Manual Muscle Testing-8 Research Articles

High-intensity resistance training improves quality of life, muscle endurance and strength in patients with myositis: a randomised controlled trial

Myositis is associated with reduced quality of life, which is accompanied by significant impairments in muscle endurance and strength, altogether representing cardinal traits in patients with myositis. This randomised controlled trial aimed to investigate the effect of high-intensity resistance training on quality of life in patients with myositis. Thirty-two patients with established, stable myositis were randomised to 16 weeks of high-intensity resistance training (intervention group) or 16 weeks of usual care (control group). Primary outcome was quality of life assessed as the change in the physical component summary score (PCS) of the Short Form-36 health questionnaire from baseline to post-intervention. Secondary outcomes included functional capacity measures, such as functional index 3, and International Myositis Assessment and Clinical Studies Group (IMACS) disease activity and damage core set measures, including manual muscle testing 8 (MMT8). The primary outcome PCS showed an improvement in favour of high-intensity resistance training with a between-group difference of 5.33 (95% CI 0.61; 10.05) (p = 0.03). Additionally, functional index 3 showed a between-group difference indicating greater gains with high-intensity resistance training 11.49 (95% CI 3.37; 19.60) (p = 0.04), along with a between-group improvement in MMT8 1.30 (95% CI 0.09; 2.51) (p = 0.04). High-intensity resistance training for 16 weeks effectively improved quality of life in patients with myositis. Clinical measures of muscle endurance and muscle strength were also found to improve with high-intensity resistance training, while patients stayed in disease remission. Consequently, progressively adjusted high-intensity resistance training is feasible and causes no aggravation of the disease, while benefitting patients with myositis.Clinical trial registration: Clinicaltrials.gov ID: NCT04486261—https://clinicaltrials.gov/study/NCT04486261.

Anti-FHL1 autoantibodies in adult patients with myositis: a longitudinal follow-up analysis.

To determine prevalence and clinical associations of anti-FHL1 autoantibodies in patients with idiopathic inflammatory myopathies (IIM), and to evaluate autoantibody levels over time. Sera at the time of diagnosis from patients with IIM (n = 449), autoimmune disease controls (DC, n = 130), neuromuscular diseases (NMD, n = 16) and healthy controls (HC, n = 100) were analyzed for anti-FHL1 autoantibodies by Enzyme-Linked ImmunoSorbent Assay (ELISA). Patients with IIM FHL1+ and FHL1- were included in a longitudinal analysis. Serum levels were correlated to disease activity. Autoantibodies to FHL1 were more frequent in patients with IIM (122/449, 27%) compared with DC (Autoimmune DC and NMD, 13/146, 9%, p< 0.001) and HC (3/100,3%, p< 0.001). Anti-FHL1 levels were higher in IIM [median (IQR)=0.62 (0.15-1.04)] in comparison with DC [0.22 (0.08-0.58)], HC [0.35 (0.23-0.47)] and NMD [0.48 (0.36-0.80)] p< 0.001. Anti-FHL1+ patients with IIM were younger at time of diagnosis compared with the anti-FHL1- group (p= 0.05) and were seronegative for other autoantibodies in 25%.In the first follow-up anti-FHL1+ sample 20/33 (60%) positive at baseline had turned negative for anti-FHL1 autoantibodies. Anti-FHL1 autoantibodies rarely appeared after initiating treatment. Anti-FHL1 autoantibody levels correlated with CK (r = 0.62, p= 0.01), disease activity measure MYOACT (n = 14, p= 0.004) and inversely with manual muscle test-8 (r=-0.59, p= 0.02) at baseline. Anti-FHL1 autoantibodies were present in 27% of patients with IIM, of these 25% were negative for other autoantibodies. Other autoimmune diseases had lower frequencies and levels. Anti-FHL1 levels often decreased with immunosuppressive treatment, correlated with disease activity measures at diagnosis and rarely appeared after start of treatment.

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

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

Evaluating disease status in idiopathic inflammatory myopathies with quantitative muscle ultrasound.

