ab negative patients achieved moderate/major improvement. A significant glucocorticoid-sparing effect was only observed in the ARS-ab positive group (P = 0.001). The most frequent adverse events were infections. One ARS-ab positive and two ARS-ab negative patients died during follow-up period. Conclusion Irrespectively of their autoantibody status, a majority of subjects treated with several rituximab cycles had moderate/major improvement. In addition, ARS-ab positive subjects experienced a significant glucocorticoid-sparing effect.

Objectives To estimate the annual direct and indirect costs associated with Idiopathic Inflammatory Myopathies (IIM) over time, including the pre-diagnostic period. Methods A cohort of incident adult IIM patients (n = 673) was identified from the Swedish National Patient Register from 2010 to 2016 and matched with general population comparators (n = 3343). Follow-up started at IIM diagnosis and corresponding date in the general population. International Classification of Diseases codes (ICD-10) were used for IIM case definition. Costs were calculated using national register data. Results The costs related to IIM started to increase 2 years before diagnosis. In the year following diagnosis, the mean annual IIM cost was €21 639 compared to €4816 in the general population. Five years after diagnosis, the mean annual cost in the IIM cohort was €12 796. Outpatient visits, hospitalizations and productivity loss were the components driving the increment in overall annual disease-related expenditures. Indirect costs accounted for a significant portion of IIM long-term societal costs. The highest costs were found in individuals of working age with cancer-associated IIM. Conclusions The mean annual costs in IIM were 3 to 5 times higher than in the general population in the 5-year period following diagnosis. These costs started to increase long before diagnosis, were at their peak in the year post-diagnosis and remained elevated thereafter. Indirect costs contributed to a substantial portion of this increment. Early in the IIM disease course, clinicians and allied health professionals should aim to improve function, reduce damage and address barriers to return-to-work to mitigate these costs.

Background The objective of the study was to explore the disease pathways activated in the inflammatory foci of skin lesions in cutaneous lupus erythematosus (CLE) and dermatomyositis (DM). Methods Skin biopsies acquired from active CLE and DM lesions, patient (PC), and also healthy controls (HC) were investigated. Biopsy sections were examined by a pathologist, inflammatory foci were laser micro-dissected and captured, and proteins within captured tissue were detected in an unbiased manner by mass spectrometry. Protein pathway analysis was performed by the string-db.org platform. Findings of interest were confirmed by immunohistochemistry (IHC). Results Proteome investigation identified abundant expression of interferon-regulated proteins (IRP) as a common feature of CLE and DM. Interleukin (IL)-16 was the only abundant cytokine differentially expressed in CLE compared to DM. Caspase-3, an enzyme that cleaves IL-16 into its active form, was detected in low levels. Significantly higher proportion of IL-16- and caspase-3-positive cells was identified in CLE lesions in comparison with DM, PC, and HC. Proteomic results indicate more abundant complement deposition in CLE skin lesions. Conclusions Using unbiased mass spectrometry investigation of CLE and DM inflammatory infiltrates, we confirmed that high IRP expression is a common feature of both CLE and DM, while IL-16 is the only differentially expressed cytokine in CLE. IHC confirmed high expression of IL-16 and caspase-3 in CLE. Our novel molecular findings indicate that IL-16 detection could be useful in differential diagnostics between the two conditions that can display similar histopathological appearance. IL-16 could be of interest as a future therapeutic target for CLE.

Objectives: This study aimed to assess the contribution of traditional/disease-related risk factors and biomarkers linked to arterial and venous thrombotic events (TEs) in patients with idiopathic inflammatory myopathies (IIMs). Method: The occurrence of arterial and/or venous TEs at the time of or after IIM diagnosis was retrospectively evaluated in a cohort of 253 patients with IIMs, resulting in a final population of 246 IIM patients, 51 with reported TE (cases) and 195 without a history of TE (comparators). Information on disease characteristics and traditional risk factors for arterial and venous TE (essential hypertension, diabetes, dyslipidaemia, smoking, malignancy) was retrieved. Serum levels of anti-phospholipid antibodies (aPLs) and adhesion molecules were analysed at the time of IIM diagnosis and at the time of the TE in cases. Results: One in five IIM patients (21%) had experienced a TE, arterial TE in 22 and venous TE in 29 patients, with a peak prevalence within 5 years after diagnosis. Among traditional/disease-related risk factors, only older age was associated with both arterial and venous TEs, after adjusting for other covariates. Low serum levels of e-selectin were associated with higher odds of developing a TE, without specific association with either arterial or venous TEs. Only 6% of IIM patients had aPLs, with no significant difference between cases and comparators. Conclusions: An increased risk of both venous and arterial TEs should be considered in IIM patients, particularly close to diagnosis and in elderly people. Low serum levels of e-selectin may predict TE in IIM patients, but the underlying biological mechanism is not known.

Objective To investigate the content validity of several patient-reported outcome measures (PROMs) in patients with idiopathic inflammatory myopathies (IIM). Methods Seven individual PROM instruments were selected by the Outcome Measures in Rheumatology (OMERACT) Myositis Working Group relating to the following domains: pain, fatigue, physical function and physical activity. Twenty patients from the Johns Hopkins Myositis Center were selected for one-on-one face-to-face or phone interviews for cognitive interviewing of individual PROMs to assess comprehension and content validity. Additionally, patients were asked if they thought muscle symptoms, an area originally identified in qualitative studies, were encapsulated by the other four domains. Results The majority of patients (>70%) felt that each of the instruments was clear, easy to read and understand, and could be used for assessment of its domain. Two-thirds (66%) of patients felt that ‘muscle symptoms’ were captured by the other domains. Conclusions We provided evidence to support adequate content validity for several PROMs. Further research is needed to determine whether ‘muscle symptoms’ warrant a separate domain.

Objective To examine the association between idiopathic inflammatory myopathy (IIM) and cancer before and after IIM diagnosis. Methods We used prospectively collected nationwide register data to design a case-control study to investigate the occurrence of cancer before IIM, and a cohort study to investigate the occurrence of cancer after IIM. Patients diagnosed with IIM between 2002 and 2016 in Sweden, were compared to the general population. The association between cancer and IIM was estimated before and after IIM diagnosis via logistic regression and Cox regression models, respectively. Results We included 1419 patients with IIM and 7045 individuals from the general population. The overall odds of cancer before IIM diagnosis were increased in IIM compared to the general population, adjusted odds ratio (AOR) 1.5, 95% confidence interval (CI) 1.3–1.8. This association was also noted after IIM diagnosis, adjusted hazard ratio (AHR) 1.7 (95% CI 1.4–2.0), or one additional cancer in every 125 IIM patients per year. Colorectal (AOR 2.1), lung (AOR 5.4) and ovarian (AOR 7.0) cancers were associated with IIM before diagnosis. Oropharyngeal (AHR 9.1) and cervical (AHR 3.8) cancers, malignant melanoma (AHR 3.2) and non-melanoma skin cancer (AHR 3.1) were associated with IIM after diagnosis. Adenocarcinomas were associated with dermatomyositis before diagnosis and squamous cell cancers after IIM diagnosis. Lymphatic hematopoietic cancers were associated with IIM both before and after diagnosis. Conclusions The cancer types that occur before IIM diagnosis differ from the ones that occur after diagnosis. This may have an impact on screening decisions for IIM.

