Current approach to muscle imaging in myositis.

PURPOSE OF REVIEW: Muscle imaging is commonly utilized in idiopathic inflammatory myopathies (IIM) for diagnostic evaluation, selection of muscle biopsy site, and differentiating between disease activity versus damage. In this review, we discuss the current state and recent developments in the use of muscle imaging modalities including muscle magnetic resonance imaging (MRI), ultrasound (US), and positron emission tomography (PET) scan. RECENT FINDINGS: Muscle MRI is a clinically useful tool in evaluation of IIM with studies showing good correlations between pattern of morphological changes on MRI and histopathological findings on muscle biopsy. The use of computer aided diagnostics to enable quantification of muscle pathology will be a welcome development for future studies and trials. New studies highlight that muscle US could be a particularly useful point of care tool in longitudinal monitoring of patients with active myositis. Muscle FDG-PET scan shows inflammatory activity in IIM muscle and can also provide additional information on extra-muscular manifestations and cancer screening. Utilization of novel tracers is an exciting development for IIM evaluation. SUMMARY: Muscle MRI remains the gold standard for muscle imaging in IIM. Growing literature on muscle US and PET scan highlight their promising applications in IIM.

Current efforts and historical perspectives on classification of idiopathic inflammatory myopathies.

PURPOSE OF REVIEW: The classification of idiopathic inflammatory myopathies is challenging due to the large number of clinical, serological, histopathological and genetic findings, as well as the latest findings and developments in the field of myositis research. The latest official classification criteria are the 2017 European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) classification criteria for adult and juvenile idiopathic inflammatory myopathies, which have been extensively reviewed in recent years for their applicability, sensitivity and specificity. RECENT FINDINGS: The sensitivity and specificity of the 2017 ACR/EULAR criteria are sometimes performing better, but usually at the same level as the previous criteria. A large number of further suggestions for amendments to the criteria have been made. In particular there is a need to revise the criteria with regard to the addition of new myositis-specific autoantibodies, newly defined subgroups (especially antisynthetase syndrome, immune medicated necrotizing myopathy and overlap myositis) and possibly the addition of further diagnostic procedures (for instance, muscle MRI or PET CT) to improve the accuracy and timeliness of the criteria. SUMMARY: Efforts to optimize the myositis classification criteria have been extensive in recent years and a new global interdisciplinary collaboration of clinicians is currently taking place based on the previous results with the aim of revising the 2017 EULAR/ACR classification criteria.

Current myositis clinical trials and tribulations.

With improved understanding of disease pathogenesis and availability of outcome measures, there has been a remarkable increase in the number of therapeutic clinical trials in idiopathic inflammatory myopathies (myositis) over the last three years reaching as many as five trials per site. These trials share similar design and inclusion/exclusion criteria resulting in a competitive clinical trial landscape in myositis. While these are exciting times for the myositis field, we have a number of concerns about the design and conduct of the myositis trials. These include competitive landscape, lengthy placebo arms, underrepresentation of minority groups among participants, use of patient reported outcome measures with limited/no data on validity in myositis, antiquated disease classification criteria, and unclear performance of the ACR/EULAR Myositis Response Criteria in skin-predominant patients despite inclusion of these patients in trials. In this viewpoint, we further discuss these concerns and offer potential solutions such as including patient perspectives in the trial design and adoption of innovative frameworks.

A patient centered assessment of the 2016 ACR-EULAR Myositis Response Criteria: evaluating the meaningfulness of response.

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.

Associations between 6-minute walk distance and physiologic measures and clinical outcomes in myositis-associated interstitial lung disease.

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.

Serum cytokine profiles of adults with idiopathic inflammatory myopathies.

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.

Performance of the 2017 EULAR/ACR Classification Criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups: a scoping review.