Muscle strength, functional status, and muscle enzymes are conventionally used to evaluate disease status in idiopathic inflammatory myopathies (IIM). This study aims to investigate the role of quantitative muscle ultrasound in evaluating disease status in IIM patients. Patients with IIM, excluding inclusion body myositis, were recruited along with age- and sex-matched healthy controls (HC). All participants underwent muscle ultrasound and clinical assessments. Six limb muscles were unilaterally scanned using a standardized protocol, measuring muscle thickness (MT) and echo intensity (EI). Results were compared with HC, and correlations were made with outcome measures. Twenty IIM patients and 24 HC were recruited. The subtypes of IIM were dermatomyositis (6), necrotizing myositis (6), polymyositis (3), antisynthetase syndrome (3), and nonspecific myositis (2). Mean disease duration was 8.7 ± 6.9 years. There were no significant differences in demographics and anthropometrics between patients and controls. MT of rectus femoris in IIM patients was significantly lower than HC. Muscle EI of biceps brachii and vastus medialis in IIM patients were higher than HC. There were moderate correlations between MT of rectus femoris and modified Rankin Scale, Physician Global Activity Assessment, and Health Assessment Questionnaire, as well as between EI of biceps brachii and Manual Muscle Testing-8. Muscle ultrasound can detect proximal muscle atrophy and hyperechogenicity in patients with IIM. The findings correlate with clinical outcome measures, making it a potential tool for evaluating disease activity of patients with IIM in the late phase of the disease.

Skeletal muscle injury in COVID infection: Frequency and patterns.

Little is known about skeletal muscle injury with coronavirus disease 2019 (COVID-19). We estimate the frequency and explore the patterns of skeletal muscle injury in acute COVID-19. A cohort of COVID patients with mild to moderate symptoms were evaluated in a COVID-designated hospital between May and December 2021 and followed for 2 weeks. Skeletal muscle injury was assessed according to creatine kinase (CK) levels, Manual Muscle Test-8 (MMT-8) score, and the Health Assessment Questionnaire (HAQ) score. Injury was defined as CK >200 IU/L with an MMT-8 score < 76. The association between such injury and severity and outcomes were evaluated using cross-tabulations. Two hundred fifty participants with a mean age of 50.2 years (SD: 17.2) were included. One hundred nine (43.6%) were women; 84 (34%) developed severe disease. Median CK levels were 91 IU/L (IQR 56-181). [Correction added on 17 November 2023, after first online publication: In the preceding sentence, the IQR was corrected from '56,181'.] Patients with weakness on the MMT-8 (n = 247, 98.8%) and disability on the HAQ (n = 107; 42.8%) were common. Neck flexor muscles were prominently affected. Skeletal muscle injury was seen in 22.4% (95% CI: 17.4-28.1). There was no significant association between skeletal muscle injury and maximal severity of illness or short-term outcomes. Disability increased over 14 days in most survivors (n = 172, 72.3%) and this was not seen in those with mild disease (OR: 0.4, 95% CI: 0.22-0.70). Skeletal muscle injury appears to be common in people presenting with mild to moderate COVID infection.

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

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

Upregulation of the CD155-CD226 Axis Is Associated With Muscle Inflammation and Disease Severity in Idiopathic Inflammatory Myopathies.

The CD155-CD226/T-cell Ig and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) pathway plays a critical role in regulating T-cell responses and is being targeted clinically. However, research on the role of this pathway in autoimmune diseases is limited. This study aimed to investigate the expression and tissue-specific roles of CD155-CD226/TIGIT pathway molecules in the inflamed muscles of patients with idiopathic inflammatory myopathies (IIMs). Immunohistochemistry, Western blot analysis, and polychromatic immunofluorescence staining were performed to examine the expression of CD155, CD226, and TIGIT in skeletal muscle biopsies from 30 patients with dermatomyositis (DM), 10 patients with amyopathic DM (ADM), 20 patients with immune-mediated necrotizing myopathy (IMNM), 5 patients with dysferlinopathy, and 4 healthy controls. Flow cytometry analysis was used to analyze the functions of T cells with different phenotypes. Strong expression of CD155 was observed in patients with DM and IMNM, while its expression was largely negative in those with ADM and dysferlinopathy and healthy controls. The costimulatory receptor CD226 was highly expressed on muscle-infiltrating cells, while the coinhibitory receptor TIGIT was expressed at low levels. These infiltrating CD226+ cells were mainly activated effector T cells that localized adjacent to CD155-expressing myofibers, but were faintly detectable within the muscle fascicles lacking CD155. A strong positive correlation between CD155 and CD226 expression scores was also observed. Polychromatic immunofluorescence staining revealed that CD155+ muscle cells coexpressed major histocompatibility complex classes I and II, and tumor necrosis factor alpha expression was detected in CD226+ T cells at their close sites with the myofibers. Furthermore, the expression levels of CD155 and CD226 showed a positive correlation with creatine kinase, lactate dehydrogenase, and the muscle histopathology damage scores and an inverse correlation with the Manual Muscle Testing-8 scores. In addition, CD155 and CD226 expressions were significantly decreased in representative patients who achieved remission posttreatment. These findings demonstrate that the CD155-CD226 axis is highly activated in inflamed muscle tissues of patients with IIM and is associated with muscle disease severity. Our data uncover the immunopathogenic role of the axis in the pathology of IIMs.

