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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.

The idiopathic inflammatory myopathies (IIM) are heterogeneous diseases, thought to be initiated by immune activation in genetically predisposed individuals. In this study we imputed variants from the Immunochip array using a large reference panel to fine-map associations and identify novel associations in IIM.We analysed 2,565 Caucasian IIM samples collected through the Myositis Genetics Consortium (MYOGEN) and 10,260 ethnically-matched controls. We imputed 1,648,116 variants from the Immunochip array using the Haplotype Reference Consortium panel and conducted association analysis on IIM, and clinical and serological subgroups.The human leukocyte antigen (HLA) locus was consistently the most significantly associated region. Four non-HLA regions reached genome-wide significance, three in the whole IIM cohort (SDK2 and LINC00924 - both novel, and STAT4), with evidence of independent variants in STAT4, and NAB1 in the polymyositis (PM) subgroup. We also found suggestive evidence of association with loci previously associated with other autoimmune rheumatic diseases (TEC and LTBR). We identified more significant associations than those previously reported in IIM, for STAT4 and DGKQ in the total cohort, for NAB1 and FAM167A-BLK loci in PM, and CCR5 in inclusion body myositis. We found enrichment of variants among DNase I hypersensitivity sites and histone marks associated with active transcription within blood cells.We report novel and strong associations in IIM and PM, and localise signals to single genes and immune cell types. This article is protected by copyright. All rights reserved.

Published by Elsevier Ltd., Background: Differences in the distribution of individual-level clinical risk factors across regions do not fully explain the observed global disparities in COVID-19 outcomes. We aimed to investigate the associations between environmental and societal factors and country-level variations in mortality attributed to COVID-19 among people with rheumatic disease globally. Methods: In this observational study, we derived individual-level data on adults (aged 18-99 years) with rheumatic disease and a confirmed status of their highest COVID-19 severity level from the COVID-19 Global Rheumatology Alliance (GRA) registry, collected between March 12, 2020, and Aug 27, 2021. Environmental and societal factors were obtained from publicly available sources. The primary endpoint was mortality attributed to COVID-19. We used a multivariable logistic regression to evaluate independent associations between environmental and societal factors and death, after controlling for individual-level risk factors. We used a series of nested mixed-effects models to establish whether environmental and societal factors sufficiently explained country-level variations in death. Findings: 14 044 patients from 23 countries were included in the analyses. 10 178 (72·5%) individuals were female and 3866 (27·5%) were male, with a mean age of 54·4 years (SD 15·6). Air pollution (odds ratio 1·10 per 10 μg/m3 [95% CI 1·01-1·17]; p=0·0105), proportion of the population aged 65 years or older (1·19 per 1% increase [1·10-1·30]; p, MAG is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant numbers K01 AR070585 and K24 AR074534 [JY]). KDW is supported by the Department of Veterans Affairs and the Rheumatology Research Foundation Scientist Development award. JAS is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant numbers K23 AR069688, R03 AR075886, L30 AR066953, P30 AR070253, and P30 AR072577), the Rheumatology Research Foundation (K Supplement Award and R Bridge Award), the Brigham Research Institute, and the R. Bruce and Joan M. Mickey Research Scholar Fund. NJP is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (T32-AR-007258). AD-G is supported by grants from the Centers for Disease Control and Prevention and the Rheumatology Research Foundation. RH was supported by the Justus-Liebig University Giessen Clinician Scientist Program in Biomedical Research to work on this registry. JY is supported by grants from the National Institutes of Health (K24 AR074534 and P30 AR070155).

Objective To assess the role of the anti-TIF1γ auto-antibody (aAb) IgG2 isotype as a biomarker of cancer in anti-TIF1γ aAb-positive adult DM. Methods International multicentre retrospective study with the following inclusion criteria: (i) diagnosis of DM according to ENMC criteria; (ii) presence of anti-TIF1γ IgG aAb determined using an in-house addressable laser bead immunoassay (ALBIA) from cryopreserved serums sampled at time of DM diagnosis and (iii) available baseline characteristics and follow-up data until the occurrence of cancer and/or a minimum follow-up of 1 year for patients without known cancer at diagnosis. Detection and quantification of anti-TIF1γ IgG2 aAb was done using the in-house ALBIA. In addition, a recent ELISA commercial kit was used for anti-TIF1γ IgG aAb quantification. Results A total of 132 patients (mean age 55±15 years) of whom 72 (54.5%) had an associated cancer were analysed. The association between the presence of cancer and the presence of anti-TIF1γ IgG2 aAb was statistically significant (P = 0.026), with an OR of 2.26 (95% CI: 1.10, 4.76). Patients with cancer displayed significantly higher anti-TIF1γ IgG2 aAb ALBIA values with a median value of 1.15 AU/ml (IQR: 0.14–9.76) compared with 0.50 AU/ml (IQR: 0.14–1.46) for patients without cancer (P = 0.042). In addition, patients with cancer displayed significantly higher anti-TIF1γ IgG aAb ELISA values with a median value of 127.5 AU/ml (IQR: 81.5–139.6) compared with 93.0 AU/ml (IQR: 54.0–132.9) for patients without cancer (P = 0.004). Conclusion These results suggest considering anti-TIF1γ IgG2 ALBIA and IgG ELISA values as biomarkers of cancer in anti-TIF1 γ aAb-positive adult DM.

