Idiopathic Inflammatory Myositis Patients Research Articles

Effectiveness of generic tofacitinib in idiopathic inflammatory myositis (IIM)-a retrospective analysis from Indian Myositis Registry (MyoIN).

Determine domain-based-outcomes and steroid-sparing efficacy of generic tofacitinib in IIM. This is a multicenter retrospective study wherein clinical phenotype, autoantibody profile, prior immunosuppressives, and outcomes at 3, 6, and 12months were retrieved for IIM patients prescribed tofacitinib. Overall clinical response was assessed as complete or partial remission as per physician judgment. Changes in cutaneous and calcinosis domain were recorded as per physician global assessment (PGA), lung domain as per medical research council (MRC) dyspnea scale, and muscle strength by Manual Muscle Testing-8 (MMT-8). Forty-two patients of IIM with mean age 38.7 ± 16years; (76.2% (N = 32) women), median duration of illness 48 (19;88) months were included. Commonest indication for initiating tofacitinib was either for refractory or as steroid sparing for cutaneous domain (N = 25/42, 59.5%) followed by calcinosis (N = 16/42, 38%). Overall complete and/or partial remission was achieved in 23/37 (64.8%), 30/35 (85.7%), and 29/30 (96.6%) patients at 3, 6, and 12months, respectively. At 12-month follow-up, there was a reduction in prednisolone dose, with absolute decrease from a daily dose of 17.5mg (IQR 5;50) to 2.5mg (IQR 0;5) (p < 0.001). Individual domain assessments revealed improvement in cutaneous domain [16/25 (64%)] and calcinosis [6/15 (40%)]. Adverse effects included herpes zoster (N = 2/42, 4.8%) and dyslipidemia (N = 4/42, 9.5%). Treatment with generic tofacitinib significantly reduces the daily dose of corticosteroids and is effective in cutaneous domain including calcinosis in IIM. • This multicenter retrospective study is the first real-world data from India, elucidatingsteroid sparing efficacyof generic tofacitinib in patients with inflammatory myositis. • Domain-based outcome assessment suggests good clinical improvement especially in cutaneous domain, even those with refractory disease. • Modest benefits were evident in calcinosis, but its effect on the muscle and pulmonary domain appears limited.

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 &amp;gt;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.

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.

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.

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.

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.

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 &amp;lt; 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.

PET-MRI in idiopathic inflammatory myositis: a comparative study of clinical and immunological markers with imaging findings

BackgroundWe sought to determine the utility of PET-MRI in diagnosing Idiopathic Inflammatory Myositis (IIM), and look for association between FDG uptake and clinical, pathological and laboratory parameters.MethodsA retrospective, observational study was conducted on IIM patients having positive serum autoantibodies and who underwent PET-MRI (3-Tesla SIEMENS Biograph MR scanner) between 2017 and 2021. Thirty patients who underwent PET-MRI to detect systemic metastasis without muscle involvement formed the control group.ResultsIn the IIM cohort, female: male sex ratio was 1.73, mean age at diagnosis was 40.33 years, and the mean duration of illness was 7 months. 33.33% of patients had severe limb weakness. Mi2B (43.33%), Mi2A (43.33%), PL-7(10%), PL-12(6.67%), SRP (16.67%), Tif1gamma (3.33%), NxP2 (3.33%), Ro-52(40%), PM-Scl, U1-RNP, ANA (26.67%) were the serum autoantibodies identified. Using SUV max Ratio to quantify FDG uptake, PET-MRI showed a sensitivity of 100% with 93.3% specificity in diagnosing IIM.FDG uptake was maximum in proximal lower limb region followed by proximal upper limb. Multivariate regression analysis showed that the severity of muscle weakness, serum Mi2B antibody positivity and serum creatinine kinase levels had a significant positive correlation with FDG uptake (value of 0.005, 0.043, 0.042, respectively for whole-body FDG uptake). FDG uptake also showed good correlation with histopathological features and muscle MRI, but there was no significant association with treatment response. Three female patients in our cohort had primary malignancy involving the breast, uterus, and cervix.ConclusionsPET-MRI is a promising diagnostic modality for IIM. PET-MRI reflects the severity of muscle inflammation, showing good association with various clinical/laboratory parameters, histopathology, and muscle MRI. Parameters associated with severe muscle inflammation in PET-MRI—clinical severity of muscle weakness, Mi2B positivity, and serum creatine kinase levels—may be used as clinical/laboratory markers of disease severity in IIM. PET-MRI has the added advantage of detection of systemic malignancy.