Semi-quantitative thigh magnetic resonance imaging scores in assessing disease activity and determining long-term clinical outcome in idiopathic inflammatory myopathies: a causal mediation analysis.

To evaluate the relationship of thigh MRI (t-MRI) with manual muscle testing-8 (MMT-8), muscle enzymes and autoantibodies. To determine the causal and mediating factors resulting in poor recovery of MMT-8 in inflammatory myositis (IIM). This was a single-centre retrospective study in IIM patients. t-MRI was semi-quantitatively scored for muscle oedema, fascial oedema, muscle atrophy and fatty infiltration. Spearman correlation of t-MRI scores was done with muscle enzymes at baseline, and MMT-8 at baseline and on follow-up. Causal mediation analysis was performed with age, sex, symptom duration, autoantibodies, diabetes and BMI as independent variables, follow-up MMT-8 as dependent and t-MRI scores as mediating variables. Baseline evaluation was done on 59 and follow-up on 38 patients. Median follow-up of the cohort was 31 (10-57) months. Baseline MMT-8 negatively correlated with muscle oedema (r = -0755), fascial oedema (r = -0.443) and muscle atrophy (r = -0.343). Creatinine kinase (r = 0.422) and aspartate transaminase (r = 0.480) positively correlated with muscle oedema. Follow-up MMT-8 correlated negatively with baseline atrophy (r = -0.497) and fatty infiltration (r = -0.531). On follow-up, MMT-8 males had positive total effect (estimate (95%CI)) via atrophy [2.93 (0.44, 4.89)] and fatty infiltration [2.08 (0.54, 3.71)]. Antisynthetase antibody had a positive total effect via fatty infiltration [4.50 (0.37, 7.59)]. Age had a negative total effect via atrophy [-0.09 (0.19, -0.01)] and fatty infiltration [-0.07 (-0.15, -0.01)]. Disease duration had a negative total effect via fatty infiltration [-0.18 (-0.27, -0.02)]. Baseline fatty infiltration and muscle atrophy resulting from older age, female sex, longer disease duration and absent anti-synthetase antibodies, partly mediate muscle recovery in IIM.

Increased expression of the p-STAT3/IL-17 signaling pathway in patients with dermatomyositis.

The aim is to explore the roles of phosphorylated signal transduction and activator of transcription 3 (p-STAT3) and interleukin (IL)-17 in patients with dermatomyositis (DM). A total of 20 DM patients and 12 healthy controls were enrolled. Flow cytometry combined with counting was used to detect the number of Th17 cells. Western blotting and immunohistochemistry were used to examine the muscle levels of p-STAT3 and IL-17, and serum levels of IL-17 were measured by enzyme-linked immunosorbent assays. Muscle p-STAT3 and IL-17 levels, the number of Th17 cells, and serum IL-17 levels were markedly increased in DM. p-STAT3 and IL-17 were co-expressed in the muscle of DM patients. The p-STAT3 levels were correlated with the number of Th17 cells as well as muscle and serum IL-17 levels. The correlations of the p-STAT3 level with elevated levels of transaminases, myocardial enzymes, and the health assessment questionnaire score were significantly positive, while the correlation with manual muscle testing-8 was significantly negative. A receiver operating characteristic curve indicated the good predictive value of p-STAT3 for the occurrence of DM. The increased p-STAT3/IL-17 signaling pathway activation in DM patients may induce muscle inflammation and necrosis, and it may be a potential target for DM.

Experience with the use of mycophenolate mofetil in juvenile idiopathic inflammatory myopathies.

The objective of this study was to evaluate the efficacy and safety of MMF in juvenile idiopathic inflammatory myopathies (JIIMs). Patients diagnosed with JIIM and treated with MMF enrolled in the Juvenile Dermatomyositis Research Group (JDRG) in the UK or followed at the Giannina Gaslini Institute in Genoa, Italy, were included. The following information was collected retrospectively at MMF initiation, at 3, 6 and 12 months after treatment start, and at last follow-up visit: clinical manifestations, laboratory data, physicians' subjective assessment of disease activity, standardized outcome measures of muscle strength/endurance, cutaneous disease activity, physical function, global disease activity, cumulative damage, and ongoing treatment. Of the 29 patients included, 23 had juvenile DM and 6 had overlap myositis. During administration of MMF, improvement in measures of muscle strength, skin disease activity, and overall disease activity was seen, with an increase in the frequency of normal scores for Manual Muscle Test-8 from 50.0% to 83.3%, Childhood Myositis Activity Score from 53.5% to 88.9%, muscle component of DAS from 55.2% to 84.2%, skin component of DAS from 31.0% to 42.1%, visual analogue scale for skin disease activity from 25.0% to 47.4%, and visual analogue scale for overall disease activity from 7.1% to 42.1%. The number of patients with inactive disease increased from 10.3% at baseline to 68.5% at last follow-up. CS dose was significantly reduced, from 0.3 to 0.1 mg/kg/day. No relevant side effects were reported. Our experience suggests that MMF is a valuable therapeutic option for the management of JIIM.

