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ObjectivesInflammatory myopathy or myositis is a heterogeneous family of immune-mediated diseases including dermatomyositis (DM), antisynthetase syndrome (AS), immune-mediated necrotising myopathy (IMNM) and inclusion body myositis (IBM). Immune checkpoint inhibitors (ICIs) can also cause myositis (ICI-myositis). This study was designed to define gene expression patterns in muscle biopsies from patients with ICI-myositis.MethodsBulk RNA sequencing was performed on 200 muscle biopsies (35 ICI-myositis, 44 DM, 18 AS, 54 IMNM, 16 IBM and 33 normal muscle biopsies) and single nuclei RNA sequencing was performed on 22 muscle biopsies (seven ICI-myositis, four DM, three AS, six IMNM and two IBM).ResultsUnsupervised clustering defined three distinct transcriptomic subsets of ICI-myositis: ICI-DM, ICI-MYO1 and ICI-MYO2. ICI-DM included patients with DM and anti-TIF1γ autoantibodies who, like DM patients, overexpressed type 1 interferon-inducible genes. ICI-MYO1 patients had highly inflammatory muscle biopsies and included all patients that developed coexisting myocarditis. ICI-MYO2 was composed of patients with predominant necrotising pathology and low levels of muscle inflammation. The type 2 interferon pathway was activated both in ICI-DM and ICI-MYO1. Unlike the other types of myositis, all three subsets of ICI-myositis patients overexpressed genes involved in the IL6 pathway.ConclusionsWe identified three distinct types of ICI-myositis based on transcriptomic analyses. The IL6 pathway was overexpressed in all groups, the type I interferon pathway activation was specific for ICI-DM, the type 2 IFN pathway was overexpressed in both ICI-DM and ICI-MYO1 and only ICI-MYO1 patients developed myocarditis.

ObjectivesIn dermatomyositis (DM), autoantibodies are associated with unique clinical phenotypes. For example, anti-TIF1γ autoantibodies are associated with an increased risk of cancer. The purpose of this study was to discover novel DM autoantibodies.MethodsPhage ImmunoPrecipitation Sequencing using sera from 43 patients with DM suggested that transcription factor Sp4 is a novel autoantigen; this was confirmed by showing that patient sera immunoprecipitated full-length Sp4 protein. Sera from 371 Johns Hopkins patients with myositis (255 with DM, 28 with antisynthetase syndrome, 40 with immune-mediated necrotising myopathy, 29 with inclusion body myositis and 19 with polymyositis), 80 rheumatological disease controls (25 with Sjogren’s syndrome, 25 with systemic lupus erythematosus and 30 with rheumatoid arthritis (RA)) and 200 healthy comparators were screened for anti-SP4 autoantibodies by ELISA. A validation cohort of 46 anti-TIF1γ-positive patient sera from the University of Pittsburgh was also screened for anti-Sp4 autoantibodies.ResultsAnti-Sp4 autoantibodies were present in 27 (10.5%) patients with DM and 1 (3.3%) patient with RA but not in other clinical groups. In patients with DM, 96.3% of anti-Sp4 autoantibodies were detected in those with anti-TIF1γ autoantibodies. Among 26 TIF1γ-positive patients with anti-Sp4 autoantibodies, none (0%) had cancer. In contrast, among 35 TIF1γ-positive patients without anti-Sp4 autoantibodies, 5 (14%, p=0.04) had cancer. In the validation cohort, among 15 TIF1γ-positive patients with anti-Sp4 autoantibodies, 2 (13.3%) had cancer. By comparison, among 31 TIF1γ-positive patients without anti-Sp4 autoantibodies, 21 (67.7%, pConclusionsAnti-Sp4 autoantibodies appear to identify a subgroup of anti-TIF1γ-positive DM patients with lower cancer risk.

BackgroundSignificant gaps are present in the evidence of the spectrum and severity of COVID-19 infection in idiopathic inflammatory myopathies (IIM). IIM patients typically require immunosuppressive therapy, may have multiple disease sequelae, and frequent comorbidities, and thus may be more susceptible to severe COVID-19 infection and complications (1). The possibility of attenuated immunogenicity and reduced efficacy of COVID-19 vaccines due to concomitant immunosuppressive medication is a major concern in these patients, and there is little data available on COVID-19 vaccine breakthrough infections (BI) in IIM (2).ObjectivesThis study aimed to compare disease spectrum and severity and COVID-19 BI in patients with IIM, other systemic autoimmune and inflammatory diseases (SAIDs) and healthy controls (HCs).MethodsWe developed an extensive self-reporting electronic-survey (COVAD survey) featuring 36 questions to collect respondent demographics, SAID details, COVID-19 infection history, COVID-19 vaccination details, 7-day post vaccination adverse events and patient reported outcome measures using the PROMIS tool. After pilot testing, validation, translation into 18 languages on the online platform surveymonkey.com, and vetting by international experts, the COVAD survey was circulated in early 2021 by a multicenter study group of >110 collaborators in 94 countries. BI was defined as COVID-19 infection occurring more than 2 weeks after receiving 1st or 2nd dose of a COVID-19 vaccine. We analyzed data from the baseline survey for descriptive and intergroup comparative statistics based on data distribution and variable type.Results10900 respondents [mean age 42 (30-55) years, 74% females and 45% Caucasians] were analyzed. 1,227 (11.2%) had IIM, 4,640 (42.6%) had other SAIDs, and 5,033 (46.2%) were HC. All respondents included in the final analysis had received a single dose of the vaccine and 69% had received 2 primary doses. Pfizer (39.8%) was the most common vaccine received, followed by Oxford/AstraZeneca (13.4%), and Covishield (10.9%). IIM patients were older, had a higher Caucasian representation and higher Pfizer uptake than other SAIDs, and HC. A higher proportion of IIM patients received immunosuppressants than other SAIDs.IIMs were at a lower risk of symptomatic pre-vaccination COVID-19 infection compared to SAIDs [multivariate OR 0.6 (0.4-0.8)] and HCs [multivariate OR 0.39 (0.28-0.54)], yet at a higher risk of hospitalization due to COVID-19 compared to SAIDs [univariate OR 2.3 (1.2-3.5)] and HCs [multivariate OR 2.5 (1.1-5.8)]. BIs were very uncommon in IIM patients, with only 17 (1.4%) reporting BI. IIM patients were at a higher risk of contracting COVID-19 prior to vaccination than ≤2 weeks of vaccination [univariate OR 8 (4.1-15)] or BI [univariate OR 4.6 (2.7-8.0)]. BIs were equally severe compared to when they occurred prior to vaccination in IIMs, and were comparable between IIM, SAIDs, and HC (Figure 1), though BI disease duration was shorter in IIMs than SAIDs (7 vs 11 days, p 0.027). 13/17 IIM patients with BI were on immunosuppressants.ConclusionIIM patients experienced COVID-19 infection less frequently prior to vaccination but were at a higher risk of hospitalization and requirement for oxygen therapy compared with patients with HC. Breakthrough COVID-19 infections were rare (1.4%) in vaccinated IIM patients, and were similar to HC and SAIDs, except for shorter disease duration in IIM.References[1]Brito-Zerón P, Sisó-Almirall A, Flores-Chavez A, Retamozo S, Ramos-Casals M. SARS-CoV-2 infection in patients with systemic autoimmune diseases. Clin Exp Rheumatol. 2021 Jun;39(3):676–87.[2]Wack S, Patton T, Ferris LK. COVID-19 vaccine safety and efficacy in patients with immune-mediated inflammatory disease: Review of available evidence. J Am Acad Dermatol. 2021 Nov;85(5):1274–84.AcknowledgementsThe authors thank all members of the COVAD study group for their invaluable role in the collection of data. The authors thank all respondents for filling the questionnaire. The authors thank The Myositis Association, Myositis India, Myositis UK, the Myositis Global Network, Cure JM, Cure IBM, Sjögren’s India Foundation, EULAR PARE, and various other patient support groups and organizations for their invaluable contribution in the dissemination of this survey among patients which made the data collection possible. The authors also thank all members of the COVAD study group.Disclosure of InterestsLatika Gupta: None declared, Leonardo Santos Hoff: None declared, Naveen R: None declared, Parikshit Sen: None declared, Samuel Katsuyuki Shinjo: None declared, Jessica Day Grant/research support from: JD has received research funding from CSL Limited, James B. Lilleker: None declared, Vishwesh Agarwal: None declared, Sinan Kardes: None declared, Minchul Kim: None declared, Ashima Makol: None declared, Marcin Milchert: None declared, Tamer A Gheita: None declared, Babur Salim: None declared, Tsvetelina Velikova: None declared, Abraham Edgar Gracia-Ramos: None declared, Ioannis Parodis Speakers bureau: IP has received research funding and/or honoraria from Amgen, AstraZeneca, Aurinia Pharmaceuticals, Elli Lilly and Company, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceuticals, Novartis and F. Hoffmann-La Roche AG., Consultant of: IP has received research funding and/or honoraria from Amgen, AstraZeneca, Aurinia Pharmaceuticals, Elli Lilly and Company, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceuticals, Novartis and F. Hoffmann-La Roche AG., Grant/research support from: IP has received research funding and/or honoraria from Amgen, AstraZeneca, Aurinia Pharmaceuticals, Elli Lilly and Company, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceuticals, Novartis and F. Hoffmann-La Roche AG., Albert Selva-O’Callaghan: None declared, Elena Nikiphorou Speakers bureau: EN has received speaker honoraria/participated in advisory boards for Celltrion, Pfizer, Sanofi, Gilead, Galapagos, AbbVie, Lilly, Consultant of: EN has received speaker honoraria/participated in advisory boards for Celltrion, Pfizer, Sanofi, Gilead, Galapagos, AbbVie, Lilly, Grant/research support from: EN holds research grants from Pfizer and Lilly., Tulika Chatterjee: None declared, Ai Lyn Tan Speakers bureau: ALT has received honoraria for advisory boards and speaking for Abbvie, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB., Consultant of: ALT has received honoraria for advisory boards and speaking for Abbvie, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB., Arvind Nune: None declared, Lorenzo Cavagna: None declared, Miguel A Saavedra: None declared, Nelly Ziade Speakers bureau: NZ has received speaker fees, advisory board fees and research grants from Pfizer, Roche, Abbvie, Eli Lilly, NewBridge, Sanofi-Aventis, Boehringer Ingelheim, Janssen, Pierre Fabre; none is related to this manuscript, Consultant of: NZ has received speaker fees, advisory board fees and research grants from Pfizer, Roche, Abbvie, Eli Lilly, NewBridge, Sanofi-Aventis, Boehringer Ingelheim, Janssen, Pierre Fabre; none is related to this manuscript, Grant/research support from: NZ has received speaker fees, advisory board fees and research grants from Pfizer, Roche, Abbvie, Eli Lilly, NewBridge, Sanofi-Aventis, Boehringer Ingelheim, Janssen, Pierre Fabre; none is related to this manuscript, Johannes Knitza: None declared, Masataka Kuwana: None declared, Oliver Distler Speakers bureau: OD has/had consultancy relationship with and/or has received research funding from or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three years: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, Baecon, Blade, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos, Glenmark, GSK, Horizon (Curzion), Inventiva, iQvia, Kymera, Lupin, Medac, Medscape, Mitsubishi Tanabe, Novartis, Roche, Roivant, Sanofi, Serodapharm, Topadur and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Consultant of: OD has/had consultancy relationship with and/or has received research funding from or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three years: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, Baecon, Blade, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos, Glenmark, GSK, Horizon (Curzion), Inventiva, iQvia, Kymera, Lupin, Medac, Medscape, Mitsubishi Tanabe, Novartis, Roche, Roivant, Sanofi, Serodapharm, Topadur and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Grant/research support from: OD has/had consultancy relationship with and/or has received research funding from or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three years: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, Baecon, Blade, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos, Glenmark, GSK, Horizon (Curzion), Inventiva, iQvia, Kymera, Lupin, Medac, Medscape, Mitsubishi Tanabe, Novartis, Roche, Roivant, Sanofi, Serodapharm, Topadur and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Hector Chinoy Speakers bureau: HC has been a speaker for UCB, Biogen., Consultant of: HC has received consulting fees from Novartis, Eli Lilly, Orphazyme, Astra Zeneca, Grant/research support from: HC has received grant support from Eli Lilly and UCB, Vikas Agarwal: None declared, Rohit Aggarwal Consultant of: RA has/had a consultancy relationship with and/or has received research funding from the following companies-Bristol Myers-Squibb, Pfizer, Genentech, Octapharma, CSL Behring, Mallinckrodt, AstraZeneca, Corbus, Kezar, and Abbvie, Janssen, Alexion, Argenx, Q32, EMD-Serono, Boehringer Ingelheim, Roivant., Grant/research support from: RA has/had a consultancy relationship with and/or has received research funding from the following companies-Bristol Myers-Squibb, Pfizer, Genentech, Octapharma, CSL Behring, Mallinckrodt, AstraZeneca, Corbus, Kezar, and Abbvie, Janssen, Alexion, Argenx, Q32, EMD-Serono, Boehringer Ingelheim, Roivant.

