IMPAIRED HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHIES: A CROSS-SECTIONAL ANALYSIS FROM AN INTERNATIONAL E-SURVEY

BackgroundComprehensive and large-scale assessment of health-related quality of life in patients with idiopathic inflammatory myopathies (IIMs) worldwide is lacking. The second COVID-19 vaccination in autoimmune disease (COVAD-2) study [1] is an international, multicentre, self-reported e-survey assessing several aspects of COVID-19 infection and vaccination as well as validated patient-reported outcome measures (PROMs) to outline patient experience in various autoimmune diseases (AIDs), with a particular focus on IIMs.ObjectivesTo investigate physical and mental health in a global cohort of IIM patients compared to those with non-IIM autoimmune inflammatory rheumatic diseases (AIRDs), non-rheumatic AIDs (NRAIDs), and those without AIDs (controls), using Patient-Reported Outcome Measurement Information System (PROMIS) global health data obtained from the COVAD-2 survey.MethodsDemographics, AID diagnoses, comorbidities, disease activity, treatments, and PROMs were extracted from the COVAD-2 database. The primary outcomes were PROMIS Global Physical Health (GPH) and Global Mental Health (GMH) scores. Secondary outcomes included PROMIS physical function short form-10a (PROMIS PF-10a), pain visual analogue scale (VAS), and PROMIS Fatigue-4a scores. Each outcome was compared between IIMs, non-IIM AIRDs, NRAIDs, and controls. Factors affecting GPH and GMH scores in IIMs were identified using multivariable regression analysis.ResultsA total of 10,502 complete responses from 1582 IIMs, 4700 non-IIM AIRDs, 545 NRAIDs, and 3675 controls, which accrued as of May 2022, were analysed. Patients with IIMs were older [59±14 (IIMs) vs. 48±14 (non-IIM AIRDs) vs. 45±14 (NRAIDs) vs. 40±14 (controls) years, p<0.001] and more likely to be Caucasian [82.7% (IIMs) vs. 53.2% (non-IIM AIRDs) vs. 62.4% (NRAIDs) vs. 34.5% (controls), p<0.001]. Among IIMs, dermatomyositis (DM) and juvenile DM were the most common (31.4%), followed by inclusion body myositis (IBM) (24.9%). Patients with IIMs were more likely to have comorbidities [68.1% (IIMs) vs. 45.7% (non-IIM AIRDs) vs. 45.1% (NRAIDs) vs. 26.3% (controls), p<0.001] including mental disorders [33.4% (IIMs) vs. 28.2% (non-IIM AIRDs) vs. 28.4% (NRAIDs) vs. 17.9% (controls), p<0.001].GPH median scores were lower in IIMs compared to NRAIDs or controls [13 (interquartile range 10–15) IIMs vs. 13 (11–15) non-IIM AIRDs vs. 15 (13–17) NRAIDs vs. 17 (15–18) controls, p<0.001] and PROMIS PF-10a median scores were the lowest in IIMs [34 (25–43) IIMs vs. 40 (34–46) non-IIM AIRDs vs. 47 (40–50) NRAIDs vs. 49 (45–50) controls, p<0.001]. GMH median scores were lower in AIDs including IIMs compared to controls [13 (10–15) IIMs vs. 13 (10–15) non-IIM AIRDs vs. 13 (11–16) NRAIDs vs. 15 (13–17) controls, p<0.001]. Pain VAS median scores were higher in AIDs compared to controls [3 (1–5) IIMs vs. 4 (2–6) non-IIM AIRDs vs. 2 (0–4) NRAIDs vs. 0 (0–2) controls, p<0.001]. Of note, PROMIS Fatigue-4a median scores were the highest in IIMs [11 (8–14) IIMs vs. 8 (10–14) non-IIM AIRDs vs. 9 (7–13) NRAIDs vs. 7 (4–10) controls, p<0.001].Multivariable regression analysis in IIMs identified older age, male sex, IBM, comorbidities including hypertension and diabetes, active disease, glucocorticoid use, increased pain and fatigue as the independent factors for lower GPH scores, whereas coexistence of interstitial lung disease, mental disorders including anxiety disorder and depression, active disease, increased pain and fatigue were the independent factors for lower GMH scores.ConclusionBoth physical and mental health are significantly impaired in patients with IIMs compared to those with non-IIM AIDs or those without AIDs. Our results call for greater attention to patient-reported experience and comorbidities including mental disorders to provide targeted approaches and optimise global well-being in patients with IIMs.Reference[1]Fazal ZZ, Sen P, Joshi M, et al. COVAD survey 2 long-term outcomes: unmet need and protocol. Rheumatol Int. 2022;42:2151–58.AcknowledgementsThe authors a e grateful to all respondents for completing the questionnaire. The authors also thank The Myositis Association, Myositis India, Myositis UK, the Myositis Global Network, Cure JM, Cure IBM, Sjögren's India Foundation, EULAR PARE for their contribution to the dissemination of the survey. Finally, the authors wish to thank all members of the COVAD study group for their invaluable role in the data collection.Disclosure of InterestsAkira Yoshida: None declared, Yuan Li: None declared, Vahed Maroufy: None declared, Masataka Kuwana Speakers bureau: Boehringer Ingelheim, Ono Pharmaceuticals, AbbVie, Janssen, Astellas, Bayer, Asahi Kasei Pharma, Chugai, Eisai, Mitsubishi Tanabe, Nippon Shinyaku, Pfizer, Consultant of: Corbus, Mochida, Grant/research support from: Boehringer Ingelheim, Ono Pharmaceuticals, Naveen Ravichandran: None declared, Ashima Makol Consultant of: Boehringer-Ingelheim, Parikshit Sen: None declared, James B. Lilleker: None declared, Vishwesh Agarwal: None declared, Sinan Kardes: None declared, Jessica Day Grant/research support from: CSL Limited, Marcin Milchert: None declared, Mrudula Joshi: None declared, Tamer A Gheita: None declared, Babur Salim: None declared, Tsvetelina Velikova: None declared, Abraham Edgar Gracia-Ramos: None declared, Ioannis Parodis Grant/research support from: Amgen, AstraZeneca, Aurinia Pharmaceuticals, Eli Lilly, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceuticals, Novartis, and F. Hoffmann-La Roche, Elena Nikiphorou Speakers bureau: Celltrion, Pfizer, Sanofi, Gilead, Galapagos, AbbVie, Eli Lilly, Consultant of: Celltrion, Pfizer, Sanofi, Gilead, Galapagos, AbbVie, Eli Lilly, Grant/research support from: Pfizer, Eli Lilly, Ai Lyn Tan Speakers bureau: AbbVie, Gilead, Janssen, Eli Lilly, Novartis, Pfizer, UCB, Consultant of: AbbVie, Gilead, Janssen, Eli Lilly, Novartis, Pfizer, UCB, Arvind Nune: None declared, Lorenzo Cavagna: None declared, Miguel A Saavedra Consultant of: AbbVie, GlaxoSmithKline, Samuel Katsuyuki Shinjo: None declared, Nelly Ziade Speakers bureau: AbbVie, Boehringer-Ingelheim, Eli Lilly, Janssen, Pfizer, Roche, Consultant of: AbbVie, Boehringer-Ingelheim, Eli Lilly, Janssen, Pfizer, Roche, Grant/research support from: AbbVie, Boehringer-Ingelheim, Eli Lilly, Janssen, Pfizer, Roche, Johannes Knitza: None declared, Oliver Distler Speakers bureau: AbbVie, Amgen, Bayer, Boehringer Ingelheim, Janssen, Medscape, Novartis, Consultant of: 4P-Pharma, AbbVie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, iQvia, Horizon, Inventiva, Janssen, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe, Novartis, Prometheus, Redxpharma, Roivant, Sanofi, Topadur, Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Kymera, Mitsubishi Tanabe, Novartis, Roche, Hector Chinoy Grant/research support from: Eli Lilly, UCB, Vikas Agarwal: None declared, Rohit Aggarwal Consultant of: Mallinckrodt, Octapharma, CSL Behring, Bristol Myers-Squibb, EMD Serono, Kezar, Pfizer, AstraZeneca, Alexion, Argenx, Boehringer Ingelheim (BI), Corbus, Janssen, Kyverna, Roivant, Merck, Galapagos, Actigraph, Abbvie, Scipher, Horizontal Therapeutics, Teva, Biogen, Beigene, ANI Pharmaceutical, Nuvig, Capella, CabalettaBio, Grant/research support from: Bristol Myers-Squibb, Pfizer, Mallinckrodt, Janssen, Q32, EMD Serono, Boehringer Ingelheim, Latika Gupta: None declared.