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OBJECTIVE To assess the incidence of venous thromboembolic events (VTEs) in patients with idiopathic inflammatory myopathies (IIMs), to compare the incidence of VTEs in IIM to the incidence in the general population, and to identify patient categories at high risk and investigate the development of risk in relation to a diagnosis of IIM. METHODS Using nationwide registers, we identified a cohort of 440 individuals with newly diagnosed IIM and 4,459 individuals from the general population. Patients with IIM were diagnosed between 2005 and 2011. The start of follow-up was the date of IIM diagnosis and the corresponding date in the general population. VTE was defined as hospital care with an International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code indicating VTE, with a filled prescription for anticoagulant medication. Incidence rates including 95% confidence intervals (95% CIs) were calculated, and Cox proportional hazards models were used to compare the risk of VTE in patients with IIM to the risk in the general population. RESULTS The incidence of VTEs was higher in patients with IIM than in the general population and was highest in patients who previously had cancer, who were ages >71 years when diagnosed with IIM, or who had dermatomyositis. The overall hazard ratio (HR) of VTE comparing the IIM cohort to the general population was 7.81 (95% CI 4.74, 12.85). The HR was highest the first year after IIM diagnosis, with HR 26.6 (95% CI 10.4, 68.0). CONCLUSION Patients with IIM are at increased risk of VTE compared to the general population, especially during the first year after the diagnosis. Preventive measures should be focused on patients who previously have had cancer, who are ages >71 years when diagnosed, or who have dermatomyositis.

Objectives: To investigate the expression of IL-18 in symptomatic and asymptomatic muscle tissues of patients with PM and DM and the effects of conventional immunosuppressive treatment on such expression. Methods: Two cohorts of patients were included in this study. The first cohort consisted of 10 new-onset myositis patients. IL-18 expression was compared between symptomatic and asymptomatic muscle biopsies that were taken prior to treatment. The second cohort consisted of another 10 patients with repeated muscle biopsies before and after 8 months with conventional immunosuppressive treatment. Using immunohistochemistry, IL-18 expression in muscle tissues was compared before and after treatment. Biopsies from seven healthy individuals were included as controls. Results: IL-18 expression was predominantly localized to inflammatory cells and capillaries in patients and mostly to capillaries in healthy controls. Total IL-18 expression in muscle tissues from the new-onset patients, at both symptomatic and asymptomatic sites, was significantly higher compared with healthy controls (P = 0.007 and P = 0.002) with no statistical difference in appearances between symptomatic and asymptomatic sites. The number of IL-18 positive capillaries was not different among symptomatic, asymptomatic and healthy muscles. Total IL-18 expression appeared lower in biopsies from patients receiving and improving with immunosuppressive treatment, particularly the number of IL-18 positive inflammatory cells but not the number of IL-18 positive capillaries, which was consistent with significantly decreased expression of CD68+ macrophages (P = 0.04). Conclusion: IL-18 is highly expressed in muscle tissue in the context of inflammatory myopathies and based on its plausible effector functions could provide a novel therapeutic target in future.

The idiopathic inflammatory myopathies (IIMs; also known as myositis) are a heterogeneous group of disorders in which a common feature is chronic inflammation of skeletal muscle, leading to muscle weakness. Other organs are frequently affected in IIMs, such as the skin, joints, lungs, gastrointestinal tract and heart, contributing to morbidity and mortality. Currently, IIMs are most often subclassified into polymyositis, dermatomyositis and inclusion body myositis, but this subclassification has limitations as these subgroups often have overlapping clinical and histopathological features, and outcomes vary within the subgroups; additionally, subgroups without considerable myopathy are not included. A new way of subgrouping patients could be on the basis of the presence of myositis-specific autoantibodies. These autoantibodies are associated with distinct clinical features and, moreover, can help to identify subsets of IIMs in which extramuscular symptoms, such as skin manifestations, arthritis or interstitial lung disease, might be the presenting or predominant feature when muscle symptoms are mild or absent. The recognition that subphenotypes with single-organ involvement other than muscles exist is important for identifying patients with early disease, for clinical care demanding team management and in designing clinical studies to improve our understanding of this heterogeneous disease to develop new therapies.

Background We aimed to explore pressure pain sensitivity and the function of segmental and plurisegmental exercise-induced hypoalgesia (EIH) in persons with rheumatoid arthritis (RA) compared with healthy control subjects (HC). Methods Forty-six participants with RA (43 female, 3 male) and 20 HC (16 female, 4 male) participated in the study. Pressure pain thresholds, suprathreshold pressure pain at rest, and segmental and plurisegmental EIH during standardised submaximal contractions were assessed by algometry. Assessments of EIH were made by performing algometry alternately at the contracting (30% of the individual maximum) right m. quadriceps and the resting left m. deltoideus. Results Participants with RA had higher sensitivity to pressure pain (RA, 318 kPa; HC, 487 kPa; p 0.05). Conclusions Our results indicate a generally increased pain sensitivity but normal function of EIH among persons with RA and offer one possible explanation for pain reduction observed in this group of patients following clinical exercise programmes. Trial registration ISRCTN registry, ISRCTN25539102. Retrospectively registered on 4 March 2011.

Objective.To investigate muscle impairment (isometric and dynamic) and disease activity during the first year after diagnosis of polymyositis (PM) and dermatomyositis (DM), and to study the relationship between muscle impairment, patient-reported health, and disease activity.Methods.Seventy-two patients enrolled in the Swedish Myositis Register, 2003–2010, were followed prospectively. The Manual Muscle test (MMT-8; isometric muscle strength), the Functional Index of myositis test (FI-2; dynamic, repetitive muscle function), and disease activity (6-item core set) were retrieved at the time of diagnosis, and after 6 and 12 months. Self-reported health (Medical Outcomes Study Short Form-36; SF-36) was retrieved at 12 months.Results.At the time of diagnosis, median (Q1–Q3) for the FI-2 was 27.2% (7.9–60.5%) of maximal score compared to 93.8% (92.5–98.8%) of maximal MMT-8. At 12 months, the FI-2 and the MMT-8 improved to 29.4% (16.5–60.7%; p < 0.05) and 96.1% (88.1–99.4%), respectively (p < 0.01). At 12 months, 45% of patients improved ≥ 20%, and 27% worsened ≥ 20% in FI-2 score, while 10% improved ≥ 20% in MMT-8. Physician’s global visual analog scale (VAS), Health Assessment Questionnaire, and creatine phosphokinase levels improved significantly at 12 months (p < 0.05–0.001) while patient’s global and extramuscular VAS remained unchanged. The SF-36 physical function correlated strongly with the FI-2 (rs = 0.74; CI 0.55–0.85) and moderately with the MMT (rs = 0.54; CI 0.27–0.73), with lower correlations between muscle function and other SF-36 domains.Conclusion.Patients with PM/DM were characterized by impaired dynamic repetitive muscle function (DRMF) that correlated well with patient-reported physical function. Assessment of DRMF adds information regarding muscle impairment in these patients.

ObjectivesTo study the effects of abatacept on disease activity and on muscle biopsy features of adult patients with dermatomyositis (DM) or polymyositis (PM).MethodsTwenty patients with DM (n=9) or PM (n=11) with refractory disease were enrolled in a randomised treatment delayed-start trial to receive either immediate active treatment with intravenous abatacept or a 3 month delayed-start. The primary endpoint was number of responders, defined by the International Myositis Assessment and Clinical Studies Group definition of improvement (DOI), after 6 months of treatment. Secondary endpoints included number of responders in the early treatment arm compared with the delayed treatment arm at 3 months. Repeated muscle biopsies were investigated for cellular markers and cytokines.Results8/19 patients included in the analyses achieved the DOI at 6 months. At 3 months of study, five (50%) patients were responders after active treatment but only one (11%) patient in the delayed treatment arm. Eight adverse events (AEs) were regarded as related to the drug, four mild and four moderate, and three serious AEs, none related to the drug. There was a significant increase in regulatory T cells (Tregs), whereas other markers were unchanged in repeated muscle biopsies.ConclusionsIn this pilot study, treatment of patients with DM and PM with abatacept resulted in lower disease activity in nearly half of the patients. In patients with repeat muscle biopsies, an increased frequency of Foxp3+ Tregs suggests a positive effect of treatment in muscle tissue.