ObjectivesMyositis is a heterogeneous family of diseases including dermatomyositis (DM), immune-mediated necrotising myopathy (IMNM), antisynthetase syndrome (AS) and inclusion body myositis (IBM). Myositis-specific autoantibodies define different subtypes of myositis. For example, patients with anti-Mi2 autoantibodies targeting the chromodomain helicase DNA-binding protein 4 (CHD4)/NuRD complex (a transcriptional repressor) have more severe muscle disease than other DM patients. This study aimed to define the transcriptional profile of muscle biopsies from anti-Mi2-positive DM patients.MethodsRNA sequencing was performed on muscle biopsies (n=171) from patients with anti-Mi2-positive DM (n=18), DM without anti-Mi2 autoantibodies (n=32), AS (n=18), IMNM (n=54) and IBM (n=16) as well as 33 normal muscle biopsies. Genes specifically upregulated in anti-Mi2-positive DM were identified. Muscle biopsies were stained for human immunoglobulin and protein products corresponding to genes specifically upregulated in anti-Mi2-positive muscle biopsies.ResultsA set of 135 genes, includingSCRT1andMADCAM1, was specifically overexpressed in anti-Mi2-positive DM muscle. This set was enriched for CHD4/NuRD-regulated genes and included genes that are not otherwise expressed in skeletal muscle. The expression levels of these genes correlated with anti-Mi2 autoantibody titres, markers of disease activity and with the other members of the gene set. In anti-Mi2-positive muscle biopsies, immunoglobulin was localised to the myonuclei, MAdCAM-1 protein was present in the cytoplasm of perifascicular fibres, and SCRT1 protein was localised to myofibre nuclei.ConclusionsBased on these findings, we hypothesise that anti-Mi2 autoantibodies could exert a pathogenic effect by entering damaged myofibres, inhibiting the CHD4/NuRD complex, and subsequently derepressing the unique set of genes defined in this study.

