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Objective: To evaluate clinical associations of anti-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) antibody (Ab) and statin exposure in necrotizing myopathy (NM) patients. Methods: NM without a known myositis-specific autoantibody (MSA) was ascertained from a large single-centre myositis database between 1985 and 2012. A comparison NM cohort included 32 anti-SRP+ autoantibody patients, and other control groups included 74 non-NM myositis patients and 21 non-myositis controls. Sera from all cases and controls were tested using a validated anti-HMGCR enzyme-linked immunosorbent assay. Clinical features including statin use and anti-HMGCR Ab status were compared between cases and controls. Results: Of the 256 NM muscle biopsies reviewed, only 48 subjects with available sera were identified as traditional MSA-negative NM. Anti-HMGCR positivity was significantly (p < 0.001) associated with MSA-negative NM [48% (23/48)] compared to all of the myositis and non-myositis controls [5% (6/127)]. Most anti-HMGCR Ab-positive NM patients had high titres of anti-HMGCR (83%) and a history of statin exposure (78%), along with severe muscle weakness, high creatine kinase (CK) levels (90% ≥ 5000 IU/L), a paucity of other organ manifestations, and the need for immunosuppression with prednisone and methotrexate, but generally favourable outcomes. Anti-HMGCR serum levels were associated with baseline CK levels but not muscle weakness. Conclusion: HMGCR Ab-positive NM patients are associated with statin exposure, have severe muscle weakness and high CK at presentation, lack other organ manifestations, and generally have favourable outcomes from immunosuppression. Anti-HMGCR Abs should be assessed in MSA-negative NM patients, particularly those with a history of statin exposure. [ABSTRACT FROM AUTHOR]

Background: Different mediators are involved in pain and edema induction during different stages of inflammation. Then, treatment of them encounters some difficulties. Medicinal plants are an important source of substances which are claimed to induce anti-inflammatory effects. This study was aimed to investigate anti-inflammatory and analgesic effects of Olea europaea L.methanolic extract on male NMRI mouse. Methods: Methanolic extraction was done for leaf of Olea europaea L. and different doses (200, 300 and 400 mg/kg) were intraperitoneally (i.p.) adminstered to male NMRI mice. Analgesic and anti-inflammatory effects of extract was measured during both phases of Formalin test, Acetic acid induced visceral pain and xylene inflammation tests. A standard analgesic and anti-inflammatory drug such as indomethacin, dexamethasone and morphine were administered in positive control groups where appropriates. Results: Results indicated significant dose-dependent analgesic and anti-inflammatory effects of methanolic extract of Olea europaea L. leaf on pain which induced by formalin (both phase) and acetic acid, and inflammation caused by xylene. Conclusion: Our findings Showed that administration of methanolic extract of Olea europaea L.leaf can suppress pain and inflammation dose dependently which, may mediate via different components of extract. However, more investigations need to be done. [ABSTRACT FROM AUTHOR]

Currently, standardized magnetic resonance imaging (MRI) scoring systems and protocols for assessment of idiopathic inflammatory myopathies (IIMs) in children and adults are lacking. Therefore, we will perform a scoping review of the literature to collate and evaluate the existing semi-quantitative and quantitative MRI scoring systems and protocols for the assessment and monitoring of skeletal muscle involvement in patients with IIMs. The aim is to compile evidence-based information that will facilitate the future development of a universal standardized MRI scoring system for both research and clinical applications in IIM. A systematic search of electronic databases (PubMed, EMBASE, and Cochrane) will be undertaken to identify relevant articles published between January 2000 and October 2023. Data will be synthesized narratively. This scoping review seeks to comprehensively summarize and evaluate the evidence on the scanning protocols and scoring systems used in the assessment of diagnosis, disease activity, and damage using skeletal muscle MRI in IIMs. The results will allow the development of consensus recommendations for clinical practice and enable the standardization of research methods for the MRI assessment of skeletal muscle changes in patients with IIMs., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The Myositis Interstitial Lung Disease Nintedanib Trial (MINT) is a hybrid trial, which is enrolling patients both at local sites and remotely via a decentralised site. The trial will investigate the efficacy and safety of nintedanib in patients with progressive myositis-associated interstitial lung disease (MA-ILD)., Methods/design: MINT is an exploratory, prospective randomised placebo-controlled trial. Eligible patients will have myositis and evidence of fibrosing ILD on high-resolution computed tomography (HRCT), be taking standard of care medications for myositis, and meet criteria for ILD progression within the prior 24 months based on decline in FVC, worsened fibrosis on HRCT, and/or worsened dyspnoea. Patients will be randomised 1:1 to receive nintedanib 150 mg twice daily or placebo for 12 weeks then open-label nintedanib for 12 weeks. Patients will be enrolled at local sites and a decentralised site. Most study visits will be completed remotely using telemedicine or digital health technologies. The primary endpoint is the change in Living with Pulmonary Fibrosis (L-PF) questionnaire dyspnoea domain score at week 12. Other endpoints include changes in other L-PF questionnaire domains, lung function, imaging, and physical activity, and assessment of adverse events. Data collected using remote versus clinic enrolment, and using home versus clinic spirometry, will be compared., Discussion: MINT is an innovative, hybrid trial that will evaluate the effects of nintedanib on symptoms, quality of life, and ILD progression in patients with progressive MA-ILD and provide valuable information on the utility of decentralised recruitment and remote data collection in clinical trials., Trial Registration: Clinicaltrials.gov NCT05799755 (date of registration: 05/04/2023)., (© 2024. The Author(s).)

Objective: Anti-synthetase syndrome (ASSD) is a rare systemic autoimmune rheumatic disease (SARD) with significant heterogeneity and no shared classification criteria. We aimed to identify clinical and serological features associated with ASSD that may be suitable for inclusion in the data-driven classification criteria for ASSD., Methods: We utilized a large, international, multi-center "Classification Criteria for Anti-synthetase Syndrome" (CLASS) project database, which includes both ASSD patients and controls with mimicking conditions, namely SARDs and/or interstitial lung disease (ILD). The local diagnoses of ASSD and controls were confirmed by project team members. We employed univariable logistic regression and multivariable Ridge regression to evaluate clinical and serological features associated with an ASSD diagnosis in a randomly selected subset of the cohort., Results: Our analysis included 948 ASSD cases and 1077 controls. Joint, muscle, lung, skin, and cardiac involvement were more prevalent in ASSD than in controls. Specific variables associated with ASSD included arthritis, diffuse myalgia, muscle weakness, muscle enzyme elevation, ILD, mechanic's hands, secondary pulmonary hypertension due to ILD, Raynaud phenomenon, and unexplained fever. In terms of serological variables, Jo-1 and non-Jo-1 anti-synthetase autoantibodies, antinuclear antibodies with cytoplasmic pattern, and anti-Ro52 autoantibodies were associated with ASSD. In contrast, isolated arthralgia, dysphagia, electromyography/MRI/muscle biopsy findings suggestive of myopathy, inflammatory rashes, myocarditis, and pulmonary arterial hypertension did not differentiate between ASSD and controls or were inversely associated with ASSD., Conclusion: We identified key clinical and serological variables associated with ASSD, which will help clinicians and offer insights into the development of data-driven classification criteria for ASSD., (This article is protected by copyright. All rights reserved.)