GENE ANALYSIS REVEALED THE USEFULNESS OF TRIPLE THERAPY WITH BARICITINIB, RITUXIMAB AND TACROLIMS FOR ANTI-MDA5 ANTIBODY POSITIVE DERMATOMYOSITIS (MDA5-DM)

BackgroundAnti-MDA5 antibody positive dermatomyositis (MDA5-DM) is characterized by high mortality due to rapid progressive ILD. MDA5 is a cytosolic protein and a family of RIG-I like receptor, which functions as a virus RNA sensor and induces the production of such as type-1 IFN. Although little is known about the pathogenesis of MDA5-DM, it is notable that the similarities were reported between COVID-19 infection and MDA5-DM. It may suggest that there is a common underlying autoinflammatory mechanism. We reported that in MDA5-DM, (1) RIG-I-like receptor signaling is enhanced and (2) antiviral responses such as type 1 IFN signaling are also enhanced as compare with anti-ARS-antibody positive DM, and (3) the key for survival is suppression of RIG-I-like and IFN signaling (EULAR2022, POS0390). We also found that a significant role for uncontrolled macrophage in the pathogenesis of ILD by our autopsy case. Recently, it has been reported that tacrolimus (TAC) and cyclophosphamide (CY) combination therapy (TC-Tx) has improved the prognosis of cases with early onset of the disease, but there are cases that cannot be saved. Therefore, we devised BRT therapy (BRT-Tx). The Tx combines baricitinib (BAR), which inhibits GM-CSF and IFN-mediated signaling and effectively suppresses uncontrolled macrophages, with rituximab (RTX) and TAC, which rapidly inhibits B and T cell interaction and ultimately prevents anti-MDA5 antibody production.ObjectivesTo determine the differences in gene expression between BRT and TC-Tx for MDA5-DM in peripheral blood.MethodsTotal of 6 MDA5-DM (TC: 3, BRT: 3) were included and all of them had multiple poor prognostic factors. Peripheral whole blood was collected at just before and 2-3 months after the treatment. RNA was extracted, and quantified using a next-generation sequencer. Differentially Expressed Genes (DEGs) were identified by pre vs. post treatment. Gene Ontology (GO), clustering and Gene Set Variation Analysis (GSVA) were performed to DEGs. As one BRT case was added since our last year's report, we also reanalyzed the surviving vs. fatal cases. The IFN signature was scored separately for Types 1, 2, and 3, and the changes between pre- and post-treatment were investigated.ResultsTwo of three cases with TC died during treatment, while all three cases on BRT recovered. The cluster analysis of the DEGs separated deaths from survivors, not by type of treatment. Comparing surviving and dead cases, GO analysis revealed that the immune system via immunoglobulins and B cells was significantly suppressed in surviving cases. GO analysis of DEGs in each therapeutic group showed that expression of B cell-related genes such as lymphocyte proliferation and B cell receptor signaling pathway were significantly suppressed in BRT-Tx. On the other hand, TC-Tx significantly suppressed such pathways as cell proliferation and cell surface receptor signaling, and was less specific for the target cells than BRT-Tx. The changes in IFN signature score after treatment showed an increase in type 2 and 3 IFN scores in all fatal cases and an increase in type 1 IFN score in one fatal case.ConclusionBRT-Tx significantly suppressed gene expression associated with B cells, while TC-Tx was characterized by low specificity of therapeutic targets and suppression of total cell proliferation. Comparison of surviving and dead cases revealed that the combination of RTX contributed to the success of treatment, as suppression of the immune system mediated by immunoglobulins and B cells is the key for survival. Analysis of the IFN signature revealed an increase in IFN score after treatment in fatal cases, indicating that the combination of BAR is beneficial. The superiority of BRT-Tx seems clear from the fact that all patients survived with BRT-Tx while only one/three patients survived with TC-Tx.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsMoe Sakamoto: None declared, Yu Nakai: None declared, Yoshiharu Sato: None declared, Yoshinobu Koyama Speakers bureau: Abbvie, Asahikasei, Ayumi, BMS, Esai, Eli-Lilly, Mitsubishi Tanabe, Grant/research support from: Abbvie, GSK.

CLINICAL SIGNIFICANCE OF SERUM FERRITIN IN PATIENTS WITH SYSTEMIC SCLEROSIS

BackgroundThe main systemic sclerosis (SSc) manifestations are skin thickening, microangiopathy and ischemic changes in tissues, fibrotic damage to the lungs, heart, kidneys, and digestive system, arthritis, and myopathy. Acute phase reactants (APR) like erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) reflect inflammation activity in various inflammatory conditions. Ferritin is a protein bound to iron;low serum ferritin indicates iron deficiency and/or anemia. Instead, high ferritin levels are associated with inflammatory and non-inflammatory conditions such as dermatomyositis, pulmonary fibrosis, lupus, systemic COVID-19, vasculitis, tissue damage, thromboembolic complications, and metastatic cancer. The possible role of ferritin in SSc as APR is unclear.ObjectivesWe aimed to assess whether ferritin levels can reflect the severity of SSc and predict the outcome.Methods241 files of SSc patients with information on serum ferritin level (ferritin over 300 mg/dL is considered elevated) who visited the Rambam Rheumatology Institute in the years 2004-2021were used for retrospective analysis. Patients' demographic, clinical, laboratory, imaging, and respiratory function data were collected from electronic hospital files. Statistics included Student's T-test, Pearson's chi-squared test, and Kaplan-Meier curve;statistical significance was determined as p<0.05.Results36 patients (FerEl-SSc) had elevated ferritin values;the rest (n=205) represented the second group (FerNor-SSc). Significant differences were seen in gender (male 44.4% - 15.6%), disease duration (4.56 - 7.7 years), modified Rodnan skin score (12.3 - 6.9), as well as in incidence of lung (65.7% - 38.7%), heart (51.4% - 21.1%), and renal (28.6% - 5.9%) involvement. Increased ferritin correlated with elevated ESR, CRP, creatinine, creatine kinase, troponin, and reduced hemoglobin, impaired pulmonary function tests and reduced left ventricular ejection fraction on echocardiography. Patients with elevated ferritin had a significant increase in mortality rates (52.8% and 35.1%) and non-significant reduction in survival.ConclusionOur study demonstrated that ferritin has a potential as a sensitive marker for SSc severity in term of skin thickening, vital organ complications, and mortality. The ferritin test is simple and inexpensive, it can add to the complex SSc assessment and contribute to treatment decision-making in complicated SSc.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