POS0839 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL TO EVALUATE EFFICACY AND SAFETY OF SC ABATACEPT IN ADULTS WITH ACTIVE IDIOPATHIC INFLAMMATORY MYOPATHY

BackgroundLimited therapies are available for patients with idiopathic inflammatory myopathy (IIM), a heterogenous group of chronic, systemic, autoimmune inflammatory diseases characterized by progressive muscle weakness and/or distinct skin rashes.1 Abatacept, a selective co-stimulation modulator, may be a useful treatment option.2ObjectivesTo evaluate efficacy, safety, and tolerability of abatacept + standard of care (SOC) in patients with IIM compared with SOC alone (placebo).MethodsA 24-week, randomized, double-blind, placebo-controlled phase 3 trial of SC abatacept (125 mg weekly) + SOC (corticosteroids and immunosuppressants alone or combined; NCT02971683) in patients with active, treatment-refractory IIM (Manual Muscle Testing-8 [MMT-8] ≤ 135) was performed. Primary endpoint was proportion of patients meeting International Myositis Assessment and Clinical Studies definition of improvement (IMACS DOI) at week 24. Change from baseline in myositis Functional Index-2 (FI-2), HAQ-DI, Myositis Disease Activity Assessment Tool (MDAAT), and Myositis Response Criteria (MRC) were secondary endpoints with safety. Post hoc analyses by disease subtype were performed.ResultsOverall, 148 patients were randomized (75 abatacept; 73 placebo); IIM subtypes were dermatomyositis (DM; 53.3% vs 57.5%), polymyositis (PM; 25.3% vs 34.2%), and autoimmune necrotizing myopathy (ANM; 21.3% vs 8.2%). Mean baseline MMT-8 and HAQ-DI scores were 112.7 and 1.5, respectively. Approximately 90% of patients completed week 24. Week 24 IMACS DOI rates were abatacept 56.0% vs placebo 42.5% (adjusted odds ratio, 1.8 [95% CI, 0.9–3.5]; P = 0.083). Pre-specified IMACS DOI analysis showed no differences for patients with DM but notable benefit for those with non-DM subtypes, PM and ANM (Table 1). Secondary endpoints showed similar differences (Table 1). MRC at day 169 by category is shown in Figure 1. Proportion of AEs (69.3% and 75.3%) and serious AEs (5.3% and 5.5%) were similar in the abatacept and placebo arms.Table 1.Primary and secondary (mean change from baseline at week 24) endpointsOutcomeIIMAbataceptPlaceboNominal P value (abatacept vs placebo) or adjusted mean difference from placebo (95% CI)IMACS DOI,a n/N (%)All42/75 (56.0)31/73 (42.5)P = 0.083DM22/40 (55.0)21/42 (50.0)P = 0.679Non-DM20/35 (57.1)10/31 (32.3)P = 0.040FI-2All4.1 (1.3)1.2 (1.4)2.9 (0 to 5.8)DM2.3 (1.6)0.3 (1.4)1.9 (−2.3 to 6.2)Non-DM3.2 (1.4)−0.6 (1.5)3.7 (−0.3 to 7.8)HAQ-DIAll−0.31 (0.07)0.20 (0.07)−0.12 (−0.28 to 0.04)DM−0.31 (0.08)−0.19 (0.07)−0.11 (−0.32 to 0.10)Non-DM−0.25 (0.09)−0.07 (0.09)−0.18 (−0.44 to 0.07)MDAAT, Extramuscular Global Activity, (95% CI)bAll−1.56 (−1.96 to −1.16)−1.40 (−1.81 to −0.99)−0.16 (−0.63 to 0.30)DM−1.90 (−2.43 to −1.37)−1.85 (−2.35 to 1.36)−0.05 (−0.77 to 0.68)Non-DM−1.09 (−1.46 to −0.72)−0.85 (−1.27 to −0.43)−0.24 (−0.80 to 0.32)MMT-8All12.9 (1.9)11.0 (2.0)1.8 (−2.7 to 6.4)DM14.4 (2.2)14.0 (2.2)0.4 (−5.7 to 6.4)Non-DM12.1 (2.5)7.8 (2.7)4.3 (−3.0 to 11.7)Physician Global AssessmentbAll−2.89 (0.30)−2.69 (0.30)−0.20 (−0.92 to 0.52)DM−2.78 (0.29)−2.43 (0.28)−0.35 (−1.15 to 0.46)Non-DM−2.35 (0.43)−2.21 (0.48)−0.14 (−1.43 to 1.15)Patient Global AssessmentbAll−1.4 (0.31)−0.98 (0.32)−0.38 (−1.11 to 0.35)DM−1.4 (0.33)−1.4 (0.31)−0.00 (−0.91 to 0.90)Non-DM−1.2 (0.41)−0.3 (0.44)−0.93 (−2.14 to 0.29)Data are adjusted mean change from baseline score (SE) unless stated.aDefined as improvement of ≥ 20% in 3 IMACS core measures, worsening by ≥ 25% in ≤ 2 IMACS core measure scores, and a reduction of &lt; 25% in MMT-8; b100 mm visual analog scale.ConclusionIn this double-blind trial of SC abatacept vs placebo, abatacept failed to meet primary or secondary endpoints. Post hoc analyses suggest a treatment benefit in patients with PM and ANM (not DM) when treated with abatacept. Abatacept use was well tolerated.

