Idiopathic Inflammatory Myositis Research Articles

P133 Anti-synthetase syndrome: an experience from a tertiary referral center

Abstract Background/Aims Anti-synthetase syndrome (ASS) is a subset of Idiopathic inflammatory myositis (IIMs). It is a syndromic diagnosis classified by Connors et al. and Solomon et al. criteria. Raynaud’s phenomenon (RP), fever, arthritis, mechanics hands, ILD and myositis constitute this syndrome along with the classical Anti-aminoacyl tRNA synthetase antibodies (ARS). About 25% of IIMs patients are classified as ASS. This study was planned to evaluate the prevalence of ASS; their phenotype, antibody subtypes, treatment responsiveness and outcomes. Methods All consecutive ASS patients were enrolled in the study fulfilling Connors et al. criteria during January, 2016 to August2023. Their demographic details, clinical features, laboratory and imaging features, treatment were analyzed. ARS were considered positive on a Line Immunoassay with cutoff >6U/ML using BlueDriverQuantrix-ANA25 Screen IgG kit (includes Jo1, Pl-7, Pl-12) from D-tek, Belgium including three ASS antibodies (Jo-1, PL-12, PL-7). Anti EJ, OJ antibodies were not present in the kit. Descriptive analysis were used to describe disease characteristics. Results Among 139 total IIM patients, 21(15%) patients were diagnosed with ASS. All patients fulfilled Connors et al. criteria while 66.6% patients fulfilled stricter criteria by Solomon et al. Mean(±SD) age group was 43(±16.4) years. 71.4% were Females. Anti Jo-1 was the predominant antibody seen in 66.6% while Anti PL-12 and Anti Pl-7 antibodies were present in 19% and 14.3% respectively. 66.6% had ANA positivity and MAA antibodies were seen in 52.3%. Rash was seen in 61.9%, mechanics hands in 38%, RP in 52.3% fever in 38% ,arthritis in 57%, myositis 62% and ILD in 80.9%. NSIP (66.6%) was the predominant type, followed by OP (9.5%) and UIP (4.7%). Median (IQR) CPK level was 736 (210-4556)U/L. Anti Jo-1 patients had higher prevalence of mechanics hands and rash whereas ILD was observed in all cases of Anti PL-7 and Anti PL-12 antibodies. Malignancy was seen in two patients (Malignant fibrous histiocytoma, Metastatic Pancreatic carcinoma). Mean (SD) MMT8 score was 62.8(±22.2) at presentation . Treatment is with steroids in all cases followed by maintenance with azathioprine in 57.1%, Methotrexate in 14.2%. Rituximab was used in 14.2%, cyclophosphamide in 9.5% and mycophenolate mofetil in 23.8%. Mortality was seen in one patient with respiratory failure. Lung involvement was severe in patients with both MSA and MAA positivity. 62% patients were in remission. Conclusion ILD and Arthritis were the main presenting complaints in our cohort. Myositis is relatively less prevalent in ASS. NSIP was the predominant ILD subtype. Non Jo-1 group had high MAA positivity. Jo-1 was associated with mechanic’s hands and rash. Malignancy was less prevalent in ASS. All patients with PL-7 and PL-12 antibodies had lung involvement. Biologics were required in few refractory cases. Disclosure P. Khatri: None. J.R. Yadavalli: None. S. Dhuria: None. N. Negalur: None. K. Shivam: None. R. Gupta: None.

Therapeutic intersections: Expanding benefits of CD19 CAR T cells from cancer to autoimmunity

Anti-CD19 CAR Tcells were among the last decade's scientific breakthroughs, achieving remarkable remissions in patients with B cell leukemias and lymphomas. Now, the engineered cell therapies are traversing disease indications into autoimmunity and resolving disease symptoms in patients with systemic lupus erythematosus (SLE), idiopathic inflammatory myositis, and systemic sclerosis.1.