Introduction: Recruitment for idiopathic inflammatory myopathies (IIM) research is a challenge due to the rarity of the disease and the scarcity of specialized myositis centers. Online recruitment may be a feasible alternative to reach rare disease patients. We evaluated various online recruitment methods in a large longitudinal IIM cohort., Methods: The "Myositis Patient Centered Tele-Research" (My Pacer) is a prospective 6-month observational study of IIM, recruited online and through traditional clinic visits. We utilized diverse recruitment methods, such as physician referrals, social media, websites, direct emails, and partnerships with patient-support organizations. Participants self-enrolled and completed pre-screening, e-consenting, and release of medical information via the study-specific app or website. We compared the effectiveness of various recruitment and enrollment methods and the characteristics of the population recruited., Results: A total of 841 participants completed the pre-screening; 408 completed e-consent and registration. From those, 353 (86.5%) were remotely recruited. Email (201; 49.26%) and social media (77; 18.87%) were important recruitment tools. Patient-support organizations were responsible for disseminating the study to 312 (75.46%) participants. The study app was used by 232 (65.72%) individuals for enrollment, with app users being slightly younger than website users (p = 0.001). Participants were mostly female 317 (77.76%), mean age of 54.84 years, White 328 (80.42%), Black 49 (12%), Asian 13 (3.26%), and non-Hispanic 378 (92.65%). Our study reached all U.S. regions and 45 (90%) U.S. states., Conclusions: Social media and partnerships with patient-support organizations lead to a high rate of recruitment, with a wide reach, and a reasonably diverse population., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Objective: The 6-min walk test (6MWT) is a simple test widely used to assess sub-maximal exercise capacity in chronic respiratory diseases. We explored the relationship of 6-min walk distance (6MWD) with measurements of physiological, clinical, radiographic measures in patients with myositis-associated interstitial lung disease (MA-ILD)., Method: We analyzed data from the Abatacept in Myositis Associated Interstitial lung disease (Attack My-ILD) study, a 48-week multicentre randomized trial of patients with anti-synthetase antibodies and active MA-ILD. 6MWD, forced vital capacity (FVC), diffusing capacity (DLCO), high resolution CT, and various physician/patient reported outcome measures were obtained during the trial. Spearman's correlations and repeated-measures analysis with linear mixed-effects models were used to estimate the associations between 6MWD and various physiologic, clinical and radiographic parameters both cross-sectionally and longitudinally., Results: Twenty participants with a median age of 57, 55% male and 85% white were analyzed. Baseline 6MWD did not associate with baseline PFTs. Repeated-measures analysis showed 6MWD over time associated with FVC over time, but not with DLCO. 6MWD over time also correlated with UCSD dyspnea score, Borg scores, as well as global disease activity and muscle strength over time. Emotional role functioning, vitality, general health and physical functioning scores by short form 36 also correlated with 6MWD over time., Conclusions: : Exploratory work in a small cohort of MA-ILD demonstrated 6MWD over time associated with parallel changes in FVC and patient reported outcomes of dyspnea, but not with DLCO. Larger studies are needed to validate the reliability, responsiveness and utility of the 6MWT in MA-ILD., Clinical Trial Registration: ClinicalTrials.gov, NCT03215927., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Idiopathic Inflammatory Myopathies (IIM) are rare and characterized by heterogeneous manifestations and clinical trajectories. Utilizing tele-research methods has the potential to improve participant recruitment and advance the understanding of the disease. We aimed to evaluate disease characteristics in IIM patients throughout the U.S. and compare these parameters between patients recruited remotely through mobile application or website vs those recruited locally in myositis clinics., Methods: "Myositis Patient Centered Tele-Research" (My PACER) is a multicentre prospective observational study of U.S. IIM subjects, competitively recruited through traditional in-person clinic visits (Center-Based Cohort [CBC]), and remotely using mobile application or website and social media (Tele-Research Cohort [TRC]). Data collection comprised baseline demographic and clinical variables, encompassing symptoms, organ involvement, diagnostic tests results and medication use., Results: The study included 120 IIM patients, 82 in the TRC and 38 in the CBC. The average age was 55 ± 13.4, 75% females and 81% Caucasians. Both cohorts exhibited similar demographic characteristics. Overall, 41% dermatomyositis, 27% polymyositis, 23% anti-synthetase syndrome, and 9% necrotizing myositis patients were enrolled, with comparable subtypes prevalence among cohorts (p= 0.85). The groups demonstrated similarities in multiple clinical factors, including muscle enzymes, diagnostic delay, employment status, various patient and physician-reported outcomes, functional tests, and the frequency of abnormal findings in chest CT, pulmonary function tests, and electromyography. TRC patients received biologics and csDMARDs more frequently (p< 0.001 and p= 0.013, respectively)., Conclusion: Tele-research recruitment yielded a patient cohort resembling traditionally recruited patients demographically and clinically, indicating its effectiveness for robust and diverse patient recruitment in clinical studies., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Anti-melanoma differentiation-associated gene 5 antibody-positive (MDA5+) dermatomyositis patients exhibit clinical features that vary by geographical and ethnic/genetic distribution. We therefore investigated whether B cell epitope profiles and corresponding clinical features distinguished two independent cohorts of MDA5+ dermatomyositis., Methods: We used ELISA-based methods to determine the relationship between antibody recognition of overlapping 155 amino acid MDA5 subfragments and clinical features of 17 MDA5+ dermatomyositis patients from Japan. Associations between clinical features and standardized anti-MDA5 subfragment antibody titers were assessed via Brunner Munzel testing and compared with clinical/serological profiles of an independent North American cohort. ROC analyses and Kaplan-Meier curves were used to further assess the relationship between anti-MDA5 fragment antibody levels and specific clinical features/outcomes., Results: Clinical characterization of a Japanese cohort of 17 MDA5+ dermatomyositis patients revealed a high prevalence of arthritis (47%) and interstitial lung disease (ILD) (100%). Serological profiling demonstrated predominant antibody recognition of MDA5 fragments A (aa 1-155), B (aa 130-284), and E (aa 517-671) in a pattern that was distinct from North American MDA5+ patients (n = 24) whose sera preferentially recognized fragment H (aa 905-1026). Statistical analysis revealed a striking association between anti-fragment A antibody levels and rapidly progressive ILD (RP-ILD) among Japanese patients (p< 0.01). ROC and Kaplan Meier curves also demonstrated a strong relationship between anti-fragment A antibody levels, RP-ILD, and pulmonary death in combined cohort analyses., Conclusions: Japanese and North American MDA5+ dermatomyositis patients manifest markedly different B cell epitope profiles that are associated with higher prevalence of RP-ILD and worse clinical outcome among Japanese patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive (MDA5+) dermatomyositis patients exhibit a variety of clinical features. We therefore investigated whether patterns of B-cell epitope recognition