Aim: Heat shock protein 90 (Hsp90) is a molecular chaperone regulating immune response. We aimed to assess systemic Hsp90 as a biomarker for spondyloarthritis (SpA). Materials & methods: Total of 80 axial SpA (axSpA) and 22 psoriatic arthritis patients and a corresponding number of age- and sex-matched healthy controls (HC) were included. Plasma Hsp90 levels were measured by ELISA. Results: Hsp90 was significantly increased in axSpA patients compared with HC (median interquartile range: 15.7 [10.5–19.8] vs 8.3 [6.6–11.8] ng/ml, p

Background/Aims Anti-synthetase syndrome (ASS) represents a distinct entity within myositis spectrum disorders; however, correct classification of patients with anti-tRNA synthetase autoantibodies and skin manifestations akin to dermatomyositis (DM) remains uncertain. Our aim was to compare clinical characteristics, skin involvement, and malignancy, between patients with ASS and DM, classified by disease-specific autoantibodies. Methods Data from 05/2009-03/2016 from 9 countries from the prospective, myositis EuroMyositis registry were downloaded. Those with anti-tRNA synthetase autoantibodies (Jo-1/PL-7/PL-12/OJ/EJ/KS) were classified as ASS, and those with Mi-2/TIF1-γ/NXP2/SAE/MDA5 autoantibodies as DM. Clinical phenotypes including malignancies (except skin malignancies) were tabulated. Characteristics of patients with skin involvement (excluding mechanic’s hands and Raynaud’s phenomenon) were compared using Fisher’s exact test with Bonferroni corrected p-values. Results Of 3,067 patients, 2,028 had autoantibody profiling results (66.1%), of which 783 (38.6%) were positive for at least one of the autoantibodies being considered. Five patients with dual autoantibody specificities were excluded. Of the remaining 778, 320 (41.1%) were classified as DM, and 458 (58.9%) as ASS. Median age at diagnosis was 48.2 years (interquartile range [IQR] 37.5 to 57.8) in the DM cohort and 49 (IQR 38.3 to 62.2) in the ASS cohort. Skin involvement was present in 277 (86.6%) DM patients (DM skin) vs 204 (44.5%) ASS patients (ASS skin) (pcorr Conclusion Patients with ASS have frequent skin involvement but also a distinct clinical phenotype compared to DM. These findings may inform the development of future classification criteria for ASS. Disclosure R.M. Hum: None. J.B. Lilleker: None. J.A. Lamb: None. W.E. Ollier: None. G. Wang: None. L.R. Wedderburn: None. L.P. Diederichsen: None. J. Schmidt: None. P. Oakley: None. O. Benveniste: None. M.G. Danieli: None. K. Danko: None. N.T.P. Thuy: None. M.V.D. Mercado: None. H. Andersson: None. B.D. Paepe: None. J.L.D. Bleecker: None. B. Maurer: None. L.J. McCann: None. N. Pipitone: None. N. McHugh: None. P. New: None. J. Vencovsky: None. I.E. Lundberg: None. H. Chinoy: None.

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Idiopathic inflammatory myopathies (IIM), also known as myositis, are a heterogeneous group of autoimmune disorders with varying clinical manifestations, treatment responses and prognoses. Muscle weakness is usually the classical clinical manifestation but other organs can be affected, including the skin, joints, lungs, heart and gastrointestinal tract, and they can even result in the predominant manifestations, supporting that IIM are systemic inflammatory disorders. Different myositis-specific auto-antibodies have been identified and, on the basis of clinical, histopathological and serological features, IIM can be classified into several subgroups - dermatomyositis (including amyopathic dermatomyositis), antisynthetase syndrome, immune-mediated necrotizing myopathy, inclusion body myositis, polymyositis and overlap myositis. The prognoses, treatment responses and organ manifestations vary among these groups, implicating different pathophysiological mechanisms in each subtype. A deeper understanding of the molecular pathways underlying the pathogenesis and identifying the auto-antigens of the immune reactions in these subgroups is crucial to improving outcomes. New, more homogeneous subgroups defined by auto-antibodies may help define disease mechanisms and will also be important in future clinical trials for the development of targeted therapies and in identifying biomarkers to guide treatment decisions for the individual patient.