POS0905 CHARACTERISATION OF SWEDISH MYOSITIS PATIENTS WITH ANTI-MDA5 AUTOANTIBODIES AND CORRELATION OF CLINICAL FEATURES WITH AUTOANTIBODY LEVELS

BackgroundThe association between anti-melanoma differentiation association protein 5 autoantibodies (aMDA5) and rapidly progressive interstitial lung disease (RP-ILD) in clinically amyopathic dermatomyositis is well established in Asian population cohorts. In western cohorts, ILD has been strongly associated with aMDA5 but data regarding RP-ILD have been more conflicting. It is also suggested that western cohorts have more pronounced myopathic features than Asian.ObjectivesTo characterise the disease manifestations of a Swedish aMDA5 positive idiopathic inflammatory myositis (IIM) cohort and to explore antigen reactivity of the MDA5 protein.MethodsFirst available serum samples collected from 28 consecutive patients with IIM and positive aMDA5 ever tested by ELISA, Line Blot (LB) or Immunoprecipitation, attending Karolinska University Hospital between 1999 and 2021, were included. Clinical data including presence of anti-SSA autoantibodies by ELISA or LB was retrieved retrospectively. An in-house ELISA was used to screen serum samples for reactivity against a recombinant MDA5 protein (rMDA5, aa A110-D1025, UniProt ID Q9BYX4) and seven MDA5-derived constructs containing different domains. Correlations between aMDA5 reactivity levels and clinical data were explored.ResultsNine patients showed no reactivity to any of the rMDA5 constructs by ELISA and were excluded from further analysis.Reactivity against rMDA5 was confirmed by ELISA in 19 patients (median 184.7 µg/mL (interquartile range (IQR) 277.07). The cohort included 13 male and 6 female patients, 94% Caucasian, with mean age at diagnosis of 41.05 years (standard deviation (SD) 10.5). Median disease duration at time of sampling was 0 months (IQR 1). All patients except one had signs of muscle involvement (muscle weakness, elevated muscle enzymes, muscle oedema or muscle biopsy consistent with myositis). At diagnosis 63.2% of patients reported muscle weakness (21.1 % had a manual muscle test 8 score &lt;75). Dermatological findings were observed in 17/19 (89.7 %). During disease course nine patients (47.4%) had confirmed arthritis.ILD was diagnosed in 16/19 patients (84.2%), four of these (25%) developed a RP-ILD. One patient passed away due to RP-ILD and one required a lung transplant. Patients with ILD had a statistically significant higher mean age at diagnosis than those without (42.8.5 (SD 10.3) vs 31.3 (SD 4.7) years, p=0.02). Patients developing RP-ILD were not significantly older than patients with chronic ILD. Respiratory symptoms were reported by 75% of patients with ILD at time of diagnosis. The mean total lung capacity (TLC) of the ILD cohort was 68% (SD 17), mean diffusion capacity of carbon monoxide (DLCO) was 59% (SD 15) and mean forced vital capacity (FVC) was 62% (SD 19). There was a higher proportion of patients with CRP ≥ 3 times the reference range at diagnosis amongst patients with FVC &lt;70 % than patients with FVC &gt;70 % (88.9 % vs 16.7 %, p= 0.01).Ten patients (52.6%) had anti-SSA autoantibodies, all had ILD. Anti-SSA positive patients had a statistically significant lower TLC than those without (62% vs 79% respectively, p=0.04) and a lower FVC (57% vs 76% respectively, p=0.05).We found a weak non-statistically significant negative correlation between titres of aMDA5 and TLC, DLCO and FVC (Pearson coefficients -0.187, -0.289, -0.130 respectively). Frequency of ILD was higher in patients with aMDA5 titres &gt;100 µg/mL than those with titers &lt;100, but not statistically significant (81.3% vs 18.8%, respectively).ConclusionIn this Caucasian cohort of aMDA5 positive IIM patients, ILD was present in over 80% of patients, of these, one quarter had RP-ILD. Older patients were more likely to present with ILD. Anti-SSA positivity and higher CRP levels were associated with worse lung function. We found a weak negative correlation between aMDA5 titres and lung function tests, as well as a trend of higher frequency of ILD in patients with higher aMDA5 titres. Muscle and skin involvement were found in a high proportion of patients.AcknowledgementsD. Demirdal &amp; E. Van Gompel contributed equally to this abstract.Disclosure of InterestsDeniz Demirdal: None declared, Eveline Van Gompel: None declared, Edvard Wigren: None declared, Maryam Dastmalchi: None declared, Begum Horuluoglu: None declared, Angeles Shunashy Galindo-Feria: None declared, Susanne Gräslund: None declared, Karine Chemin: None declared, Ingrid E. Lundberg Shareholder of: Roche and Novartis., Consultant of: Consulting fees from Corbus Pharmaceuticals Inc, Astra Zeneca, Bristol Myer´s Squibb, Corbus Pharmaceutical, EMD Serono Research &amp; Development Institute, Argenx, Octapharma, Kezaar, Orphazyme, and Janssen, Grant/research support from: Research grants from Astra Zeneca, Antonella Notarnicola Speakers bureau: compensation for lecture at conference sponsored by Boehringer Ingelheim.