are linked to the clinical course of MDA5+ dermatomyositis., Methods: Our cross-sectional study used ELISA-based methods to determine the relationship between antibody recognition of overlapping 155 amino acid MDA5 subfragments and clinical features of 24 MDA5+ myositis patients. Correlations between clinical features and standardized anti-MDA5 subfragment antibody titres were assessed via Spearman's rank correlation coefficients., Results: Twenty-four MDA5+ patients submitted serum samples within a median of 0 (interquartile range, 0-74) days from the initial clinic visit. In addition to typical dermatomyositis rashes, these patients exhibited muscle symptoms (n = 11), vascular dysfunction (n = 9) and interstitial lung disease (ILD) (n = 16). Female patients exhibited higher titres of antibodies recognizing fragment H (aa 905-1026) compared with male patients. Muscle involvement was associated with higher levels of anti-fragment F (aa 646-801) antibody. Conversely, patients with vascular abnormalities had higher anti-fragment B (aa 130-284) and E (aa 517-671) antibody titres than those without vascular dysfunction. Four patients died due to ILD progression and showed higher anti-fragment A (aa 1-155) antibody titres than the other 20 patients. Differences in the ratio of anti-fragment to anti-full-length MDA5 antibody titres were found for sex (H: anti-MDA5) and vascular dysfunction (anti-fragment B, E: anti-MDA5)., Conclusions: Various clinical features of MDA5+ dermatomyositis correlated with levels of antibodies targeting selected subfragments of this autoantigen, providing a link between fragment-specific immune responses and disease course., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: The ACR-EULAR Myositis Response Criteria (Total Improvement Score [TIS]) is a composite measure calculated using changes in myositis core set measures. It is unclear if achieving improvement per TIS reflects improvement in any symptoms of myositis patients. In this study, we examined the association between achieving TIS improvement and patient-centered outcome measures (PCOMs)., Methods: Adults with myositis were enrolled in a prospective study with baseline and 6-month visits. Six core set measures were collected at each visit along with the following PCOMs: Fatigue (visual analogue scale [VAS] and short form 36 [SF36]), pain (VAS, SF36), health-related quality of life (SF-36), physical function (PROMIS-physical function, SF36, sit-to-stand, timed up-and-go, and six-min walk) and physical activity (actigraphy). Mann-Whitney U was used to compare PCOMs between improvement groups. Spearman correlation and regression models were used for correlation and association between TIS and PCOMs, respectively., Results: Of 50 patients (six polymyositis, 24 dermatomyositis, 9 necrotizing myopathy, 11 anti-synthetase syndrome) enrolled (mean age: 52, 60% female), 21 patients satisfied the TIS improvement criteria at 6-months. PCOMs including fatigue, pain, quality of life, physical activity and physical function demonstrated significantly greater improvement in patients who had minimal TIS improvement compared with those with no improvement. Greater PCOM improvements were seen with moderate-major TIS improvement. TIS correlated moderately-strongly with most PCOMs., Conclusion: Achieving improvement criteria was accompanied by significant clinical improvements in fatigue, pain, health-related quality of life, physical function, and physical activity. These results support the use of TIS as a clinically meaningful metric of improvement., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: There is an unmet need to develop patient-reported outcomes (PRO) measures for Idiopathic Inflammatory Myopathies (IIM). To investigate the feasibility, compliance, and psychometric properties of NIH's Patient-Reported Outcomes Measurement Information System (PROMIS) physical function-20 (PF-20) in a large U.S. IIM population., Methods: "Myositis Patient Centered Tele-Research" (My PACER) is a multicentre prospective observational study of IIM patients, competitively recruited through traditional in-person clinic visits (Center-Based Cohort [CBC]), and remotely using smartphone and web-based technology (Tele-Research Cohort [TRC]). The CBC was further randomly divided (1:1 ratio) into a traditional local sub-cohort, and a remote sub-cohort. Data collected included PRO and other patient self-assessments monthly for 6 months. Clinician-reported outcomes were obtained at baseline and 6 months., Results: 120 IIM patients were enrolled (82 TRC/38 CBC, mean age 55 ± 13.4, 75% females, 81% Caucasians), with similar demographics and mean PROMIS PF-20 score between cohorts. The PROMIS PF-20 score was not associated with age, sex or race. The compliance and completion rates were similar between TRC and CBC as well as sub-cohorts. PROMIS PF-20 showed strong test-retest reliability at 1 month. PROMIS PF-20 was significantly associated with all core set measures except extra-muscular global and CK, as well as with most of symptoms, function and physical activity measures. PROMIS PF-20 illustrated concordant change with myositis response criteria and patient assessment, with a large effect size., Conclusions: PROMIS PF-20 demonstrates favorable psychometric properties including reliability, validity and responsiveness in a large cohort of myositis patients, with similar adherence in local or remotely enrolled patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: The CLASS (Classification Criteria of Anti-Synthetase Syndrome) project is a large international multicentre study that aims to create the first data-driven anti-synthetase syndrome (ASSD) classification criteria. Identifying anti-aminoacyl tRNA synthetase antibodies (anti-ARS) is crucial for diagnosis, and several commercial immunoassays are now available for this purpose. However, using these assays risks yielding false-positive or false-negative results, potentially leading to misdiagnosis. The established reference standard for detecting anti-ARS is immunoprecipitation (IP), typically employed in research rather than routine autoantibody testing. We gathered samples from participating centers and results from local anti-ARS testing. As an "ad-interim" study within the CLASS project, we aimed to assess how local immunoassays perform in real-world settings compared to our central definition of anti-ARS positivity., Methods: We collected 787 serum samples from participating centres for the CLASS project and their local anti-ARS test results. These samples underwent initial central testing using RNA-IP. Following this, the specificity of ARS was reconfirmed centrally through ELISA, line-blot assay (LIA), and, in cases of conflicting results, protein-IP. The sensitivity, specificity, positive likelihood ratio and positive and negative predictive values were evaluated. We also calculated the inter-rater agreement between central and local results using a weighted κ co-efficient., Results: Our analysis demonstrates that local, real-world detection of anti-Jo1 is reliable with high sensitivity and specificity with a very good level of agreement with our central definition of anti-Jo1 antibody positivity. However, the agreement between local immunoassay and central determination of anti-non-Jo1 antibodies varied, especially among results obtained using local LIA, ELISA and "other" methods., Conclusions: Our study evaluates the performance of real-world identification of anti-synthetase antibodies in a large cohort of multi-national patients with ASSD and controls. Our analysis reinforces the reliability of real-world anti-Jo1 detection methods. In contrast, challenges persist for anti-non-Jo1 identification, particularly anti-PL7 and rarer antibodies such as anti-OJ/KS. Clinicians should exercise caution when interpreting anti-synthetase antibodies, especially when commercial immunoassays test positive for non-anti-Jo1 antibodies.