BackgroundCOVID-19 vaccines have been proven to be safe and effective in the healthy population at large. However, significant gaps remain in the evidence of their safety in patients with systemic autoimmune and inflammatory disorders (SAIDs). Patients and rheumatologists have expressed concerns regarding vaccination triggered allergic reactions, thrombogenic events, and other adverse events (ADEs) contributing to vaccine hesitancy (1)ObjectivesThis study aimed to assess and compare short term COVID-19 vaccination associated ADEs in patients with SAIDs and healthy controls (HC) seven days post-vaccination, as well as between patients with SAIDs receiving different vaccines.MethodsWe developed an comprehensive, patient self-reporting electronic-survey to collect respondent demographics, SAID details, COVID-19 infection history, COVID-19 vaccination details, 7-day post vaccination adverse events and patient reported outcome measures using the PROMIS tool. After pilot testing, validation, translation into 18 languages on the online platform surveymonkey.com, and vetting by international experts, the survey was circulated in early 2021 by a multicenter study group of >110 collaborators in 94 countries. ADEs were categorized as injection site pain, minor ADEs, major ADEs, and hospitalizations. We analyzed data from the baseline survey for descriptive and intergroup comparative statistics based on data distribution and variable type (data as median, IQR).Results10900 respondents [42 (30-55) years, 74% females and 45% Caucasians] were analyzed. 5,867 patients (54%) with SAIDs were compared with 5033 HCs. All respondents included in the final analysis had received a single dose of the vaccine and 69% had received 2 primary doses. Pfizer (39.8%) was the most common vaccine received, followed by Oxford/AstraZeneca (13.4%), and Covishield (10.9%). Baseline demographics differed by an older SAID population (mean age 42 vs. 33 years) and a greater female predominance (M:F= 1:4.7 vs. 1:1.8) compared to HCs.79% had minor and only 3% had major vaccine ADEs requiring urgent medical attention overall. In adjusted analysis, among minor ADEs, abdominal pain [multivariate OR 1.6 (1.14-2.3)], dizziness [multivariate OR 1.3 (1.2-1.5)], and headache [multivariate OR 1.67 (1.3-2.2)], were more frequent in SAIDs than HCs. Overall major ADEs [multivariate OR 1.9 (1.6-2.2)], and throat closure [multivariate OR 5.7 (2.9-11.3)] were more frequent in SAIDs though absolute risk was small (0-4%) and rates of hospitalization were similarly small in both groups, with a small absolute risk (0-4%). Specific minor ADEs frequencies were different among different vaccine types, however, major ADEs and hospitalizations overall were rare (0-4%) and comparable across vaccine types in patients with SAIDs (Figure 1).Figure 1.A. Post Vaccination ADEs in SAIDs compared to HCs. B. Proportions of post COVID-19 vaccination ADEs in SAIDs by vaccine type.ConclusionVaccination against COVID-19 is relatively safe and tolerable in patients with SAIDs. Certain minor vaccine ADEs are more frequent in SAIDs than HCs in this study, though are not severe and do not require urgent medical attention. SAIDs were at a higher risk of major ADEs than HCs, though absolute risk was small, and did not lead to increased hospitalizations. There are small differences in minor ADEs between vaccine types in patients with SAIDs.References[1]Boekel L, Kummer LY, van Dam KPJ, Hooijberg F, van Kempen Z, Vogelzang EH, et al. Adverse events after first COVID-19 vaccination in patients with autoimmune diseases. Lancet Rheumatol. 2021 Aug;3(8):e542–5.AcknowledgementsThe authors thank all members of the COVAD study group for their invaluable role in the collection of data. The authors thank all respondents for filling the questionnaire. The authors thank The Myositis Association, Myositis India, Myositis UK, the Myositis Global Network, Cure JM, Cure IBM, Sjögren’s India Foundation, EULAR PARE, and various other patient support groups and organizations for their invaluable contribution in the dissemination of this survey among patients which made the data collection possible. The authors also thank all members of the COVAD study group.Disclosure of InterestsParikshit Sen: None declared, Naveen R: None declared, Arvind Nune: None declared, James B. Lilleker: None declared, Vishwesh Agarwal: None declared, Sinan Kardes: None declared, Minchul Kim: None declared, Jessica Day Grant/research support from: JD has received research funding from CSL Limited., Marcin Milchert: None declared, Tamer A Gheita: None declared, Babur Salim: None declared, Tsvetelina Velikova: None declared, Abraham Edgar Gracia-Ramos: None declared, Ioannis Parodis Speakers bureau: IP has received research funding and/or honoraria from Amgen, AstraZeneca, Aurinia Pharmaceuticals, Elli Lilly and Company, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceuticals, Novartis and F. Hoffmann-La Roche AG., Consultant of: IP has received research funding and/or honoraria from Amgen, AstraZeneca, Aurinia Pharmaceuticals, Elli Lilly and Company, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceuticals, Novartis and F. Hoffmann-La Roche AG., Grant/research support from: IP has received research funding and/or honoraria from Amgen, AstraZeneca, Aurinia Pharmaceuticals, Elli Lilly and Company, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceuticals, Novartis and F. Hoffmann-La Roche AG., Albert Selva-O’Callaghan: None declared, Elena Nikiphorou Speakers bureau: EN has received speaker honoraria/participated in advisory boards for Celltrion, Pfizer, Sanofi, Gilead, Galapagos, AbbVie, Lilly, Consultant of: EN has received speaker honoraria/participated in advisory boards for Celltrion, Pfizer, Sanofi, Gilead, Galapagos, AbbVie, Lilly, Grant/research support from: EN has received speaker honoraria/participated in advisory boards for Celltrion, Pfizer, Sanofi, Gilead, Galapagos, AbbVie, Lilly, and holds research grants from Pfizer and Lilly., Tulika Chatterjee: None declared, Ai Lyn Tan Speakers bureau: ALT has received honoraria for advisory boards and speaking for Abbvie, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB., Consultant of: ALT has received honoraria for advisory boards and speaking for Abbvie, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB., Grant/research support from: ALT has received honoraria for advisory boards and speaking for Abbvie, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB., Lorenzo Cavagna: None declared, Miguel A Saavedra: None declared, Samuel Katsuyuki Shinjo: None declared, Nelly Ziade Speakers bureau: NZ has received speaker fees, advisory board fees and research grants from Pfizer, Roche, Abbvie, Eli Lilly, NewBridge, Sanofi-Aventis, Boehringer Ingelheim, Janssen, Pierre Fabre; none is related to this manuscript., Consultant of: NZ has received speaker fees, advisory board fees and research grants from Pfizer, Roche, Abbvie, Eli Lilly, NewBridge, Sanofi-Aventis, Boehringer Ingelheim, Janssen, Pierre Fabre; none is related to this manuscript., Grant/research support from: NZ has received speaker fees, advisory board fees and research grants from Pfizer, Roche, Abbvie, Eli Lilly, NewBridge, Sanofi-Aventis, Boehringer Ingelheim, Janssen, Pierre Fabre; none is related to this manuscript., Johannes Knitza: None declared, Masataka Kuwana: None declared, Oliver Distler Speakers bureau: OD has/had consultancy relationship with and/or has received research funding from or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three years: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, Baecon, Blade, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos, Glenmark, GSK, Horizon (Curzion), Inventiva, iQvia, Kymera, Lupin, Medac, Medscape, Mitsubishi Tanabe, Novartis, Roche, Roivant, Sanofi, Serodapharm, Topadur and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Consultant of: OD has/had consultancy relationship with and/or has received research funding from or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three years: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, Baecon, Blade, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos, Glenmark, GSK, Horizon (Curzion), Inventiva, iQvia, Kymera, Lupin, Medac, Medscape, Mitsubishi Tanabe, Novartis, Roche, Roivant, Sanofi, Serodapharm, Topadur and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Grant/research support from: OD has/had consultancy relationship with and/or has received research funding from or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three years: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, Baecon, Blade, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos, Glenmark, GSK, Horizon (Curzion), Inventiva, iQvia, Kymera, Lupin, Medac, Medscape, Mitsubishi Tanabe, Novartis, Roche, Roivant, Sanofi, Serodapharm, Topadur and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Hector Chinoy Speakers bureau: HC has served as a speaker for UCB, Biogen., Consultant of: HC has received consulting fees from Novartis, Eli Lilly, Orphazyme, Astra Zeneca, Grant/research support from: HC has received grant support from Eli Lilly and UCB, Vikas Agarwal: None declared, Rohit Aggarwal Consultant of: RA has/had a consultancy relationship with and/or has received research funding from for the following companies-Bristol Myers-Squibb, Pfizer, Genentech, Octapharma, CSL Behring, Mallinckrodt, AstraZeneca, Corbus, Kezar, Kyverna, Janssen, Roivant, Boehringer Ingelheim, Argenx, Q32, Alexion, EMD Serono, Jubliant, Abbvie, Janssen, Alexion, Argenx, Q32, EMD-Serono, Boehringer Ingelheim, Roivant., Grant/research support from: RA has/had a consultancy relationship with and/or has received research funding from for the following companies-Bristol Myers-Squibb, Pfizer, Genentech, Octapharma, CSL Behring, Mallinckrodt, AstraZeneca, Corbus, Kezar, Kyverna, Janssen, Roivant, Boehringer Ingelheim, Argenx, Q32, Alexion, EMD Serono, Jubliant, Abbvie, Janssen, Alexion, Argenx, Q32, EMD-Serono, Boehringer Ingelheim, Roivant., Latika Gupta: None declared

BackgroundIdiopathic inflammatory myopathies (IIM) are a rare, multisystem, heterogeneous diseases, and contribute to high psychological burden. The patients’ perception of physical health, deteriorating independence and social and environmental relationships may not always be a direct function of disease activity. To face with these aspects, several worldwide specialized organization have recommended the use of patient reported outcome measures (PROMs) both in clinical trials and observational studies to highlight patient’s perception of the disease (1). Unfortunately, data on fatigue scores in IIM is limited.ObjectivesWe compared fatigue VAS scores in patients with IIM, autoimmune diseases (AIDs) and healthy controls (HCs) and triangulated them with PROMIS physical function in a large international cohort made up of answers from the e-survey regarding the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study.MethodsData of 16327 respondents was extracted from the COVAD database on August 31th 2021. VAS fatigue scores were compared between AID, HC and IIM using univariate followed by multivariate analysis after adjusting for baseline differences. We further performed a propensity score matched analysis on 1827 subjects after adjusting for age, gender and ethnicity. The Kruskal-Wallis test was used for continuous variables and chi-square test for categorical variables, and Bonferroni’s correction was applied for the post hoc analyses considering IIMs as a reference group.ResultsWe analyzed answers from 6988 patients, with a mean age of 43.8 years (SD 16.2). The overall percentage of female was 72% and the population ethnicity was mainly composed of White (55.1%), followed by Asian (24.6%), and Hispanic (13.8%). The overall fatigue VAS was 3.6 mm (SD 2.7). IIMs VAS was 4.8 mm (SD 2.6), AIDs 4.5 mm (SD 2.6), and HC 2.8 mm (SD 2.6) (P P 0.084), albeit significantly higher than the HCs (P P P =1) the differences disappeared and IIMs and AIDs had comparable fatigue levels across all levels of disease activity, although the fatigue discrepancies with HCs were substantially confirmed.After application of a multivariate linear regression analysis we found that lower fatigue VAS scores were related to HC (P P P ConclusionOur study confirms that there is a higher prevalence of fatigue in all the AIDs patients, with comparable VAS scores between IIMs and other AIDs. We can also read our data commenting that females and/or Caucasians patients suffer a higher impact of this manifestation of chronic autoimmune diseases upon their lives. This is why these subjects, to our judgement, should be carefully evaluated during outpatients visits and to whom we should spend some extra time to discuss health related issues and how to improve them.References[1]Regardt, M. et al. OMERACT 2018 Modified Patient-reported Outcome Domain Core Set in the Life Impact Area for Adult Idiopathic Inflammatory Myopathies. J. Rheumatol.46, 1351–1354 (2019).Figure 1.distribution of Fatigue VAS scores in the three population evaluated. IIM idiopathic inflammatory myositis; AID autoimmune diseases; HC healthy controls; * P < 0,05.Disclosure of InterestsNone declared