CD19 CAR T-Cell Therapy in Autoimmune Disease — A Case Series with Follow-up

BackgroundTreatment for autoimmune diseases such as systemic lupus erythematosus (SLE), idiopathic inflammatory myositis, and systemic sclerosis often involves long-term immune suppression. Resetting aberrant autoimmunity in these diseases through deep depletion of B cells is a potential strategy for achieving sustained drug-free remission.MethodsWe evaluated 15 patients with severe SLE (8 patients), idiopathic inflammatory myositis (3 patients), or systemic sclerosis (4 patients) who received a single infusion of CD19 chimeric antigen receptor (CAR) T cells after preconditioning with fludarabine and cyclophosphamide. Efficacy up to 2 years after CAR T-cell infusion was assessed by means of Definition of Remission in SLE (DORIS) remission criteria, American College of Rheumatology–European League against Rheumatism (ACR–EULAR) major clinical response, and the score on the European Scleroderma Trials and Research Group (EUSTAR) activity index (with higher scores indicating greater disease activity), among others. Safety variables, including cytokine release syndrome and infections, were recorded.ResultsThe median follow-up was 15 months (range, 4 to 29). The mean (±SD) duration of B-cell aplasia was 112±47 days. All the patients with SLE had DORIS remission, all the patients with idiopathic inflammatory myositis had an ACR–EULAR major clinical response, and all the patients with systemic sclerosis had a decrease in the score on the EUSTAR activity index. Immunosuppressive therapy was completely stopped in all the patients. Grade 1 cytokine release syndrome occurred in 10 patients. One patient each had grade 2 cytokine release syndrome, grade 1 immune effector cell–associated neurotoxicity syndrome, and pneumonia that resulted in hospitalization.ConclusionsIn this case series, CD19 CAR T-cell transfer appeared to be feasible, safe, and efficacious in three different autoimmune diseases, providing rationale for further controlled clinical trials. (Funded by Deutsche Forschungsgemeinschaft and others.)

Evaluating the risk of ischemic stroke at a young age in patients with autoimmune inflammatory rheumatic diseases: a population-based cohort study in Taiwan.

Recent studies have demonstrated an increased incidence of ischemic stroke among patients with certain autoimmune inflammatory rheumatic diseases (AIIRDs). However, the associations between young stroke and AIIRDs have not been fully investigated. This study aimed to evaluate the risk of ischemic stroke among young patients with AIIRDs. The National Health Insurance Research Database in Taiwan was utilized to establish cohorts of patients with AIIRDs diagnosed between 2004 and 2015, who were compared with 1,000,000 control participants. Cox proportional hazards regression models were used to calculate the hazard ratio of ischemic stroke and young ischemic stroke for individual AIIRDs after adjustment for relative risk factors. During the study period, a total of 64,120 patients with AIIRDss and 1,000,000 control patients were identified. The overall mean follow-up time was 5.33 years. There were 223 (0.8%) and 1,923 (0.3%) young ischemic stroke-related hospitalizations among patients with AIIRDs and controls, respectively. The incidence rate of young ischemic stroke was 0.08 in patients with rheumatoid arthritis, 0.08 in patients with Sjögren's syndrome, 0.26 in patients with systemic lupus erythematosus, 0.17 in patients with idiopathic inflammatory myositis, 0.24 in patients with systemic sclerosis, 0.05 in patients with Behçet's disease, and 0.44 in patients with systemic vasculitis, versus 0.05 per 100 person-years in the general population. The adjusted hazard ratios for young ischemic stroke were 1.07 (95% CI 0.70-1.43) for rheumatoid arthritis, 1.39 (95% CI 0.94-2.06) for Sjögren's syndrome, 5.79 (95% CI 4.68-7.17) for systemic lupus erythematosus, 2.07 for idiopathic inflammatory myositis (95% CI 0.98-4.38), 2.79 for systemic sclerosis (95% CI 1.38-5.63), 0.82 for Behçet's disease (95% CI 0.26-2.55), and 4.15 (95% CI 1.96-8.82) for systemic vasculitis. Patients younger than 50 years with systemic lupus erythematosus, systemic sclerosis, or systemic vasculitis have a significantly elevated risk of developing ischemic stroke. Further research is needed to elucidate the pathogenesis of accelerated atherosclerosis in these AIIRDs.

Utility of positron emission tomography as a new tool for muscle involvement in patients with idiopathic inflammatory myositis: a controlled study.

Idiopathic inflammatory myositis (IIM) represents a rare group of disease that can affect multiple organs in addition to the muscles. 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is an emerging scanning method that is widely used in diagnosing, staging and response to treatment in patients with cancer. In this study, we aimed to evaluate the muscle involvement in PET/CT which was performed for malignancy screening and its correlation with myositis-specific antibodies (MSA) and/or myositis-associated antibodies (MAA) in patients with IIM. IIM patients who fulfilled 2017 EULAR/ACR classification criteria and had PET-CT scans during the active phase of myositis (within two weeks of starting steroids) were included into the study. Age and sex matched participants with history of malignancy (non-IIM patients) were defined as control group. Data of 160 IIM patients were evaluated and 34 patients (of 64.7% female) whose PET/CT results were available, included into the study. Fourteen patients with diagnosis of malignancy without IIM (non-IIM patients) defined as the control group. Sensitivity and specificity of a positive FDG muscle uptake were 37.1% and 100%, 65.7% and 92.9%, 91.4% and 7.1% compared to liver, mediastinum and LTM uptakes, respectively. In multivariate analysis, higher baseline CRP (p=0.017, confidence interval [CI] 95%: 1.03-1.36, OR:1.18) and LDH (p=0.029, CI 95%:1.001-1.017, OR:1.01) levels were associated with muscle PET/CT positivity. In patients with active IIM, median muscle FDG uptake with PET/CT was higher compared to non-IIM. PET/CT may be used for the evaluation of extent and activity in patients with IIM.