Summary Background Patients with primary systemic vasculitis or polymyalgia rheumatica might be at a high risk for poor COVID-19 outcomes due to the treatments used, the potential organ damage cause by primary systemic vasculitis, and the demographic factors associated with these conditions. We therefore aimed to investigate factors associated with COVID-19 outcomes in patients with primary systemic vasculitis or polymyalgia rheumatica. Methods In this retrospective cohort study, adult patients (aged ≥18 years) diagnosed with COVID-19 between March 12, 2020, and April 12, 2021, who had a history of primary systemic vasculitis (antineutrophil cytoplasmic antibody [ANCA]-associated vasculitis, giant cell arteritis, Behcet's syndrome, or other vasculitis) or polymyalgia rheumatica, and were reported to the COVID-19 Global Rheumatology Alliance registry were included. To assess COVID-19 outcomes in patients, we used an ordinal COVID-19 severity scale, defined as: (1) no hospitalisation; (2) hospitalisation without supplemental oxygen; (3) hospitalisation with any supplemental oxygen or ventilation; or (4) death. Multivariable ordinal logistic regression analyses were used to estimate odds ratios (ORs), adjusting for age, sex, time period, number of comorbidities, smoking status, obesity, glucocorticoid use, disease activity, region, and medication category. Analyses were also stratified by type of rheumatic disease. Findings Of 1202 eligible patients identified in the registry, 733 (61·0%) were women and 469 (39·0%) were men, and their mean age was 63·8 years (SD 17·1). A total of 374 (31·1%) patients had polymyalgia rheumatica, 353 (29·4%) had ANCA-associated vasculitis, 183 (15·2%) had giant cell arteritis, 112 (9·3%) had Behcet's syndrome, and 180 (15·0%) had other vasculitis. Of 1020 (84·9%) patients with outcome data, 512 (50·2%) were not hospitalised, 114 (11·2%) were hospitalised and did not receive supplemental oxygen, 239 (23·4%) were hospitalised and received ventilation or supplemental oxygen, and 155 (15·2%) died. A higher odds of poor COVID-19 outcomes were observed in patients who were older (per each additional decade of life OR 1·44 [95% CI 1·31–1·57]), were male compared with female (1·38 [1·05–1·80]), had more comorbidities (per each additional comorbidity 1·39 [1·23–1·58]), were taking 10 mg/day or more of prednisolone compared with none (2·14 [1·50–3·04]), or had moderate, or high or severe disease activity compared with those who had disease remission or low disease activity (2·12 [1·49–3·02]). Risk factors varied among different disease subtypes. Interpretation Among patients with primary systemic vasculitis and polymyalgia rheumatica, severe COVID-19 outcomes were associated with variable and largely unmodifiable risk factors, such as age, sex, and number of comorbidities, as well as treatments, including high-dose glucocorticoids. Our results could be used to inform mitigation strategies for patients with these diseases. Funding American College of Rheumatology and the European Alliance of Associations for Rheumatology.

Objectives To describe the prevalence and clinical associations of autoantibodies to a novel autoantigen, eukaryotic initiation factor 3 (eIF3), detected in idiopathic inflammatory myositis. Methods Sera or plasma from 678 PM patients were analysed for autoantigen specificity by radio-labelled protein immunoprecipitation (IPP). Samples immunoprecipitating the same novel autoantigens were further analysed by indirect immunofluorescence and IPP using pre-depleted cell extracts. The autoantigen was identified through a combination of IPP and MALDI-TOF mass spectrometry, and confirmed using commercial antibodies and IPP-western blots. Additional samples from patients with DM (668), DM-overlap (80), PM-overlap (191), systemic sclerosis (150), systemic lupus erythematosus (200), Sjogren’s syndrome (40), rheumatoid arthritis (50) and healthy controls (150) were serotyped by IPP as disease or healthy controls. Results IPP revealed a novel pattern in three PM patients (0.44%) that was not found in disease-specific or healthy control sera. Indirect immunofluorescence demonstrated a fine cytoplasmic speckled pattern for all positive patients. Mass spectrometry analysis of the protein complex identified the target autoantigen as eIF3, a cytoplasmic complex with a role in the initiation of translation. Findings were confirmed by IPP-Western blotting. The three anti-eIF3-positive patients had no history of malignancy or interstitial lung disease, and had a favourable response to treatment. Conclusion We report a novel autoantibody in 0.44% of PM patients directed against a cytoplasmic complex of proteins identified as eIF3. Although our findings need further confirmation, anti-eIF3 appears to correlate with a good prognosis and a favourable response to treatment.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): AZV CR, Czech health research council MHCR, Ministry of Health Dzech republic Background Systemic inflammation, limited mobility, and glucocorticoid treatment in Idiopathic inflammatory myopathies (IIM) can have a negative impact on intermediate metabolic pathways, especially on lipid metabolism. Purpose The aim of this study was to assess the differences in the lipid profile of IIM patients and healthy controls (HC) and the association with disease-specific features. Methods 133 patients with IIM (106 females; mean age 60.3; disease duration 2.2 years; dermatomyositis, DM 47 / polymyositis, PM 41 / immune-mediated necrotizing myopathy, IMNM 45) and 133 age-/sex-matched HC (106 females, mean age 60.2) were included. Data are presented as median (IQR). Results Several differences in disease activity, the dose of glucocorticoids, prevalence of comorbidities, and serum lipid levels were observed among the three subtypes of IIM. Lipid profile parameters, especially levels of negative cardiovascular predictive markers such as TC, TG, LDL-C, Apo-B, and the atherogenic index were significantly higher compared to HC. The most significant changes were observed in IMNM compared to age-/sex-matched HC. Levels of TC, TG, LDL-C, apo-B, and non-HDL negatively correlated with disease duration but positively with laboratory markers of disease activity and the current prednisone equivalent dose. Higher levels of HDL-C were associated with decreased levels of CRP, which is in line with the negative correlation of apo-A levels with CRP, CK, and myoglobin. Conclusions: We have observed significant alterations in serum lipid parameters in our IIM patients compared to healthy age-/sex-matched individuals. Differences were also found among the three IIM subtypes. These alterations were associated with laboratory parameters of disease activity and the current dose of corticosteroids. Abstract Figure. Results - lipidogram in IIM and HC

SB4, SB2, and SB5 are biosimilars of etanercept (ETN), infliximab (INF), and adalimumab (ADA), respectively. This pooled analysis evaluated the immunogenicity of these treatments across three phase...