Objectives: There is a paucity of available biomarkers of disease activity in idiopathic inflammatory myopathies (IIM), and serum cytokines/chemokines hold potential as candidate biomarkers. We aimed to determine serum cytokine profiles of IIM patients with active disease as compared to patients in remission and healthy controls., Methods: The IIM patients with active disease (included patients enrolled in repository corticotropin injection trial), in remission, and healthy controls were enrolled in this cross-sectional observational study. Serum concentrations of 51 cytokines/chemokines were obtained by utilising a bead-based multiplex cytokine assay (Luminex®). The myositis core set measures were obtained for all the patients. Cytokines with the best predictive ability to differentiate these clinical groups were assessed with three methods: 1) Least Absolute Shrinkage and Selection Operator modelling, 2) stepwise approach, and 3) logistic regression model., Results: Twenty-one IIM patients with active disease, 11 IIM patients in remission and 10 healthy controls were enrolled. Myositis patients had elevated levels of chemokines that attract eosinophils (eotaxin) and dendritic cells, NK cells, cytotoxic T-cells and monocytes/macrophages (CXCL-9, IP-10), cytokines that drive T-helper 1 responses (TNF-a, lymphotoxin-a), matrix degrading enzymes (MMP-3 and -9), and IGFBP-2 compared to healthy controls. Myositis patients with active disease had higher levels of lymphotoxin-a, CXCL-9, MIP-1a, MIP-1b and MMP-3 than patients in remission., Conclusions: This study demonstrated differences in cytokine profiles of IIM patients (active and inactive disease) compared to healthy controls and identified some cytokines that could potentially be used as biomarkers. Larger longitudinal studies are needed to validate our findings.

Objectives: Patient-reported global disease activity (patient-global) is a myositis core set measure. Understanding the drivers of patient-global is important in patient assessment, and disagreements between physician and patient perception of disease activity may negatively impact shared decision making. We examined the determinants of patient-global and discordance between patient-global and physician-reported global disease activity (physician-global) in idiopathic inflammatory myopathies (IIMs)., Methods: Adults with IIM were enrolled in a prospective observational cross-sectional study. The following myositis outcome measures were collected: patient-global, physician-global, extramuscular and muscle disease activity, manual muscle testing, HAQ, creatine kinase, fatigue, pain, Patient-Reported Outcomes Measurement Information System physical function, 36-item Short Form, sit to stand, timed up and go, 6-minute walk and Actigraph steps/min/day count. A linear regression model was used to determine the contribution of each measure to patient-global. Discordance was defined as ≥3 points difference between patient-global and physician-global., Results: Fifty patients [60% females; mean age 51.6 years (s.d. 14.9)] with probable/definite IIM (EULAR/ACR classification criteria for IIM) were enrolled. Physical function and fatigue measures contributed to patient-global the most, followed by measures of pain, physical activity, quality of life and muscle disease, while physician-global was primarily driven by muscle disease activity. Patient-global was discordant with physician-global in 30% of the patients, of which patient-global was higher than physician-global in 66%. Pain, fatigue and physical activity contributed more to patient-global than physician-global., Conclusion: Fatigue, pain and physical activity are important driving factors of the differences observed in the patient vs physician assessment of myositis disease activity. Understanding the gap between patient and physician perspectives may help provide better patient-centred care., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Competing Interests: There are no conflicts of interest.

Objective: COVID-19 vaccines have a favorable safety profile in patients with autoimmune rheumatic diseases (AIRDs) such as idiopathic inflammatory myopathies (IIMs); however, hesitancy continues to persist among these patients. Therefore, we studied the prevalence, predictors and reasons for hesitancy in patients with IIMs, other AIRDs, non-rheumatic autoimmune diseases (nrAIDs) and healthy controls (HCs), using data from the two international COVID-19 Vaccination in Autoimmune Diseases (COVAD) e-surveys., Methods: The first and second COVAD patient self-reported e-surveys were circulated from March to December 2021, and February to June 2022 (ongoing). We collected data on demographics, comorbidities, COVID-19 infection and vaccination history, reasons for hesitancy, and patient reported outcomes. Predictors of hesitancy were analysed using regression models in different groups., Results: We analysed data from 18 882 (COVAD-1) and 7666 (COVAD-2) respondents. Reassuringly, hesitancy decreased from 2021 (16.5%) to 2022 (5.1%) (OR: 0.26; 95% CI: 0.24, 0.30, P < 0.001). However, concerns/fear over long-term safety had increased (OR: 3.6; 95% CI: 2.9, 4.6, P < 0.01). We noted with concern greater skepticism over vaccine science among patients with IIMs than AIRDs (OR: 1.8; 95% CI: 1.08, 3.2, P = 0.023) and HCs (OR: 4; 95% CI: 1.9, 8.1, P < 0.001), as well as more long-term safety concerns/fear (IIMs vs AIRDs - OR: 1.9; 95% CI: 1.2, 2.9, P = 0.001; IIMs vs HCs - OR: 5.4 95% CI: 3, 9.6, P < 0.001). Caucasians [OR 4.2 (1.7-10.3)] were likely to be more hesitant, while those with better PROMIS physical health score were less hesitant [OR 0.9 (0.8-0.97)]., Conclusion: Vaccine hesitancy has decreased from 2021 to 2022, long-term safety concerns remain among patients with IIMs, particularly in Caucasians and those with poor physical function., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: In dermatomyositis (DM), autoantibodies are associated with unique clinical phenotypes. For example, anti-TIF1γ autoantibodies are associated with an increased risk of cancer. The purpose of this study was to discover novel DM autoantibodies., Methods: Phage ImmunoPrecipitation Sequencing using sera from 43 patients with DM suggested that transcription factor Sp4 is a novel autoantigen; this was confirmed by showing that patient sera immunoprecipitated full-length Sp4 protein. Sera from 371 Johns Hopkins patients with myositis (255 with DM, 28 with antisynthetase syndrome, 40 with immune-mediated necrotising myopathy, 29 with inclusion body myositis and 19 with polymyositis), 80 rheumatological disease controls (25 with Sjogren's syndrome, 25 with systemic lupus erythematosus and 30 with rheumatoid arthritis (RA)) and 200 healthy comparators were screened for anti-SP4 autoantibodies by ELISA. A validation cohort of 46 anti-TIF1γ-positive patient sera from the University of Pittsburgh was also screened for anti-Sp4 autoantibodies., Results: Anti-Sp4 autoantibodies were present in 27 (10.5%) patients with DM and 1 (3.3%) patient with RA but not in other clinical groups. In patients with DM, 96.3% of anti-Sp4 autoantibodies were detected