The 2017 EULAR/ACR classification criteria for adult/juvenile idiopathic inflammatory myopathies (IIM) were established using a data-driven approach by an international group of myositis experts to allow classification of IIM and its major subtypes. Since their publication, the performance of the criteria has been tested in multiple cohorts worldwide and significant limitations have been identified. Moreover, the understanding and classification of IIM have evolved since 2017. This scoping review was undertaken as part of a large international project to revise the EULAR/ACR criteria and aims to i) summarise the evidence from the current literature on the performance characteristics of the 2017 EULAR/ACR classification criteria in various cohorts and IIM subtypes, and ii) delineate the factors that need to be considered in the revision of the classification criteria. A systematic search of Medline (via PubMed), Cumulative Index to Nursing and Allied Health Literature, and conference abstract archives was conducted independently by three investigators for studies on the EULAR/ACR criteria published between October 2017 and January 2023. This scoping review of 19 articles and 13 abstracts revealed overall good performance characteristics of the EULAR/ACR criteria for IIM, yet deficiencies in lack of inclusion of certain IIM subtypes, such as immune mediated necrotising myopathy, amyopathic dermatomyositis, antisynthetase syndrome and overlap myositis. Published modifications that may improve the performance characteristics of the criteria for classification of IIM subtypes were also summarised. The results of this review suggest that a revision of the EULAR/ACR criteria is warranted.

Collaborative research in myositis-related disorders: MIHRA, a global shared community model.

Myositis International Health and Research Collaborative Alliance (MIHRA) is a newly formed purpose-built non-profit charitable research organization dedicated to accelerating international clinical trial readiness, global professional and lay education, career development and rare disease advocacy in IIM-related disorders. In its long form, the name expresses the community's scope of engagement and intent. In its abbreviation, MIHRA, conveys linguistic roots across many languages, that reflects the IIM community's spirit with meanings such as kindness, community, goodness, and peace. MIHRA unites the global multi-disciplinary community of adult and pediatric healthcare professionals, researchers, patient advisors and networks focused on conducting research in and providing care for pediatric and adult IIM-related disorders to ultimately find a cure. MIHRA serves as a resourced platform for collaborative efforts in investigator-initiated projects, consensus guidelines for IIM assessment and treatment, and IIM-specific career development through connecting research networks.MIHRA's infrastructure, mission, programming and operations are designed to address challenges unique to rare disease communities and aspires to contribute toward transformative models of rare disease research such as global expansion and inclusivity, utilization of community resources, streamlining ethics and data-sharing policies to facilitate collaborative research. Herein, summarises MIHRA operational cores, missions, vision, programming and provision of community resources to sustain, accelerate and grow global collaborative research in myositis-related disorders.

Discordance between patient- and physician-reported disease activity in adult idiopathic inflammatory myopathy.

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.

Correlation between B cell epitope profile and clinical features of anti-MDA5 antibody-positive dermatomyositis.

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 titers 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 titers of antibodies recognizing fragment H (aa 905-1026) compared to 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 titers than those without vascular dysfunction. Four patients died due to ILD progression and showed higher anti-fragment A (aa 1-155) antibody titers than the other 20 patients. Differences in the ratio of anti-fragment to anti-full length MDA5 antibody titers 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.

Performance of the 2016 ACR-EULAR myositis response criteria in juvenile dermatomyositis therapeutic trials and consensus profiles.