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The main muscular symptom of inflammatory myopathies is muscle weakness. It is mostly symmetrical and proximally located in patients with polymyositis (PM), dermatomyositis (DM), and immune mediated necrotising myopathy (IMNM). In IBM it is usually asymmetric and more often distal. In amyopathic DM weakness may not be present or clinically obvious and sometimes can only be found when tested for. Muscle pain may be present, but not as a main symptom, and if predominant, it should raise suspicion for other diagnosis. Muscular weakness is usually caused by disease activity, but also acquired muscle damage or drug-induced myopathy could be the reason. Dysphagia is a frequent symptom and is due to active inflammation of upper esophagus muscles. Treatment-resistant dysphagia may be the consequence of muscle fibrosis. MRI is a useful technique to visualize inflammation, which manifests as edema on MR images. Atrophy, fibrosis, and fatty infiltration can also be observed. A number of conditions may mimic inflammatory myopathy. The presence of ocular or facial muscle involvement, scapular winging, second-wind phenomenon, prominent distal weakness, exercise-induced cramps, fasting-associated symptoms, fasciculations, myotonia, and dominant pain but also nonresponse to treatment, absence of myositis autoantibodies, lack of any extramuscular symptoms, and possibly also history of the use of myopathic drugs should lead to suspicion of neuropathy, muscle dystrophy, metabolic myopathy, endocrinopathy, toxic myopathy, or fibromyalgia.

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.

The Central European Congress of Rheumatology (CECR) has been organized by seven Central European countries: Austria, Croatia, Czech Republic, Hungary, Poland, Slovakia, and Slovenia. These countries have lots of similarities, but also differences, with respect to rheumatology research. In this paper, based on questionnaires, we wish to demonstrate achievements and difficulties in rheumatology research performed in our region.

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.

ObjectivesDespite the therapeutic value of current rheumatoid arthritis (RA) treatments, agents with alternative modes of action are required. Mavrilimumab, a fully human monoclonal antibody targeting the granulocyte–macrophage colony-stimulating factor receptor-α, was evaluated in patients with moderate-to-severe RA.MethodsIn a phase IIb study (NCT01706926), patients with inadequate response to ≥1 synthetic disease-modifying antirheumatic drug(s), Disease Activity Score 28 (DAS28)−C reactive protein (CRP)/erythrocyte sedimentation rate ≥3.2, ≥4 swollen joints despite methotrexate (MTX) were randomised 1:1:1:1 to subcutaneous mavrilimumab (150, 100, 30 mg), or placebo every other week (eow), plus MTX for 24 weeks. Coprimary outcomes were DAS28−CRP change from baseline to week 12 and American College of Rheumatology (ACR) 20 response rate (week 24).Results326 patients were randomised (150 mg, n=79; 100 mg, n=85; 30 mg, n=81; placebo, n=81); 305 completed the study (September 2012–June 2013). Mavrilimumab treatment significantly reduced DAS28−CRP scores from baseline compared with placebo (change from baseline (SE); 150 mg: −1.90 (0.14), 100 mg: −1.64 (0.13), 30 mg: −1.37 (0.14), placebo: −0.68 (0.14); pSignificantly more mavrilimumab-treated patients achieved ACR20 compared with placebo (week 24: 73.4%, 61.2%, 50.6% vs 24.7%, respectively (pConclusionsMavrilimumab significantly decreased RA disease activity, with clinically meaningful responses observed 1 week after treatment initiation, representing a novel mechanism of action with persuasive therapeutic potential.Trial registration numberNCT01706926; results.

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.

Objective.In an eHealth setting, to investigate intra- and interrater reliability and agreement of joint assessments and Disease Activity Score using C-reactive protein (DAS28-CRP) in patients with rheumatoid arthritis (RA) and test the effect of repeated joint assessment training.Methods.Patients with DAS28-CRP ≤ 5.1 were included in a prospective cohort study (clinicaltrials.gov: NCT02317939). Intrarater reliability and agreement of patient-performed joint counts were assessed through completion of 5 joint assessments over a 2-month period. All patients received training on joint assessment at baseline; only half of the patients received repeated training. A subset of patients was included in an appraisal of interrater reliability and agreement comparing joint assessments completed by patients, healthcare professionals (HCP), and ultrasonography. Cohen’s κ coefficients and intraclass correlation coefficients (ICC) were used for quantifying of reliability of joint assessments and DAS28-CRP. Agreement was assessed using Bland-Altman plots.Results.Intrarater reliability was excellent with ICC of 0.87 (95% CI 0.83–0.90) and minimal detectable change of 1.13. ICC for interrater reliability ranged between 0.69 and 0.90 (good to excellent). Patients tended to rate DAS28-CRP slightly higher than HCP. In patients receiving repeated training, a mean difference in DAS28-CRP of −0.08 was observed (limits of agreements of −1.06 and 0.90). After 2 months, reliability between patients and HCP was similar between groups receiving single or repeated training.Conclusion.Patient-performed assessments of joints and DAS28-CRP in an eHealth home-monitoring solution were reliable and comparable with HCP. Patients can acquire the necessary skills to conduct a correct joint assessment after initial and thorough training. [clinicaltrials.gov (NCT02317939)]