in those with anti-TIF1γ autoantibodies. Among 26 TIF1γ-positive patients with anti-Sp4 autoantibodies, none (0%) had cancer. In contrast, among 35 TIF1γ-positive patients without anti-Sp4 autoantibodies, 5 (14%, p=0.04) had cancer. In the validation cohort, among 15 TIF1γ-positive patients with anti-Sp4 autoantibodies, 2 (13.3%) had cancer. By comparison, among 31 TIF1γ-positive patients without anti-Sp4 autoantibodies, 21 (67.7%, p<0.001) had cancer., Conclusions: Anti-Sp4 autoantibodies appear to identify a subgroup of anti-TIF1γ-positive DM patients with lower cancer risk., Competing Interests: Competing interests: YJ, IP-F, KP, MC-D, MJK, JA, TEL, ET, CVO, SM-K, CC-R, JCM, JMG-J, AS-O'C and ALM report no competing interests. CAM has received support from NIH grant 1K23AR075898 and the Jerome L. Greene Foundation; reconsulting fees from Guidepoint Consultations and Boehringer Ingelheim; and payment for expert testimony from the Department of Justice–Vaccine Injury Compensation Program. BMW received support from NIH grant Z01-DE000704. SD received support grants or contract from BMS, Boehringer-Ingelheim and Genentech/Roche; royalties or licences from UpToDate; consulting fees from Boehringer-Ingelheim; payment for presentations from France Foundation; support for travel from Boehringer-Ingelheim; participates in an advisory board for Galecto and Galapagos; and is a senior medical advisor for the Pulmonary Fibrosis Foundation and the American Thoracic Society. JJP received support from NIH grant K23AR073927; grants or contracts from Pfizer, Kezer and Corbus; royalties from UpToDate; and consulting fees from Pfizer, Kezar, EMD Serono, Proivant and Guidepoint Consultation. RA received grants or contracts from Mallinckrodt, Q32, Pfizer, EMD-Serono and Bristol Myers-Squibb; and consulting fees from Mallinckrodt, EMD Serono, Octapharma, Kezar, CSL Behring, Pfizer, Bristol Myers-Squibb, Astrazeneca, Alexion, Boehringer-Ingelheim, Argenx, Corbus, Roivant, Jannsen, Merck, Kyverna, Galapagos, Actigraph, Abbvie, Scipher, Horizon Therapeutics, Teva and Beigene. LC-S received grants or contracts from Pfizer, Corbus and Kezar; royalties from Inova Diagnostics; consulting fees from Janssen, Boehringer-Ingelheim, Mallinckrodt, EMD-Serono, Argenx, Allogene and Horizon Therapeutics; expert testimony for Bendin Sumrall and Ladner LLC, Feldman, Kleidman Coffey, & Sappe LLP Downs Ward Bender Hauptmann & Herzog, P.A., and Sulloway and Hollis; and patents from Inova Diagnostics and RDL. HBL received support from NIH grant R01GM136724; is a founder of ImmuneID, Portal Bioscience and Alchemab; and is an advisor to TScan Therapeutics., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To assess the efficacy and tolerability of tocilizumab in a multicenter, randomized, double-blind, placebo-controlled trial in refractory adult patients with dermatomyositis (DM) and polymyositis (PM)., Methods: Thirty-six subjects with probable or definite DM/PM were enrolled in a 6-month phase 2B clinical trial and randomized 1:1 to receive tocilizumab (8 mg/kg intravenously) or placebo every 4 weeks for 24 weeks. Eligible subjects had either a DM rash, a myositis-associated autoantibody or an adjudicated PM diagnosis. Active disease was defined by at least three of six abnormal core set measures (CSMs), including a manual muscle testing (MMT)-8 score of less than 136/150. If the MMT-8 score was greater than 136, then a cutaneous score of 3 or more (10 cm visual analogue scale) was required along with three additional abnormal CSMs indicating disease activity. The primary endpoint compared the Total Improvement Score (TIS) between both arms from week 4 to 24. Secondary outcomes included time to meeting minimal TIS improvement, changes in CSMs, time to worsening, steroid-sparing effect, proportion of subjects meeting more stringent improvement criteria, and safety outcomes., Results: There was no significant difference (P = 0.86) in the TIS over 24 weeks between tocilizumab and placebo arms. The secondary endpoints of time to improvement (minimal, moderate, or major), time to worsening, CSM changes, safety outcomes, and steroid-sparing effect were also not significantly different between arms., Conclusion: Tocilizumab was safe and well tolerated but did not meet the primary or secondary efficacy outcomes in refractory DM and PM in this 24-week phase 2B study., (© 2022 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

As treatment of refractory idiopathic inflammatory myopathies (IIM) has been challenging, there is growing interest in assessing new therapies that target various pathways implicated in the pathogenesis of IIM. In the largest clinical trial to date, rituximab was studied in adult and juvenile myositis, but the primary outcome was not met despite 83 percent of subjects with refractory myositis meeting the definition of improvement. The U.S. Food and Drug Administration (FDA) has recently granted approval to Octagam 10% immune globulin intravenous (IVIg), for the treatment of adult dermatomyositis based on impressive results from a double-blind placebo-controlled trial. Anti-tumor necrosis factor (anti-TNF) utility in IIM is not recommended and recent reports suggest this therapy may induce systemic autoimmune disease including myositis. Further, anti-IL6 therapy cannot be recommended as a recent trial of tocilizumab failed to reach its primary endpoint. Further studies are needed to assess the role of newer therapies such as abatacept (inhibition of T cell co-stimulation), sifalimumab (anti-IFNα), Janus kinase [JAK] inhibitors, apremilast (phosphodiesterase 4 inhibitor), and KZR-616 (selective inhibitor of the immunoproteasome) given their biological plausibility and encouraging recent small-case series results. The future of IIM therapy will depend on exploring biomarkers implicated in the etiopathogenesis of IIM, improvements in myositis classification based on serological and histopathological features, and well-designed controlled clinical trials using validated consensus outcome measures., Competing Interests: Conflict of interest statement Clinical trial support: Genentech, Bristol Myers Squibb, CSL Behring, Argenx, Janssen, Kezar, Octapharma Advisory Board: Pfizer, Teva, (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: Inflammatory myopathies are characterized by muscle weakness that limits the activities of daily living. Daily step count is an accepted metric of physical activity. Wearable technologies such as Fitbit® enable tracking of daily step counts. We assessed the psychometric properties of Fitbit® and compared the accuracy of Fitbit® step counts to ActiGraph®., Methods: This was a pilot, proof of concept, prospective observational study with four visits at 0, 1, 3 and 6 months in PM, DM, necrotizing myopathy (NM) or anti-synthetase syndrome (AS) subjects. Six core set measures (manual muscle testing, physician global disease activity, patient global disease activity, and extra-muscular disease activity, HAQ-Disability Index and creatine kinase), three functional tests (six-min walk, timed up-and-go, sit-to-stand tests) and SF-36 physical function-10 (PF10) were collected at