TYPE I INTERFERON SCORE IS ASSOCIATED WITH THE SEVERITY AND POOR PROGNOSIS IN ANTI-MDA5 ANTIBODY-POSITIVE DERMATOMYOSITIS PATIENTS

BackgroundAnti-MDA5 antibody-positive dermatomyositis (anti-MDA5+DM) is a rare autoimmune disease associated with a high mortality rate due to rapid-progressive interstitial lung disease (RP-ILD), particularly in East Asia[1]. MDA5, acts as a cytoplasmic sensor of viral RNA, thus activating antiviral responses including the type I interferon (IFN) signaling pathway[2]. The involvement of type 1 IFN in the pathogenesis of MDA5+DM has been proposed based on the significantly elevated expression of its downstream stimulated genes(ISG) in muscle, skin, lung, and peripheral blood[3;4]. Janus kinase inhibitor, which targets the IFN pathway, combined with glucocorticoid could improve the survival of early-stage MDA5+DM-ILD patients[5]. In clinical practice, there is still an urgent demand for sensitive biomarkers to facilitate clinical risk assessment and precise treatment.ObjectivesThis study aimed to investigate the clinical significance of interferon score, especially IFN-I score, in patients with anti-MDA5+DM.MethodsDifferent subtypes of idiopathic inflammatory myopathy, including anti-MDA5+DM(n=61), anti-MDA5-DM(n=20), antisynthetase syndrome(ASS,n=22),polymyositis(PM,n=6) and immune-mediated necrotizing myopathy(IMNM,n=9), and 58 healthy controls were enrolled.. A multiplex quantitative real-time PCR(RT-qPCR) assay using four TaqMan probes was utilized to evaluate two type I ISGs (IFI44, MX1, which are used for IFN-I score), one type II ISG (IRF1), and one housekeeping gene (HRPT1). Clinical features and disease activity index were compared between high and low IFN-I score groups in 61 anti-MDA5+DM patients. The association between laboratory findings and the predictive value of baseline IFN-I score level for mortality was analyzed.ResultsThe IFN scores were significantly higher in patients with anti-MDA5+DM than in HC (Figure 1A). The IFN-I score correlated positively with serum IFN α(r = 0.335, P =0.008), ferritin (r = 0.302, P = 0.018), and Myositis Disease Activity Assessment Visual Analogue Scale (MYOACT) score(r=0.426, P=0.001). Compared with patients with low IFN-I scores, patients with high IFN-I scores showed increased MYOACT score, CRP, AST, ferritin, and the percentages of plasma cells (PC%) but decreased lymphocyte count, natural killer cell count, and monocyte count. The 3-month survival rate was significantly lower in patients with IFN-I score > 4.9 than in those with IFN-I score ≤ 4.9(72.9% vs. 100%, P=0.044)(Figure 1B).ConclusionIFN score, especially IFN-I score, detected by multiplex RT-qPCR, can be a valuable biomarker for monitoring disease activity and predicting mortality in anti-MDA5+DM patients.References[1]I.E. Lundberg, M. Fujimoto, J. Vencovsky, R. Aggarwal, M. Holmqvist, L. Christopher-Stine, A.L. Mammen, and F.W. Miller, Idiopathic inflammatory myopathies. Nat Rev Dis Primers 7 (2021) 86.[2]G. Liu, J.H. Lee, Z.M. Parker, D. Acharya, J.J. Chiang, M. van Gent, W. Riedl, M.E. Davis-Gardner, E. Wies, C. Chiang, and M.U. Gack, ISG15-dependent activation of the sensor MDA5 is antagonized by the SARS-CoV-2 papain-like protease to evade host innate immunity. Nat Microbiol 6 (2021) 467-478.[3]G.M. Moneta, D. Pires Marafon, E. Marasco, S. Rosina, M. Verardo, C. Fiorillo, C. Minetti, L. Bracci-Laudiero, A. Ravelli, F. De Benedetti, and R. Nicolai, Muscle Expression of Type I and Type II Interferons Is Increased in Juvenile Dermatomyositis and Related to Clinical and Histologic Features. Arthritis Rheumatol 71 (2019) 1011-1021.[4]Y. Ye, Z. Chen, S. Jiang, F. Jia, T. Li, X. Lu, J. Xue, X. Lian, J. Ma, P. Hao, L. Lu, S. Ye, N. Shen, C. Bao, Q. Fu, and X. Zhang, Single-cell profiling reveals distinct adaptive immune hallmarks in MDA5+ dermatomyositis with therapeutic implications. Nat Commun 13 (2022) 6458.[5]Z. Chen, X. Wang, and S. Ye, Tofacitinib in Amyopathic Dermatomyositis–Associated Interstitial Lung Disease. New England Journal of Medicine 381 (2019) 291-293.AcknowledgementsThis work was supported by the National Natural Science Foundation of China [81974251], and Shanghai Hospital Develop ent Center, Joint Research of New Advanced Technology Project [SHDC12018106]Disclosure of InterestsNone Declared.