The effect of COVID-19 pandemic on idiopathic inflammatory myositis patients: a single centre experience.

Pandemic caused by coronavirus disease (COVID-19) determines the life of clinicians and patients since 2 years. We have a lot of information about disease course, treatment and protection against virus, but less on the prognosis of infection in patients with idiopathic inflammatory myopathies (IIM). Also few data are available on triggered humoral response and side effects after vaccination. Our goal was to assess by a retrospective cross-sectional study the above data in our cohort (176 IIM patients) by identifying COVID-19 positive patients and follow disease course. Incidence and complications of vaccination were determined by questionnaires. 101 patients volunteered for complex blood test. By June 1st, 2021 significantly higher incidence of COVID 19 infections (34.7%) were identified comparing to the national prevalence (8.2%). A third of these infections occurred asymptomatically or mild. Patients requiring hospitalisation had a significantly longer disease duration and a higher incidence of anti-Jo-1 antibody. All patients infected by COVID-19 became seropositive regardless the immunosuppressive therapy or symptoms severity. 54.3% of the patients received anti-COVID-19 vaccine. 72.3% of patients became seropositive after vaccination. Higher antibody titer against spike protein was detected after Pfizer-BioNTech vaccination compared to others. Patients receiving steroid therapy had decreased post-vaccination antibody response compared to those without steroid treatment. No major post-vaccination infection was observed. Based on our results, myositis may be associated with an increased risk of COVID-19 infection. Independent risk factor for hospitalisation are longer disease duration and anti-Jo1 positivity. Anti-SARS-CoV2 vaccines seem safe and tolerable and strongly recommended for that population.

Profiling of Myositis Specific Antibodies and Composite Scores as an Aid in the Differential Diagnosis of Autoimmune Myopathies.