each visit. Patients wore waist-worn Fitbit® One and ActiGraph® T3X-BT concurrently for 7 days/month for 6 months., Results: Twenty-four (10 DM, 8 PM/NM, 6 AS) patients (17 females/7 males; 91% Caucasian) were enrolled. Test-retest reliability of daily steps was strong in 1-month follow-up (ICC 0.89). Daily steps and peak 1-min cadence showed moderate-strong correlations with physician global disease activity, patient global disease activity, HAQ-Disability Index, SF-36 PF10 and all three functional tests. Fitbit® and ActiGraph® step counts demonstrated good agreement and strong correlation (ICC 0.96)., Conclusion: Fitbit® daily steps and peak 1-min cadence are reliable and valid measures of physical activity in a cohort of myositis patients. This pilot data suggests that Fitbit® has a potential for use in clinical practice and trials to monitor physical activity in myositis patients, but larger studies are needed for further validation., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background/objective: Immune-mediated necrotizing myopathy (IMNM) is a subtype of myositis that is associated with a refractory phenotype and poorer prognosis. The aim of the study was to provide single large center experience of outcomes of intravenous immunoglobulin (IVIg) for patients with IMNM using longitudinally collected data., Methods: This case series longitudinally evaluated 4 of the 6 myositis core set measures at baseline and at 3 and 6 months after IVIg on 20 adult IMNM patients from 2014 to 2019 at the University of Pittsburgh. We assessed patients for improvement in core set measures, prednisone dose, adverse effects, and by the "limited" ACR/EULAR 2016 myositis response criteria. The mean differences in CK and manual muscle testing (MMT-8) were compared using a paired t test. A clinically significant response was defined as a >10% absolute improvement in the MMT-8 and a >50% absolute reduction in serum CK at 6 months of IVIg., Results: Intravenous immunoglobulin treatment was associated with marked improvement in IMNM patients, with 85% of patient meeting clinically significant response. The median (interquartile range) relative percent improvement in CK level was 96% (85%-98%) and in MMT was 29% (14%-36%) at 6 months.There was a significant reduction in the mean (SD) dose of prednisone at 6 months and had minimal adverse effects. In addition, with IVIg, most (13/14) patients had at least minimal improvement as per ACR/EULAR 2016 myositis response criteria., Conclusions: Based on objective, meaningful improvement in MMT-8 and CK as well as marked reduction in prednisone doses with acceptable tolerability, early implementation of IVIg should be considered in adult IMNM., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Idiopathic inflammatory myopathies (IIMs) cause proximal muscle weakness, which affects the ability to carry out the activities of daily living. Wearable physical activity monitors (PAMs) objectively assess continuous activity and potentially have clinical usefulness in the assessment of IIMs. We examined the psychometric characteristics for PAM outcomes in IIMs., Methods: Adult IIM patients were prospectively evaluated (at baseline, 3 months and 6 months) in an observational study. A waist-worn PAM (ActiGraph GT3X-BT) assessed average step counts/minute, peak 1-minute cadence, and vector magnitude/minute. Validated myositis core set measures (CSMs) including manual muscle testing (MMT), physician global disease activity (MD global), patient global disease activity (Pt global), extramuscular disease activity (Ex-muscular global), HAQ-DI (HAQ disability index), muscle enzymes, and patient-reported physical function were evaluated. Test-retest reliability, construct validity, and responsiveness were determined for PAM measures and CSMs, using Pearson correlations and other appropriate analyses., Results: A total of 50 adult IIM patients enrolled [mean (s.d.) age, 53.6 (14.6); 60% female, 94% Caucasian]. PAM measures showed strong test-retest reliability, moderate-to-strong correlations at baseline with MD global (r = -0.37 to -0.48), Pt global (r=-0.43 to -0.61), HAQ-DI (r = -0.47 to -0.59) and MMT (r = 0.37-0.52), and strong discriminant validity for categorical MMT and HAQ-DI. Longitudinal associations with MD global (r=-0.38 to -0.44), MMT (r = 0.50-0.57), HAQ-DI (r = -0.45 to -0.55) and functional tests (r = 0.30-0.65) were moderate to strong. PAM measures were responsive to MMT improvement ≥10% and moderate-to-major improvement on ACR/EULAR myositis response criteria. Peak 1-minute cadence had the largest effect size and standardized response means., Conclusion: PAM measures showed promising construct validity, reliability, and longitudinal responsiveness; especially peak 1-minute cadence. PAMs are able to provide valid outcome measures for future use in IIM clinical trials., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Abstract: Dermatomyositis (DM) is a subset of idiopathic inflammatory myopathy with characteristic cutaneous manifestations and muscle weakness. Conventional treatments for DM include glucocorticoids and other immunosuppressive or immunomodulatory agents including hydroxychloroquine, methotrexate, azathioprine, mycophenolate mofetil, tacrolimus, cyclosporine, and intravenous immunoglobulin. Refractory patients require more aggressive or novel therapies. Apremilast has not been studied for the management of refractory cutaneous DM. We report a case of a patient with refractory DM with severe scalp pruritus treated with apremilast who demonstrated significant improvement in her skin disease and complete resolution of scalp pruritus., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Idiopathic inflammatory myopathies (IIM) are a group of diseases characterized by muscle weakness, which limit activities of daily living. Patient Reported Outcomes Measurement Information System (PROMIS) is a set of outcome measures developed using NIH funding, but has not yet been studied in adult IIM. Currently, the most commonly used PROs in IIM are Health Assessment Questionnaire (HAQ-DI) and SF-36 physical function-10 (PF10), both of which have several limitations. In this study, we investigated psychometric properties of PROMIS physical function-20 (PF-20) and compared to HAQ-DI and SF-36 PF10., Methods: Patients with IIM completed PROMIS PF-20 and six myositis core set measures [manual muscle testing (MMT), physician (MD-GDA), patient (PT-GDA) and extra-muscular global disease activity, HAQ-DI and creatine kinase], SF-36 PF10 and functional tests [six-minute walk, timed up-and-go and sit-to-stand tests] at monthly visits over 6-months. Total improvement score (TIS) using 2016 ACR/EULAR myositis response criteria was obtained as measures of change., Results: Fifty patients [mean age, 51.6; 60% females] were enrolled; 6 PM, 24 DM, 9 NM and 11 with AS. PROMIS PF-20 showed strong test-retest reliability when repeated in 1-month. PROMIS PF-20 had moderate-strong correlations with MD-GDA, PT-GDA, MMT, HAQ-DI, SF-36 PF10, and functional tests indicating good convergent validity. Change in PROMIS PF-20 strongly correlated with TIS demonstrating good