ObjectivesTo investigate the association between infection or respiratory tract disease and future risk of developing idiopathic inflammatory myopathy (IIM).MethodsA case–control study was performed using Swedish nationwide registers. Adults with newly diagnosed IIM were identified (2002–2011) from the National Patient Register (NPR) and the Swedish Rheumatology Register (n=957). Controls were matched by age, sex and place of residence (n=9476). Outpatient visits and hospitalisations preceding IIM diagnosis indicating infection or respiratory disease were identified from NPR. Conditional logistic regression models were used to calculate OR and 95% CI. Sensitivity analyses were performed by varying the exposure definition, adjusting for previous healthcare consumption and excluding individuals with connective tissue disease, IIM lung phenotype or IIM-associated cancer.ResultsPreceding infections were more common in IIM cases compared with controls (13% vs 9%) and were associated with an increased risk of IIM (OR 1.5, 95% CI 1.2 to 1.9). Gastrointestinal and respiratory tract infections were associated with an increased risk of IIM while cutaneous infections were not.Preceding respiratory tract disease was present in 10% of IIM cases and 4% of controls (OR 2.3, 95% CI 1.8 to 3.0). Both upper and lower respiratory tract diseases were associated with an increased risk of IIM.Variations in exposure and outcome definitions did not greatly affect the results.ConclusionsInfections and respiratory tract diseases are associated with an increased risk of IIM which suggests that the triggering of the immune system may take place outside the skeletal muscle.

PURPOSE OF REVIEW To discuss the needs for international collaborations between investigators in different disciplines working with myositis and with patients with myositis. RECENT FINDINGS Recent advances in detection of several myositis-specific autoantibodies that are associated with distinct clinical phenotypes, will enable studies in new well defined clinically homogenous subgroups of myositis This is likely to lead to development of new information on molecular pathogenesis that might be different in different myositis subgroups. Subgrouping patients according to autoantibody profile may also be important to assess outcome, to identify prognostic biomarkers and in clinical trials. As these are rare disorders international collaboration is essential to enrol large enough cohorts of the subgroups. To facilitate such collaboration we have developed a web-based international myositis register, www.euromyositis.eu, which includes validated outcome measures and patient reported outcome measures. This register is to support research but also to support decision-making in the clinic. We welcome investigators to join the Euromyositis register. SUMMARY Myositis is a heterogeneous disorder with varying treatment response and outcome. There is a high unmet need for new therapies which can only be achieved by increased knowledge on molecular disease mechanisms. Subgrouping patients according to autoantibody profile may be a new way forward to get a better understanding on disease mechanisms and to develop novel therapies.

Objectives To estimate the incidence rate and prevalence of idiopathic inflammatory myopathies (IIMs) in Sweden across clinical subgroups, age, sex, educational level and place of residence and to assess the robustness of register-based case definitions. Methods IIM was identified from the Swedish National Patient Register and the Swedish Rheumatology Quality Register. The base case definition required ⩾2 visits indicating IIM (first ever with a consecutive visit within 1-12 months for incident cases) and the robustness was tested by applying a more liberal and a stricter definition. Results Using the base case definition, 558 incident IIM patients were identified between 2007 and 2011. The incidence was estimated to 11 (13 for women and 9.7 for men) per 1 000 000 person years and was stable across case definitions. Incidence increased with age and peaked at the 50-79 years age groups. No differences were observed between different levels of education and place of residence. We identified 1267 IIM patients on 1 January 2012 corresponding to a prevalence of 14 per 100 000. Conclusion We present nationwide register-based incidence and prevalence estimates for IIM, robust across three different case definitions. In contrast to many other reports, we did not find incidence by age to be bimodal and we found no explanation of incidence variation across education and residency. These register-based case definitions can be included in future population-based studies to better understand disease aetiology, risk factors and comorbidities.

ObjectiveTo develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups.MethodsCandidate variables were assembled from published criteria and expert opinion using consensus methodology. Data were collected from 47 rheumatology, dermatology, neurology and paediatric clinics worldwide. Several statistical methods were used to derive the classification criteria.ResultsBased on data from 976 IIM patients (74% adults; 26% children) and 624 non-IIM patients with mimicking conditions (82% adults; 18% children), new criteria were derived. Each item is assigned a weighted score. The total score corresponds to a probability of having IIM. Subclassification is performed using a classification tree. A probability cut-off of 55%, corresponding to a score of 5.5 (6.7 with muscle biopsy) ‘probable IIM’, had best sensitivity/specificity (87%/82% without biopsies, 93%/88% with biopsies) and is recommended as a minimum to classify a patient as having IIM. A probability of ≥90%, corresponding to a score of ≥7.5 (≥8.7 with muscle biopsy), corresponds to ‘definite IIM’. A probability of ConclusionsThe European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for IIM have been endorsed by international rheumatology, dermatology, neurology and paediatric groups. They employ easily accessible and operationally defined elements, and have been partially validated. They allow classification of ‘definite’, ‘probable’ and ‘possible’ IIM, in addition to the major subgroups of IIM, including juvenile IIM. They generally perform better than existing criteria.

Background: It is known from clinical practice and observational studies that elderly patients with a diagnosis of inflammatory rheumatic diseases (IRD) bear a significantly increased risk for cardiovascular diseases such as coronary artery disease (CAD) and heart failure. The molecular mechanism, however, is still not known. Recently, high mobility group protein B1 (HMGB1), a ubiquitous, highly conserved single polypeptide expressed in all mammal eukaryotic cells, has been identified to mediate myocardial dysfunction in vitro once released from the nuclei of cardiomyocytes. Objective: To investigate whether HMGB1 and its receptors are expressed in cardiac muscles of elderly patients with CAD with or without IRD. Methods: HMGB1 and its 3 well-known receptors, receptor for advanced glycation end products, Toll-like receptor 2 (TLR2), and TLR4, were examined by immunohistochemistry on myocardial biopsy specimens from 18 elderly patients with CAD (10 with IRD, 8 without IRD). Furthermore, total HMGB1 protein levels were measured by Western blot from the cardiac biopsies in 5 patients with and 5 without IRD. Results: Pathologic cytosolic HMGB1 in cardiomyocytes was massively recorded in all patients with IRD, but only slightly expressed in 1 patient without IRD. Total HMGB1 levels were also consistently lower in myocardial muscle biopsies of patients with IRD compared to those without IRD. Furthermore, all 3 HMGB1 receptors were expressed in cardiomyocytes of all patients. Conclusion: The increased cytosolic expression of HMGB1 in cardiomyocytes and the lower total amount of HMGB1 in the cardiac specimens of IRD patients is consistent with a greater release of HMGB1 from the myocardial nuclei in IRD than non-IRD individuals. Thus, the HMGB1 signaling pathways may be more easily activated in elderly CAD patients with concomitant IRD and trigger a detrimental inflammatory process causing severe cardiovascular problems. Therefore, targeting HMGB1 in IRD patients might reduce the risk for cardiovascular events.

Impaired left atrial dynamics and its improvement by guided physical activity reveal left atrial strain as a novel early indicator of reversible cardiac dysfunction in rheumatoid arthritis.

Polymyositis (PM) and dermatomyositis (DM) are chronic autoimmune diseases characterized by skeletal muscle inflammation in which interstitial lung disease (ILD) is found in up to 78% of cases1. Clinically amyopathic DM, a subset of DM without objective muscle weakness, and positivity for antimelanoma differentiation-associated gene 5 autoantibodies (anti-MDA5) are known risk factors for rapidly progressive ILD (RPILD)2,3,4. We present a patient with DM, anti-MDA5 antibodies, and RPILD who successfully underwent a bilateral lung transplantation. This report was approved by the Regional Ethical Committee of Stockholm (2005/792-31/4 and 2011/1374-32). A 38-year-old white man presented with a 4-month history of uncharacteristic skin rash, mild muscle weakness, arthralgia, and exertional dyspnea. His physical examination revealed heliotrope rash, Gottron papules, periungual erythema, mechanic’s hands, small buccal mucosa erosions, fingertip ulcers, and muscle weakness. Cardiopulmonary auscultation was unremarkable. His complete blood count and muscle enzymes were normal. Erythrocyte sedimentation rate was > 90 mm/h, and C-reactive protein was 37 mg/l. He was positive for anti-Ro52 by Immunoblot, but the following were negative: anti-Mi2, anti-SRP, anti-Jo1, anti-PL7, anti-PL12, anti-dsDNA, anti-Sm, anti-Scl-70, anti-Scl-100, anti-SS/B, anti-RNP, rheumatoid factor, antinuclear antibody, and antineutrophil cytoplasmic antibodies. Muscle histopathology showed fiber size variation. A chest computer tomography (CT) showed unspecific basal reticular infiltrates. The patient was started on … Address correspondence to Dr. I.E. Lundberg, Rheumatology Unit, Karolinska University Hospital, Stockholm 17176, Sweden. E-mail: Ingrid.lundberg{at}ki.se.