BackgroundEvaluation of physical function is fundamental in the management of idiopathic inflammatory myopathies (IIMs). Patient-Reported Outcome Measurement Information System (PROMIS) is a National Institute of Health initiative established in 2004 to develop patient-reported outcome measures (PROMs) with improved validity and efficacy. PROMIS Physical Function (PF) short forms have been validated for use in IIMs [1].ObjectivesTo investigate the physical function status of IIM patients compared to those with non-IIM autoimmune diseases (AIDs) and healthy controls (HCs) utilizing PROMIS PF data obtained in the coronavirus disease-2019 (COVID-19) Vaccination in Autoimmune Diseases (COVAD) study, a large-scale, international self-reported e-survey assessing the safety of COVID-19 vaccines in AID patients [2].MethodsThe survey data regarding demographics, IIM and AID diagnosis, disease activity, and PROMIS PF short form-10a scores were extracted from the COVAD study database. The disease activity (active vs inactive) of each patient was assessed in 3 different ways: (1) physician’s assessment (active if there was an increased immunosuppression), (2) patient’s assessment (active vs inactive as per patient), and (3) current steroid use. These 3 definitions of disease activity were applied independently to each patient. PROMIS PF-10a scores were compared between each disease category (IIMs vs non-IIM AIDs vs HCs), stratified by disease activity based on the 3 definitions stated above, employing negative binominal regression model. Multivariable regression analysis adjusted for age, gender, and ethnicity was performed clustering countries, and the predicted PROMIS PF-10a score was calculated based on the regression result. Factors affecting PROMIS PF-10a scores other than disease activity were identified by another multivariable regression analysis in the patients with inactive disease (IIMs or non-IIM AIDs).Results1057 IIM patients, 3635 non-IIM AID patients, and 3981 HCs responded to the COVAD survey until August 2021. The median age of the respondents was 43 [IQR 30-56] years old, and 74.8% were female. Among IIM patients, dermatomyositis was the most prevalent diagnosis (34.8%), followed by inclusion body myositis (IBM) (23.6%), polymyositis (PM) (16.2%), anti-synthetase syndrome (11.8%), overlap myositis (7.9%), and immune-mediated necrotizing myopathy (IMNM) (4.6%). The predicted mean of PROMIS PF-10a scores was significantly lower in IIMs compared to non-IIM AIDs or HCs (36.3 [95% (CI) 35.5-37.1] vs 41.3 [95% CI 40.2-42.5] vs 46.2 [95% CI 45.8-46.6], P < 0.001), irrespective of disease activity or the definitions of disease activity used (physician’s assessment, patient’s assessment, or steroid use) (Figure 1). The largest difference between active IIMs and non-IIM AIDs was observed when the disease activity was defined by patient’s assessment (35.0 [95% CI 34.1-35.9] vs 40.1 [95% CI 38.7-41.5]). Considering the subgroups of IIMs, the scores were significantly lower in IBM in comparison with non-IBM IIMs (P < 0.001). The independent factors associated with low PROMIS PF-10a scores in the patients with inactive disease were older age, female gender, and the disease category being IBM, PM, or IMNM.ConclusionPhysical function is significantly impaired in IIMs compared to non-IIM AIDs or HCs, even in patients with inactive disease. The elderly, women, and IBM groups are the worst affected, suggesting that developing targeted strategies to minimize functional disability in certain groups may improve patient reported physical function and disease outcomes.References[1]Saygin D, Oddis CV, Dzanko S, et al. Utility of patient-reported outcomes measurement information system (PROMIS) physical function form in inflammatory myopathy. Semin Arthritis Rheum. 2021; 51: 539-46.[2]Sen P, Gupta L, Lilleker JB, et al. COVID-19 vaccination in autoimmune disease (COVAD) survey protocol. Rheumatol Int. 2022; 42: 23-9.AcknowledgementsThe authors thank all respondents for filling the questionnaire. The authors thank The Myositis Association, Myositis India, Myositis UK, the Myositis Global Network, Cure JM, Cure IBM, Sjögren’s India Foundation, EULAR PARE, and various other patient support groups and organizations for their invaluable contribution in the dissemination of this survey among patients which made the data collection possible. The authors also thank all members of the COVAD study group.Disclosure of InterestsNone declared

Background:There is a well-recognized association between cancer and myositis, so cancer screening at diagnosis is recommended.Objectives:We aim to report the results of our cancer screening strategy and to ascertain the reliability of using PET/CT to identify cancer-associated myositis (CAM) in a large cohort of patients with myositis from a single center over 10 years.Methods:This retrospective observational study included all patients diagnosed with any type of myositis except for inclusion body myositis. Cancer screening strategy was individualized according to clinical and serological data, including PET/CT as the main test to detect occult cancer (OC). Procedures derived from a positive PET/CT were registered. Qualitative data expressed as percentages, and quantitative data as the median with the interquartile range were analyzed. A ROC curve was used to estimate the reliability of PET/CT for CAM diagnosis.Results:Seventy-seven out of 131 patients underwent a PET/CT for OC screening. The performance of the PET/CT in patients with myositis at disease onset yielded an area under the curve ROC of 0.87 (0.73-0.97) for CAM diagnosis. Invasive procedures in 7 (9%) patients without a final diagnosis of cancer did not cause derived complications. Patients not evaluated for OC did not develop cancer after a median follow-up of 3.3 years (1.7-6.7).Conclusion:Cancer screening strategy should be individualized. PET/CT at myositis onset seems to be an efficient approach to rule out CAM. This practice does not seem to significantly increase harm to patients related to the additional tests needed to clarify inconclusive results.Disclosure of Interests:None declared

Background:Several reports have shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may trigger a vigorous immune response that could lead to the appearance of various autoantibodies such as antinuclear antibodies, antiphospholipid antibodies or anti-neutrophil cytoplasmic antibodies, among others. Moreover, the pulmonary involvement in SARS-CoV-2 may resemble that of patients with anti-MDA5 positive syndrome or acute form of antisynthetase syndrome.Objectives:Our aim was to analyse the presence of anti-MDA5 and other myositis-specific autoantibodies such as the antisynthetase antibodies in patients diagnosed with severe acute respiratory syndrome caused by SARS-CoV-2.Methods:Retrospective observational study performed in a tertiary care center. We included 28 patients admitted to the intensive care unit with severe acute respiratory syndrome, 14 at the onset of the disease (group A) and 14 after 30 days of being treated in an intensive care unit (group B). Chest CT was performed at the admission. We analyzed the presence of anti-MDA5 and antisynthetase antibodies by immunoblot (Euroimmune®) and in those who were positive we performed a confirmatory test by immunoprecipitation.Results:All chest CT showed bilateral ground glass pattern. Three out of 14 patients of group A (12 males, 86%, mean ± SD age 67.1 ± 12.2) were positive for antisynthetase antibodies (2 anti-PL7, 1 anti-Jo1), and 6 out of 14 patients of the group B (6 males, 48%, mean ± SD age 68.7 ± 8.1) were positive to antisynthetase antibodies (2 anti-PL7, 2 anti-PL-12, 1 anti-EJ, 1 anti-OJ+PL7). Immunoblots also show positivity for other myositis-specific or associated antibodies, such as anti-TIF1g, anti-PM75, anti-SAE and anti-SRP. All of these results found by immunoblotting were negative by immunoprecipitation. None of the 28 patients were positive for anti-MDA5 antibodies.Conclusion:Severe SARS-CoV-2 pneumonia is characterized by ground glass pattern in chest CT, as it is found in anti-MDA5 or antisynthetase syndrome. The positivity of several myositis related autoantibodies showed in immunoblot appears to be more related to the vigorous immune response producing polyclonal immunoglobulins than triggering a real myositis-associated interstitial lung disease. Clinicians must be aware about these false positive results in patients with severe COVID-19 acute respiratory syndrome.References:[1]Xu Q. MDA5 should be detected in severe COVID-19 patients. Med Hypotheses. 2020; 143:109890.[2]Giannini M, Ohana M, Nespola B, Zanframundo G, Geny B, Meyer A. Similarities between COVID-19 and anti-MDA5 syndrome: what can we learn for better care? Eur Respir J. 2020; 56:2001618.[3]Vlachoyiannopoulos PG, Magira E, Alexopoulos H, Jahaj E, Theophilopoulou K, Kotanidou A, Tzioufas AG. Autoantibodies related to systemic autoimmune rheumatic diseases in severely ill patients with COVID-19. Ann Rheum Dis. 2020 Dec;79(12):1661-1663Disclosure of Interests:None declared