responsiveness. HAQ-DI and SF-36 PF10 exhibited similar validity and responsiveness; HAQ-DI was found to have a ceiling effect., Conclusion: PROMIS PF-20 demonstrates favorable psychometric properties in a large cohort of myositis patients and offers distinct advantages., Competing Interests: Declaration of Competing Interest Authors declare no conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: Muscle weakness in idiopathic inflammatory myopathies (IIMs) is conventionally assessed using manual muscle testing (MMT). However, more objective tools must be developed to accurately and reliably quantify muscle strength in myositis patients. Hand-held dynamometry (HHD) is a quantitative, portable device with reported reliability in neuromuscular disorders. Our aim was to assess the reliability, validity and responsiveness of HHD in myositis., Methods: Myositis patients [DM, necrotizing myopathy (NM), PM and anti-synthetase syndrome] evaluated at the University of Pittsburgh myositis centre were prospectively enrolled. Each patient was assessed at 0, 3 and 6 months for validated outcome measures of myositis disease activity and physical function. At each visit, muscle strength was assessed using both MMT and HHD (Micro FET2, Hoggan Health Industries, Draper, UT, USA). The reliability, validity and responsiveness of the HHD was assessed using standard statistical methods., Results: Fifty IIM patients (60% female; mean age 51.6 years; 6 PM, 9 NM, 24 DM and 11 anti-synthetase syndrome) were enrolled. HHD showed strong test-retest intrarater reliability (r = 0.96) and interrater reliability (r = 0.98). HHD correlated significantly with the MMT score (r = 0.48, P = 0.0006) and myositis disease activity and functional measures. Longitudinal analysis showed a significant and strong association between the HHD and MMT as well as 2016 ACR/EULAR myositis response criteria (r = 0.8, P < 0.0001) demonstrating responsiveness. The mean effect size and standardized response mean of HHD was large: 0.95 and 1.03, respectively. MMT had a high ceiling effect compared with HHD., Conclusion: HHD demonstrated strong reliability, construct validity and responsiveness in myositis patients. External validation studies are required to confirm these findings., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Idiopathic inflammatory myopathies (IIM) are a group of autoimmune diseases characterized by proximal muscle weakness. H. P. Acthar gel [repository corticotropin injection (RCI)] is a formulation of adrenocorticotropic hormone and has been approved by Food and Drug Administration for use in IIM; however, literature is limited. In this study, we report longitudinal follow-up of myositis patients treated with RCI., Methods: Patients with refractory IIM who were enrolled in the prospective, open-label RCI trial were included in this study. The post-trial follow-up period was 6 months with assessments every 2 months, which included myositis core set measures including extra-muscular global, muscle and patient global disease activities, HAQ, and manual muscle testing., Results: Two patients were lost to follow-up after finalization of the trial, and the remaining eight patients were enrolled in the follow-up study. One patient remained on RCI after the trial. In the follow-up period, four of eight patients had flare at on average 4.1 months after the RCI trial. Among the patients who flared, three required an increase in prednisone. One patient was restarted on RCI at 5.5 months, but had minimal improvement after 3 months. Four patients who remained stable continued to satisfy criteria for the definition of improvement through the 6-month follow-up. However, none showed any further improvement in the primary or secondary efficacy outcomes after the initial RCI trial., Conclusion: To our knowledge, this is the first study reporting the follow-up results of patients treated with standard dose and duration of Acthar. We believe that our study will provide the basis for the development of future randomized RCI trials in IIM., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The idiopathic inflammatory myopathies, particularly dermatomyositis, are associated with an increased risk of cancer. Lung, ovarian, breast, colon, prostate, and cervical cancers, and hematologic malignancies, are among the most common associated cancers. Risk stratification for cancer in patients with myositis is based on clinical risk factors/red flags, myositis clinical subtypes, and myositis-specific autoantibodies. Clinical risk factors include older age at disease onset, male gender, dysphagia, acute onset/refractory myositis, cutaneous ulceration, necrosis/vasculitis, and elevated inflammatory markers. Appropriate screening strategies are based on the risk level. Further studies are warranted to determine the role of advanced imaging and comprehensive cancer screening., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: Some patients with cutaneous DM demonstrate incomplete responses to conventional therapy while some, including those with extra-cutaneous manifestations, experience disease recurrences. Janus kinase/signal transducers and activators of transcription pathway inhibition has been reported to mitigate IFN signalling, which is thought to contribute to disease pathogenesis in DM. Four cases of refractory DM responsive to tofacitinib have been reported in the literature. Our case series investigated the use of tofacitinib in refractory cutaneous DM., Methods: Our case series includes four subjects with refractory DM who received tofaticinib after failure of several immunosuppressive and immunomodulatory agents., Results: All four subjects responded well to tofacitinib with significant improvement in cutaneous and extra-cutaneous manifestations., Conclusion: Tofacitinib can improve cutaneous and inflammatory articular manifestations in refractory DM., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Novel classification schemes for idiopathic inflammatory myopathy are based on serologic and histopathologic features. The presence of specific myositis autoantibodies may correspond to particular clinical phenotypes. Patients with a known diagnosis of inflammatory myopathy require a prompt clinical evaluation and the assessment of myositis-associated autoantibodies. Patients possessing autoantibodies associated with ILD or those with any pulmonary symptoms should undergo pulmonary functions tests and high-resolution computed tomography scanning of their lungs. Despite the lack of placebo-controlled trials, systemic glucocorticoids are considered the mainstay of initial treatment of myositis-associated ILD. Glucocorticoid-sparing agents are often started concomitantly with glucocorticoids, particularly in patients with moderate or severe disease. The first-line conventional immunosuppressive drugs include either mycophenolate mofetil or azathioprine, and when they fail or if the features are rapidly progressive, more aggressive therapy includes tacrolimus or cyclosporine, rituximab, intravenous immunoglobulin, or cyclophosphamide used either alone or in various combinations., (Copyright © 2019. Published by Elsevier Ltd.)