Cardiovascular Risk in Myositis Patients Compared to the General Population: Preliminary Data From a Single-Center Cross-Sectional Study.

BackgroundIdiopathic inflammatory myopathies (IIM) are associated with systemic inflammation, limited mobility, and glucocorticoid therapy, all of which can lead to metabolism disturbances, atherogenesis, and increased cardiovascular (CV) risk. The aim of this study was to assess the CV risk in IIM patients and healthy controls (HC), and its association with disease-specific features.MethodsThirty nine patients with IIM (32 females; mean age 56; mean disease duration 4.8 years; dermatomyositis: n = 16, polymyositis: n = 7, immune-mediated necrotizing myopathy: n = 8, anti-synthetase syndrome: n = 8) and 39 age-/sex-matched HC (32 females, mean age 56) without rheumatic diseases were included. In both groups, subjects with a history of CV disease (angina pectoris, myocardial infarction, cerebrovascular, and peripheral arterial vascular events) were excluded. Muscle involvement, disease activity, and tissue damage were evaluated (Manual Muscle Test-8, Myositis Intention to Treat Activity Index, Myositis Damage Index). Comorbidities and current treatment were recorded. All participants underwent examinations of carotid intima-media thickness (CIMT), pulse wave velocity (PWV), ankle-brachial index (ABI), and body composition (by densitometry and bioelectric impedance). The risk of fatal CV events was evaluated by the Systematic COronary Risk Evaluation (SCORE, charts for the European population) and its modifications.ResultsCompared to HC, there was no significant difference in IIM patients regarding blood pressure, ABI, PWV, CIMT, and the risk of fatal CV events by SCORE or SCORE2, or subclinical atherosclerosis (CIMT, carotid plaques, ABI, and PWV). The calculated CV risk scores by SCORE, SCORE2, and SCORE multiplied by the coefficient 1.5 (mSCORE) were reclassified according to the results of carotid plaque presence and CIMT; however, none of them was demonstrated to be significantly more accurate. Other significant predictors of CV risk in IIM patients included age, disease duration and activity, systemic inflammation, lipid profile, lean body mass, and blood pressure.ConclusionsNo significant differences in CV risk factors between our IIM patients and HC were observed. However, in IIM, CV risk was associated with age, disease duration, duration of glucocorticoid therapy, lipid profile, and body composition. None of the currently available scoring tools (SCORE, SCORE2, mSCORE) used in this study seems more accurate in estimating CV risk in IIM.

Performance of timed function tests as outcome measures in idiopathic inflammatory myopathy-results from a single-centre cohort.

To evaluate performance of timed function tests (TFTs) in assessing muscle strength and endurance as determined by Manual Muscle Testing 8 (MMT-8) and Functional Index 2 (FI-2), respectively, in idiopathic inflammatory myopathies (IIM). This cohort study included 42 IIM patients satisfying 2017 EULAR/ACR criteria. Patients were classified as active (n = 18) or inactive disease (n = 24) based on clinical status at baseline. MMT-8, FI-2, 30 s rise from chair test, 30 s 1 kg arm rise test and 2-min walking distance (2MWD) were administered at baseline, 3 months and 6 months. Pearson rank correlation analysis and receiver operating curves were performed to assess the performance of timed function tests. All patients were followed up at 3 months and 39 completed 6 months' follow-up. All the three TFTs had excellent convergent (r > 0.7, P < 0.05) and divergent validity (P < 0.05). Only 2MWD had moderate to strong correlation with ΔMMT-8 at 3 and 6 months among those with active disease (P = 0.001). All the TFTs correlated with ΔFI-2 in active disease but only Δ2MWD correlated with ΔFI-2 in inactive disease at 6 months (r = 0.506, P = 0.036). At a cut-off of 5% improvement in MMT-8, 2MWD had an area under the curve (AUC) of 0.868 with 95% sensitivity with 2% improvement at 3 months. To detect a 10% ΔMMT-8, Δ2MWD at a cut of 8% and 7% had an AUC of 0.909 and 0.893 with a sensitivity of 92% at 3 and 6 months, respectively (P < 0.05). 2MWD is a reliable indicator of muscle strength, endurance and treatment response. The 2MWD can be self-administered by patients, making it a potential patient-reported outcome measure.