Rituximab compared to intravenous cyclophosphamide in adults with connective tissue disease-associated interstitial lung disease: the RECITAL RCT

Background Interstitial lung disease frequently complicates systemic autoimmune disorders including scleroderma, idiopathic inflammatory myositis and mixed connective tissue disease, resulting in considerable morbidity and mortality. Based on the results of trials undertaken in scleroderma, cyclophosphamide is the standard of care for individuals with severe or progressive connective tissue disease-associated interstitial lung disease. Observational studies suggest that the anti-CD20 monoclonal antibody, rituximab is an effective rescue therapy in treatment of refractory connective tissue disease-associated interstitial lung disease, but it has not been studied as first-line therapy in clinical trials. Objectives To compare the safety and efficacy of rituximab against that of cyclophosphamide as treatment for individuals with severe, progressive interstitial lung disease associated with scleroderma, idiopathic inflammatory myositis or mixed connective tissue disease. Methods This was a Phase IIb, multicentre, randomised, double-blind, double-dummy study assessing the superiority of rituximab compared with cyclophosphamide, conducted in rheumatology or interstitial lung disease units at 11 UK centres. The study recruited individuals with extensive and/or progressive connective tissue disease-associated interstitial lung disease, excluding those with significant comorbidities, including airflow obstruction. Participants were randomised 1 : 1 to receive either rituximab 1 g given intravenously, twice at an interval of 2 weeks, or intravenous cyclophosphamide given monthly for 6 months at a dose of 600 mg/m2 body surface area. The primary end point for the study was the change in forced vital capacity at 24 weeks. Secondary end points included safety and tolerability, corticosteroid exposure, forced vital capacity change at 48 weeks and patient-reported quality of life. A cost-effectiveness analysis was undertaken to assess the impact of rituximab use in the United Kingdom National Health Service. Results One hundred and one subjects (70 females) with a mean age of 56.3 years were randomised; 51 to rituximab and 50 to cyclophosphamide. Ninety-seven were included in the modified intention-to-treat population for the primary and secondary efficacy analyses (49 in the rituximab group and 48 in the cyclophosphamide group). 38.6% had scleroderma, 44.6% idiopathic inflammatory myositis and 16.8% mixed connective tissue disease. Four subjects withdrew prior to the first dose of therapy (two in each arm). At 24 weeks, both rituximab and cyclophosphamide improved forced vital capacity from baseline [(mean ± standard deviation) 97 ± 234 and 99 ± 329 ml, respectively]. Using an adjusted mixed-effects model corrected for diagnosis and baseline forced vital capacity the difference in forced vital capacity at 24 weeks between rituximab and cyclophosphamide was −40 ml (95% CI −153 to 74 ml), p = 0.49. Other physiological and quality-of-life parameters improved in both arms following treatment but were not statistically significantly different between groups. Numerically fewer adverse events were reported by subjects receiving rituximab. Corticosteroid exposure over the 48 weeks of the trial was numerically less in the rituximab arm [13,291 (±14,657) mg of hydrocortisone equivalent per subject in the cyclophosphamide arm versus 11,469 (±10,041) mg per subject in the rituximab group; these differences did not reach statistical significance]. Limitations of the study include a disproportionate number of subjects being recruited from a single centre and insufficient subjects in each subgroup to determine whether there were treatment differences between individual connective tissue diseases. Based on the results of the trial, from a UK healthcare payer perspective, rituximab is more cost-effective than cyclophosphamide as a treatment for severe or progressive connective tissue disease-interstitial lung disease. Conclusions Rituximab improved forced vital capacity and patient-reported quality of life at 24 weeks but was not superior to cyclophosphamide. Rituximab should be considered as a therapeutic alternative to cyclophosphamide in individuals with connective tissue disease-associated interstitial lung disease requiring systemic therapy. Future work should explore the role of repeated dosing of rituximab and the use of rituximab earlier in the course of connective tissue disease-associated interstitial lung disease. Trial registration This trial is registered as ISRCTN16474148. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation Programme (NIHR award ref: 11/116/03) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 4. See the NIHR Funding and Awards website for further award information.

Rare presentation of rare disease: Idiopathic inflammatory myositis presenting initially as acute respiratory distress syndrome.

Rare presentation of rare disease: Idiopathic inflammatory myositis presenting initially as acute respiratory distress syndrome.