(1) Background: Myositis specific antibodies (MSA) represent important diagnostic and stratification tools in idiopathic inflammatory myositis (IIM) patients. Here we aimed to evaluate the clinical performance of MSA profiled by a novel particle based multi-analyte technology (PMAT) in IIM and subsets thereof. (2) Methods: 264 IIM patients and 200 controls were tested for MSA using PMAT (Inova Diagnostics, research use only). Diagnostic performance was analyzed and composite scores were generated. (3) Results: The sensitivity/specificity of the individual MSA were: 19.7%/100% (Jo-1), 7.2%/100.0% (Mi-2), 3.0%/99.0% (NXP2), 3.8%/100.0% (SAE), 2.7%/100.0% (PL-7), 1.9%/99.5 (PL-12), 1.1%/100.0% (EJ), 15.5%/99.5% (TIF1γ), 8.3%/98.5% (MDA5), 6.1%/99.0% (HMGCR) and 1.9%/98.5% (SRP). Of all IIM patients, 180/264 tested positive for at least one of the MSAs. In the individual control group, 12/200 (6.0%) tested positive for at least one MSA, most of which had levels close to the cut-off (except one SRP and one PL-12). Only 6/264 (2.3%) IIM patients were positive for more than one antibody (MDA5/HMGCR, EJ/PL-7, 2 x MDA5/TIF1γ, EJ/SAE, SAE/TIF1γ). The overall sensitivity was 68.2% paired with a specificity of 94.0%, leading to an odds ratio of 33.8. The composite scores showed good discrimination between subgroups (e.g., anti-synthetase syndrome). (4) Conclusion: MSA, especially when combined in composite scores (here measured by PMAT), provide value in stratification of patients with IIM.

Mycophenolate in idiopathic inflammatory myositis: outcome data of a large South Asian cohort.

Consensus on treatment of idiopathic inflammatory myositis (IIM), particularly with regard to flares and interstitial lung disease (ILD), does not exist. We studied the long-term outcome and treatment response in our large, retrospective cohort of adult South-Asian patients exclusively with IIM. Electronic records of IIM patients satisfying inclusion and exclusion criteria were studied longitudinally at presentation, at 3, 6, 12, 18 and 24 months and thereafter yearly till their last follow up (F/u) visit. Depending on clinical, imaging, and muscle enzyme profile during the F/u period, patients were categorised as complete (CR) and partial responders (PRs). Parameters favouring CR were assessed using multivariate logistic regression analysis. Outcome parameters and flares on immunosuppressants (IS) were then assessed in patients with/without ILD. Two hundred thirty-two patients with median F/u duration of 44.5 months (25-80.25) were included. ILD was seen in 40.1%. Patients with non-Jo1 anti-synthetase antibodies (n=26) were numerically more than those with Jo-1 antibody (n=24). CR status was attained by 50.9% patients. Absence of pericardial effusion (p=0.042, OR 4.223, 95% CI: 1.05-16.9) and presence of Gottron's rash (p=0.044, OR 1.78, 95% CI 1.017-3.121) at baseline predicted CR by multivariate regression. Majority received mycophenolate during the entire F/u period. Discontinuation of steroids was feasible in 51.7% after a median duration of 24 months (18-42). After excluding patients with ILD, flares were numericallylesser in patients only on mycophenolate compared with those only on methotrexate (p=0.06). Further flares were curtailed when switchedfrom other agentsto mycophenolate. Mycophenolate is an effective treatmentoption in IIM patients with and without co-existing ILD. Presence of Gottron's rash and absence of pericardial effusion were found to be predictors of favourable clinical outcome in this largest single-centre study.

Myositis-specific and myositis-associated autoantibodies in a large Indian cohort of inflammatory myositis