Background:Gastric antral vascular ectasia (GAVE) is one of the gastrointestinal (GI) manifestations related to systemic sclerosis (SSc). It can be presented as iron deficiency anemia or even upper gastrointestinal bleeding. GAVE is diagnosed by endoscopy observing an image of confluent vascular ectasias that is oriented longitudinally on the folds of the antrum in the appearance of “watermelon”. The definitive treatment for this manifestation consists in endoscopy guided fulguration when the clinical situation allows it.Objectives:The objective was to study a cohort of SSc patients at their first endoscopy. The clinical characteristics, laboratory tests and treatments received from SSc patients with GAVE were compared to those without this GI manifestation.Methods:From the cohort of patients with SSc in Hospital Universitari Vall d’Hebron, a total of 269 patients who had undergone at least one endoscopy during follow-up were selected. Twenty seven were diagnosed with GAVE. We compared the clinical, analytical and treatment characteristics of these patients with the remaining 242 who did not present GAVE. The statistical study was carried out using the SPSS 20.0 package (Chicago, IL), a p Results:The prevalence of GAVE in SSc patients was 10.0%. Patients with GAVE had a higher median age SSc onset taking into account the first non-Raynaud’s phenomenon (RP) symptom attributable to the disease (56.6 vs 48.0 years, p = 0.001). The median age at first endoscopy was 56.5 years in GAVE group compared with 61.7 in the group without GAVE.Compared with SSc patients without GAVE, patients with GAVE had a higher prevalence of Barrett’s esophagus (14.8% vs. 3.7%, p = 0.011), intestinal involvement (37% vs. 18.6%, p = 0.024) and a trend towards a lower prevalence of interstitial lung disease (25.9% vs 45.0%, p = 0.057).No difference was identified in the prevalence of scleroderma renal crisis. Patients with GAVE presented a higher frequency of early or active Cutolo capillaroscopy pattern with a predominance of enlarged capillaries or megacapillaries (84.6% vs 62.4%, p = 0.025), greater frequency of anti-centromere antibodies (63.0% vs. 42.1%, p = 0.039) and a trend towards a lower proportion of anti-topoisomerase I (3.7% vs. 18.6%, p = 0.052). No difference was found in prevalence of anti-RNA polymerase III antibodies between groups. Patients with GAVE were treated less frequently with non-glucocorticoid immunosuppressants prior to diagnostic endoscopy (0% vs 20.2%, p = 0.010). The 33.3% of patients with GAVE were treated with endoscopic fulguration, and 66.7% of them received supplementary treatment with oral iron.Conclusion:SSc patients with GAVE had higher age at SSc onset, more frequency of Barrett’s esophagus and intestinal involvement, prevalence of anti-centromere antibodies, early or active Cutolo scleroderma pattern and lower prior non-glucocorticoids treatment.References:[1]Ghrénassia E, Avouac J, Khanna D, T.Derk C, Distler O, Suliman Y, et al. Prevalence, Correlates and Outcomes of Gastric Antral Vascular Ectasia in Systemic Sclerosis: A EUSTAR Case-control Study. The Journal of Rheumatology. 2014; 41:1.Disclosure of Interests:None declared

Background:A nailfold capillaroscopy procedure is a non-invasive, low-cost, and well-established examination that can be used to diagnose several rheumatic autoimmune diseases and support the necessary follow-up of patients. While the clinical implications of the technique are known, a rigorous and in-depth examination of nailfold capillaries remains as one of the major challenges to produce new advances in research and diagnosis, due to practical limitations for analysing the whole nailfold area of each patient. The difference between the different patterns established by Maricq and Cutolo makes it possible to predict the evolution that the patient will present. We introduce Capillary.io, an automatic image reading system able to recognize capillaries in images obtained with any microscope, generate automatic measurements of each capillary and take advantage of this information to report capillary morphology and patterns.Objectives:to determine the ability to detect active and early scerodermiform patterns of Capillary.io.Methods:Forty-nine complete capillaroscopies, reported by expert capillaroscopists according to the different patterns manually (gold standard), were compared with the pattern detection capability of Capillary.io. A scoring system based on the algorithm of the Spanish Capillaroscopy Study Group (GREC) was performed and interpreted by capillary.io for the global interpretation of each of the capillaroscopies analyzed.Results:Overall, 37 of the 49 capillaroscopies reported agreed with the diagnosed pattern (75.51%). Separately, the early pattern presented a concordance of 77.27% and the active pattern of 74.07%. In reference to the findings detected by the Capillary.io system, the mean overall density was 5.01 capillaries/mm in the group with the active pattern compared to 6.46 capillaries/mm in the early pattern. The density of dilations and megacapillaries was 2.81/mm and 1.21/mm in the active pattern group versus 4.69/mm and 0.4/mm in the early pattern group. Global diameters were greater in the active pattern group with an apical mean of 37.3 μm compared to 28.5 μm in the early pattern subgroup.Conclusion:Capillary.io is a simple, easy-to-learn web system for interpreting capillaroscopic images of nail folds. It can be a very useful tool to standardize the interpretation of capillaroscopic images, not only individually for each capillary, but also jointly through the detection of different patterns.References:[1]Chen K, Wang J, Pang J, Cao Y, Xiong Y, Li X, et al. MMDetection: Open MMLab Detection Toolbox and Benchmark. arXiv preprint arXiv:190607155 2019;.[2]Cutolo M, Pizzorni C, Sulli A. Nailfold videocapillaroscopy assessment of microvascular damage in systemic sclerosis - Reply. The Journal of Rheumatology 2000 11;27:2722–2723.[3]Cutolo M, Trombetta AC, Melsens K, Pizzorni C, Sulli A, Ruaro B, et al. Automated assessment of absolute nailfold capillary number on videocapillaroscopic images: Proof of principle and validation in systemic sclerosis. Microcirculation 2018 May;25(4):e12447.[4]Smith V, Vanhaecke A, Herrick AL, Distler O, Guerra MG, Denton CP, et al. Fast track algorithm: How to differentiate a “scleroderma pattern” from a “non-scleroderma pattern”. Autoimmu- nity Reviews 2019 nov;18(11):102394.[5]Tavakol ME, Fatemi A, Karbalaie A, Emrani Z, Erlandsson BE. Nailfold Capillaroscopy in Rheumatic Diseases: Which Parameters Should Be Evaluated? BioMed Research International 2015;2015:1–17.Disclosure of Interests:Eduardo Ramos Shareholder of: Co-founder and shareholder of Capillary.io, Alfredo Guillén-Del-Castillo: None declared, Carmen Pilar Simeón-Aznar: None declared, Borja Gracia Tello Shareholder of: Co-founder and shareholder of Capillary.io, Vicent Fonollosa Pla: None declared, Albert Selva-O’Callaghan: None declared, Luis Sáez-Comet: None declared, Elena Martínez Robles: None declared, Juan José Rios: None declared, Gerard Espinosa: None declared, Jose Antonio Todolí Parra: None declared, Jose Luis Callejas-Rubio: None declared, Norberto Ortego: None declared, Begoña Marí-Alfonso: None declared, Mayka Freire: None declared, Patricia Fanlo: None declared

Background:Idiopathic inflammatory myopathies are a heterogenous group of systemic autoimmune diseases. Several phenotypes have been linked to specific autoantibodies. Clinically amyopathic dermatomyositis with rapidly progressive interstitial lung disease, the most severe form of ILD, is associated with the anti-MDA5 antibodies. However not all the patients with dermatomyositis and anti-MDA5 positive antibodies develop this severe condition.Objectives:We aim to define different phenotypes from a large cohort of patients diagnosed with dermatomyositis who were positive to anti-MDA5 antibodies.Methods:We retrospective analyzed the clinical and immunological data of 90 anti-MDA5 patients [50 female, 55.6%, mean (SD) age at diagnosis 47 (15.4) yrs.] with dermatomyositis recruited from a multicenter register in Spain (MEDRA5) including 30 hospitals. All the patients fulfill de International Myositis Classification Criteria (EULAR/ACR) for dermatomyositis (score >90%). Anti-MDA5 were detected by means of commercial immunoblot (EUROIMMUN©). The chi-square test was used to assess the relationships between qualitative variables. The Kruskal-Wallis test was used to compared medians between groups.Results:Sixty-six patients (73.3%) were diagnosed with clinically amyopathic dermatomyositis. Three different phenotypes linked with the anti-MDA5 antibody were identified. Group 1: patients with rapidly-ILD phenotype (28 patients, 31.1%), group 2: antisynthetase-like phenotype (23 patients, 25.5%), and group 3: non-ILD phenotype (39 patients, 43.3%). Clinical and immunological comparison between the groups disclosed that age at disease onset was higher (median, IQR) in patients from group 1 [53 (43-60)] vs. group 2 [46 (40-56)] or group 3 [42(41-51)] (p=0.01); disease onset was more frequent in spring in patients from group 1 (46.5%) than in the rest of the groups (21.7% and 28.9%) (pConclusion:Three different phenotypes of patients positive to anti-MDA5 were identified. The presence or not of ILD, or the different type (rapidly progressive or not) of ILD were the main feature that allow to differentiate these phenotypes, which are relevant in clinical practice.References:[1]Allenbach Y, Uzunhan Y, Toquet S, et al; French Myositis Network. Different phenotypes in dermatomyositis associated with anti-MDA5 antibody: Study of 121 cases. Neurology. 2020;95: e70-e78.Acknowledgements:List of contributors of MEDRA5 group: Aguilar-García J (Internal Medicine, Hospital Costa del Sol, Marbella), Carrión-Barberá I (Rheumatology, Hospital del Mar, Barcelona), Cobo-Ibañez T (Rheumatology, Hospital Infanta Sofía, San Sebastián de los Reyes), de Escalante-Yangüela B (Internal Medicine, Hospital Clínico Lozano Blesa, Zaragoza), Fonseca-Aizpuru EM (Internal Medicine, Hospital de Cabueñes, Gijón), González-Cubillo L (Intensive Medicine, Hospital Universitario de Cruces, Barakaldo), González-Gay MA (Rheumatology, Hospital Marqués de Valdecilla, Santander), Prieto-González S (Internal Medicine, Hospital Clinic, Barcelona), Ruiz-Román A (Rheumatology, Hospital Universitario Virgen del Rocío, Sevilla), Calero-Paniagua I (Internal Medicine, Hospital Virgen de la Luz, Cuenca), Callejas-Rubio JL (Internal Medicine, Hospital Clínico San Cecilio, Granada), Gil-Vila A (Internal Medicine, Hospital Vall d’Hebron, Barcelona), de Miguel-Campo B (Internal Medicine, Hospital Doce de Octubre, Madrid), García-Sevilla R (Pneumology, Hospital General Universitario de Alicante, Alicante), Iriarte-Fuster A (Internal Medicine, Hospital de Bellvitge, Hospitalet de Llobregat), Jovani-Casano V (Rheumatology, Hospital General Universitario de Alicante, Alicante), Lozano-Rivas N (Rheumatology, Hospital Virgen de la Arritxaca, Murcia), Martín-Gascón M (Internal Medicine, Hospital Morales Meseguer, Murcia), Martinez-González O (Rheumatology, Hospital Universitario de Salamanca, Salamanca), Monteagudo-Jiménez M (Internal Medicine, Hospital Parc Taulí, Sabadell), Mora-Ortega GM (Pneumology, Hospital Universitario Infanta Sofía, San Sebastián de los Reyes), Moral-Moral Pedro (Internal Medicine, Hospital Universitari i Politecnic La Fe, Valencia), Pérez-De Pedro I (Interna Medicine, Hospital Regional Universitario de Málaga, Málaga), Picazo-Talavera MR (Rheumatology, Hospital del Sureste, Madrid), Rubio-Rivas M (Internal Medicine, Hospital de Bellvitge, Hospitalet de Llobregat)Disclosure of Interests:None declared