Dermatomyositis with multiple organ involvement: a case report and literature review

Background: Dermatomyositis (DM) is a chronic autoimmune disorder characterized by muscle and skin inflammation, a part of the idiopathic inflammatory myositis (IIM). Even though the disease is idiopathic, there are multifactorial factors related to dermatomyositis. This care report aimed to describe a DM case in a male patient to increase the knowledge and management of DM patients. Case description: A 44-year-old Filipino male was referred to the emergency department (ED) of Siloam Hospital Mataram complaining of muscle pain and weakness with skin rashes 3 weeks before admission. Before the skin rash started, he had enlarged femoral lymph nodes in both thighs. The patient was afebrile with normal vital signs and was prescribed ibuprofen and amoxicillin. After that, he experienced skin rashes around his neck and the back of his ears with minimal pruritus. The symptoms worsened, making him unable to open his mouth and hard to breathe. In the ED, he also threw up dark-colored blood twice. Supporting examination showed elevated transaminase, increased LDH, and creatinine kinase. Biopsy results showed a histologic pattern of dermatomyositis. During hospitalization, he received a high-dose systemic steroid, antibiotic, and symptomatic treatment. He was discharged with a good outcome and planned to continue medical treatment in his country. Conclusion: Dermatomyositis is an idiopathic autoimmune disease involving skin and internal organs. It is a multifactorial disease yet with unclear etiopathogenesis. Specific treatment guidelines for DM are not yet established, but initial systemic corticosteroid and additional steroid-sparring agents may exhibit good outcomes.

Responsiveness and meaningful thresholds of PROMIS pain interference, fatigue, and physical function forms in adults with idiopathic inflammatory myopathies: Report from the OMERACT Myositis Working Group

BackgroundA series of qualitative studies conducted by the OMERACT Myositis Working Group identified pain interference, fatigue, and physical function as highly important life impact domains for adults with idiopathic inflammatory myositis (IIM). In this study, our goal was to assess the responsiveness and minimal important difference of PROMIS pain interference (6a), fatigue (7a), and physical function (8b). MethodsAdults with IIM from USA, Netherlands, Korea, Sweden, and Australia with two "clinical" visits were enrolled in this prospective study. Anchor questions on a Likert scale were collected at baseline, and manual muscle testing (MMT), physician and patient reported global disease activity, and PROMIS instruments were collected at both visits. Responsiveness was assessed with i) ANOVA, ii) paired t-test, effect size and standardized response mean, and iii) Pearson correlation. Minimal important difference (MID), minimal important change (MIC) and minimal detectable change (MDC) values were calculated. Results114 patients with IIM (median age 60, 60 % female) completed both visits. Changes in PROMIS instruments were significantly different among anchor categories. Patients who reported improvement had a significant improvement in their PROMIS scores with at least medium effect size, while patients who reported worsening and stability did not show a significant change with weak effect size. PROMIS instruments had weak to moderate correlations with MMT, patient and physician global disease activity. MID was approximately 2–3 points for Pain Interference and 3–4 points for Fatigue and Physical Functionforms based on the method used. MIC was approximately 4–5 for improvement of all the instruments, while MDC was 1.7–2 points for Pain Interference and Physical Function and 3.2–3.9 for Fatigue. ConclusionThis study provides evidence towards the responsiveness of the PROMIS instruments in a large international prospective cohort of adults with IIM supporting their use as PROMs in adult myositis.

Long Term Outcomes in Idiopathic Inflammatory Myositis: An Observational Epidemiologic Study over 15 Years.

We report a longitudinal observational cohort of idiopathic inflammatory myositis (IIM) focusing on the long-term clinical outcome and associated parameters. IIM patients were classified as per Bohan and Peter criteria. In those with ≥ 24 months of follow-up; the treatment response, functional outcomes, and damage at last follow-up were recorded. Complete clinical response and clinical remission as defined by Oddis et al., was used to define outcomes at last follow-up. The cohort consists of 175 patients, mean age 40.9 (+12.6) years, M:F 1:3.3; and the major subsets were dermatomyositis (44.6%), overlap myositis (25.7%), antisynthetase syndrome (6.3%), polymyositis (14.3%), and juvenile DM/OM (8.6%). Ninety-four patients have followed up for 24 months or more, with the median (IQR) of 65(35,100.7) months. Of them, 74.1% and 11.8% had complete and partial clinical responses respectively at the last follow-up. In our cohort 40.2% were off-steroids and 13.8% were in clinical remission at the last follow-up. Complete clinical response was associated with better functional outcomes and lesser damage as determined by HAQ-DI of 0[OR10.9; 95%CI (3.3,160)], MRS [OR 3.2; 95%CI (1.4,7.3)] and lesser MDI [OR 1.7; 95% CI (1.1,2.7)] respectively as compared to partial response (unadjusted analysis). Baseline parameters and IIM subsets did not significantly influence the functional outcome and damage. The mortality rate in our cohort is 24/175 (13.7%), the disease-specific mortality rate being 9.1%. Large majority of deaths were early, associated with active disease. We report good long-term outcomes in all major myositis subsets. Partial clinical response to treatment is associated with worse functional outcomes and damage accrual. Death occurs early in association with active disease.