6-month multidisciplinary follow-up and outcomes of patients with paediatric inflammatory multisystem syndrome (PIMS-TS) at a UK tertiary paediatric hospital: a retrospective cohort study

Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) is a new, rare, post-infectious complication of SARS-CoV-2 infection in children. We aimed to describe the 6-month outcomes of PIMS-TS. This retrospective cohort study comprised children (aged <18 years) who fulfilled the UK Royal College of Paediatrics and Child Health (RCPCH) diagnostic criteria for PIMS-TS and were admitted to Great Ormond Street Hospital (London, UK) between April 4 and Sept 1, 2020. Patients were followed up by a multidisciplinary team of specialists at 6 weeks and 6 months after admission. Biochemical and functional outcomes were analysed. 46 children were included in this study. The median age at presentation was 10·2 years (IQR 8·8-13·3), 30 (65%) patients were male and 16 (35%) were female, 37 (80%) were from minority ethnic groups, and eight (17%) had pre-existing comorbidities. All patients had elevated markers of systemic inflammation at baseline. None of the patients died. By 6 months, systemic inflammation was resolved in all but one patient. 38 (90%) of 42 patients who had positive SARS-CoV-2 IgG antibodies within 6 weeks of admission remained seropositive at 6 months. Echocardiograms were normal in 44 (96%) of 46 patients by 6 months, and gastrointestinal symptoms that were reported in 45 (98%) of 46 patients at onset were present in six (13%) of 46 patients at 6 months. Renal, haematological, and otolaryngological findings largely resolved by 6 months. Although minor abnormalities were identified on neurological examination in 24 (52%) of 46 patients at 6 weeks and in 18 (39%) of 46 at 6 months, we found minimal functional impairment at 6 months (median Expanded Disability Status Scale score 0 [IQR 0-1]). Median manual muscle test-8 scores improved from 53 (IQR 43-64) during hospital admission to 80 (IQR 68-80) at 6 months, but 18 (45%) of 40 patients showed 6-min walk test results below the third centile for their age or sex at 6 months. PedsQL responses revealed severe emotional difficulties at 6 months (seven [18%] of 38 by parental report and eight [22%] of 38 by self report). 45 (98%) of 46 patients were back in full-time education (virtually or face to face) by 6 months. Despite initial severe illness, few organ-specific sequelae were observed at 6 months. Ongoing concerns requiring physical re-conditioning and mental health support remained, and physiotherapy assessments revealed persisting poor exercise tolerance. Longer-term follow-up will help define the extended natural history of PIMS-TS. None.

Calcinosis in refractory dermatomyositis improves with tofacitinib monotherapy: a case series

Dear Editor, We report three patients with refractory DM and calcinosis who were part of an open-label clinical trial [Study of Tofacitinib in Refractory Dermatomyositis (STIR)] [1] who also had improvement in their calcinosis that coincided with improvement on muscle MRI after 3 months of treatment. Minimum Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) of >5 and/or Manual Muscle Testing-8 (MMT-8) <142 was required to enrol in the study. This study was approved by the Johns Hopkins Institutional Review Board and each patient gave written informed consent. Patient 1 is a 50-year-old female with a history of NXP-2 positive refractory DM for 14 years prior to enrolment in the STIR study. Her initial presentation was manifested by proximal muscle weakness and dysphagia and classic rash including Gottron’s papules and V-neck sign. She developed calcinosis of the left calf within 3 months of the onset of her DM, which progressed to include her thighs. While she had improvement in her muscle disease with immunosuppression, her continued skin disease activity prompted entry into the STIR study. There was an improvement in her skin disease with tofacitinib (see CDASI scores in Supplementary Table S1, available at Rheumatology online). Her muscle strength was full power at entry into the study. On imaging, there was elevated signal of the intramuscular and subcutaneous reticular areas on baseline bilateral thigh muscle MRI. After 3 months of treatment, the patient noticed an improvement in her calcinosis in the calf and thighs, which was also confirmed on muscle MRI (Fig. 1A–D).