Career situation of first and presenting author Student for a master or a PhD. Introduction Systemic sclerosis (SSc) is accompanied by stiffness and contraction of tissue, predominantly of the skin, caused by fibrosis and resulting in reduced quality of life. The aim of our study was to determine the effect of specialized physical-occupational intervention (POI) on hand/face function and strength, and quality of life of SSc patients. Objectives The study included a total of 55 patients who fulfilled the EULAR/ACR criteria for SSc (2013) and had skin involvement leading to hand-function impairment and mouth handicap. 25 patients were recruited into the intervention group (IG) and 30 patients into the control group (CG). Both groups received educational material for home exercise, but only the IG underwent a 6 month intervention with a subsequent 6 month follow-up period. Methods Patients were assessed by a physician and a physiotherapist blinded to intervention at months 0, 3, 6, and 12, and parameters evaluating hand/face and quality of life were recorded. Patients also filled out PRO (patient reported outcomes) questionnaires and provided blood for routine laboratory analysis and bio-banking. Data analysis was done between groups and within the group. Results Compared to the observed statistically significant deterioration in the CG, we found a statistically significant improvement in the IG in objectively assessed function and strength of hand, distance between incisors and lips and functional ability (SHAQ). Only numerical improvements in the IG during the intervention compared to numerical deterioration in CG that did not reach statistical significance were observed in subjectively assessed hand function and mouth handicap, functional ability (HAQ) and in some domains of QoL (SF-36) and fatigue (FIS–in cognitive function). During the follow-up period, there was a significant deterioration or stagnation of the achieved positive results in the IG. Conclusions Our specialized POI intervention led to a significant improvement in the observed parameters that was clinically significant in a substantial proportion of patients, and prevention of the expected worsening of hand/face function and strength and quality of life. Acknowledgements Supported by AZV-16-33574A, SVV for FTVS UK 2019-260466, MHCR 023728. Disclosure of Interest None declared

Career situation of first and presenting author Student for a master or a PhD. Introduction Skeletal muscle, pulmonary and articular involvement in idiopathic inflammatory myopathies (IIM) limit the mobility/self-sufficiency of patients, and can have a negative impact on body composition. Objectives To assess body composition and physical activity of IIM patients and healthy controls (HC). Methods 54 patients with IIM (45 females; mean age 57.7; disease duration 5.8 years; PM, 22/DM, 25/IMNM, 7) and 54 age-/sex-matched HC (45 females, mean age 57.7) without rheumatic/tumor diseases were included. PM/DM patients fulfilled Bohan/Peter criteria for PM/DM. We assessed anthropometric parameters and body composition (by densitometry: iDXA Lunar, and by bioelectric impedance: BIA2000-M), and physical activity (by Human Activity Profile questionnaire, HAP). Routine biochemistry analysis was performed after 8 hours of fasting. Disease activity was evaluated by MITAX and MYOACT activity score, muscle involvement by manual muscle test (MMT-8) and functional index 2 (FI2). Results Compared to HC, patients with IIM had significantly increased body fat% (BF%) but significantly decreased lean body mass (LBM), bone mineral density (BMD) and increased extracellular mass/body cell mass (ECM/BCM) ratio, which reflects worse muscle predispositions for physical activity and deteriorated nutritional status. Disease duration negatively correlated with BMD and LBM (assessed by BIA). Disease activity assessed by MITAX and MYOACT positively correlated with LBM (assessed by both BIA and DXA), as well as with basal metabolic rate (BMR), and fat free mass (FFM). CRP was positively associated with BF% (iDXA and BIA). Higher BF% (iDXA) was associated with worse physical endurance (FI2) and worse ability to perform physical activity (HAP). MMT-8 score negatively correlated with ECM/BCM ratio. Conclusions We found significant negative changes in body composition of our IIM patients compared to healthy age-/sex-matched individuals, associated with their disease activity and duration, inflammatory status, skeletal muscle involvement, and physical activity. These data could reflect their impaired nutritional status and predispositions for physical exercise, aerobic fitness and performance. References None. Acknowledgements Supported by AZV NV18–01-00161A, MHCR 023728 and GAUK 312218 Disclosure of Interest None declared.