Antibody predictors of mortality and lung function trends in myositis spectrum interstitial lung disease.

The impact of autoantibody profiles on prognosis of idiopathic inflammatory myositis associated interstitial lung disease (IIM-ILD) and myositis spectrum ILD with Myositis Specific Antibodies (MSA) remains unclear. This retrospective cohort study examines whether serological profiles are associated with mortality and longitudinal lung function change. Baseline clinical/demographic characteristics and follow-up lung function of consecutive adult patients with IIM-ILD or Interstitial Pneumonia with Autoimmune Features (IPAF) positive for MSAs were extracted from three hospitals. Univariate and multi-variate Cox-Proportional Hazards analyses were used to compare mortality between autoantibodies. Regression models were used to analyse lung function trends. Of 430 included patients, 81% met IIM criteria, 19% were IPAF-MSA. On univariate analysis, risk factors associated with mortality included higher age, Charlson Co-morbidity Index and CRP; and lower BMI, baseline TLCO% and FEV1%. Compared to anti-MDA5-negativity, anti-MDA5-positivity (MDA5+) was associated with high mortality in the first 3 months (HR 65.2. 95%CI 14.1, 302.0), while no significant difference was seen thereafter (HR 0.55, 95%CI 0.14, 2.28). On multi-variate analysis, combined anti-synthetase antibodies carried a reduced risk of mortality (HR 0.63), although individually, mortality was reduced in anti-Jo1 + (HR 0.61, 95%CI 0.4-0.87) and increased in anti-PL7+ patients (HR 2.07, 95%CI 1.44-2.99). Anti-MDA5+ was associated with slow improvement in %FVC over the first 3 years, while anti-PL7+ was linked with a slow decline from 12 months onwards. Among autoantibody profiles in myositis spectrum disorders, anti-MDA5+ and anti-PL7+ confer higher mortality risks. Survivors of an early peak of mortality in anti-MDA5+ disease appear to have a favourable prognosis.

Clinical profile of anti-NXP-2 antibody-positive inflammatory myositis and outcome in an Indian population.

Myositis-specific antibodies (MSA) play an important role in the clinical presentation and prognosis of patients with idiopathic inflammatory myositis (IIM). Anti-NXP-2 is one of the newly described MSA. We aimed to describe various clinical presentations associated with anti-NXP2 antibodies and assess response to treatment. In this retrospective study, the electronic medical records of all patients who tested positive for anti-NXP2 during June 2019 to April 2022 were screened. Details of demography, clinical presentation, and treatment data were recorded. The anti-NXP2 was tested using the Euro line test kit. Any patient who had an intensity of ≥1+ was considered testing positive. The diagnosis of IIM was reviewed after applying the 2017 European League of Rheumatology (EULAR)/American College of Rheumatology (ACR) criteria of myositis. Among the 660 suspected patients, 470 (71.2%) patients were positive for IIM, and 28 (5.95%) patients were positive for anti-NXP2. From anti-NXP2-antibody positive, 21/470 (4.46%) patients fulfilled criteria for IIM. Among 12 adult (57.14%) patients with IIM, 7 (58.33%) presented as polymyositis (PM) and 5 (41.6%) as dermatomyositis (DM) with median age at presentation of 45 (IQR: 25-58) years. Calcinosis and subcutaneous oedema were observed in 4 (19%) and 2 (9.52%), respectively; myalgia in 6 (28.6%); and distal muscle weakness in 5 (23.8%) patients. Malignancy at the time of diagnosis was observed in two adults with IIM (16.7%), one with DM (intraductal breast cancer), and another with PM (anaplastic large cell lymphoma). Remaining, 9 had juvenile dermatomyositis (JDM) with a median age of 4 (IQR: 3-8) years. Seven (77.8%) patients with JDM had skin rash specific for DM (heliotrope rash and Gottron's papule). None of the patients had cardiac and lung involvement, while GI symptoms, especially dysphagia, were present in 5 (23.8%) patients. During a median follow-up of 19 months (IQR: 12-26 months), 19/19 patients reported improvement and were in remission with treatment. The current study shows that adult DM patients with anti-NXP-2 autoantibodies have a unique clinical phenotype. Its presentation differs between adult and JDM, even in different parts of the world. Muscle weakness is mild and responds to treatment. Dysphagia needs more time and aggressive IS for improvement as compared to other muscle involvement. Key Points • Anti-NXP-2 antibody presentation varied from adult to child, as in different parts of the world. • In Indian adult patients, non-specific skin manifestations were more common, whereas in JDM, specific skin features were common. • There was less likely involvement of the lung and heart. But more risk of GI involvement requiring aggressive management. • Adult with anti-NXP-2 antibody should be screened for malignancy at the time of presentation.