CLINICAL CHARACTERISTICS OF PEDIATRIC PATIENTS WITH RHEUMATIC DISEASES UNDER TREATMENT WITH BIOLOGICAL THERAPY: INFORMATION FROM BIOBADAMEX

BackgroundThe advent of biologic treatment (bDMARD) in childhood rheumatic diseases (RD) has changed their evolution and prognosis. Evidence is robust for diseases such as juvenile idiopathic arthritis (JIA) and systemic lupus erythematosus (SLE), but in other diseases we still have to learn which is the ideal therapy, time to discontinuation and the potential adverse events (AE) in short and long term.ObjectivesIdentify the clinical and treatment characteristics of pediatric patients with rheumatic diseases with bDMARD treatment and describe the development of AE.MethodsBIOBADAMEX is a prospective ongoing cohort of Mexican patients with RD using bDMARDs since 2016. We included all patients younger than 18 years of age registered in BIOBADAMEX. Descriptive statistics were used for the baseline characteristics and the Chi-square test to analyze the differences between the characteristics of the groups in relation to the development of AE.ResultsA total of 45 patients were included, 31 (69%) of them female, mean age of 13.3 (±3.6) years. (Table 1).The most frequent diagnosis was JIA 25 (56%), followed by SLE 9 (20%), uveitis 5 (11%), polymyositis/dermatomyositis and hidradenitis 2 (4%) respectively;systemic sclerosis and CINCA 1 patient (2%) respectively. The mean duration disease in years was 4.67 (±2.1). Nine patients (20%) used a biologic prior to the current;23 (51%) patients had comorbidities.The most frequent bDMARDs used was Adalimumab (ADA) in 17 (38%) patients followed by Rituximab in 15 (33%) and Tocilizumab in 10 (22%), Infliximab, Abatacept and Canakinumab were used in one patient respectively.When compared by groups, ADA and Tocilizumab were the most used bDMARDs in JIA, Rituximab the only one used in SLE and PM/DM, and ADA the only one for uveitis.15 patients discontinued biological treatment, 4 (27%) due to AE. 82% used an additional synthetic DMARD, being methotrexate the most used in 48% of patients. Steroids were used by 21 (47%) of the patients with a median dose of 10mg (IQR 5 - 25).Fifteen AEs were recorded: 7 (47%) were infections, 5 of these (71%) were COVID;allergies and neutropenia in 2 (13%) patients respectively. By disease infections were more frequent in patients with JIA and Uveitis;neutropenia only occurred in patients with JIA (p 0.95). 87% of the AEs were non-serious, 1 patient with JIA presented a severe AE and one patient with SLE a fatal AE associated with COVID (p 0.93), with no statistically significant difference between groups.ConclusionJIA is the most frequent indication to use bDMARD as worldwide reported. The AE in this analysis are similar to previous registries in terms of the prevalence of infections, in our group the most frequent infectious complication was COVID, being fatal in one patient related with rituximab in SLE. Our study did not find statistically significant differences in the development of AE between diseases;however, they will continue to be reported and the number of patients in the registry will increase.References[1] Sterba,Y.et al. Curr Rheumatol Rep 2016;18,45[2] Fuhlbrigge RC, et al. 2021;47(4):531-543.Table 1.Baseline CharacteristicsBaseline characteristics (n = 45)n%Female, n(%)3168.9Age, media (SD)13.3 (±3.6)Index Body Mass, media (SD)19.6 (±4.9)Dx n(%)n %- JIA25 55.6- SLE9 20- PM/DM2 4.4- Uveitis5 11.1- Hidradenitis2 4.4- Systemic sclerosis1 2.2- CINCA1 2.2Disease duration(years) media (IQR)4.67±2.1Current treatment n(%)n %- Infliximab1 2.2- Adalimumab17 37.8- Rituximab15 33.3- Abatacept1 2.2- Tocilizumab10 22.2- Canakinumab1 2.2Treatment duration (months) median (IQR)4.5 (0.56 – 36.9)Treatment suspension, n(%)15 (33.2)Months to suspension, median (IQR)0.66 (0.46 – 1)Discontinue cause, n(%)n %- Inefficacy1 6.6- Remission1 6.6- Side effects4 26.6- Others5 33.3- Unknown4 26.6Steroids use, n(%):21 46.7Steroids dose (mg), median (IQR)10 5 – 25DMARDs use n(%):37 82.2AE, n(%):15 33.3By disease:AE TypeInfectionAllergyNeutropeniaOtherChi2JIA31230.95SLE1101Uveitis3000Acknowledgements:NIL.Disclosure of InterestsSamara Mendieta: None declare , Alfonso Torres: None declared, Fedra Irazoque-Palazuelos: None declared, Sandra Sicsik: None declared, Iris Jazmin Colunga-Pedraza: None declared, Daniel Xavier Xibille Friedmann: None declared, Deshire Alpizar-Rodriguez Employee of: Scientific advisor in GSK-Mexico, VIJAYA RIVERA TERAN: None declared.

Severe juvenile dermatomyositis with specific liver involvement onset concomitant with COVID-19 infection: A case report

Juvenile Dermatomyositis (JDM) is an autoimmune disease that involves skin, muscle and internal organ disorders. Its mechanisms still not well established, but the triggering role of viral infections has been described. In this context, the effect of the COVID-19 on the onset of autoimmune disorders such as JDM remains a matter of study and research. We report a severe JDM, following a confirmed COVID-19 infection in a previously healthy 8 year-old boy who presented with various skin lesions and a cholestatic liver involvement. Laboratory findings were consistent with an inflammatory myositis and an autoimmune liver disease. Skin and muscle biopsies confirmed the diagnosis of JDM. The therapy choice was difficult. Finally, he received a second line therapy of the JDM with a favorable outcome. The liver fragment analysis showed a steatosis. This case supports the hypothesis of COVID-19 triggering role in the genesis of JDM and autoimmune diseases.Copyright © 2023 Scientific Publishers of India. All rights reserved.

PRE-EXPOSURE PROPHYLAXIS WITH TIXAGEVIMAB/CILGAVIMAB: SINGLE CENTRE EXPERIENCE IN A COHORT OF RHEUMATIC PATIENTS

BackgroundVaccination against SARS-CoV2 had a critical role in the fight against COVID19 pandemic.A weaker humoral response to COVID19 vaccine has been found in rheumatic patients treated with Rituximab (RTX) or Mycophenolate Mofetil (MMF)[1]. Despite the evidence that anti-SARS-CoV-2 mRNA vaccines can elicit a T-cell response [2], some data show that even the cellular immunity could be impaired in rheumatic patients [3] but COVID19 serology is the only parameter that is feasible to measure in daily practice.Tixagevimab+cilgavimab are two human-derived monoclonal antibodies administered parenterally and authorized by regulatory agencies in February 2022 for pre-exposure prophylaxis (PrEP) against COVID19 from different virus variants in fragile patients.ObjectivesTo demonstrate safety and effectiveness of tixagevimab+cilgavimab.MethodsPatients with autoimmune rheumatic diseases undergoing immunosuppressive treatment with RTX or MMF during the vaccination campaign were enrolled between April and June 2022. All patients must have anti-spike antibody levels below the protective threshold (defined by anti-spike IgG titre <250 BAU/ml) after receiving at least 2 vaccine doses.Patients were monitored with a questionnaire every month about COVID19 symptoms (including respiratory and gastrointestinal symptoms, anosmia and ageusia, skin rash and potential contact with COVID19+ subjects) and were checked for anti-spike and anti-nucleocapside antibodies titres every 2 months for a total of a 6 month follow-up. MMF dose was reduced at 1 g/die at the time of vaccine administration.ResultsFifteen patients were enrolled: 9 participants had a connective tissue disease (CTD;1 dermatomyositis, 3 anti-syntethase syndrome, 4 systemic sclerosis, 1 systemic lupus erythematosus) and 6 had vasculitis (all granulomatosis with polyangiitis). 12 of them received RTX in the preceding 12 months and 3 were taking MMF.About safety, the therapy was very well tolerated and only 4 patients (26%) reported a non-severe adverse event in the 2 weeks following drug administration (2 myalgia, 1 headache, 1 fatigue), none of them requiring hospitalization nor pharmacologic treatment.Regarding effectiveness, 3/15 patients contracted SARS-Cov2 infection (20%) with mild symptoms and no need for hospitalization nor oxygen therapy. Only 1 of them received an antiviral drug (nirmatrelvir+ritonavir). All infected patients had a CTD diagnosis. No significant correlation was observed between the type of rheumatic disease and the risk of infection or response to tixagevimab+cilgavimab.ConclusionNone of our patients developed severe adverse events after tixagevimab+cilgavimab administration and, among the 3 SARS-CoV2 infected patients, none required hospitalization nor oxygen therapy.We conclude that in our experience tixagevimab+cilgavimab is a safe and useful complementary immunization strategy to vaccination for COVID19 prophylaxis.These data will be implemented in a larger study, comprehending various immunocompromised patients from several departments.References[1] Furer et al., Ann Rheum Dis, 2021[2] Mangalakumari et al., Nat Rev Immunol, 2020[3] Picchianti-Diamanti et al., Front Immunol, 2021Charateristic of the cohortIdentificativeAgeDiagnosisRTX/MMFSARS-CoV2 InfectionHospitalizationAntiviral drugs180SScMMF-//270ASSDRTX+nono370ASSDRTX+noyes452GPARTX-//551GPARTX-//649SSc+SSjRTX-//768SScMMF-//847LESRTX-//964ASSDRTX-//1068GPARTX-//1123GPARTX-//1258DMRTX+nono1361SScMMF-//1475GPARTX-//1569GPARTX-//Figure 1.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