Background:Antisynthetase syndrome (ASS) is characterized by inflammatory myopathy, interstitial lung disease, arthritis, mechanical hands and Raynaud phenomenon, among other features. Recent studies have shown that idiopathic inflammatory myopathies (IIM) may develop cardiac involvement, either ischemic (coronary artery disease) or inflammatory (myocarditis). We wonder if characteristic lung interstitial involvement (interstitial lung disease) that appears in patients with the ASS may also affect the myocardial interstitial tissue. New magnetic resonance mapping techniques could detect subclinical myocardial involvement, mainly as edema (increase extracellular volume in interstitium and extracellular matrix), even in the absence of visible late Gadolinium enhancement (LGE).Objectives:Our aim was to describe the presence of interstitial myocarditis in a group of patients with ASS.Methods:Cross-sectional, observational study performed in a tertiary care center. We included 13 patients diagnosed with ASS (7 male, 53%, mean (SD) age at diagnosis 56,8 years (±11,8)). The patients were consecutively selected from our outpatient myositis clinic. Myositis specific and associated antibodies were performed by means of line immunoblot (EUROIMMUN©). Cardiac magnetic resonance (CMR) was performed on all patients. The study protocol includes functional cine magnetic resonance and standard late gadolinium enhancement (LGE), as well as novel parametric T1 and T2 mapping sequences (modified look locker inversion recovery sequences - MOLLI) with extracellular volume (ECV) calculation 20 minutes after the injection of a gadolinium-based contrast material.Results:CMR could not be performed in one patient due to anxiety. All patients studied (12) had a normal biventricular function, without alteration of segmental contraction. A third (4 out of 12, 33%) of the studied patients showed elevated T2 myocardial values without focal LGE, half of them (2/4) with an elevated ECV, consistent with myocardial edema. Two patients with normal T2 values showed unspecific LGE focal patterns, one in the right ventricle union points and another with mild interventricular septum enhancement (Figure 1). None of the patients studied refer any cardiac symptomatology. All the four patients with T2 mapping alterations (100%) had interstitial lung involvement, but only 4 out of 8 (50%) of the rest ASS patients without T2 mapping positivity. The autoimmune profile was as follows: 10 anti-Jo1/Ro52, 1 anti-EJ/Ro52, 2 anti-PL12.Conclusion:Myocarditis, although subclinical, appears to be a feature in ASS patients. T1 and T2 mapping sequences might be valuable to detect and monitor subclinical cardiac involvement in these patients. The possibility that the same etiopathogenic mechanism may be involved in the interstitial tissue in lung and myocardium is raised. More studies must be done in order to assert the prevalence of myocarditis in ASS.References:[1]Dieval C et al. Myocarditis in Patients With Antisynthetase Syndrome: Prevalence, Presentation, and Outcomes. Medicine (Baltimore). 2015 Jul;94(26):e798.[2]Myhr KA, Pecini R. Management of Myocarditis in Myositis: Diagnosis and Treatment. Curr Rheumatol Rep. 2020 Jul 22; 22:49.[3]Sharma K, Orbai AM, Desai D, Cingolani OH, Halushka MK, Christopher-Stine L, Mammen AL, Wu KC, Zakaria S. Brief report: antisynthetase syndrome-associated myocarditis. J Card Fail. 2014 Dec;20(12):939-45.Figure 1.Cardiac magnetic resonance images from ASS patients.Disclosure of Interests:None declared

Background:Nailfold Capillaroscopy is a simple, inexpensive and non-invasive technique that allows microvascular damage to be observed, gaining recent importance in the diagnosis, monitoring and prognosis of many diseases with microangiopathy. However, the variability in the results interpretation has led to the development of new computerized systems that allow the automatic analysis of capillaroscopic images.Objectives:to compare the degree of agreement between the automatic system Capillary.io and a gold standard obtained from the agreement of 9 expert capillaroscopists and to know the degree of the interobserver reliability To demonstrate the validity of the system to detect normal and enlarged capillaries, hemorrhages, megacapillaries, ramifications and tortuosities.Methods:a cross-sectional study was performed in which 300 random and anonymous nailfold capillaroscopic images (1165 capillaries) were analyzed by 9 experienced observers. The degree of interobserver agreement was calculated from the 5 users. Likewise, the system performed an automatic assessment of the images and their agreement with the gold standard was calculated (interobserver agreement greater than 5, 6, 7, 8 and 9 successively). The validity of the program for each variable was also analyzed using sensitivity and specificity, positive and negative predictive values, and likelihood ratios, as well as their degree of agreement using the weighted kappa statistic (95% CI, p Results:the degree of interobserver agreement was 76.5% for the agreement of 5 or more observers, progressively decreasing to 15.4% for the 9 observers. Capillary.io obtained higher levels of agreement, reaching 97.7% for the 9 observers. Statistically significant results were obtained in the automated detection of all the morphological alterations analyzed Capillary.io presented a sensitivity (S) of 79.82% and a specificity (E) of 82% in the recognition of normal capillaries. The automatized system was able to recognize enlarged capillaries with a sensitivity of 86.97% and a specificity of 81.38%. Megacapillaries were detected with 89.41% sensitivity and 78.75% specificity. Similarly, the system was able to detect tortuosities (S 66.94%; E 67.71%), ramifications (S 54.34%; E 58.61%) and hemorrhages (S 71.36; E 73.97%).Conclusion:Capillary.io demonstrated a high degree of agreement with the gold standard, stronger with greater consensus among observers. It was able to detect with great sensitivity and specificity hemorrhages and megacapillaries, very relevant alterations in microangiopathies.References:[1]Roldán LMC, Franco CJV, Navas MAM. Capillaroscopy in systemic sclerosis: A narrative literature review. Rev Colomb Reumatol; 2016; 23: 250-8.[2]Ingegnoli F, Gualtierotti R, Lubatti C, Bertolazzi C, Gutierrez M, Boracchi P, et al. Nailfold capillary patterns in healthy subjects: A real issue in capillaroscopy. Microvasc Res. 2013;90:90-5.[3]Cutolo M, Pizzorni C, Secchi ME, Sulli A. Capillaroscopy. Best Pract Res Clin Rheumatol. 2008; 22:1093-108.[4]Tavakol ME, Fatemi A, Karbalaie A, Emrani Z, Erlandsson BE. Nailfold Capillaroscopy in Rheumatic Diseases: Which Parameters Should Be Evaluated? BioMed Res Int. 2015; 2015: 974530.[5]Smith V, Herrick AL, Ingegnoli F, Damjanov N, De Angelis R, Denton CP, et al. Standardisation of nailfold capillaroscopy for the assessment of patients with Raynaud’s phenomenon and systemic sclerosis. Autoimmunity Reviews. 2020; 19: 102458.Disclosure of Interests:Borja Gracia Tello Shareholder of: Co-founder and shareholder of Capillary.io., Eduardo Ramos Shareholder of: Co-founder and shareholder of Capillary.io., Carmen Pilar Simeón-Aznar: None declared, Vicent Fonollosa Pla: None declared, Alfredo Guillén-Del-Castillo: None declared, Albert Selva-O’Callaghan: None declared, Luis Sáez-Comet: None declared, Elena Martínez Robles: None declared, Juan José Rios: None declared, Gerard Espinosa: None declared, Jose Antonio Todolí Parra: None declared, Jose Luis Callejas-Rubio: None declared, Norberto Ortego: None declared, Begoña Marí-Alfonso: None declared, Mayka Freire: None declared, Patricia Fanlo: None declared