Career situation of first and presenting author Student for a master or a PhD. Introduction Idiopathic inflammatory myopathies (IIM) are characterized by inflammation and atrophy of skeletal muscles, pulmonary and articular involvement, which leads to functional impairment, reduced quality of life including sexual life. Objectives The aim of this study was to assess sexual functions/quality of life and pelvic floor function in female IIM patients compared to age-/sex-matched healthy controls (HC). Methods In total, 22 women with IIM [mean age: 55.1, disease duration: 7.9 years, dermatomyositis (DM, 8)/polymyositis (PM, 10)/necrotizing myopathy (IMNM, 3)/inclusion body myositis (IBM, 1)], who fulfilled the Bohan/Peter 1975 criteria for DM/PM, and 22 healthy controls (mean age: 55.1 years) filled in 12 well-established and validated questionnaires assessing sexual function and pelvic floor function, fatigue, physical activity and depression. We used the following questionnaires: Female Sexual Function Index (FSFI), Brief Index of Sexual Function for Women (BISF-W), Sexual Quality of Life Questionnaire (SQoL-F), Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12), Pelvic Floor Distress Inventory Questionnaire (PFIQ7), Fatigue Impact Scale (FIS), Beck’s Depression Inventory II (BDI II), Health Assessment Questionnaire (HAQ) and Human Activity Profile (HAP). Results Compared to HC, patients with IIM had significantly higher prevalence and greater severity of sexual dysfunction (FSFI, BISF-W: in all subscales as well as total scores), dysfunction of pelvic floor (PISQ-12), and worse sexual quality of life (SQoL-F). Worse scores in IIM patients were associated with elevated muscle enzyme levels [lactate dehydrogenase: FSFI (r=−0.524, p=0.0123), BISFW (r=−0.528, p=0.0115)], greater fatigue [FIS: FSFI (r=−0.434, p=0.0438), BISF-W (r=−0.488, p=0.0211), SQoL-F (r=−0.488, p=0.0070), PISQ-12 (r=0.643, p=0.0013)], more severe depression [BDI-II: PISQ-12 (r=0.474, p=0,0258)], deteriorated quality of life [HAQ: PISQ-12 (r=0.476, p=0.0252)], and worse ability to perform physical activities [HAP: FSFI (r=0.437, p=0.0417), BISF-W (r=0.451, p=0.0351), PISQ-12 (r=−0.494,p=0.0195)]. Conclusions Women with IIM reported significantly disturbed sexual function, sexual quality of life and pelvic floor function than age-matched healthy controls. Worse scores in IIM were associated with disease activity, physical activity, fatigue, depression and quality of life. Acknowledgements Supported by AZV-16-33574A, MHCR 023728, and SVV – 2 60 373. Disclosure of Interest None declared.

Career situation of first and presenting author Student for a master or a PhD. Introduction Systemic sclerosis (SSc) is a chronic autoimmune disease leading to various physical and psychological impairments including sexual dysfunction. Objectives The aim of this study was to assess sexual functions/quality of life and pelvic floor function in female SSc patients compared to age-/sex-matched healthy controls (HC), and to analyze the potential impact of disease activity, fatigue, physical activity and depression. Methods In total, 41 women with SSc (mean age: 50.9, disease duration: 5.8 years, lcSSc/dcSSc: 18/23, mRSS: 13.6, ESSG activity index: 2.5), who fulfilled the ACR/EULAR 2013 criteria, and 41 healthy controls (mean age: 50.9) without rheumatic diseases filled in 12 well-established and validated questionnaires assessing sexual function/quality of life, pelvic floor function, fatigue, physical activity and depression. We used the following questionnaires: Female Sexual Function Index (FSFI), Brief Index of Sexual Function for Women (BISF-W), Sexual Quality of Life Questionnaire (SQoL-F), Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12), Pelvic Floor Distress Inventory Questionnaire (PFIQ7), Fatigue Impact Scale (FIS), Beck’s Depression Inventory II (BDI II), Health Assessment Questionnaire (HAQ), Scleroderma Health Assessment Questionnaire (SHAQ) and Human Activity Profile (HAP). Results Compared to HC, patients with SSc had significantly higher prevalence and greater severity of sexual dysfunction (FSFI, BISF-W: in all subscales as well as total scores), dysfunction of pelvic floor (PISQ-12, PFIQ7), and worse sexual quality of life (SQol-F) (table). Worse scores in SSc patients were associated with higher disease activity [ESSG activity index: SQol-F (r=−0.364, p=0.0443)], greater fatigue [FIS correlated negatively with both FSFI, and BISF-W], more severe depression [BDI-II: FSFI (r=−0.553, p=0.0002), BISF-W (r=−0.514, p=0.0007)], deteriorated quality of life [SHAQ: FSFI (r=−0.536, p=0.0003), BISF-W (r=−0.563, p=0.0001), SQol-F (r=−0.338, p=0.0382), PISQ-12 (r=0.563, p=0.0051)], and worse ability to perform physical activities [HAP: FSFI (r=0.407, p=0.0082), BISF-W (r=0.409, p=0.0078)]. Conclusions Women with SSc reported significantly impaired sexual function, sexual quality of life and pelvic floor function than age-matched healthy controls. Worse scores in SSc were associated with disease activity, physical activity, fatigue, depression and quality of life. Acknowledgements Supported by AZV-16-33574A, MHCR 023728, and SVV – 2 60 373. Disclosure of Interest None declared.