Myositis is a heterogeneous group of autoimmune diseases encompassing a large spectrum of clinical manifestations including some patients presenting with no muscle involvement. Thus, the clinician must be aware that arthritis, certain cutaneous features, interstitial lung disease (ILD), or dysphagia may dominate the clinical picture. Further, autoantibody detection, muscle immunohistochemistry, and advances in muscle imaging such as MRI have modified the approach to diagnosis and treatment in myositis. In the last decades, several diagnostic and classification criteria were developed for myositis, with varying strengths and limitations. In this chapter, we will review criteria developed for polymyositis (PM), dermatomyositis (DM), immune-mediated necrotizing myopathy (IMNM), overlap myositis (OM), cancer-associated myositis, and sporadic inclusion body myositis (sIBM). We will also discuss the 2017 EULAR/ACR classification criteria for juvenile and adult myositis led by international myositis experts using a robust data-driven process.

Objective.To examine the reproductive pattern of women with idiopathic inflammatory myopathy (IIM) compared to the general population.Methods.Population-based, nationwide registers were used to identify offspring of women with IIM and comparators.Results.Women with IIM in general had similar reproductive patterns as the comparators, whereas in those diagnosed between 26 and 45 years of age, there was an overall trend for fewer children as well as a higher proportion of nulliparity and a lower fertility rate in women with dermatomyositis than their comparators.Conclusion.Reproductive attention should be paid to patients with IIM diagnosed during the childbearing period.

Background: To date, there has not been a Phase 3 study evaluating efficacy and safety of a new chemical entity solely in subjects with dermatomyositis (DM). There is no precedence for design of such a pivotal study, including selection of patients or efficacy outcomes. Objectives: Develop a Phase 3 study design for testing efficacy and safety of lenabasum in DM that would be acceptable to experts and for registration purposes. Methods: Lenabasum is a synthetic, non-immunosuppressive, selective cannabinoid receptor type 2 agonist that activates resolution of innate immune responses. Lenabasum had acceptable safety and tolerability and improved multiple physician-reported and patient-reported efficacy outcomes in a 16-week double-blinded, randomized, placebo-controlled Phase 2 trial in DM subjects with refractory, skin-predominant involvement, as well as in the open-label extension of that study. The Phase 3 trial design was based on Phase 2 data, input from a steering committee of experts in DM clinical trials, and recommendations made by regulatory authorities in the US, EU, Sweden, and Japan. Results: A global, double-blind, randomized, interventional design was chosen to provide an unbiased assessment of the efficacy, safety and tolerability of lenabasum 20 mg bid and 5 mg bid compared to placebo in the treatment of DM. A 52-week treatment duration was selected to provide safety and efficacy data adequate to support chronic treatment. Subjects with DM were classified by Peter and Bohan criteria or the 2017 EULAR/ACR classification criteria for DM (both amyopathic DM and classic DM). Subjects will be required to have active disease, as assessed by an expert and based on a range of muscle, skin, and other disease manifestations. Subjects must be on stable doses of current DM treatments with any background immunosuppressive medications allowed except prednisone ≥ 20 mg per day or equivalent. This inclusivity allows testing of efficacy and safety of lenabasum in the setting of current treatment practice and reduces risk of disease flare early in the study. The primary efficacy outcome is change from baseline in 2016 ACR/EULAR Total Improvement Score (TIS) for DM and polymyositis. This composite outcome has six domains that broadly capture improvement in disease activity, is relevant to the range of manifestations in DM, and is applicable to the assessment of efficacy in the target patient population. Secondary efficacy outcomes were chosen to assess how the subject functions (Short Form – 36 physical functioning domain), major organ involvement (MMT-8, CDASI activity score, and a new Investigator Global Assessment scale of skin activity designed specifically for this study), and lung function (FVC). Change in oral corticosteroid dose also will be captured. Conclusion: To our knowledge, this is the first Phase 3 study in DM with a new molecular entity. As such, agreement with experts and regulatory authorities on design represents a step forward in the development pathway of new treatments for DM. Disclosure of Interests: Victoria Werth: None declared, Chester V Oddis Grant/research support from: Support of clinical research from Roche/Genentech and BMS, Consultant for: Corbus: Previous Steering Committee consultation; No longer being paid as a Corbus consultant, Ingrid E. Lundberg Grant/research support from: Dr. Lundberg has received honoraria from Bristol Myers Squibb and MedImmune and is currently receiving a research grant from Bristol Myers Squibb and from Astra Zeneca., Consultant for: She is a scientific advisor for Bristol Myers Squibb, and aTyr, David Fiorentino Grant/research support from: Pfizer - to support analysis of human tissue from patients with dermatomyositis, Consultant for: Pfizer—design and operation of clinical trial in DM Corbus—design of clinical trial in DM 23 and me—ad hoc consulting Admiryx—ad hoc consulting Janssen—SAB for PSOLAR database Beigene—paid consultant, Caitlin Cornwall Shareholder of: Corbus Pharmaceuticals, Inc., Employee of: Corbus Pharmaceuticals, Inc., Nancy Dgetluck Employee of: Corbus Pharmaceuticals, Inc., Scott Constantine Shareholder of: Corbus Pharmaceuticals, Inc., Employee of: Corbus Pharmaceuticals, Inc., Barbara White Shareholder of: Corbus Pharmaceuticals, Inc., Employee of: Corbus Pharmaceuticals, Inc.

Background: Thromboembolic cardiovascular diseases (CVD), affecting both arterial and venous sides, are one of the leading causes of death in patients with Idiopathic Inflammatory Myopathies (IIM), with highest peak of mortality within the first year after diagnosis (1). Objectives: To assess the prevalence of traditional and disease-related risk factors for arterial and venous thrombotic events (TE) in patients with IIM by comparing those reporting TE (cases) with those without history of TE (comparators). To compare clinical characteristics, autoantibody profile inclusive antiphospholipid antibodies (aPL) and serum levels of adhesion molecules (VCAM, ICAM and e-selectin) between cases and comparators as well as between cases reporting arterial vs venous TE. Methods: Using national and international registries, and medical charts, we identified 58 cases and 195 comparators with IIM followed at Karolinska University Hospital between 1993 and 2014. Information on gender, age at the time of diagnosis, IIM subgroup, presence of interstitial lung disease (ILD), myositis specific antibodies (MSAs), was retrospectively collected. Information on traditional risk factors for arterial and venous TE (essential hypertension, diabetes, dyslipidemia, smoking, malignancy) was retrieved for both groups. Serum levels of aPL and adhesion molecules were analyzed in stored sera from the time of diagnosis in both groups, before TE in cases and in 40 age and gender matched heathy controls (HC). Results: One out of 5 IIM patients (22,92%) had suffered from at least one TE, which was observed especially during the first 5 years after diagnosis. Myocardial infarction was the most frequent TE, followed by pulmonary embolism and deep venous thrombosis. In the multivariate analysis, male gender and older age were independent risk factors for TE. Essential hypertension had statistically significant higher prevalence in cases than comparators. Arterial TE was more common in polymyositis, while venous TE occurred more frequently in patients with dermatomyositis, history of malignancy and in those with MSAs. At time of IIM diagnosis, the prevalence of aPL was 6% with no difference between cases and comparators. Significantly higher levels of VCAM and ICAM were obtained in IIM patients compared to HC (Fig.1 and Fig.2). ICAM levels were found significantly higher in comparators than cases (Fig.2). Lower levels of e-selectin were associated with higher odds of developing TE, especially in males and older patients, with no difference between arterial and venous TE (Fig.3). Conclusion: A high risk of arterial and venous TE should be taken into account in patients with IIM, particularly close to time of diagnosis, with extra attention in male patients and older individuals. Preventive measures should be considered especially in patients with concomitant essential hypertension and malignancy. Lower serum levels of e-selectin might predict TE in IIM patients but the mechanism for this risk factor is not known. Reference [1] Dobloug GC, Svensson J, Lundberg IE, Holmqvist M. Mortality in idiopathic inflammatory myopathy: results from a Swedish nationwide population-based cohort study. Ann Rheum Dis. 2018;77(1):40-7. Disclosure of Interests: Antonella Notarnicola: None declared, Simone Barsotti: None declared, Linnea Nasman: None declared, Quan Tang: None declared, Marie Holmqvist: None declared, Ingrid E. Lundberg Grant/research support from: Dr. Lundberg has received honoraria from Bristol Myers Squibb and MedImmune and is currently receiving a research grant from Bristol Myers Squibb and from Astra Zeneca., Consultant for: She is a scientific advisor for Bristol Myers Squibb, and aTyr, Aleksandra Antovic: None declared