Observational longitudinal study to assess the outcome of patients with idiopathic inflammatory myositis using validated tools.

There have been major changes in the classification and treatment of patients with idiopathic inflammatory myositis (IIM) in the last 2 decades. A major challenge is to identify the parameters that can affect the outcome and prognosis of these patients. Here, we have longitudinally followed a well-characterized cohort of IIM patients in a rheumatology center and reported the outcome using the validated tools. Patients with a clinical diagnosis of IIM and a follow-up duration of greater than 2 years were prospectively included in the study. The duration of the study was 6 years: July 2016-July 2022. Clinical details and follow-up were recorded using pro-formas and outcomes were noted using validated tools. Ethics approval and written informed consent were taken. Forty patients had a clinical diagnosis of IIM. Mean follow-up duration was 43.8 (15) months. Out of 40 patients, 32 (80%) achieved remission (8 patients each were off corticosteroid and off treatment for >6 months), 5 (12%) expired and 3 (8%) had active disease. Disease course was non-relapsing in 22/35 (73%) patients. Mean manual muscle testing-8 score (n = 29) and myositis disease activity assessment tool score (n = 35) at the final visit were 75.6 (6.8) and 0.048 (0.07) respectively. Thirteen patients had damage (37%). Patients with disease duration >1 year at the time of presentation were more likely to develop chronic-continuous disease course (P = .023, odds ratio [OR] = 7.6), more frequently required second-line or third-line immunosuppression (P = .001, OR = 24) with higher myositis damage index score (p = .0002, OR = 47). IIM patients had good outcomes with the majority achieving remission and near-complete muscle recovery. However, the patients presenting late to the rheumatologists were more likely to have smoldering disease, more immunosuppressive medicines, and greater accumulated damage.

An Unusual Presentation of Anti Pm/Scl Antibody-positive Idiopathic Inflammatory Myositis

ABSTRACT Idiopathic inflammatory myopathies are the heterogeneous group of diseases that affect multiple systems apart from the skeletal muscles, preferentially affecting the proximal skeletal muscle. We present a rare case with quadriparesis, purely involvement of proximal muscles without any extra muscular symptoms with positive Anti Pm/Scl antibodies. Our patients was 52 year old male who presented to be symptomatic with generalized swelling all over the body followed by progressive pure proximal group of muscles motor weakness of all four limbs without sensory involvement. He also developed oropharyngeal weakness, in the form of nasal regurgitation of food and significant weight loss. C reactive protein was 22 mg/L, erthryocyte sedimentation rate was 30 mm after 1 h, and liver enzymes were also increased (aminotransferase was 236 U/L and alanine aminotransferase was 145 U/L). His lactate dehydrogenase was 1175 U/L whereas creatinine kinase was 3290 U/L. His ANA profile was positive for Anti Pm/ Scl antibodies. MRI of both thighs was suggestive of diffuse inflammatory changes in both lower limbs and pelvic girdle and PET CT was suggestive of increased uptake in proximal limb muscles. He was managed with pulse Inj Methylprednisolone and intravenous Immunoglobulin. This followed by oral prednisolone for a few months than slow tapering. In Conclusion that Anti Pm/Scl antibody positive idiopathic inflammatory myositis can also present atypically without any other systemic manifestation and weakness in lower limb more than upper limbs. Idiopathic inflammatory myopathies disease is one of the treatable diseases that repones to immunomodulation therapy.

Juvenile idiopathic inflammatory myositis: an update on pathophysiology and clinical care.

The childhood-onset or juvenile idiopathic inflammatory myopathies (JIIMs) are a heterogenous group of rare and serious autoimmune diseases of children and young people that predominantly affect the muscles and skin but can also involve other organs, including the lungs, gut, joints, heart and central nervous system. Different myositis-specific autoantibodies have been identified that are associated with different muscle biopsy features, as well as with different clinical characteristics, prognoses and treatment responses. Thus, myositis-specific autoantibodies can be used to subset JIIMs into sub-phenotypes; some of these sub-phenotypes parallel disease seen in adults, whereas others are distinct from adult-onset idiopathic inflammatory myopathies. Although treatments and management have much improved over the past decade, evidence is still lacking for many of the current treatments and few validated prognostic biomarkers are available with which to predict response to treatment, comorbidities (such as calcinosis) or outcome. Emerging data on the pathogenesis of the JIIMs are leading to proposals for new trials and tools for monitoring disease.

Clinical and laboratory characteristics of idiopathic inflammatory myositis in Saudi patients: A retrospective study in a single tertiary centre.