EXPERIENCE WITH TIXAGEVIMAB AND CILGAVIMAB (EVUSHELD) IN 86 RHEUMATIC PATIENTS UNDERGOING ANTI-B CELL THERAPY WITH RITUXIMAB.

The problem of prevention of coronavirus disease 2019 (COVID-19) in patients with immune-mediated inflammatory rheumatic diseases (IMRD) remains highly relevant. The presence of IRD is associated with a high risk of disease and severe course of COVID-19 during immunosuppressive treatment, primarily anti-B cell therapy with rituximab (RTX), and a low level of post-vaccination response in such patients. A new strategy for the prevention and treatment of COVID-19 are virus-neutralizing monoclonal antibodies to coronavirus;currently, combined long-acting monoclonal antibodies tixagevimab and cilgavimab (Evusheld) are registered for prevention in the world and the Russian Federation. . Tixagevimab and cilgavimab (TC) show neutralizing activity against SARS-CoV-2, including the Omicron strain, primarily its variants BA.4, BA.5, BA.2.75 ("Centaur"). Objective - to evaluate the efficacy and safety of TC for pre-exposure prophylaxis of COVID-19 in rheumatic patients receiving RTX, based on a prospective observational study. Materials and methods. The main group included 86 patients with various IMRD receiving RTX: 50 of them had ANCA-associated systemic vasculitis (AAV), 15 - rheumatoid arthritis, 9 - Sjogren's syndrome (SS), 4 - IgG4-related disease, 3 - systemic lupus erythematosus (SLE), 3 - dermatomyositis (DM), 2 - systemic scleroderma (SSD). Median age was 59 (19-82) years;male: female ratio - 1:1,8. From March 26 to August 30 2022, patients received a single intramuscular injection of TC in a total dose of 300 mg, mainly after RTX (in 52% of cases, in 28% on the next day after RTX). The control group included 42 patients with AAV (median age - 45 (35-71) years;male: female ratio - 1:1), also treated with RTX, who did not receive pre-exposure prophylaxis of TC. The duration of observation was 7 months, until November 1 2022. At this time, 98% of confirmed cases of coronavirus in the Russian Federation were Omicron. A telephone and/or online survey of patient has been conducted to detect cases of COVID-19 and adverse reactions. Results. In the TC group, confirmed coronavirus infection have been detected in 17 (20%) patients (AAV - 10, SS - 3, SSD - 2, SLE - 1, DM - 1), with fever in 7 (8%), only in one case hospitalization was required (lung damage was not detected in computed tomography), in two cases, according to CT mild lung damage (CT 1-2), there were no deaths. Good TC's tolerability was noted, signs not associated with COVID-19 or progression of IMRD after administration of TC were observed in 8 (9%) patients (GPA - 3 MPA - 1, RA - 2, SLE - 1, IgG4-related disease - 1), adverse reactions definitely associated with the use of TC were not found. The most serious event not associated with coronavirus infection was the progression of polyneuropathy in a patient with RA. In the control group, 3 (7%) patients were diagnosed with COVID-19, one with severe lung injury (CT 3, pulmonary embolism) and death. Conclusions. The data of clinical studies and our own clinical experience evidence the effectiveness of the use of a combination of long-acting monoclonal antibodies TC (Evusheld), registered for indications for pre-exposure prophylaxis and treatment of COVID-19. Patients with IMRD treated with RTX have a favorable safety profile of TC. The introduction of virus-neutralizing monoclonal antibodies, a new drug class for the prevention and treatment of infectious diseases, opens significant prospects for improving the prognosis of patients with IRD.Copyright © 2023 Ima-Press Publishing House. All rights reserved.

FLARES AFTER COVID-19 INFECTION IN PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHIES: RESULTS FROM THE COVAD STUDY