Career situation of first and presenting author Student for a master or a PhD. Introduction Fibrosis of the skin and visceral organs, especially digestive tract, and musculoskeletal involvement in systemic sclerosis (SSc) can have a negative impact on body composition and physical activity. Objectives The aim was to assess body composition and physical activity of SSc patients and healthy controls (HC) and the association with selected inflammatory cytokines in SSc. Methods 59 patients with SSc (50 females; mean age 52.5; disease duration 6.7 years; lcSSc:34/dcSSc:25) and 59 age-/sex-matched HC (50 females, mean age 52.5) without rheumatic or tumour diseases were included. SSc patients fulfilled ACR/EULAR 2013 criteria. We assessed body composition (densitometry: iDXA Lunar, bioelectric impedance: BIA-2000-M), physical activity (Human Activity Profile, HAP questionnaire), disease activity (ESSG activity index) and serum levels of 27 cytokines (commercial multiplex ELISA kit, Bio-Rad Laboratories). Data are presented as mean ±SD. Results Compared to HC, patients with SSc had significantly lower body mass index (BMI), body fat% (BF%) and visceral fat weight (VF), and also significantly decreased lean body mass (LBM), and bone mineral density (BMD). Compared to HC, patients with SSc had increased extracellular mass/body cell mass (ECM/BCM) ratio, reflecting deteriorated nutritional status and worse muscle predispositions for physical activity. Increased ECM/BCM in SSc positively correlated with disease activity (ESSG), skin score (mRSS) and inflammation (CRP, ESR), and was associated with worse quality of life (HAQ, SHAQ), fatigue (FSS), and decreased physical activity (HAP). ESSG negatively correlated with BF%. HAP positively correlated with BMD. Increased serum levels of several inflammatory cytokines were associated with alterations of body composition. Conclusions Compared to healthy age-/sex-matched individuals we found significant negative changes in body composition of our SSc patients, which are associated with the disease activity and physical activity, and could reflect their nutritional status, and gastrointestinal and musculoskeletal involvement. Serum levels of certain inflammatory cytokines were associated with alterations of body composition in SSc patients. References none Acknowledgements Supported byAZV NV18–01-00161A, MHCR 023728 and GAUK 312218. Disclosure of Interest None declared.

Figure S4. Data are shown for the full set analysis of DAS28-CRP remission criteria at week 12. (DOCX 80 kb)

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.

Figure S2. Analysis of change from baseline in DAS28-CRP score in TNF-IR patients 1a/ Graph of the mean change of DAS28 in the TNF-IR patients from baseline over the 12â weeks study duration period (DAS28-CRPâ =â 28-joint Disease Activity Score) 1b/ table of the DAS-28 values corresponding to the graph. (DOCX 17 kb)

Figure S3. Data are shown for the full set analysis of outcomes for the ACR categorical responses at week 12. (DOCX 20 kb)

Myositis is a heterogeneous group of autoimmune diseases, with different pathogenic mechanisms contributing to the different subsets of disease. The aim of this study was to test whether the autoantibody profile in patients with myositis is associated with a type I interferon (IFN) signature, as in patients with systemic lupus erythematous (SLE). Patients with myositis were prospectively enrolled in the study and compared to healthy controls and to patients with SLE. Autoantibody status was analysed using an immunoassay system and immunoprecipitation. Type I IFN activity in whole blood was determined using direct gene expression analysis. Serum IFN-inducing activity was tested using peripheral blood cells from healthy donors. Blocking experiments were performed by neutralizing anti-IFNAR or anti-IFN-α antibodies. Patients were categorized into IFN high and IFN low based on an IFN score. Patients with autoantibodies against RNA-binding proteins had a higher IFN score compared to patients without these antibodies, and the IFN score was related to autoantibody multispecificity. Patients with dermatomyositis (DM) and inclusion body myositis (IBM) had a higher IFN score compared to the other subgroups. Serum type I IFN bioactivity was blocked by neutralizing anti-IFNAR or anti-IFN-α antibodies. To conclude, a high IFN score was not only associated with DM, as previously reported, and IBM, but also with autoantibody monospecificity against several RNA-binding proteins and with autoantibody multispecificity. These studies identify IFN-α in sera as a trigger for activation of the type I IFN pathway in peripheral blood and support IFN-α as a possible target for therapy in these patients.

A European League Against Rheumatism (EULAR) task force was established to define points to consider on use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Based on a systematic literature review and pregnancy exposure data from several registries, statements on the compatibility of antirheumatic drugs during pregnancy and lactation were developed. The level of agreement among experts in regard to statements and propositions of use in clinical practice was established by Delphi voting. The task force defined 4 overarching principles and 11 points to consider for use of antirheumatic drugs during pregnancy and lactation. Compatibility with pregnancy and lactation was found for antimalarials, sulfasalazine, azathioprine, ciclosporin, tacrolimus, colchicine, intravenous immunoglobulin and glucocorticoids. Methotrexate, mycophenolate mofetil and cyclophosphamide require discontinuation before conception due to proven teratogenicity. Insufficient documentation in regard to fetal safety implies the discontinuation of leflunomide, tofacitinib as well as abatacept, rituximab, belimumab, tocilizumab, ustekinumab and anakinra before a planned pregnancy. Among biologics tumour necrosis factor inhibitors are best studied and appear reasonably safe with first and second trimester use. Restrictions in use apply for the few proven teratogenic drugs and the large proportion of medications for which insufficient safety data for the fetus/child are available. Effective drug treatment of active inflammatory rheumatic disease is possible with reasonable safety for the fetus/child during pregnancy and lactation. The dissemination of the data to health professionals and patients as well as their implementation into clinical practice may help to improve the management of pregnant and lactating patients with rheumatic disease.