Idiopathic inflammatory myopathies (IIMs) may present as a primary autoimmune disorder, or overlap with other autoimmune/connective tissue diseases. The aetiology of IIM likely includes interactions between genetic and environmental factors. Several genetic variants common to multiple autoimmune disorders have been identified in recent genome-wide association studies (GWAS). A Myositis Genetics Consortium dermatomyositis (DM) GWAS also suggests genetic overlap with other autoimmune disorders.1 We sought to extend these findings to identify novel genetic risk factors in a large cohort of adult/juvenile patients with DM and polymyositis (PM), by genotyping immune-related single nucleotide polymorphisms (SNPs) not captured through the DM GWAS.1 SNPs significantly associated (p

Objective: To describe the methodology used to develop new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups. Methods: An international, multidisciplinary group of myositis experts produced a set of 93 potentially relevant variables to be tested for inclusion in the criteria. Rheumatology, dermatology, neurology, and pediatric clinics worldwide collected data on 976 IIM cases (74% adults, 26% children) and 624 non-IIM comparator cases with mimicking conditions (82% adults, 18% children). The participating clinicians classified each case as IIM or non-IIM. Generally, the classification of any given patient was based on few variables, leaving remaining variables unmeasured. We investigated the strength of the association between all variables and between these and the disease status as determined by the physician. We considered three approaches: (1) a probability-score approach, (2) a sum-of-items approach criteria, and (3) a classification-tree approach. Results: The approaches yielded several candidate models that were scrutinized with respect to statistical performance and clinical relevance. The probability-score approach showed superior statistical performance and clinical practicability and was therefore preferred over the others. We developed a classification tree for sub-classification of patients with IIM. A calculator for electronic devices, such as computers and smart phones, facilitates the use of the EULAR/ACR classification criteria. Conclusions: The new EULAR/ACR classification criteria provide a patient’s probability of having IIM for use in clinical and research settings. The probability is based on a score obtained by summing the weights associated with a set of criteria items.

Background A statin-associated autoimmune myopathy with anti-HMGCR antibodies has recently been described. Identification of these patients is of paramount importance because immunosuppressive therapy is usually needed for clinical improvement. Herein we report a new pattern of immunofluorescence (IIF) that could alert of the presence of this antibody in routine autoantibody screening on kidney, liver, stomach sections. Objectives Our objective was to study the concordance of this IIF pattern with anti-HMGCR in a series of patients with immune-mediated necrotizing myopathy (IMNM). Methods Seventeen patients diagnosed with IMNM positive for anti-HMGCR antibodies were tested for the presence of IIF pattern. As a control group, 90 patients diagnosed with systemic autoimmune diseases (SLE, autoimmune hepatitis, systemic sclerosis, rheumatoid arthritis, Sjogren syndrome, and dermatomyositis – 15 from each group), and 45 patients treated with statins (15 with familial severe dyslipidemia, 15 with a recent cerebrovascular event – treated high dose of atorvastatin, and 15 from the community) were also studied. Anti-HMGCR antibodies were measured by means of two ELISA assays: a in-house confirmed by blot using hidroxi-methil-glutharil-CoA (Sigma H7039) as antigen and commercial QUANTA Lite HMGCR ELISA Innova (San Diego). Indirect immunofluorescence studies on triple tissue (rat liver, kidney and stomach) was performed using Nova Lite assay (Innova Diagnostic, San Diego, USA). We used different commercial substrates (Innova, Euroimmune, ByoSistems, and Aeskulides) in order to confirm that the reactivity of the pattern do not depend on the commercial source. Indirect immunofluorescence on HEp-2 Slides (INOVA Diagnostics, Inc., San Diego Hep-2 ANA slides) was also performed. Immunoabsorption studies were performed using HMGCR human antigen (Sigma, St Louis, MO,USA) at different dilutions (PBS 10%) in those patients with a positive IIF pattern Results A cytoplasmatic pattern in scattered hepatocytes with perivascular distribution was observed in 15 out of 17 (88%) IMNM positive for anti-HMGCR antibodies. No patients from the autoimmune systemic disease group or those treated with statins disclosed this characteristic pattern. Consequently, the overall agreement between rat triple tissue IIF and ELISA confirmed by blot was 98.7% (kappa 0.93). Dispersed hepatocyte cytoplasmatic pattern (DHCP) was specifically absorbed by incubation with human purified antigen. A granular cytoplasmatic fluorescence pattern was observed in 6 out of 17 (35%) patients with human Hep cells. Conclusions A new distinctive IIF pattern on routine rat triple tissue is described in patients diagnosed with IMNM whit anti-HMGCR antibodies. It could be useful to alert of the presence of anti-HMGCR antibodies when performing a routine unexpensive autoantibody profile. Disclosure of Interest None declared

Background Antisynthetase syndrome (ASS) can be a life-threatening condition. Patients with ASS in the context of idiopathic inflammatory myositis (IIM) have been described to have a worse prognosis compared to patients either with dermatomyositis (DM) or polymyositis (PM) alone. Objectives To evaluate survival and mortality in a large cohort of Spanish patients with anti-Jo1 ASS and compare it with mortality rates of Spanish general population. Methods From March 2011 to June 2014 we conducted a national multicentre study, including retrospective and prospective data, among members of the GEAS-IIM Group of the SEMI. Clinicians from 18 Spanish centers participated in the development of a registry of patients with Anti-Jo1 ASS. For data collection a specific electronic database including broad information about demographic and clinical data was developed. Continuous variables were compared by the t-student or non-parametric Mann-Whitney tests when appropriated, while X2 test were used to compare categorical variables. The Kaplan-Meier method and long-rank tests were used to compare survival between groups. The standardized mortality ratio (SMR) was calculated using the Spanish mortality registry. Results were expressed with its 95% interval confiance (IC). Results A total of 148 anti-Jo1 ASS patients, 90 women (60.8%), were included in the study. Mean (SD) age at diagnosis was 50.8 (16) years. Range follow-up was 1.3 to 412 months [mean (SD) 95 (76.4) months], with only 12 patients with a follow-up fewer than 12 months. Fifteen percent of patients had ILD as the unique main ASS clinical manifestation, other 15% had myositis and 69.3% had both ILD and myositis. Thirty seven patients (25%) died after a median follow-up of 70.3 months (range 4.9 – 308 months). The SMR (95%IC) was 4.77 (3.31-6.67). Main causes of death included respiratory failure (6.8%), cancer (6.1%), infection (4.1%), myositis (2.7%) and acute cardiovascular events (1.3%). A directly ASS-related death were considered in 18 patients (46.6%). Estimated survival rate (95% IC) was 87.5% (81.6% - 93.4%) and 75.4% (66.4% - 84.4%) at 5 and 10 years respectively. Median survival rate (95% IC) was 20.3 years (13.8-26.8 years). No difference in survival was found between patients with myositis (DM or PM) and those with ILD without associated myopathy. The presence of cancer (p=0.02) and an advanced age at ASS diagnosis (p Conclusions Mortality in ASS patients is four-fold and a half higher than in the general population. Mortality can be directly attributed to ASS in near a half of the cases. Respiratory failure, cancer and infection are the main causes of death. Estimated survival rate at 10 years is around 75%. References Marie I. Morbidity and mortality in adult polymyositis and dermatomyositis. Curr Rheumatol Rep.2012;14:275-285. Disclosure of Interest None declared

Objectives To assess cumulative organ damage in juvenile dermatomyositis (JDM) patients after long term disease and to establish the possible relationship between the final damage score and the treatment received during the first year of disease. Methods A retrospective study was conducted in a cohort of patients with JDM followed in a Unit of Pediatric Rheumatology from December 1985 to October 2013. The cumulative organ damage was evaluated using the Myositis Damage Index (MDI), a score which assesses the presence of damage in 11 organs/systems (minimal score value 0- maximum 38). This score includes two variants: the cumulative MDI score which covers all damage present for at least 6 months during the entire disease course and the actual MDI score which measures the damage that is clinically detectable at the time of the visit. A physician visual analogue scale (VAS) (0-10 cm) was used to assess the severity of total damage at last follow-up. Data regarding the received treatment was recorded. Results The sample included 16 patients, 8 females and 8 males. The mean age at diagnosis was 7.68 years (range 2.75-14.4). The mean time of follow-up since disease onset was 11 years (range 1.2-28). Patients who received disease modifying anti-rheumatic drugs (DMARD) biological or not biological during the first year of JDM course were considered as “aggressively” treated (n=11), while patients who didn9t receive immunomodulatory drugs during the first year were considered as “non aggressively” treated (N=5). Data referred to extension and severity of damage is recorded in table 1 (see below). MDI score after 1 year of follow-up, cumulative MDI and actual MDI measured at last follow-up as well as the physician assessment of the severity of total damage (VAS) are expressed as mean and range. The systems more frequently involved were: skin (87.5%), muscular (87.5%), endocrine (43.75%) and skeletal (25%). Conclusions Data obtained suggests that in JDM intensification of treatment during the first year after disease onset could be a factor that determines the total cumulative damage to the same extent as the clinical course. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4398