Background: Anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab) is one of the most clinically important myositis specific antibodies. It has been found to be associated with severe cutaneous and pulmonary complications. Nonetheless, there appears to be geographical variations in the prevalence and phenotypic presentation of the antibody [1]. We conducted the first comparative study of two ethno-geographically different idiopathic inflammatory myopathy (IIM) cohorts focusing on anti-MDA5 Ab, using standardized classification criteria, antibody detection methods and clinical features assessment. Objectives: The objectives of the study were to compare the prevalence of the anti-MDA5 Ab and its associated clinical features between Chinese IIM patients in Hong Kong and Caucasian patients in Sweden. Methods: This multicenter retrospective cohort study was conducted on IIM patients followed up in the rheumatology clinic or admitted to the rheumatology wards of the participating hospitals in Hong Kong and Sweden with anti-MDA5 Ab tested between September 2015 and August 2018. The diagnosis of IIM was based on the 2017 European League Against Rheumatism/American College of Rheumatology Classification Criteria with definite or probable cases being included. Demographics and clinical features were collected by reviewing the medical records. A commercial line blot immunoassay kit (EUROIMMUN) was used to detect the anti-MDA5 autoantibodies. Results: Altogether, 409 patients with IIM (Sweden: 206, Hong Kong: 203) were recruited. The Swedish patients were generally older (mean age 58.1 vs 51.5 years, p Conclusion: The distinct clinical profiles identified in the Chinese and Swedish IIM patients with anti-MDA5 Ab could depend on different genetic or environmental factors, and may enhance our knowledge about the clinical utility of the antibody and help deciphering the pathogenesis of this complex disease. Reference [1] So H, Ip R, Wong V, Yip R. Analysis of anti-melanoma differentiation-associated gene 5 antibody in Hong Kong Chinese patients with idiopathic inflammatory myopathies: diagnostic utility and clinical correlations. Int J Rheum Dis2018;21(5):1076-1081. Disclosure of Interests: Ho SO: None declared, Tak Lung Victor Wong: None declared, Maryam Dastmalchi: None declared, Valerie Leclair: None declared, Fabricio Espinosa-Ortega: None declared, Ingrid E. Lundberg Grant/research support from: Dr. Lundberg has received honoraria from Bristol Myers Squibb and MedImmune and is currently receiving a research grant from Bristol Myers Squibb and from Astra Zeneca., Consultant for: She is a scientific advisor for Bristol Myers Squibb, and aTyr

Background The current biomarkers for the diagnosis and monitoring of diseased and injured skeletal muscles, such as creatine kinase (CK), have limited tissue specificity and incapability to differentiate between pathological and physiological changes. Thus, new biomarkers with improved diagnostic certainty are needed. Skeletal troponin I (skTnI) is a promising new biomarker for injured and diseased skeletal muscle tissue. Although studies have reported that circulating skTnI levels are elevated in response to trauma, exercise and various muscular diseases (1), its clinical utility to serve as a diagnostic indicator has largely been unexplored. Objectives Our aim was to develop and validate a novel assay for skTnI, and to assess its clinical performance with idiopathic inflammatory myopathy (IIM) patients. Methods A two-step fluoroimmunoassay was used to analyze the levels of skTnI in samples from healthy reference individuals (n=125), trauma patients (n=151), and patients with IIM (n=94). Later, skTnI and CK levels in patients with IIM were compared according to their disease activity status (active, pre-active or stable). Results The limit of detection was 1.2 ng/ml, and the upper reference limit (90th percentile) was 5.4 ng/ml. The median skTnI concentrations were Conclusion With the developed skTnI assay, IIM patients were identified from healthy individuals and from patients with traumatic muscular injuries. Also, skTnI was shown to outperform CK in detecting IIM patients in different disease activity statuses. Reference [1] Kiely PDW, Bruckner FE. Serum skeletal troponin I in inflammatory muscle disease: Relation to creatine kinase, CKMB and cardiac troponin I. Ann Rheum Dis 2000;59:750–1. Disclosure of Interests Katriina Bamberg: None declared, Laura Mehtala: None declared, Olli Arola: None declared, Seppo Laitinen: None declared, Pauliina Nordling: None declared, Marjatta Strandberg: None declared, Niko Strandberg: None declared, Johanna Paltta: None declared, Markku Mali: None declared, Fabricio Espinosa-Ortega: None declared, Laura Pirila Consultant for: Abbvie, Novartis, Eli Lilly, MSD Finland, Pfizer, UCB, Roche, Jansen- Cilag, Sandoz, Speakers bureau: Pfizer, Ingrid E. Lundberg Grant/research support from: Dr. Lundberg has received honoraria from Bristol Myers Squibb and MedImmune and is currently receiving a research grant from Bristol Myers Squibb and from Astra Zeneca., Consultant for: She is a scientific advisor for Bristol Myers Squibb, and aTyr, Tanja Savukoski: None declared, Kim Pettersson: None declared