BackgroundThe Idiopathic Inflammatory Myositis (IIM) are heterogenous with distinct clinical phenotypes associated with specific myositis specific antibodies (MSA) and myositis associated antibodies (MAA). ObjectivesTo evaluate the frequency, pattern and associations of MSA/MAA in a large Indian cohort of IIM. MethodsAdult and juvenile IIM (2017 ACR/EULAR criteria), were recruited in the MyoCite cohort between 2017and 2020 at a tertiary center in Northern India. Standardized clinical and laboratory variables were extracted from the database archive. Serum samples were evaluated for the presence of MSAs/MAAs by Line immunoassay and anti-nuclear antibodies (ANA) by Immunofluorescence assay (IFA). The prevalence and clinical associations of different MSA/MAAs were assessed. ResultsMSA and MAAs were tested in 250 IIM patients (214 adults, 36 children) of age [40 (30–49), 13 (7.5–16) years] and disease duration [ 7 (3–17), 6 (2–17) months] comprising predominantly of Dermatomyositis (DM) followed by Overlap myositis (OM). MSAs/MAAs were found in 148 (59.2%, 60.7% adults and 50% JIIM), of which two-thirds were MSA (95, 64% overall). Two cases (0.8%) had more than one MSA. In adult IIM, the most common MSA was anti-Jo-1 (10%), whereas it was anti-MDA5 and anti-NXP2 4 (11%) each in Juvenile IIM (JIIM). 76.0% (172/226) were ANA positive, with speckled pattern being the most common (37%,). Nearly two-thirds (54, 61%) of those with negative ANA had MSA/ MAA. Nearly half (18/54, 54.6%) had MSA associated with cytoplasmic patterns. ARS (anti-aminoacyl-tRNA synthetase) were associated with mechanic's hands (OR-7.06), ILD (OR-4.4), and arthritis (OR-2.23). Clinical associations of anti-Jo-1 and non-Jo-1 Anti synthetase syndrome (ASS) did not differ. Anti-MDA-5 associated with oral ulcers (OR-8.3), fever (OR-8.6) and weight loss (OR-7.35) in adults, and arthritis (OR-11.5), and periungual rash (OR-9.6) in children. Anti-TIF-1γ associated with photosensitivity (OR-10.44) and malignancy (OR-34) in adults, and cuticular overgrowth (OR-11.2) in children. ConclusionMyositis autoantibodies are seen in two-thirds IIMs and are associated with distinct clinical subsets. Jo-1 and non-Jo-1 ASS exhibit similar characteristics. The association of anti-TIF1 γ with malignancy was confirmed in adults. MSA/MAA were present in two-thirds of those with negative ANA and MSA were nearly always mutually exclusive.

Predictive Features and Clinical Presentation of Interstitial Lung Disease in Inflammatory Myositis

Interstitial lung disease (ILD) represents one of the most severe extra-muscular features of idiopathic inflammatory myositis (IIM). We aimed to identify any clinical and serological predictors of ILD in a monocentric cohort of 165 IIM patients.ILD+ patients were defined as having restrictive impairment in lung function tests and signs of ILD at chest high-resolution computed tomography (HRCT). Available HRCT images were centralized and classified in different ILD patterns: non-specific interstitial pneumonia (NSIP), organizing pneumonia (OP), usual interstitial pneumonia-like (UIP), indeterminate for UIP, and interstitial lung abnormalities (ILA). Lung function test data were recorded at onset, at 1 and 5 years after ILD diagnosis.ILD was found in 52 IIM patients (31.5%): 46.2% was affected by anti-synthetase syndrome (ARS), 21% by polymyositis (PM), 19% by dermatomyositis (DM), and 13.5% by overlap myositis. Most of ILD+ showed NSIP (31.9%), OP (19%), indeterminate for UIP (19%), and UIP (12.8%) patterns. At multivariate analysis, ILD was predicted by anti-Ro52 (p: 0.0026) and dyspnea (p: 0.015) at IIM onset. Most of ILD onset within is 12 months after IIM. In five cases, ILD occurs after 12 months since IIM diagnosis: these patients more frequently show dry cough and anti-Ku antibodies. Anti-Ro52 + ILD patients showed a significant increase of DLCO at 1 and 5 years of follow-up, compared with anti-Ro52 negative cases.ILD occurs in about one third of IIM and was predicted by dyspnea at onset and anti-Ro52 antibodies. Anti-Ro52 defines a subgroup of ILD showing a significant improvement of DLCO during follow-up. This retrospective study has been approved by local ethic committee (ASST-Spedali Civili of Brescia, Italy); protocol number: NP3511

Pneumocystis jirovecii Pneumonia and Other Infections in Idiopathic Inflammatory Myositis.