Background Systemic sclerosis (SSc) is a chronic autoimmune disease leading to various physical and psychological impairments including sexual dysfunction. Objectives To assess sexual functions/quality of life and pelvic floor function in female SSc patients compared to age-/sex-matched healthy controls (HC), and to analyse the potential impact of disease activity, fatigue, physical activity and depression. Methods In total, 41 women with SSc (mean age: 50.9, disease duration: 5.8 years, lcSSc/dcSSc: 18/23, mRSS: 13.6, ESSG activity index: 2.5), who fulfilled the ACR/EULAR 2013 criteria, and 41 healthy controls (mean age: 50.9) without rheumatic diseases filled in 12 well-established and validated questionnaires assessing sexual function/quality of life, pelvic floor function, fatigue, physical activity and depression. Full names of questionnaires are listed in the table 1. Data are presented as mean ±SEM. Results Compared to HC, patients with SSc had significantly higher prevalence and greater severity of sexual dysfunction (FSFI, BISF-W: in all subscales as well as total scores), dysfunction of pelvic floor (PISQ-12, PFIQ7), and worse sexual quality of life (SQol-F) (table 1). Worse scores in SSc patients were associated with higher disease activity [ESSG activity index: SQol-F (r=−0.364,p=0.0443), PFIQ7-gynaecological subscale (r=0.492,p=0.0036)], greater fatigue [all three questionnaires FSS/FIS/MAF correlated negatively with FSFI, BISF-W], more severe depression [BDI-II: FSFI (r=−0.553,p=0.0002), BISF-W (r=−0.514,p=0.0007), PFIQ7 (r=0.495,p=0,0010)], deteriorated quality of life [SHAQ: FSFI (r=−0.536,p=0.0003), BISF-W (r=−0.563,p=0.0001), SQol-F (r=−0.338,p=0.0382), PISQ-12 (r=0.563,p=0.0051), PFIQ7 (r=0.380,p=0.0142)], and worse ability to perform physical activities [HAP: FSFI (r=0.407,p=0.0082), BISF-W (r=0.409,p=0.0078)]. Conclusions Women with SSc reported significantly impaired sexual function, sexual quality of life and pelvic floor function than age-matched healthy controls. Worse scores in SSc were associated with disease activity, physical activity, fatigue, depression and quality of life. Acknowledgements Supported by AZV-16- 33574A and MHCR 023728. Disclosure of Interest None declared

Background Idiopathic inflammatory myopathies (IIM) are characterised by inflammation and atrophy of skeletal muscles, pulmonary and articular involvement, which limit the mobility/self-sufficiency of patients, and can have a negative impact on body composition. Objectives To assess body composition and physical activity of IIM patients and healthy controls (HC). Methods 54 patients with IIM (45 females/9 males; mean age 57.7; disease duration 5.8 years; polymyositis (PM, 22)/dermatomyositis (DM, 25)/necrotizing myopathy (IMNM, 7)) and 54 age-/sex-matched HC (45 females/9 males, mean age 57.7) without rheumatic diseases were included. PM/DM patients fulfilled Bohan/Peter criteria for PM/DM. Anthropometric parameters and body composition were assessed (by densitometry: iDXA Lunar, and by bioelectric impedance: BIA2000-M), and physical activity was evaluated using Human Activity Profile (HAP) questionnaire. Routine biochemistry analysis was performed after 8 hours of fasting. Muscle involvement was evaluated by manual muscle test (MMT-8) and functional index 2 (FI2). Data are presented as mean ±SD. Results Compared to HC, patients with IIM had a trend towards significantly increased body fat% as assessed by iDXA (BF%: 39.9±7.1 vs. 42.4%±7.1%, p=0.077), but significantly decreased lean body mass as assessed both by iDXA (LBM: 45.6±8.1 vs. 40.6±7.2 kg, p=0.001) and BIA (LBM: 52.6±8.8 vs. 48.7±9.0 kg, p=0.023), and increased extracellular mass/body cell mass (ECM/BCM) ratio (1.06±0.15 vs. 1.44±0.42, p DEXA was associated with worse physical endurance (FI2: r=−0.311, p=0.026) and worse ability to perform physical activity (HAP: r=−0.292, p=0.032). MMT-8 score negatively correlated with ECM/BCM ratio (r=−0.385, p=0.006). Conclusions Compared to healthy age-/sex-matched individuals we found significant negative changes in body composition of our IIM patients, which are associated with their disease duration, inflammatory status, skeletal muscle involvement, and physical activity, and could reflect their impaired nutritional status and predispositions for physical exercise, aerobic fitness and performance. Acknowledgements Supported by AZV-16–33574A and SVV-260373. Disclosure of Interest None declared