Background: Antibodies targeting a novel and muscle-specific autoantigen, the Four-and-a-half-LIM-domain 1 (anti-FHL1), have been identified in patients with idiopathic inflammatory myopathies (IIM). Objectives: The aim of this project was to evaluate when anti-FHL1 autoantibodies are present in the course of the disease and if autoantibody titers vary over time. Methods: The anti-FHL1 antibody status was obtained from a previous serological cross-sectional analysis from where we selected sera from IIM anti-FHL1+ patients (n=25) and sex and age matched sera from IIM anti-FHL1-patients (n=51), and healthy controls (HCs, n=50). Levels of anti-FHL1+ autoantibodies were evaluated by ELISA. Patients included in the study had at least one sample available at time of diagnosis and one consecutive serum sample within an interval of 36 months. All patients were followed at the Division of Rheumatology, Karolinska University Hospital from January 1982 to December 2017. HCs sera collected at a single time point were tested. Results: In the IIM group we included 76 patients with a total of 320 serum samples. Median follow-up time was 108 months, with median of 4 samples available per patient. In total, we identified the presence of anti-FHL1+ antibodies in n=31 IIM patients, corresponding to the group of anti-FHL1+ (n=25) and in anti-FHL1- (n=6) from the cross-sectional analyses. One HC had positive anti-FHL1 titers. We subdivided the patients into 4 groups: anti-FHL1+: “highly positive” (O.D.>1, n=11), “intermediate positive” (1>O.D.>0.75, n=6), “baseline negative” that seroconverted (O.D.>0.75, n= 14), and one anti-FHL1 “negative” group. All groups were compared by given OD medians at each of the point of observation. Highly positive patients had persisting high anti-FHL1 titers during the follow-up; on the contrary, both intermediate positive and baseline negative groups were fluctuating around the cut-off point. Eight of 14 (57%) patients from the group “baseline negative” seroconverted to anti-FHL1+ within the first 36 months. The anti-FHL1 “negative” group presented constant low antibody titers during the longitudinal follow-up. Conclusion: Anti-FHL1 antibody positivity was detected in patients with high titers of anti-FHL1+ autoantibodies in the first available serum sample or developed within the first 36 months after diagnosis and persisted over many years. A group of patients with intermediate levels had fluctuating positivity over the years. It is still unknown if the anti-FHL1 antibody titer is a marker of prognosis and/or damage in IIM; thus, clinical data needs to be addressed, and in-vitro experiments and biochemical characterization of this autoantibody are still required. Disclosure of Interests: Angeles Shunashy Galindo-Feria: None declared, Eliska Divisova: None declared, Catia Fernandes-Cerqueira: None declared, Maryam Dastmalchi: None declared, Edvard Wigren: None declared, Susanne Graslund: None declared, Ingrid E. Lundberg Grant/research support from: Dr. Lundberg has received honoraria from Bristol Myers Squibb and MedImmune and is currently receiving a research grant from Bristol Myers Squibb and from Astra Zeneca., Consultant for: She is a scientific advisor for Bristol Myers Squibb, and aTyr

Background Idiopathic inflammatory myopathies (IIM) are rare devastating diseases characterized by progressive muscle weakness and muscle fatigue. IIM frequently affects other organs pointing to IIM as a systemic inflammatory disease. Cardiac involvement is associated with poor prognosis. The symptoms are often subclinical and therefore overlooked. QTc prolongation has been detected in patients with systemic sclerosis (SSc). Autoantibodies are important diagnostic tools to confirm IIM and are present in approx. 60% of IIM patients. Autoantibodies are increasingly being recognized as markers for specific organ involvement. A biomarker for cardiac involvement has yet to be elucidated. Objectives The aim is to generate new knowledge about cardiac involvement in IIM detected by electrocardiography (ECG) and to evaluate possible associations between autoantibodies and cardiac involvement detected on ECG in a cohort of IIM patients compared with ECG changes in a cohort of SSc patients. Methods In a Scandinavian cohort, 263 IIM patients (130 polymyositis patients, 77 dermatomyositis patients, and 56 inclusion body myositis patients) and 102 SSc patients were investigated by ECG and basic cardiovascular and disease specific assessments according to international guidelines. IIM patients were tested for myositis specific autoantibodies (MSAs; anti-Jo-1, anti-PL-7, anti-PL-12, anti-OJ, anti-EJ, anti-SRP, anti-Mi-2, anti-MDA5, anti-TIF1 γ, anti-NPX2, anti-SAE1, anti-HMGCR) and myositis associated autoantibodies (MAAs; anti-PM/Scl75, anti-PM/Scl100, anti-Ro52, anti-Ku, anti-cN1A). Results Twenty two IIM patients (8.49%) had abnormal QRS duration versus one SSc patient (1.06%) (P = 0.012). SSc patients had significantly longer QTc duration than IIM patients (QTc = 432.7 ms ± 22.2 and 426.4 ms ± 23.6, respectively) (P = 0.03). Multivariate regression analysis revealed that increased C-reactive protein (CRP) (P = 0.008), gender (P = 0.002), and hypertension (P = 0.007) were associated with QTc duration in IIM patients. Likewise, pulmonary arterial hypertension was associated with QTc duration (P In analysis of pooled data for IIM patients and SSc patients, factors associated with QTc duration were increased CRP (P = 0.005), gender (P = 0.001), and hypertension (P = 0.01). Conclusion Both IIM patients and SSc patients had ECG changes though no particular pattern was shown. The findings support our hypothesis on cardiac involvement in IIM patients. No significant association was found between presences of either myositis specific or myositis associated autoantibodies and ECG changes. This could be due to the relatively low number of each autoantibody. There is a need to conduct larger prospective studies to identify a possible autoantibody for cardiac involvement in IIM. Acknowledgement The authors would like to thank all participating patients and the study personnel at the including centres. Disclosure of interests Sine Sondergaard Korsholm: None declared, Maryam Dastmalchi: None declared, John Bonde Knudsen: None declared, axel Cosmus Diederichsen: None declared, ingrid E. Lundberg Grant/research support from: Dr. Lundberg has received honoraria from Bristol Myers Squibb and MedImmune and is currently receiving a research grant from Bristol Myers Squibb and from astra Zeneca., Consultant for: She is a scientific advisor for Bristol Myers Squibb, and aTyr, Daniel C. Andersson: None declared, Nanna Witting: None declared, Soren Jacobsen: None declared, Tina Friis Grant/research support from: anti cN-1A ELISA kits and EUROLINE autoimmune inflammatory Myopathies 16 aG kits have been provided for a project free of charge from Euroimmun., Markus E. Krogager: None declared, Louise Pyndt Diederichsen: None declared

Background The current biomarkers for diagnosis and monitoring of injured and diseased skeletal muscles, such as creatine kinase (CK), have limited tissue specificity and incapability to differentiate between pathological and physiological changes. Thus, new biomarkers with improved diagnostic accuracy are needed. Our aim was to develop and validate a novel assay for skeletal troponin I (skTnI), and to assess its clinical performance in patients with idiopathic inflammatory myopathies (IIM). Methods A two-step fluoroimmunoassay was used to analyze samples from healthy reference individuals (n = 140), patients with trauma (n = 151), and patients with IIM (n = 61). Results The limit of detection was 1.2 ng/mL, and the upper reference limit (90th percentile) was 5.2 ng/mL. The median skTnI concentrations were Conclusions With the skTnI assay, patients with IIM were identified from healthy individuals and from patients with traumatic muscular injuries. When compared to CK, skTnI appeared to be more accurate in managing patients with low-grade IIM disease activities. The developed assay serves as a reliable analytical tool for the assessment of diagnostic accuracy of skTnI in the diagnosis and monitoring of myopathies.

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.

It is with great interest we read the letter titled ‘Detection of myositis-specific antibodies’ by Dr Vulsteke et al 1 published in the Annals of the Rheumatic Diseases . The authors analysed the presence of myositis-specific autoantibodies in patients with idiopathic inflammatory myopathies (IIM) and in controls consisting of patients with other inflammatory conditions and blood donors. These analyses were performed using three different assays. In addition, the authors studied the association of autoantibody positivity from the different assays with specific clinical phenotypes in patients with IIM. In conclusion differences in specificities between assay manufacturers and between individual antibodies were found. The authors point to the fact that autoantibody data, namely anti-Jo-1 autoantibody positivity, were included in the 2017 European League Against Rheumatism/American …

Objective.Patient-reported outcome measures (PROM) that incorporate the patient perspective have not been well established in idiopathic inflammatory myopathies (IIM). As part of our goal to develop IIM-specific PROM, the Outcome Measures in Rheumatology (OMERACT) Myositis special interest group sought to determine which aspects of disease and its effects are important to patients and healthcare providers (HCP).Methods.Based on a prior qualitative content analysis of focus groups, an initial list of 24 candidate domains was constructed. We subsequently conducted an international survey to identify the importance of each of the 24 domains to be assessed in clinical research. Patients with IIM, their caregivers, and HCP treating IIM completed the survey.Results.In this survey, a total of 638 respondents completed the survey, consisting of 510 patients, 101 HCP, and 27 caregivers from 48 countries. Overall, patients were more likely to rank “fatigue,” “cognitive impact,” and “difficulty sleeping” higher compared with HCP, who ranked “joint symptoms,” “lung symptoms,” and “dysphagia” higher. Both patients and providers rated muscle symptoms as their top domain. In general, patients from different countries were in agreement on which domains were most important. One notable exception was that patients from Sweden and the Netherlands ranked lung symptoms significantly higher compared to other countries including the United States and Australia (mean weighted rankings of 2.86 and 2.04 vs 0.76 and 0.80, respectively; p < 0.0001).Conclusion.Substantial differences exist in how IIM is perceived by patients compared to HCP, with different domains prioritized. In contrast, patients’ ratings across the world were largely similar.