Purpose of ReviewThe management of patients with idiopathic inflammatory myositis (IIM) can be complex and challenging due to the myriad of complications they can experience. The continued use of corticosteroids, in addition to the rise of combination immunosuppressive therapy, has contributed to the ongoing concern for infection. Perhaps the most feared infection in IIM patients is Pneumocystis jirovecii pneumonia (PJP) given its infrequent occurrence yet high mortality. The field has been, and continues to be, without evidence-based guidelines to help clinicians determine which patients with IIM to prescribe prophylaxis. Herein, we review this literature to provide the clinician with an up-to-date view of infections in IIM.Recent FindingsIn the past 5 years, a number of studies have been reported highlighting various infectious complications, which help us better understand their frequency and associated risk factors. In addition, data has been published on the potential harms of PJP prophylaxis, to better inform the risk/benefit of our decision-making.SummaryInfection remains a major contributor to morbidity and mortality in IIM. A better understanding of which patient subgroups are at risk for particular infections will inform optimal management strategies.

Increased risk of malignancy in patients aged over 50 with idiopathic inflammatory myositis compared to patients with osteoarthritis of the knee

Objectives: To estimate risk of malignancy in patients with idiopathic inflammatory myositis (IIM) compared to patients with knee osteoarthritis (OA).Methods: Patients with IIM and knee OA aged over 50, who had no history of malignancy, were identified using Korean National claims database from January 2012 to December 2014. They had been observed until a malignancy was diagnosed or up to the end of the study, December 2015. The incidence rate (IR) of malignancy in IIM patients was calculated and compared with knee OA patients using standardized incidence ratio (SIR).Results: A total of 634 polymyositis (PM) and 556 dermatomyositis (DM) patients were included. Overall, 100 solid (IR 270.4/10,000 person-years (PY), 95% confidence interval (CI) 217.4–323.4) and 12 hematologic malignancies (IR 32.4/10,000 PY, 95% CI 14.1–50.8) occurred. Compared with knee OA, risk of overall (SIR 1.5, 95% CI 1.2–1.8), solid (SIR 1.4, 95% CI 1.1–1.6), and hematologic malignancy (SIR 5.7, 95% CI 2.5–9.0) were increased in IIM patients. This was due to increased incidence of malignancy in DM (hematologic malignancy, SIR 8.7, 95% CI 2.7–14.7, solid malignancy, SIR 1.5, 95% CI 1.1–1.9).Conclusion: Patients with IIM, especially DM, have an increased risk of malignancy compared to patients with knee OA.

Outcomes of Pregnancy in Women With Inflammatory Myositis: A Cohort Study From India.

Idiopathic inflammatory myositis (IIM) commonly affects women in the childbearing age group. Both disease activity and immunosuppressants used may have adverse effects on fertility and outcomes of pregnancy. We explored these outcomes in a cohort of women with IIM. Women 18 years or older with IIM (Bohan and Peter criteria) were interviewed for demography, menstrual status, history of conception, outcomes, and disease features. Comparisons were drawn between pregnancies occurring before and after onset of disease. Eighty-one IIM patients with median age of 32 years (interquartile range, 26-50 years) and disease duration of 4 years (interquartile range, 2-9 years) were interviewed. Forty-five patients had dermatomyositis, 20 had polymyositis, and 16 had overlap myositis. Sixty-three patients had conceived before disease onset, resulting in 205 pregnancies and 155 live births over 315.2 patient-years of follow-up.After disease onset, there were 24 pregnancies (6 live births, 16 spontaneous abortions, and 2 induced abortions) in 7 women over 77.5 patient-years. Of the live births, 1 had cleft palate, 1 had low birth weight, and 1 was preterm. None of the patients who conceived had antiphospholipid antibodies.Obstetric complications (relative risk [RR] = 7.6; p < 0.0001) and fetal complications (RR = 2.7; p = 0.002) occurred more frequently in pregnancies after the onset of myositis, although there was no difference in maternal complications. Conception after the onset of myositis had higher risk of abortion (RR = 3.6; p < 0.0001). Women with IIM suffer from poor fetal outcomes as well as high rates of spontaneous abortion rates in the absence of clinical or serologic anti-phospholipid syndrome.