OBJECTIVES: The 2016 ACR-EULAR Response Criteria for JDM was developed as a composite measure with differential weights of six core set measures (CSMs) to calculate a Total Improvement Score (TIS). We assessed the contribution of each CSM, representation of muscle-related and patient-reported CSMs towards improvement, and frequency of CSM worsening across myositis response criteria (MRC) categories in validation of MRC. METHODS: Data from JDM patients in the Rituximab in Myositis trial (n = 48), PRINTO JDM trial (n = 139), and consensus patient profiles (n = 273) were included. Observed vs expected CSM contributions were compared using Sign test. Characteristics of MRC categories were compared by Wilcoxon tests with Bonferroni adjustment. Spearman correlation of changes in TIS and individual CSMs were examined. Agreement between physician-assessed change and MRC categories was evaluated by weighted Cohen's kappa. RESULTS: Of 457 JDM patients with IMACS CSMs and 380 with PRINTO CSMs, 9-13% had minimal, 19-23% had moderate and 41-50% had major improvement. The number of improved and absolute percentage change of CSMs increased by MRC improvement level. Patients with minimal improvement by MRC had a median of 0-1 CSM worsened, and those with moderate/major improvement had a median of zero worsening CSMs. Of patients improved by MRC, 94-95% had improvement in muscle strength and 93-95% had improvement in ≥1 patient-reported CSM. IMACS and PRINTO CSMs performed similarly. Physician-rated change and MRC improvement categories had moderate-to-substantial agreement (Kappa 0.5-0.7). CONCLUSION: The ACR-EULAR MRC perform consistently across multiple studies, supporting its further use as an efficacy end point in JDM trials.

Performance of the 2016 ACR-EULAR Myositis Response Criteria in adult dermatomyositis/polymyositis therapeutic trials and consensus profiles.

OBJECTIVE: The ACR-EULAR Myositis Response Criteria (MRC) were developed as a composite measure using absolute percentage change in six core set measures (CSMs). We aimed to further validate the MRC by assessing the contribution of each CSM, frequency of strength vs extramuscular activity improvement, representation of patient-reported outcome measures (PROM), and frequency of CSM worsening. METHODS: Data from adult dermatomyositis/polymyositis patients in the rituximab (n = 147), etanercept (n = 14), and abatacept (n = 19) trials, and consensus patient profiles (n = 232) were evaluated. The Total Improvement Score (TIS), number of improving vs worsening CSMs, frequency of improvement with and without muscle-related CSMs, and contribution of PROM were evaluated by MRC category. Regression analysis was performed to assess contribution of each CSM to the MRC. RESULTS: Of 412 adults with dermatomyositis/polymyositis, there were 37%, 24%, 25%, and 14% with no, minimal, moderate, and major MRC improvement, respectively. The number of improving CSMs and absolute percentage change in all CSMs increased by improvement category. In minimal-moderate improvement, only physician-reported disease activity contributed significantly more than expected by MRC. Of patients with at least minimal improvement, 95% had improvement in muscle-related measures and a majority (84%) had improvement in PROM. Patients with minimal improvement had worsening in a median of 1 CSM, and most patients with moderate-major improvement had no worsening CSMs. Physician assessment of change generally agreed with MRC improvement categories. CONCLUSION: The ACR-EULAR MRC performs consistently across multiple studies, further supporting its use as an efficacy end point in future myositis therapeutic trials.

A single center pilot study: assessing resident needs and faculty perceptions to improve training in rheumatology.

BACKGROUND: Internal medicine (IM) residents lack confidence in rheumatology. Due to the wide variety of topics in rheumatology, identifying the most important subjects to learn during training is vital to create future interventions to increase confidence and knowledge. The preferred teaching modality for both attendings/fellows and residents is not known. METHODS: An electronic survey was distributed to all IM residents, rheumatology fellows, and rheumatology faculty at the University of Chicago during the 2020-2021 academic year. Residents reported self-confidence levels on 10 rheumatology topics, while rheumatology attendings/fellows were asked to rank these from most to least important to learn during IM residency. All groups were asked preferred teaching modality. RESULTS: Median confidence level [interquartile range] among residents for caring for patients with rheumatological conditions was 6 [3.6-7.5] for inpatient and 5 [3.7-6.5] for outpatient settings (10 being very confident). Attendings and fellows identified the most important topics to learn during the rheumatology rotation as ordering and interpreting autoimmune serologies and musculoskeletal exam. Both attendings/fellows and residents preferred bedside teaching in the inpatient setting and case-based learning in the outpatient setting. CONCLUSIONS: While some disease-specific topics such as autoimmune serologies were identified as important rheumatology topics for IM residents to learn, more practical topics like musculoskeletal exam skills were also deemed important. This highlights the need for comprehensive interventions that focus on more than standardized exam topics alone to improve rheumatology confidence in IM residents. There are different preferences of teaching styles in various clinical settings.