A New Disease With Unknown Sequelae: Six-Month Multidisciplinary Follow-Up and Outcomes of Paediatric Inflammatory Multisystem Syndrome (PIMS-TS) Patients at a UK Tertiary Paediatric Centre

Background: Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS), a new, rare post-infectious complication of SARS-CoV-2, was first defined by the Royal College of Paediatrics and Child Health in April 2020. The natural history of PIMS-TS is unknown. Methods: Children (<18 years old) meeting diagnostic criteria for PIMS-TS were followed up by a multidisciplinary team of specialists at regular intervals over 6 months after their acute admission. Findings: 46 children were identified. Median age at presentation was 10·2 years (IQR 8·8-13·3), 65·2% were male and 80·4% from ethnic minority groups. Systemic inflammation resolved in all. 90·5% (38/42) whom had positive SARS-CoV-2 IgG within six weeks of admission remained seropositive at six months. Echocardiograms were normal in 96% at six months. Gastrointestinal symptoms, although present in 95·7% at onset were minimal in follow-up (6·5%). Objective renal, haematology, and otolaryngology findings largely resolved by six months. Whilst minor abnormalities on neurological exam were identified in 52·2% and 39·1% at six weeks and six months respectively, we found no functional impairment by Expanded Disability Status Scale (six-month median score 0, IQR 0-1). Physiotherapy assessment revealed persisting poor exercise tolerance. Despite improvement in median manual muscle test-8 scores from 53/80 (IQR 43-64) during hospitalisation to 80/80 (IQR 68-80), 45% demonstrated six-minute walk test results <3 rd centile for age/sex at six months. Parental (19%) and self-report (22%) revealed severe emotional difficulties at six months. 31·1% of parents reported anxiety about possible PIMS-TS relapse in their child with 20% taking additional isolation precautions and 22·2% were concerned about ongoing medical vulnerability. 97·8% patients were back in full-time education by six months. Interpretation: Despite initial severe illness, by six months few organ-specific sequelae were observed. Ongoing concerns requiring physical re-conditioning and mental health support remained. Longer-term follow-up will help define the extended natural history of PIMS-TS. Funding Statement: None to declare. Declaration of Interests: AB declares consultancy work for Gilead Inc. within the past three years of which the role did not impact on the writing of this manuscript. The remainder of authors have no declarations of interest to declare. Ethics Approval Statement: As the data analysis was retrospective and no additional data were collected beyond those required for standard medical care, a full ethics review under the terms of the Governance Arrangements of Research Ethics Committees in the UK was not required. A clinical audit was registered with GOSH NHS Foundation Trust Audit Committee (#2857).

Development and Testing of Reduced Versions of the Manual Muscle Test-8 in Juvenile Dermatomyositis

To develop and test shortened versions of the Manual Muscle Test-8 (MMT-8) in juvenile dermatomyositis (JDM). Construction of reduced tools was based on a retrospective analysis of individual scores of MMT-8 muscle groups in 3 multinational datasets. The 4 and 6 most frequently impaired muscle groups were included in MMT-4 and MMT-6, respectively. Metrologic properties of reduced tools were assessed by evaluating construct validity, internal consistency, discriminant ability, and responsiveness to change. Neck flexors, hip extensors, hip abductors, and shoulder abductors were included in MMT-4, whereas MMT-6 also included elbow flexors and hip flexors. Both shortened tools revealed strong correlations with MMT-8 and other muscle strength measures. Correlations with other JDM outcome measures were in line with predictions. Internal consistency was good (0.88-0.96) for both MMT-4 and MMT-6. Both reduced tools showed strong ability to discriminate between disease activity states, assessed by the caring physician or a parent (P < 0.001), and between patients whose parents were satisfied or not satisfied with illness course (P < 0.001). Responsiveness to change (assessed by both standardized response mean and relative efficiency) of MMT-4 and, to a lesser degree, MMT-6, was slightly superior to that of MMT-8. Overall, the metrologic performance of MMT-4 and MMT-6 was comparable to that of the other established muscle strength tools, which indicates that they may be suitable for use in clinical practice and research, including clinical trials. The measurement properties of these tools should be further tested in other patient populations and evaluated prospectively.

A phase 2, double-blinded, placebo-controlled trial of toll-like receptor 7/8/9 antagonist, IMO-8400, in dermatomyositis