Purpose of Review: Anti-melanoma differentiation-associated gene 5 (anti-MDA5) is a novel and highly specific myositis-associated autoantibody, which defines a unique phenotype among patients with dermatomyositis (DM)., Recent Findings: Anti-MDA5 was originally characterized in Japan in DM patients with hallmark cutaneous features and no proximal muscle weakness and termed clinically amyopathic DM (CADM). Anti-MDA5 has characteristic cutaneous manifestations which include tender palmar papules and cutaneous ulcerations, along with an increased frequency of interstitial lung disease (ILD) that can be rapidly progressive (RPILD) and fatal. This review will highlight the clinical significance of anti-MDA5 autoantibodies in Caucasian DM patients.

Purpose of Review: As treatment of refractory cases of idiopathic inflammatory myopathies (IIMs) has been challenging, there is growing interest in assessing novel biologics that target various pathways implicated in the pathogenesis of IIM., Recent Findings: In the largest clinical trial in adult and juvenile IIM assessing the effectiveness of rituximab, the primary outcome was not met but 83% of this refractory group of IIM patients met a predefined definition of improvement and rituximab demonstrated a significant glucocorticoid-sparing effect. Antitumor necrosis factor utility in IIM is generally limited by uncertain efficacy data along with recent reports suggesting their potential for inducing systemic autoimmune disease including IIM., Summary: Further research is required to evaluate the role of newer therapies such as tocilizumab (anti-interleukin-6), abatacept (inhibition of T-cell costimulation), sifalimumab (anti-interferonα) and ruxolitinib, (Janus kinase inhibitor) given their biological plausibility and encouraging recent small case series results. Future clinical trials should consider the targeting of biomarkers implicated in the etiopathogenesis of IIM, predictive factors of treatment response, recent revisions in IIM classification criteria, as well as newly developed data-driven response criteria which employ validated core set measures.

Primary burning mouth syndrome (BMS) is an oral mucosal disorder that is characterized by a chronic and often debilitating intraoral burning sensation for which no localized or systemic cause can be found. BMS most commonly affects postmenopausal women. The pathophysiology of primary BMS is not well understood. Diagnosing BMS can prove to be challenging. BMS patients can also pose a therapeutic challenge to clinicians who are consulted to evaluate these patients. Most commonly used therapies include tricyclic antidepressants, α-lipoic acid, clonazepam, and cognitive-behavioral therapy. Clinical judgment, patient counseling, and monitoring of pain are important. Further research is required to assess the effectiveness of serotonin and newer serotonin-noradrenalin reuptake inhibitors., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To determine the clinical features associated with the antimelanoma differentiation-associated gene 5 antibody (anti-MDA5) in US patients with clinically amyopathic dermatomyositis (CADM) and classic DM., Methods: Patients with CADM were consecutively selected from the University of Pittsburgh Myositis Database from 1985 to 2013. CADM was defined by a typical DM rash without objective muscle weakness and no or minimal abnormalities of muscle enzymes, electromyography, or muscle biopsy. DM was defined by Bohan and Peter criteria and was 1:1 matched (sex and age ± 5 yrs) to patients with CADM. Anti-MDA5 autoAb levels were determined using ELISA. Clinical features were compared between CADM and DM and between MDA5-positive and MDA5-negative subjects, using chi-squared and/or Mann-Whitney U tests as appropriate., Results: We identified 61 patients with CADM who were matched to 61 DM controls (female 62% vs 64%; mean age 44.8 yrs vs 48.2, p < 0.5). Anti-MDA5 frequency was the same in both cohorts (13.1%), and anti-MDA5 was significantly associated with a higher likelihood of cutaneous ulcers, digital tip ulcerations, and puffy fingers as well as interstitial lung disease (ILD). Most patients with ILD had rapidly progressive ILD (RPILD) leading to early death. Patients with CADM were more likely to have dysphagia, but there were no other clinical differences seen associated with CADM as compared to classic DM., Conclusion: Anti-MDA5 positivity had a similar frequency in US patients with CADM and DM and is associated with ILD, RPILD, cutaneous ulcers, digital tip ulceration, and poor survival.

Despite the lack of placebo-controlled trials, glucocorticoids are considered the mainstay of initial treatment for idiopathic inflammatory myopathy (IIMs) and myositis-associated ILD (MA-ILD). Glucocorticoid-sparing agents are often given concomitantly with other immunosuppressive agents, particularly in patients with moderate or severe disease. As treatment of refractory cases of idiopathic inflammatory myopathies has been challenging, there is growing interest in evaluating newer therapies including biologics that target various pathways involved in the pathogenesis of IIMs. In a large clinical trial of rituximab in adult and juvenile myositis, the primary outcome was not met, but the definition of improvement was met by most of this refractory group of myositis patients. Rituximab use was also associated with a significant glucocorticoid-sparing effect. Intravenous immune globulin (IVIg) can be used for refractory IIMs or those with severe dysphagia or concomitant infections. Anti-tumor necrosis factor (anti-TNF) utility in IIMs is generally limited by previous negative studies along with recent reports suggesting their potential for inducing myositis. Further research is required to assess the role of new therapies such as tocilizumab (anti-IL6), ACTH gel, sifalimumab (anti-IFNα), and abatacept (inhibition of T cell co-stimulation) given their biological plausibility and encouraging small case series results. Other potential novel therapies include alemtuzumab (a humanized monoclonal antibody which binds CD52 on B and T lymphocytes), fingolimod (a sphingosine 1-phosphate receptor modulator that traps T lymphocytes in the lymphoid organs), eculizumab, and basiliximab. The future investigations in IIMs will depend on well-designed controlled clinical trials using validated consensus core set measures and improvements in myositis classification schemes based on serologic and histopathologic features.