BackgroundViral infections are known triggers of disease flares in idiopathic inflammatory myopathies (IIMs). Reports of post-COVID-19 flares of IIMs have raised suspicion of a possible role of SARS-COV-2 in their onset [1,2]. However, despite rising flare rates in this vulnerable patient group during the pandemic, the risk factors for post-COVID-19 IIMs flares remain unknown [3,4].ObjectivesDisease flares among patients with idiopathic inflammatory myopathies (IIMs) can lead to significant disability, though are poorly explored in the post-COVID-19 period. We analysed risk factors for post-COVID-19 flares in a global sample of IIM patients in a subset analysis as part of the ongoing COVID-19 Vaccination in Autoimmune Diseases (COVAD) study.MethodsA cross-sectional patient self-reporting survey was circulated by the international COVAD study group (157 collaborators, 106 countries) to patients with autoimmune diseases and healthy controls from February-June 2022. Data was collected on demographics, autoimmune disease details, treatment history, comorbidities, COVID-19 history and course and COVID-19 vaccination details. Patients with IIMs who flared post COVID-19 were compared to those who did not using the χ2 test, factors found significant in univariate analysis and deemed clinically important, underwent multivariable analysis (binary logistic regression using the Enter method) with adjustment for age, gender, ethnicity, vaccine type, immunosuppression, autoimmune and non-autoimmune comorbidities, COVID-19 antibody status, and clinical symptoms of COVID-19. Statistical analyses were performed using IBM SPSS version 28.0, with statistical significance considered at p<0.05.Results15,165 respondents completed the survey of whom 1,169 contracted COVID-19. Of these, 207 had IIMs [median (IQR) age 57.0 (47.0-67.0), 71% female, 74.4% Caucasian]. We noted with concern that nearly a third of patients with IIMs (63/207, 30.4%) reported experiencing a flare. A past medical history significant for Asthma, (34.9% vs 6.9%, multivariable OR: 7.1;95%CI: 3.1-16.4, p<0.001) and specific clinical symptoms during COVID-19 including joint pains (multivariable OR: 6.05;95%CI: 1.60-22.9, p=0.008), and difficulty in breathing (multivariable OR: 3.43;95%CI: 1.09-10.8, p=0.036) were found to confer conferred a higher risk of flares (Table 1).Table 1Patient Reported Flares following COVID-19 infection among IIM patientsTotal IIMs (n=207)IIMs with flare after COVID-19 (n=63)IIMs without flare after COVID-19 (n=144)OR (95%CI)PAge (median, IQR) years57.0 (47.0-67.0)53.0 (47.0-62.0)59.0 (47.0-69.0)-0.024GenderMale Female60 (29.0) 147 (71.0)7 (11.1) 56 (88.9)53 (36.8) 91 (63.2)0.2 (0.09-0.5)< 0.001ComorbiditiesAsthma ILD32 (15.5) 31 (15.0)22 (34.9) 11 (17.5)10 (6.9) 20 (13.9)7.1 (3.1-16.4) 1.3 (0.5-2.9)<0.001 00.508Clinical features in previous COVID-19 infectionFatigue Myalgia Arthralgia Difficulty in breathing134 (64.7) 94 (45.4) 56 (27.1) 41 (19.8)52 (82.5) 44 (69.8) 36 (57.1) 27 (42.9)82 (56.9) 50 (34.7) 20 (13.9) 14 (9.7)3.5 (1.7-7.4) 4.3 (2.3-8.2) 8.2 (4.1-16.4) 6.9 (3.3-14.6)<0.001 <0.001 <0.001 <0.001ConclusionWe observed a high frequency of patients with IIM experiencing post-COVID-19 disease flares. A past history of Asthma and those with certain acute COVID-19 symptoms were at higher risk.References[1]Saud A, Naveen R, Aggarwal R, Gupta L. COVID-19 and Myositis: What We Know So Far. Curr Rheumatol Rep 2021;23:63.[2]Gokhale Y, Patankar A, Holla U, Shilke M, Kalekar L, Karnik ND, et al. Dermatomyositis during COVID-19 Pandemic (A Case Series): Is there a Cause Effect Relationship? J Assoc Physicians India 2020;68:20–4.[3]Gupta L, Lilleker JB, Agarwal V, Chinoy H, Aggarwal R. COVID-19 and myositis - unique challenges for patients. Rheumatology (Oxford) 2021;60:907–10.[4]Naveen R, Sundaram TG, Agarwal V, Gupta L. Teleconsultation experience with the idiopathic inflammatory myopathies: a prospective observational cohort study during the COVID-19 pandemic. Rheumatol Int 2021;41:67–76.Acknowledgements:NIL.Disclosure of InterestsSa dia Sasha Ali: None declared, Naveen Ravichandran: None declared, Parikshit Sen: None declared, Jessica Day Grant/research support from: JD has received research funding from CSL Limited., Mrudula Joshi: None declared, Sreoshy Saha: None declared, Rohit Aggarwal Consultant of: RA has 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, Abbvie, Janssen, Alexion, Argenx, Q32, EMD-Serono, Boehringer Ingelheim, and Roivant., Grant/research support from: RA has 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, Abbvie, Janssen, Alexion, Argenx, Q32, EMD-Serono, Boehringer Ingelheim, and Roivant., Vikas Agarwal: None declared, Hector Chinoy Speakers bureau: Speaker for UCB, and Biogen. HC was supported by the National Institution for Health Research Manchester Biomedical Research Centre Funding Scheme., Grant/research support from: Has received grant support from Eli Lilly and UCB, consulting fees from Novartis, Eli Lilly, Orphazyme, Astra Zeneca, Oliver Distler Speakers bureau: OD has consultancy relationships 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 consultancy relationships 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 consultancy relationships 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)., Carlo Vinicio Caballero: None declared, Carlos Enrique Toro Gutierrez: None declared, Dey Dzifa: None declared, Ashima Makol: None declared, Ai Lyn Tan Speakers bureau: Has received honoraria for advisory boards and speaking for Abbvie, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB., Consultant of: has received honoraria for advisory boards and speaking for Abbvie, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB., Samuel Katsuyuki Shinjo: None declared, Vishwesh Agarwal: None declared, Latika Gupta: None declared.

Appearance of Anti-MDA5 Antibody-Positive Dermatomyositis After COVID-19 Vaccination.

The direct causes of dermatomyositis, a common autoimmune disease, have not yet been accurately identified, but several studies have linked this condition to various patient-associated and environmental factors, such as viral infections and area of residence. In the present report, we describe our experience with a patient presenting with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis, which developed after vaccination against coronavirus disease 2019 (COVID-19). This patient was simultaneously diagnosed with anti-glutamic acid decarboxylase (GAD) antibody-positive slowly progressive insulin-dependent diabetes (SPIDDM); her human leukocyte antigen (HLA) test revealed that she expressed the DRB1*04:05 allele. This is important as this genotype is known to increase susceptibility to both anti-MDA5 antibody-positive dermatomyositis and type I diabetes. To the best of our knowledge, this is the first case of dermatomyositis complicated by SPIDDM identified after COVID-19 vaccination against COVID-19 and presenting with an underlying susceptible genotype. The patient's genetic predisposition may also be important for the development of autoimmune disease after COVID-19 vaccination.

Case report: Unusual patient with dermatomyositis associated with SARS-CoV-2 infection.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak is a major challenge for clinicians. SARS-CoV-2 infection results in coronavirus disease 2019 (COVID-19), and it is best known for its respiratory symptoms. It can also result in several extrapulmonary manifestations such as neurological complications potentially experienced during the course of COVID-19. The association of dermatomyositis (DM) with COVID-19 pathogenesis has not been well-studied. This study aimed to present a previously healthy 37-year-old man, a soldier by profession, with symptoms of DM on the 4th day from the onset of COVID-19. The patient presented DM symptoms with both skin and muscle manifestations. The patient suffered from cough, fever, and fatigue to begin with, and reverse-transcription polymerase chain reaction (RT-PCR) reported positive for SARS-CoV-2 infection. The laboratory findings showed, intra alia, elevated muscle enzymes CK 8253 U/l (N: <145 U/l), a positive test for myositis-specific autoantibodies (anti-Mi-2), electrodiagnostic tests exhibited features of myopathy, with the presence of muscle and skin symptoms. The patient improved with corticosteroids and immunosuppressive agent therapy. In summary, the association between COVID-19 and the development of multi-system autoimmune disorders such as DM remains unclear. Nevertheless, viral infections such as SARS-CoV-2 may likely serve as a trigger.

A machine learning analysis to evaluate the outcome measures in inflammatory myopathies.