Prevalence and clinical correlates of rheumatoid factor and anticitrullinated protein antibodies in patients with idiopathic inflammatory myopathy

ObjectiveAs rheumatoid factor (RF) and anticitrullinated protein antibodies (ACPAs) are not routinely tested in idiopathic inflammatory myositis (IIM), little is known about their prevalence and clinical implications in this patient...

Profiling Autoantibodies in Idiopathic Inflammatory Myopathies

Abstract Objects To screen autoantibodies (autoAbs) in sera of Idiopathic Inflammatory Myositis (IIM) patients and to assess their clinical significance for diagnosis, classification and disease activity evaluation. Methods IgG and IgM autoAbs were comprehensively profiled from 138 IIM patients, 70 SLE, 50 SSc and 100 normal controls (NC) using a customized autoantigen array bearing 125 myositis-specific antigens (MSA) and other autoantigens. Western blot and Immunoprecipitation were used for autoAb verification. The profile of autoAbs and correlation with clinical criteria were evaluated. Results 78% IIM patients showed positive reactivity to at least 1 MSA. The autoAbs which exhibited high prevalence in IIM are anti- Jo-1 (24.6%), MDA5 (23.2%), SAE2 (13%), SRP54 (11.6%) and DNA polymerase II (8.7%). We identified the autoAb clusters that best distinguish the 3 autoimmune disease: anti-Jo-1 and anti-MDA5 for IIM, and anti-CENP-A&amp;B and Scl-70 for SSc, and anti-chromatin/Nucleosome, anti-dsDNA, and anti-Sm/SmD for SLE. The coexistence of MSA autoAbs was observed in IIM with about 35% IIM patients carried more than 2 MSA autoAbs. The IIM patients who developed interstitial lung disease (ILD) exhibited significantly higher autoAbs against Jo-1, MDA5, Mi-2, Ro-SSA and Trptophanyl compared with the IIM without ILD (&amp;lt;0.05). The IIM patients who carried positive autoAbs against JS, TIF1γ, Mitochondrial antigen and La/SSB showed a significantly higher risk of malignancy (p&amp;lt;0.05). Based on autoAbs, we established an autoAb score for IIM prediction and evaluation. Conclusion Autoantibody profiling revealed distinct and heterogenic autoAbs in IIM which are potential biomarker for diagnosis, prognosis and classification of the disease.

Clinical contribution of myositis-related antibodies detected by immunoblot to idiopathic inflammatory myositis: A one-year retrospective study

In this study, we aimed at evaluating the contribution of an extended myositis-related antibodies (Abs) determination by immunoblot to the diagnosis, classification, and prognosis of idiopathic inflammatory myositis (IIM). Medical records of all the patients (n = 237) with myositis-related Ab requests addressed to our department over a one-year period were retrospectively analyzed. Patients were classified as IIM, auto-immune disease (AID) other than IIM, and other diagnosis, and examined for their Ab profiles as determined by immunoblot. Ab positivity was qualified semi-quantitatively as low or strong according to the manufacturer’s recommendations. Among the 45 Ab-positive patients, 49% were diagnosed an IIM, 22% another AID, and 29% another diagnosis. The clinico-serological patterns of the myositis-related Ab+ patients fully recapitulated those described in the literature. Among non-IIM patients, anti-PM-Scl was the most frequently detected Ab (38%), followed by anti-Mi-2 (15%), and anti-OJ (12%). Importantly, strong Ab positivity was significantly more detected in IIM vs. non-IIM patients (82% vs. 35%; p = .002). This difference was further increased when comparing MSAs only (95% vs. 36%; p = .0004). Accordingly, strong Ab positivity associated with high specificity (96%) and positive likelihood ratio (pLR =12) for IIM. Our data suggest that while myositis-related Ab, including MSA, can be detected by immunoblot in non-IIM patients, strong positivity is nevertheless highly predictive of IIM. In conclusion, this work suggests that relevant clinical contribution to IIM is provided by the immunoblot determination of myositis-related Ab, more especially when considering strong positive detection of MSA.