Idiopathic inflammatory myositis (IIM) in Saudi patients has been poorly studied owing to the lack of available data. This study aimed to identify the clinical and laboratory features of patients at a single tertiary care center. This retrospective study reviewed the medical records of Prince Sultan Military Medical City, Riyadh, Saudi Arabia to collect clinical and laboratory data between December 2022 and February 2017 as follows: age at disease onset, gender, follow-up duration and disease duration; clinical symptoms; laboratory result; presence and type of myositis-specific autoantibody or myositis-associated autoantibody; and type of immunosuppression, presence of malignancy, disease course, and outcome. There were 26 patients with a mean age of 36.16±13.48, and 84.6% were women. The most prevalent form of IIM was dermatomyositis (n=16, 61.5%), and the most affected organ was the skin. weakness was observed in 25 patients (96.2%), and dysphagia was the most common alarm sign (n=10, 38.5%). During follow-up, the creatine kinase level was elevated at the beginning of the disease and then decreased following treatment, with a mean of 277.73 IU/L. Of the total patients, 17 (68%) were positive for anti-nuclear antibody and 5 (19.2%) were positive for anti-Jo-1. In our patients, dermatomyositis was the most common form of myositis, and skin manifestations were the most prevalent clinical characteristics. None of the patients developed a malignancy or died.

OA29 Flares following COVID-19 vaccination in patients with idiopathic inflammatory myopathies: combined analysis from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) studies

Abstract 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. Disclosure L. Gupta: None. N. R: None. Z. Griger: None. V. Agarwal: None. P. Sen: None. M. Joshi: None. S. Saha: None. K. Jagtap: None. O. Distler: Honoraria; 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. E. Nikiphorou: Honoraria; Celltrion, Pfizer, Sanofi, Gilead, Galapagos, AbbVie, and Lilly. Grants/research support; Pfizer and Lilly. A. Tan: Honoraria; Abbvie, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB. S. Shinjo: None. N. Ziade: Honoraria; Pfizer, Roche, Abbvie, Eli Lilly, NewBridge, Sanofi-Aventis, Boehringer Ingelheim, Janssen, and Pierre Fabre. M. Milchert: None. I. Parodis: Honoraria; Amgen, AstraZeneca, Aurinia Pharmaceuticals, Elli Lilly and Company, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceuticals, Novartis and F. Hoffmann-La Roche AG. M. Kuwana: None. A. Makol: None. J. Pauling: None. C. Wincup: None. J. Lilleker: Honoraria; Sanofi Genzyme, Roche, and Biogen. A. Nune: None. J. Day: Grants/research support; CSL Limited. H. Chinoy: Consultancies; Novartis, Eli Lilly, Orphazyme, Astra Zeneca. Honoraria; UCB, and Biogen. Grants/research support; Eli Lilly and UCB. V. Agarwal: None. R. Aggarwal: Consultancies; Bristol Myers-Squibb, Pfizer, Genentech, Octapharma, CSL Behring, Mallinckrodt, AstraZeneca, Corbus, Kezar, Abbvie, Janssen, Alexion, Argenx, Q32, EMD-Serono, Boehringer Ingelheim, and Roivant.

E057 A systematic review of new rheumatic immune-mediated inflammatory diseases (R-IMID) following SARS-CoV-2 vaccinations

Abstract Background/Aims There are sporadic reports about the development of new rheumatic immune-mediated inflammatory diseases (R-IMIDs) in adults after receiving SARS-CoV-2 vaccines. This systematic review (SR) aimed to critically review and summarize the clinical profile, patient demographics, treatment, and prognosis of new-onset R-IMIDs following SARS-CoV-2 vaccination. Methods We retrieved English-language articles (Case reports and series and observational studies) on new-onset R-IMIDs following SARS-CoV-2 vaccination, published until June 2022, from standard databases (MEDLINE, Embase, Cochrane). The search strings used during the literature search incorporated ‘SARS-CoV-2 vaccination’ (along with related MeSH terms) and various key terms for R-IMIDs [which included (but was not limited to) inflammatory arthritis, connective tissue disease (CTD), vasculitis, systemic lupus erythematosus, Sjogren’s syndrome, sarcoidosis, systemic sclerosis, idiopathic inflammatory myositis, anti-synthetase syndrome, Adult-onset Stills disease (AOSD), giant cell arteritis (GCA), and polymyalgia rheumatica (PMR)]. The protocol was registered in PROSPERO (CRD42022318561). Results Of the total 2179 articles retrieved, 1986 articles were excluded following the title-abstract screening, and 107 articles that did not meet inclusion criteria. We included the remaining 86 articles (130 cases) upon full-text screening. Furthermore, we added four articles (six cases) based on a manual search, comprising 90 articles (136 cases) for final analysis. These 136 new R-IMID cases were reported from 27 different countries. Of these, more than one-third of the cases were reported from three countries (viz., Italy, Japan, and the USA). The patients had a mean age of 57 (range:17-90) years, and the majority were females (63.0%). Most patients developed R-IMIDs after receiving Pfizer-BioNTech vaccine (76; 55%), followed by Oxford AstraZeneca vaccine (35; 25%). The mean duration between SARS-CoV-2 vaccination and R-IMIDs development was 9.2 (range:1-90) days. The second dose of the vaccine resulted in more R-IMIDs (74;54%) than the first (53;39%). CTDs (34; 25%) and small vessel vasculitis (33; 24%) were the commonest R-IMID manifestations, followed by inflammatory arthritis and AOSD, each in 13 (9.5%) cases. Nearly half of the patients with CTDs had Idiopathic Inflammatory Myositis. PMR and GCA accounted for 16 (11.7%) and 5 (3.6%) cases, respectively. However, no cases of axial spondylarthritis were reported. Most (118; 86%) R-IMID patients were treated with corticosteroids, with a small number receiving steroid-sparing drugs, such as methotrexate, rituximab and cyclophosphamide. Most (125; 91%) went into either disease remission or improvement following the treatment. Only three patients were admitted to the intensive care unit (ICU) to manage their disease; One of them died due to fatal myositis and rhabdomyolysis; two surviving ICU patients had ANCA-associated vasculitis with lung involvement. Conclusion Although rare, this SR highlights the emergence of de novo R-IMIDs following SARS-CoV-2 vaccination. We cannot confirm the causality between the vaccination and the onset of R-IMID. However, further research is warranted in this area. Disclosure A. Nune: None. K. Bora: None. K.P. Iyengar: None. B. Barman: None. V. Durkowski: None. S. Venkatachalam: None. S. Bilgrami: None. L. Ottewell: None. C. Manzo: None.