OBJECTIVE: To assess the long-term outcome in patients with Idiopathic Inflammatory Myopathies (IIM), focusing on damage and activity disease indexes using artificial intelligence (AI). BACKGROUND: IIM are a group of rare diseases characterized by involvement of different organs in addition to the musculoskeletal. Machine Learning analyses large amounts of information, using different algorithms, decision-making processes and self-learning neural networks. METHODS: We evaluate the long-term outcome of 103 patients with IIM, diagnosed on 2017 EULAR/ACR criteria. We considered different parameters, including clinical manifestations and organ involvement, number and type of treatments, serum creatine kinase levels, muscle strength (MMT8 score), disease activity (MITAX score), disability (HAQ-DI score), disease damage (MDI score), and physician and patient global assessment (PGA). The data collected were analysed, applying, with R, supervised ML algorithms such as lasso, ridge, elastic net, classification, and regression trees (CART), random forest and support vector machines (SVM) to find the factors that best predict disease outcome. RESULTS AND CONCLUSION: Using artificial intelligence algorithms we identified the parameters that best correlate with the disease outcome in IIM. The best result was on MMT8 at follow-up, predicted by a CART regression tree algorithm. MITAX was predicted based on clinical features such as the presence of RP-ILD and skin involvement. A good predictive capacity was also demonstrated on damage scores: MDI and HAQ-DI. In the future Machine Learning will allow us to identify the strengths or weaknesses of the composite disease activity and damage scores, to validate new criteria or to implement classification criteria.

The impact that myocarditis for post-acute COVID-19 syndrome may be dermatomyositis-like myocarditis: A case report.

Myocarditis is often reported as a complication of COVID-19 infection or post-vaccination, but there are few reports of "myocarditis for Post-acute COVID-19 syndrome", and many unknowns still remain. Apart from that, an association between COVID-19 infection and dermatomyositis has also been reported. We describe the clinical presentation of acute myocarditis in a patient who had developed COVID-19 syndrome one-month earlier. A healthy 49-year-old man experienced typical COVID-19 symptoms. Thirty-two days later, he was admitted because of fever and severe fatigue, chest pain and bradycardia. Blood tests showed major inflammation. PCR for SARS-CoV-2 on nasopharyngeal swab (ID NOW™) was positive, but diagnosed as a previous infection due to a high CT value. Because of haemodynamic worsening with both an increase in cardiac troponin I and NT-pro BNP levels and reduced wall motion on echocardiography, acute myocarditis was suspected. Myocardial biopsy revealed severe lymphocytic infiltration and interstitial edema between myocardial fibers. These findings led to the diagnosis of fulminant myocarditis. Interestingly, myocardium was also stained with human myxovirus resistance protein 1 (MxA). We consider that there may be an aspect of "dermatomyositis-like myocarditis with SARS-CoV-2" in our case. This is the first case of fulminant myocarditis for Post-acute COVID-19 syndrome in which diagnosis of active myocarditis was proven by pathological examination following myocardial biopsy and strong association with dermatomyositis was suggested pathologically.

Incidence and Clinical Outcomes of Newonset Autoimmune Connective Tissue Diseases after Covid-19 Infection- a Systematic Literature Review

Background/Aims Cases of new autoimmune and autoinflammatory conditions have been reported among COVID-19 survivors. A literature review on newonset autoimmune connective tissue diseases (ACTDs) following infection with COVID-19 is lacking.This systematic literature review aimed to evaluate the potential association between COVID-19 infection and the development of new-onset ACTDs in adults. Methods Articles published until September 2022, investigating the association between COVID-19 infection and new-onset ACTDs were included. The ''population'' searched was patients with disease terms for autoimmune connective tissue diseases, including (but not limited to) systemic lupus erythematosus (SLE), Sjogren's syndrome, systemic sclerosis (SSc), any idiopathic inflammatory myositis (IIM), antisynthetase syndrome, mixed CTD and undifferentiated CTD (and related MeSH terms), with ''intervention'' as COVID-19 and related terms. For terms for COVID-19, a dedicated search strategy developed by the National Institute for Clinical Excellence was used.Medline, Embase, and Cochrane databases were searched, restricted to English-language articles only. Eligible articles were: case reports and series (of any sample size), observational studies, qualitative studies and randomised controlled trials. Patients developing ACTDs without prior COVID-19 or reporting flares of existing ACTDs were excluded. Information was extracted on patient demographics, new ACTDs' onset time, clinical characteristics, COVID-19 and ACTD treatment, and COVID-19 and ACTDs outcomes. The protocol was registered in PROSPERO (CRD42022358750). Results After deduplication, 2239 articles were identified. After screening title and , 2196 papers were excluded, with 43 proceeding to fulltext screening. Ultimately, 28 articles (all single case reports) were included. Of the 28 included patients, 64.3% were female. The mean age was 51.1 years (range 20-89 years). The USA reported the most cases (9/28). ACTD diagnoses comprised: 11 (39.3%) IIM (including 4 cases of dermatomyositis);7 (25%) SLE;4 (14.3%) anti-synthetase syndrome;4 (14.3%) SSc;2 (7.1%) other ACTD (one diagnosed with lupus/MCTD overlap). Of eight, four (14.3%) patients (including that with lupus/MCTD) were diagnosed with lupus nephritis. The average onset time from COVID-19 infection to ACTD diagnosis was 23.7days. A third of the patients were admitted to critical care, one for ACTD treatment for SLE with haemophagocytic lymphohistiocytosis (14 sessions of plasmapheresis, rituximab and intravenous corticosteroids) and nine due to COVID-19. The majority (80%) of patients went into remission of ACTD following treatment, while two (10%) patients died- one due to macrophage activation syndrome associated with anti-synthetase syndrome and two from unreported causes. Conclusion Our results suggest a potential association between COVID-19 infection and new-onset ACTDs, predominantly in young females, reflective of wider CTD epidemiology. The aetiology and mechanisms by which ACTDs arise following COVID-19 infection remain unknown and require more robust epidemiological data.

Flares Following Covid-19 Vaccination in Patients with Idiopathic Inflammatory Myopathies: Combined Analysis from the Covid-19 Vaccination in Autoimmune Diseases (Covad) Studies