Objectives To determine prevalence and co-existence of myositis specific autoantibodies (MSAs) and myositis associated autoantibodies (MAAs) and associated clinical characteristics in a large cohort of idiopathic inflammatory myopathy (IIM) patients. Methods Adult patients with confirmed IIM recruited to the EuroMyositis registry (n = 1637) from four centres were investigated for the presence of MSAs/MAAs by radiolabelled-immunoprecipitation, with confirmation of anti-MDA5 and anti-NXP2 by ELISA. Clinical associations for each autoantibody were calculated for 1483 patients with a single or no known autoantibody by global linear regression modelling. Results MSAs/MAAs were found in 61.5% of patients, with 84.7% of autoantibody positive patients having a sole specificity, and only three cases (0.2%) having more than one MSA. The most frequently detected autoantibody was anti-Jo-1 (18.7%), with a further 21 specificities each found in 0.2–7.9% of patients. Autoantibodies to Mi-2, SAE, TIF1, NXP2, MDA5, PMScl and the non-Jo-1 tRNA-synthetases were strongly associated (p, Highlights • Myositis specific autoantibodies very rarely coexist in the one individual allowing endotypes to be more precisely defined. • The association of anti-TIF1 and cancer-associated myositis is confirmed with a cut-off age of over 58 years. • In a large combined European myositis cohort associations of anti-SRP with carditis and anti-Mi-2 with cancer have emerged. • Myositis associated autoantibodies are strongly associated with having myositis in association with another connective tissue disease.

Background:Smoking is associated with worse treatment response1 and higher mortality2 in rheumatoid arthritis (RA).Objectives:To assess the effect of a smoking cessation intervention in a rheumatology setting.Methods:We designed a smoking cessation interventional feasibility study. RA patients who were active smokers were asked to participate. A nurse-delivered program consisting of behavioural changes techniques and voluntary pharmacotherapy was executed. The intervention was at baseline and at several time points during a 24 month period, based on the individual patient’s needs. Smoking status was collected at baseline, 6, 12, 18 and 24 months. Smoking cessation was verified by 7-days abstinence and carbon monoxide in expiratory air. The main outcome was the proportion of patients who quit smoking (QS) at 24 months.Results:A total of 99 patients were included in the study between 2011-2020. Median (IQR) age of patients was 58 (50 - 64), 69 % were female and 82% were RF and/or ACPA positive. 59% of patients had a newly diagnosed RA, (included from the early RA-track), with a median (IQR) symptom duration of 5 (2-9,5) months. Patients with established RA 41% (included from regular rheumatology department) had a median disease duration of 4 (2-8) years. After 24 months 21% quit smoking (QS) (Table 1). At months 6, 12, 18 and 24 the proportion of QS patients was 12, 13, 15 and 21, respectively. The proportion of QS patients at month 12 and continued being in the QS group throughout the study period was 10%. In the subgroup of patients who continued smoking (CS) the median number of cigarettes per day was significantly reduced at all follow-up time points (Table 1). No significant differences were observed at baseline between CS at 24 months and QS, apart from the proportion of patients who reported anxiety (extracted from EQ-5D and defined as absent or present), which was significantly fewer in the QS group (Table). In the QS group at month 24, the proportion of females was numerically lower compared to CS (52% vs. 73%, p=0.07).Table 1.Baseline demographical, clinical characteristics and number of cigarettes at specific time-points for patients who were non-smokers (QS) and smokers (CS) at month 24.QSN=21 (21%)CSN=78 (79%)Difference between QS and CS(p-value)Age*(median, IQR)60 (53-62)57 (50-64)0.94Symptom duration in early RA patients (months) (median, IQR)6 (2-12)4.5 (2-8.5)0.49Disease duration of patients with established RA (years) (median, IQR)8 (3.5-16.5)3 (2-6)0.12% females52730.07% RF and/or ACPA positive85810.70DAS28* (median, IQR)4.24 (3.13-5.72)4.11 (2.88-5.36)0.69HAQ* (median, IQR)0.75 (0.25 -1.38)0.88 (0.38-1.25)0.74VAS pain* (median, IQR)46.0 (11-60)34.5 (12-70)0.90% of patients with reported anxiety* (part of EQ5D)28580.02Smoking duration (years)(median, IQR)40 (30-50)40 (34-49)0.92Median number of cigarettes per day-at baseline10 (7-15)12 (10-20)0.22-at 6 months0 (0-3)6 (3-10)0.006-at 12 months0 (0-5)6 (3-10)0.0003-at 18 months0 (0-0)6 (2-10)0.00-at 24 months0 (0-0)6 (3-10)0.00*=measured at baselineConclusion:Smoking cessation intervention in a rheumatology clinic setting may facilitate reduced smoking or complete cessation in patients with RA. Patient who did not report anxiety were more likely to quit smoking.References:[1]Saevarsdottir, S., et al (2011). Patients with early rheumatoid arthritis who smoke are less likely to respond to treatment with methotrexate and tumor necrosis factor inhibitors: observations from the Epidemiological Investigation of Rheumatoid Arthritis and the Swedish Rheumatology Register cohorts. Arthritis Rheum, 63(1), 26-36.[2]Joseph, R´., et al (2016) Smoking-Related Mortality in Patients With Early Rheumatoid Arthritis: A Retrospective Cohort Study Using the Clinical Practice Research Datalink Arthritis Care Res (Hoboken) 68 (11) 1598-1606Acknowledgements:This study was partly funded by grants from Swedish Reumatism Association.Disclosure of Interests:Marie-Louise Karlsson Speakers bureau: MLK has recivied fee form Novartis Sverige AB, Grant/research support from: MLK had recivied finical grants from Novartis Sverige. Abbvie has fincial support brochure wich was used in the study, Katarina Hertzberg-Nyquist: None declared, Saedis Saevarsdottir Employee of: S is a part-time employee of deCODE genetics Inc., unrelated to this work., Ingrid E. Lundberg Consultant of: I Lundberg har recieved consulting fees from Corbus Pharmaceutical, EMD Serono Research & Development Institute, Octapharma AG, Orphazyme, Janssen, Kezar Life Sciences Inc., Ingrid Demmelmaie: None declared, Susanne Pettersson: None declared, Katerina Chatzidionysiou Consultant of: KC has received consultancy fees from Eli Lilly, AbbVie and Pfizer.

We have with interest read the ‘Correspondence on “EULAR/ACR classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups” by Irfan et al ’ with subtitle: improving the subtyping of dermatomyositis in the 2017 EULAR/ACR classification criteria for juvenile and adult idiopathic inflammatory myositis: value of non-classic cutaneous findings, to be published in Annals of the Rheumatic Diseases .1 Here, the authors present performance of the EULAR/ACR classification criteria2 in a cohort from India of 26 consecutive adult patients with idiopathic inflammatory myopathies (IIM). Patients with characteristic skin rashes (those included in the EULAR/ACR criteria as well as in the older Bohan and Peter criteria) were classified as having dermatomyositis (DM). The remainder of the patients were classified as polymyositis (PM) (n=12). All patients had documented muscle weakness. Of the 12 patients classified as PM, seven had non-classical skin rash such as generalised erythematous rash or malar rash and had been given the diagnosis DM by their physician. Moreover, five of these seven patients had myositis-associated autoantibodies that largely supported the clinical diagnosis of DM. The authors conclude that the sensitivities of Gottron’s papules (60%–80%) and heliotrope rash (30%) are low. The authors suggest …

Objective. Inflammatory T cell infiltrates in the skeletal muscle tissue of patients with polymyositis are dominated by CD28-negative effector (CD28(null)) T cells of both the CD4 and CD8 lineage. ...