Background Interstitial lung disease (ILD) is a potentially severe manifestation of patients with systemic sclerosis (SSc). High-resolution computed tomography (HRCT) is the reference test for diagnosis and follow-up. Objectives Our objective was to analyze the performance of the MRI, a non-ionizing exploration, compared with the HRCT, to assess the extension of SSc-associated ILD. Methods We retrospectively collected data of patients with different degrees of ILD due to SSc in which a 1.5T chest MRI (using a 15-seconds HASTE sequence) and a HRCT were performed in a maximum interval of one year. A previously validated HRCT score and new MRI score were performed to assess the extension of the ILD. Composite scores were created to make the comparisons. The regression, correlation and anatomical distribution of MRI compared with HRCT were calculated. Results Twelve patients were studied (11 women). A strong correlation was found between general MRI and total HRCT composite scores (r=0.70, p=0.01) with a significant linear relationship between them (p=0.01); a moderate correlation was observed between the general MRI and the HRCT fibrosis composite scores (r=0.64, p=0.02), also with a significant linear relationship (p=0.03). The distribution of the MRI and the HRCT composite scores was comparable, showing a predominant distribution of ILD findings in the lower zones of both lungs. Conclusions Compared with HRCT, our new MRI extension score using a 15-second-sequence MRI showed good correlation, significant linear relationship and similar anatomic distribution, suggesting that MRI may be reliable to assess the extension of ILD in SSc patients. References Brenner DJ, Hall EJ. Computed tomography–an increasing source of radiation exposure. The New England journal of medicine 2007;357:2277-84. Muller NL, Mayo JR, Zwirewich CV. Value of MR imaging in the evaluation of chronic infiltrative lung diseases: comparison with CT. AJR American journal of roentgenology 1992;158:1205-9. Lutterbey G, Grohe C, Gieseke J, et al. Initial experience with lung-MRI at 3.0T: Comparison with CT and clinical data in the evaluation of interstitial lung disease activity. European journal of radiology 2007;61:256-61. Lutterbey G, Gieseke J, von Falkenhausen M, Morakkabati N, Schild H. Lung MRI at 3.0 T: a comparison of helical CT and high-field MRI in the detection of diffuse lung disease. European radiology 2005;15:324-8. McFadden RG, Carr TJ, Wood TE. Proton magnetic resonance imaging to stage activity of interstitial lung disease. Chest 1987;92:31-9. Gaeta M, Blandino A, Scribano E, et al. Chronic infiltrative lung diseases: value of gadolinium-enhanced MRI in the evaluation of disease activity–early report. Chest 2000;117:1173-8. Yi CA, Lee KS, Han J, Chung MP, Chung MJ, Shin KM. 3-T MRI for differentiating inflammation- and fibrosis-predominant lesions of usual and nonspecific interstitial pneumonia: comparison study with pathologic correlation. AJR American journal of roentgenology 2008;190:878-85. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1587

Background Idiopathic inflammatory myopathies (IIM) may present as a primary disorder, or may overlap with connective tissue diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) or systemic sclerosis. The aetiology of IIM is largely unknown, but is thought to include a combination of genetic and environmental factors. To generate ethnically homogeneous IIM cohorts of sufficient size given its rarity, one of the largest European IIM initiatives has enabled Europe wide ascertainment of cases with EUMYONET. Numerous genome-wide association studies (GWAS) have identified many genetic variants associated with autoimmune disorders, several common to multiple disorders. This is supported by our recent dermatomyositis (DM) GWAS, suggesting genetic overlap with other autoimmune disorders1. Objectives We sought to identify additional novel genetic risk factors in adult and juvenile polymyositis (PM) and DM (not previously identified by DM GWAS), shared with other autoimmune disorders. Methods SNPs significantly associated with SLE, RA, juvenile idiopathic arthritis, coeliac disease, Crohn's disease, ulcerative colitis, psoriasis, type 1 diabetes, multiple sclerosis or systemic sclerosis were identified from published Caucasian GWAS and from the national human genome research institute catalogue of published GWAS. 233 unique SNPs were identified ( p 5% missing genotype data were excluded, resulting in 1149 cases and 3572 controls. Outside the MHC region, a non-synonymous SNP rs2304256 in the TYK2 gene was identified reaching Bonferroni-corrected significance in IIM and DM (β= -0.21, p value=0.00027; β= -0.25, p value=0.00020 respectively). Two further SNPs within the BLK gene and 2335bp 5' of BLK were associated with DM (rs2618476, β=0.24, p value=0.00062; rs13277113, β=0.25 p value=0.00045 respectively) but not with PM, supporting the results of our DM GWAS. Conclusions We have identified TYK2 as a novel association for DM, suggesting genetic overlap of DM with other autoimmune disorders, and indicating genetic heterogeneity between PM and DM. TYK2 has been associated previously with SLE, type 1 diabetes and multiple sclerosis. Further associations of the BLK gene with DM, suggests a role of B cells in its development. References 1. Miller FW et al. Arthritis Rheum. 2013 Dec; 65(12):3239-3247 Acknowledgements Funding: Arthritis Research UK (grants 18474; 14518), Intramural Research Program of the NIH, Wellcome Trust (076113; 085860). We thank all other members of the EUMYONET and Myositis Genetics Consortium (MYOGEN). Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2877

Background Idiopathic inflammatory myopathies (IIM) are systemic diseases, characterized by the presence of an inflammatory muscle infiltrate. Although more frequent in women, its relationship with pregnancy has not been extensively studied. Objectives Our goal was to analyze the interaction between pregnancy and myositis in a cohort of IIM women from a single center. Methods Fifty-one patients from a historical cohort of IIM diagnosed between 1983 and 2013 were interviewed with a specific questionnaire. Comparisons between pregnancies occurring before and after the onset of the disease were performed using generalized mixed-effect models with normal and binomial distributions adjusted for confounding factors and clustering. Results One-hundred and two pregnancies from 51 patients (41 dermatomyositis [DM] and 10 polymyositis [PM]) were analyzed. Fourteen (13.7%) pregnancies from 8 patients (5 DM, 3 PM) occurred after disease onset; clinical improvement during gestation was evident in 7 pregnancies (4 patients), 5 of them (from 2 patients) experienced a relapse of IIM symptoms afterwards, while in the rest there was no influence of pregnancy on the disease. No disease flare associated with pregnancy was observed. Two (3.9%) patients (2 DM) were diagnosed within the first 6 months after delivery and none during pregnancy. No evidence was found to support pregnancy as a trigger for myopathy (p=0.10). Conclusions Pregnancy does not seem to carry a worse prognosis for the mother nor for the fetus in patients with IIM; on the contrary, near half of the patients in our series improved clinically when they became pregnant, being common a relapse of IIM symptoms afterwards. Pregnancy does not appear to be a trigger for IIM. References Vincze M, Danko K. Idiopathic inflammatory myopathies. Best Pract Res Clin Rheumatol. 2012;26:25-45. Rider LG, Miller FW. Deciphering the clinical presentations, pathogenesis, and treatment of the idiopathic inflammatory myopathies. JAMA. 2011;305:183.90. Mastaglia FL, Phillips BA. Idiopathic inflammatory myopathies: epidemiology, classification, and diagnostic criteria. Rheum Dis Clin North Am. 2002;28:723-41. Vargas-Leguas H, Selva-O9Callaghan A, Campins-Marti M, et al. Polymyositis-dermatomyositis: incidence in Spain (1997-2004). Med Clin (Barc). 2007 24;129:721-4. Silva CA, Sultan SM, Isenberg DA. Pregnancy outcome in adult-onset idiopathic inflammatory myopathy. Rheumatology (Oxford) 2003;42:1168-72. King CR, Chow S. Dermatomyositis and pregnancy. Obstet Gynecol 1985;66:589-92. Gutierrez G, Dagnino R, Mintz G. Polymyositis/dermatomyositis and pregnancy. Arthritis Rheum 1984;27:291-4. Kanoh H, Izumi T, Seishima M, Nojiri M, Ichiki Y, Kitajima Y. A case of dermatomyositis that developed after delivery: the involvement of pregnancy in the induction of dermatomyositis. Br J Dermatol 1999;141:897-900. Vancsa A, Ponyi A, Constantin T, Zeher M, Danko K. Pregnancy outcome in idiopathic inflammatory myopathy. Rheumatol Int 2007;27:435-9.12. De Man YA, Dolhain RJ, van de Geijn FE, Willemsen SP, Hazes JM. Disease activity of rheumatoid arthritis during pregnancy: results from a nationwide prospective study. Arthritis Rheum. 2008;59:1241–8. Acknowledgements We thank Dr. Pari Basharat and Dr. Arash Lahoutiharahdashti for their critical review of the project. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1571