Background/Aims Flares following COVID-19 vaccination are an emerging concern among patients with rare rheumatic disease like idiopathic inflammatory myositis (IIMs), whereas data and understanding of this is rather limited. We aimed to study the prevalence, characteristics and determinants of IIM flares following COVID-19 vaccination. Methods CoVAD (COVID-19 Vaccination In Autoimmune Diseases) surveys are global patient self-reported e-surveys from 109 countries conducted in 2021 and 2022. Flares of IIM were defined by 4 definitions;a. patient self-reported, b. physician and immunosuppression (IS) denoted, c. sign directed (new erythematous rash, or worsening myositis or arthritis), d. MCID worsening of PROMISPF10a score between the patients who had taken both surveys. Descriptive statistics and multivariate regression were used to describe the predictors of flare. Cox-regression analysis was used to differentiate flares by IIM subtypes. Results Among the 1,278 IIM patients, aged 63 (50-71) years, 276 (21.5%) were dermatomyositis, 237 (18.5%) IBM, 899 (70.3%) were female and most were Caucasian (80.8%). Flares of IIM were seen in 123/1278 (9.6%), 163/1278 (12.7%), 112/1278 (8.7%), and 16/96 (19.6%) by definitions a-d respectively with median time to flare being 71.5 (10.7- 235) days. Muscle weakness (69.1%), and fatigue (56.9%) were the most common symptoms of flare. The predictors of self-reported flare were: inactive/disease in remission prior to first dose of vaccine (OR=4.3, 95%CI=2.4-7.6), and anxiety disorder (OR=2.2, 95%CI=1.1-4.7). Rituximab use (OR=0.3, 95%CI=0.1-0.7) and IBM (OR=0.3, 95%CI=0.1-0.7) were protective. Physician defined flares were seen more often in females, mixed ethnicity, and those with asthma, ILD, and anxiety disorder (OR ranging 1.6-7.0, all p<0.05). Notably, overlap myositis (OM) had higher HR for flare compared to polymyositis (HR=2.3, 95%CI=1.2-4.4, p=0.010). Conclusion Nearly one in ten individuals with IIM develop flares after vaccination, more so among women, those with overlap myositis, and inactive disease prior to vaccination. Formal definition of flares in IIM is needed.

An Evaluation of the Causes and Outcomes of Haemophagocytic Lymphohistiocytosis in Sheffield Teaching Hospitals: 2016 to 2021

Background/Aims Haemophagocytic lymphiohistiocytosis (HLH) is a rare, underrecognised hyperinflammatory syndrome, characterised by immune dysregulation. Without treatment, the ensuing cytokine storm leads to high mortality. Secondary HLH (sHLH) is triggered by malignancy, infection, autoimmunity and medicines;treatment with immunosuppression is consensus- rather than evidence-based and extrapolated from primary HLH. Sheffield hosts a mature HLH multidisciplinary advisory group (MDAG). Here we evaluate the cause, treatment, requirement for critical care and mortality of people with HLH managed through the MDAG in a period including the coronavirus pandemic but prior to NHS England approval of anakinra (IL-1 antagonist) for HLH. Methods This retrospective evaluation (approved locally STH 10850) identified patients from MDAG records 1st October 2016 to 30th September 2021. Data from electronic/paper records was analysed using Microsoft Excel. Results HLH triggers were infection (viral 34%, bacterial 10%), haematological (35%), rheumatological (13%) and other (8%). Rheumatological causes were Still's disease (n=5);antiphospholipid syndrome (n=2);JO1 dermatomyositis (n=1);SLE (n=1);and rheumatoid arthritis (n=1). Other causes included unknown (n=3);combined systemic JIA and sickle cell crisis (n=1);medication (alemtuzumab) (n=1);and primary HLH (n=1). Overall mortality was 53% and highest in HLH with a haematological malignancy trigger (82%) Prior to the COVID19 pandemic (pre-March 2020), the commonest trigger of HLH was haematological malignancy (47%);after March 2020, the commonest trigger was infection (64%);COVID-19 explained 42% of cases. Mortality fell from 72% to 31%. Conclusion In this real-world series of people with HLH, mortality and critical care requirement was high. HLH triggers reflect published evidence as does poor prognosis in haematological malignancy-associated HLH. No-HLH associated with non-haematological malignancy was identified;we may need to improve MDAG reach into oncology. Seeming reduction in mortality following the COVID-19 pandemic may reflect increased recognition of COVID-19 induced hyperinflammation along with locallyagreed access to anakinra for COVID-19-induced HLH. The increase in infection related HLH cases since March 2020 is explained largely by COVID-19 cases. This has led to a relative reduction in cases related to haematological malignancy. HLH requires multidisciplinary management and better research to improve treatment. (Table Presented).

Low serum level of citrullinated histone H3 in patients with dermatomyositis.

OBJECTIVES: We aimed at analyzing the serum levels of citrullinated histone H3 (CitH3) in patients with dermatomyositis (DM) and their association with disease activity. METHODS: Serum CitH3 levels were measured using enzyme-linked immunosorbent assays in serum samples obtained from 93 DM patients and 56 healthy controls (HCs). Receiver operating characteristic (ROC) curve analysis was performed to evaluate the discriminant capacity of CitH3 and other disease variables. The association between CitH3 and disease variables was analyzed using Pearson's rank correlation. RESULTS: Serum CitH3 level was significantly lower in DM patients than in HCs (p < 0.001). The ROC curve analysis revealed that CitH3 strongly discriminated DM patients from HCs (area under the curve [AUC], 0.86), and a combination of CitH3 and the ratio of neutrophil to lymphocyte counts (NLR) showed a greater diagnostic value (AUC, 0.92). Serum CitH3 levels were markedly lower in DM patients with normal muscle enzyme levels than in HCs (all p < 0.001), and when compared to an elevated group, the CitH3 levels were comparable (all p > 0.05). The CitH3 levels showed no difference between DM in active and remission groups. However, in a paired test with 18 hospitalized DM patients, the CitH3 levels were higher in remission state than in active state. Moreover, the CitH3 levels showed no correlation with disease variables that were associated with the disease activity of DM. CONCLUSIONS: Serum CitH3 level may serve as a useful biochemical marker for screening patients with DM from HCs, while its role in monitoring DM disease activity requires further research.

From Pandemic Rumors to Reality: Arthritis Development and Exacerbations in Autoimmune Diseases After COVID-19 Vaccines

Introduction: There are similarities in the pathogenesis of COVID-19 and autoimmune diseases. In addition, due to the molecular similarities between the antigens of the virus and the antigenic structures in the human body, autoimmune diseases such as arthritis may occur or exacerbate after COVID-19 vaccines. In this publication, a retrospective evaluation of the patients who applied to the Rheumatology Outpatient Clinic with arthritis and other autoimmune complaints that developed or exacerbated after the COVID-19 vaccine was performed. Materials and Methods: Patients who applied to the Rheumatology outpatient clinics of our hospital were screened retrospectively, and patients who presented with newly developed or exacerbated autoimmune complaints after COVID-19 vaccination were determined. The files of these patients were reviewed retrospectively. Demographic characteristics of the patients, history of rheumatological disease, COVID-19 vaccinations, mean time to symptom development after vaccination, localization of arthritis, laboratory findings, imaging findings, treatment and treatment response were evaluated. Results: There are seven patients who applied to Rheumatology clinics with newly developed or exacerbated autoimmune complaints after COVID-19 vaccination in the last year. Three patients (no previous history of rheumatological disease) had newly emerged inflammatory arthritis, one stable gout, and one Sjogrens syndrome patient had exacerbated arthritis and two dermatomyositis cases (one newly diagnosed and the other exacerbation). Conclusion: The benefits of the vaccines are greater than the side effects that may develop, and vaccination should be continued in line with the recommendations. Although the temporal connection between the appearance of symptoms and the vaccination procedure in our study supports the relationship with the COVID-19 vaccine, it should never be forgotten that vaccines are the most effective way to prevent the disease.