Objective Endurance exercise demonstrates beneficial effects in polymyositis/dermatomyositis (PM/DM); however, the molecular effects of exercise on skeletal muscle are incompletely understood. We undertook this controlled pilot study to investigate the effects of a 12-week endurance exercise training program on the molecular profile of skeletal muscle in patients with established PM/DM compared to a nonexercised control group of patients with established PM/DM. Methods Fifteen patients (7 in the exercise group and 8 in the control group) with paired baseline and 12-week follow-up muscle biopsy samples were included. Messenger RNA expression profiling, mass spectrometry–based quantitative proteomics, and immunohistochemical analyses were performed on muscle biopsy samples to determine molecular adaptations associated with changes in clinical measurements induced by endurance exercise. Results Compared to the control group, the exercise group improved in minutes of cycling time (P

Objective Cardiac events are a major cause of death in patients with idiopathic inflammatory myopathies. The study objective was in a controlled setting to describe cardiac abnormalities by noninvasive methods in a cohort of patients with polymyositis (PM) or dermatomyositis (DM) and to identify predictors for cardiac dysfunction. Methods In a cross-sectional study, 76 patients with PM/DM and 48 matched healthy controls (HCs) were assessed by serum levels of cardiac troponin I, electrocardiography, Holter monitoring, echocardiography with tissue Doppler imaging, and quantitative cardiac 99mTc-pyrophosphate (99mTc-PYP) scintigraphy. Results Compared to HCs, patients with PM/DM more frequently had left ventricular diastolic dysfunction (LVDD) (12% versus 0%; P = 0.02) and longer QRS and QT intervals (P = 0.007 and P < 0.0001, respectively). In multivariate analysis, factors associated with LVDD were age (P = 0.001), disease duration (P = 0.004), presence of myositis-specific or -associated autoantibodies (P = 0.05), and high cardiac 99mTc-PYP uptake (P = 0.006). In multivariate analysis of the pooled data for patients and HCs, a diagnosis of PM/DM (P < 0.0001) was associated with LVDD. Conclusion Patients with PM or DM had an increased prevalence of cardiac abnormalities compared to HCs. LVDD was a common occurrence in PM/DM patients and correlated to disease duration. In addition, the association of LVDD with myositis-specific or -associated autoantibodies and high cardiac 99mTc-PYP uptake supports the notion of underlying autoimmunity and myocardial inflammation in patients with PM/DM.

Background: There is a paucity of data on mortality and causes of death (CoDs) in patients with sporadic inclusion body myositis (sIBM), a rare, progressive, degenerative, inflammatory myopathy that typically affects those aged over 50 years. Objective: Based on patient records and expertise of clinical specialists, this study used questionnaires to evaluate physicians’ views on clinical characteristics of sIBM that may impact on premature mortality and CoDs in these patients. Methods: Thirteen physicians from seven countries completed two questionnaires online between December 20, 2012 and January 15, 2013. Responses to the first questionnaire were collated and presented in the second questionnaire to seek elaboration and identify consensus. Results: All 13 physicians completed both questionnaires, providing responses based on 585 living and 149 deceased patients under their care. Patients were reported to have experienced dysphagia (60.2%) and injurious falls (44.3%) during their disease. Over half of physicians reported that a subset of their patients with sIBM had a shortened lifespan (8/13), and agreed that bulbar dysfunction/dysphagia/oropharyngeal involvement (12/13), early-onset disease (8/13), severe symptoms (8/13), and falls (7/13) impacted lifespan. Factors related to sIBM were reported as CoDs in 40% of deceased patients. Oropharyngeal muscle dysfunction was ranked as the leading feature of sIBM that could contribute to death. The risk of premature mortality was higher than the age-matched comparison population. Conclusions: In the absence of data from traditional sources, this study suggests that features of sIBM may contribute to premature mortality and may be used to inform future studies.

Background High-intensity resistance training is unexplored in people with multiple sclerosis. Objectives To evaluate effects of high-intensity resistance training on immune markers and on measures of mood, fatigue, health-related quality of life, muscle strength, walking and cognition. Further, to describe participants' opinion and perceived changes of the training. Methods Twenty patients with relapsing–remitting multiple sclerosis performed high-intensity resistance training at an intensity of 80% of one-repetition maximum, twice a week for 12 weeks. Blood and optional cerebrospinal fluid samples, and data on secondary outcome measures were collected before and after intervention. A study-specific questionnaire was used for capturing participants' opinion. Results Seventeen participants completed the study. Plasma cytokine levels of tumor necrosis factor were significantly decreased post-intervention (p = 0.001). Exploratory cytokine analyses in cerebrospinal fluid (n = 8) did not reveal major changes. Significant and clinically important improvements were found in fatigue (p = 0.001) and health-related quality of life (p = 0.004). Measures of mood (p = 0.002), muscle strength (p ≤ 0.001), walking speed (p = 0.013) and cognition (p = 0.04) were also improved. A majority of participants evaluated the training as very good and perceived changes to the better. Conclusion High-intensity resistance training in persons with relapsing remitting multiple sclerosis with low disability had positive effects on peripheral pro-inflammatory cytokine levels, led to clinically relevant improvements in measures of fatigue and health-related quality of life, and was well tolerated. These results provide a basis for a larger randomized trial.

Polymyositis (PM) and dermatomyositis (DM) are rare, chronic inflammatory diseases leading to muscle weakness and low muscle endurance. The muscle weakness may lead to restrictions in daily activities and low health-related quality of life.This study aimed to investigate the work situation, work ability, work-related risk factors, and influence of the physical and psycho-social work environment in patients with PM and DM.Patients with PM/DM were assessed using the Work Ability Index (WAI), and the Work Environment Impact Scale (WEIS).Forty-eight patients (PM n = 25 and DM n = 23) participated (women/men: 29/19) with a mean age of 54 years (range 28-67 years, SD.10) and mean disease duration of nine years (SD.9). Forty-four percent worked full-time, 31% part-time and 25% were on full-time sick leave. More than 50% self-rated work ability as "poor" or "less good". Physically strenuous work components were present "quite to very often" in 23-79% and more in patients on sick leave ≥ 2 years. For those working, the interfering factors in the work environment concerned task and time demands. Supporting factors concerned meaning of work, interactions with co-workers and others. Self-rated work ability correlated moderately-highly positive with percentage of full-time employment, work-related risk factors and opportunities and constraints in the work environment.Poor self-rated work ability is common in patients with PM/DM indicating a need to identify interfering risk factors and support patients to enhance work performance.

Knowledge on idiopathic inflammatory myopathy (IIM) has evolved with the identification of myositis-associated and myositis-specific antibodies, development of histopathological classification and the recognition of how these correlate with clinical phenotype and response to therapy. In this paper, we outline key advances in diagnosis and histopathology, including the more recent identification of antibodies associated with immune-mediated necrotising myopathy (IMNM) and inclusion body myositis (IBM). Ongoing longitudinal observational cohorts allow further classification of these patients with IIM, their predicted clinical course and response to specific therapies. Registries have been developed worldwide for this purpose. A challenging aspect in IIM, a multisystem disease with multiple clinical subtypes, has been defining disease status and clinically relevant improvement. Tools for assessing activity and damage are now recognised to be important in determining disease activity and guiding therapeutic decision-making. The International Myositis Assessment and Clinical Studies (IMACS) group has developed such tools for use in research and clinical settings. There is limited evidence for specific treatment strategies in IIM. With significant development in the understanding of IIM and improved classification, longitudinal observational cohorts and trials using validated outcome measures are necessary, to provide important information for evidence-based care in the clinical setting.