P154 Real-world audit of patients with idiopathic inflammatory myositis-related interstitial lung disease in a European population

Abstract Background/Aims The British Society for Rheumatology (BSR) has released guidelines for managing idiopathic inflammatory myositis (IIM). Our centre operates specialist clinics for scleroderma and lupus, but to date, IIM patients are seen in a general CTD clinic. As part of work to establish a dedicated myositis clinic, we collated data on 71 patients under active follow-up with myositis spectrum disease deemed appropriate for follow-up within a specialist clinic. We aimed to review patients diagnosed with IIM-ILD and review serological immune profile, screening practices for pulmonary involvement, findings on CT/pulmonary function tests (PFTs) and pharmacological management. Methods We performed a detailed retrospective review of the notes of suitable patients, identified using diagnostic codes attached to clinic letters. Results 71 patients were identified: 14 with anti-synthetase syndrome (ARS), 21 with dermatomyositis (DM), 13 with polymyositis (PM), 3 with immune-mediated necrotising myopathy (IMNM) and 17 with overlap syndrome. 65% (46/70) of adult IIM patients were screened for pulmonary involvement. Screening practices of patients based on antibody profile and myositis subtype are further described in the table. 31% of patients (22/70) had IIM-ILD, of which 12 had ARS, 4 had PM, 1 had DM and 5 had overlap disease (2 PM/scleroderma, 1 DM/ARS, 1 DM/scleroderma and 1 scleroderma/ARS). 21/22 underwent PFTs; 53% of patients had active ILD over an average of 51.8 months. On imaging, 76.2% (16/22) had changes consistent with ILD. Ground glass change and reticulation were demonstrated in 50% of scans. In comparison, honeycombing and traction bronchiectasis was found in 22% and 44% of scans, respectively. A non-specific interstitial pneumonia (NSIP) pattern was described in 44% of scans, organising pneumonia (OP) pattern in 22%, and 17% had a mixed OP and NSIP pattern. 20/22 patients were prescribed high-dose steroids, csDMARD therapy or aggressive immunosuppression (cyclophosphamide or rituximab). Conclusion Our review demonstrates that 65% of patients with adult IIM were screened for ILD. NSIP and OP were the most common radiological appearances. Half of our cohort required aggressive immunosuppression, cyclophosphamide being the most commonly prescribed agent and mycophenolate being preferred for maintenance therapy. No patients were prescribed tacrolimus or ciclosporin. Despite treatment, 52% of patients had evidence of progressive disease on serial PFTs. Disclosure A. Loganathan: Grants/research support; Arthritis Australia. S. Sturney: None. N. Foley: None. T. Hartley: None. S. Tansley: None.

P064 Incidence and Clinical Outcomes of New-onset Autoimmune Connective Tissue Diseases after COVID-19 Infection- A Systematic Literature Review

Abstract Background/Aims Cases of new autoimmune and autoinflammatory conditions have been reported among COVID-19 survivors. A literature review on new-onset 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), anti-synthetase 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 abstract, 2196 papers were excluded, with 43 proceeding to full-text 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. Disclosure K. Kouranloo: None. M. Dey: None. H. Elwell: None. A. Nune: None.