Consumer-based activity trackers in evaluation of physical activity in myositis patients.

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.

Glucocorticoids in Myositis: Initiation, Tapering, and Discontinuation.

PURPOSE OF THE REVIEW: We discuss the evidence behind the use of glucocorticoids in myositis including a discussion of mechanism of action, dosing, tapering, and duration of therapy as well as glucocorticoid-related adverse events that are particularly important in myositis patients. RECENT FINDINGS: Studies showing reduction in mortality rates after the use of glucocorticoids, better outcomes in patients treated with glucocorticoids compared to those who did not, and reduction of inflammation in muscle biopsies provide low level evidence to support use of glucocorticoids in myositis. Early initiation of therapy is associated with better functional outcomes. Use of intravenous methylprednisolone in patients with severe disease may lead to quicker recovery and reduction in long-term glucocorticoid exposure. Steroid-related myopathy and osteoporosis are glucocorticoid side effects that are particularly relevant in myositis. The optimal dose and duration of glucocorticoid therapy in myositis currently remain elusive, and this review emphasizes the need for better quality studies in this area.

Assessment of Physical Activity and Muscle Function in Adult Inflammatory Myopathies.

PURPOSE OF REVIEW: The aim is to summarize the outcome measures used in the assessment and monitoring of muscle function and physical activity in the management idiopathic inflammatory myopathy. RECENT FINDINGS: Assessment techniques have progressed and matured over the past decade, and new options are now available to clinicians working in this field. Newer outcome measures, including the Functional Index-3 and wearable motion sensors are reviewed, as well as the current application of more established measures. The available outcome measures for use in clinical practice in idiopathic inflammatory myopathies with regard to muscle function and physical activity have expanded over the past 15 years. There are valid and reliable options for several domains and methods for assessing these factors. In a busy clinical setting, efficiency is important, but there also needs to be considered the choosing of tools that work together to give the fullest picture of the status of the patient.

Immune Checkpoint Inhibitor-Associated Myositis: A Distinct Form of Inflammatory Myopathy.

ABSTRACT: Research on the relationship between inflammatory myopathy and malignancy has grown considerably within the last century. Now, the burgeoning field of inflammatory myopathy has yet another player in the mix: immune checkpoint inhibitor-associated myositis (ICI myositis). Immune checkpoint inhibitor-associated myositis is indicated by clinical diagnosis of inflammatory myopathy after initiation of immune checkpoint inhibitor for cancer management. Current literature reflects low prevalence but high mortality associated with ICI myositis, especially when involving myasthenia gravis and myocarditis. Immune checkpoint inhibitor-associated myositis tends to have muscle pain along with weakness, infrequent presentation with dermatitis, or interstitial lung disease and is typically seronegative with scattered, endomysial inflammatory infiltrates on biopsy. The differential diagnosis of ICI myositis includes myasthenia gravis and other neurological immune-related adverse events. Therapeutic approach involves high doses of corticosteroids with a choice of steroid-sparing immunomodulating agent(s) that is primarily driven by expert opinion due to lack of robust research to support one agent over another. There is wide variation in the inclusion criteria for ICI myositis used in previous studies. We review previously used inclusion criteria and suggest an expertise-based classification criterion to provide a standardized definition and allow comparability between studies. There is a critical need for prospective translational and clinical studies that elucidate the pathophysiology of ICI myositis in order to improve evaluation and management of these patients.

Hand-held dynamometry for assessment of muscle strength in patients with inflammatory myopathies.

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.

Reliability, validity and responsiveness of physical activity monitors in patients with inflammatory myopathy.

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.

Follow-up results of myositis patients treated with H. P. Acthar gel.

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.