To the Editor: Dermatomyositis (DM) is a rare inflammatory disease of muscle and skin. DM severity is thought to be driven, in part, by type I interferon signaling.1Huard C. Gullà S.V. Bennett D.V. Coyle A.J. Vleugels R.A. Greenberg S.A. Correlation of cutaneous disease activity with type 1 interferon gene signature and interferon β in dermatomyositis.Br J Dermatol. 2017; 176: 1224-1230Crossref PubMed Scopus (50) Google Scholar Because interferon is primarily induced by toll-like receptors (TLRs) 7/9, we hypothesized that antagonizing TLR7/9 could improve DM disease activity.2Baechler E.C. Bauer J.W. Slattery C.A. et al.An interferon signature in the peripheral blood of dermatomyositis patients is associated with disease activity.Mol Med. 2007; 13: 59-68Crossref PubMed Scopus (196) Google Scholar,3Walsh R.J. Kong S.W. Yao Y. et al.Type I interferon-inducible gene expression in blood is present and reflects disease activity in dermatomyositis and polymyositis.Arthritis Rheum. 2007; 56: 3784-3792Crossref PubMed Scopus (205) Google Scholar We conducted a phase 2, multicenter, double-blind, randomized, placebo-controlled trial of IMO-8400, an oligonucleotide antagonist of TLR7/8/9, in DM.4Suárez-Fariñas M. Arbeit R. Jiang W. Ortenzio F.S. Sullivan T. Krueger J.G. Suppression of molecular inflammatory pathways by Toll-like receptor 7, 8, and 9 antagonists in a model of IL-23-induced skin inflammation.PLoS One. 2013; 8: e84634Crossref PubMed Scopus (80) Google Scholar,5Jiang W. Zhu F. Tang J. Kandimalla E. La Monica N. Agrawal S. IMO-8400, a novel TLR7, TLR8 and TLR9 antagonist, inhibits disease development in mouse models of psoriasis (119.8).J Immunol. 2012; 188: 119.8Google Scholar Thirty patients with Cutaneous Dermatomyositis Disease Area and Severity Index version 2 (CDASIv2) scores of 15 or greater were enrolled between November 2015 and June 2018. Patients were allowed to remain on stable prednisone (≤20 mg/d) and up to 1 immunomodulatory therapy from a prespecified list (Table I and Supplemental Table 1, A and B; available via Mendeley at https://doi.org/10.17632/f9vx46p3fc.1).Table IBaseline characteristics of the intent-to-treat populationCharacteristicsPlaceboIMO-84000.60 mg/kg1.8 mg/kgn11910Age, y, mean (SD)51.3 (10.6)48.3 (14.2)54.6 (14.1)Sex, n (%) Female7 (63.6)7 (77.8)9 (90.0) Male421Race, n (%) White11 (100)8 (88.9)9 (90.0) Black or African American01 (11.1)1 (10.0)CDASI, n (%) 15-201 (9.1)02 (20.0) ≥2110 (90.9)9 (100)8 (80.0)CDASI activity score, mean (SD)30.2 (9.8)33.0 (8.4)33.5 (14.7)Treatment-concomitant drugs, n (%) Systemic corticosteroids∗Methylprednisolone, prednisolone, and prednisone. (%)8 (72.7)5 (55.6)5 (50.0) DMARDs†Azathioprine, leflunomide, methotrexate, mycophenolate mofetil, and mycophenolic acid. (%)5 (45.5)6 (66.7)6 (60.0) Immunoglobulins (%)1 (9.1)01 (10.0)CDASI, Cutaneous Dermatomyositis Disease Area and Severity Index; DMARD, disease-modifying antirheumatic drugs; SD, standard deviation.∗ Methylprednisolone, prednisolone, and prednisone.† Azathioprine, leflunomide, methotrexate, mycophenolate mofetil, and mycophenolic acid. Open table in a new tab CDASI, Cutaneous Dermatomyositis Disease Area and Severity Index; DMARD, disease-modifying antirheumatic drugs; SD, standard deviation. Participants were stratified into 2 groups by CDASIv2 activity score (15-20 vs ≥21) and randomized 1:1:1 to receive weekly subcutaneous injections of IMO-8400 0.6 mg/kg, IMO-8400 1.8 mg/kg, or placebo for 24 weeks. Because IMO-8400 is associated with injection site reactions, the primary outcome used a modified CDASIv2 activity score (CDASI-a) excluding the injection site. Secondary assessments included the Manual Muscle Test 8 (MMT8). Participants were predominantly white (93.3%) and female (76.7%), with a median age of 54.5 years (Table I). The mean baseline CDASI-a was 32.1 and was generally equal across treatment arms (30.2 for placebo, 33.0 for 0.6 mg/kg, and 33.5 for 1.8 mg/kg). The most common injection site reactions were erythema, pain, and induration (Supplemental Tables II and III; available via Mendeley at https://doi.org/10.17632/f9vx46p3fc.1). Out of 30 patients, 11 discontinued the study—5 (16.7%) because of adverse events, 4 (13.3%) for lack of efficacy, and 2 (6.7%) because of withdrawal by the participant. CDASI-a improved for all groups over 24 weeks (−9.3 for 0.6 mg/kg, −8.8 for 1.8 mg/kg, and −7.3 for placebo) (Fig 1). There was no significant difference between placebo and treatment groups; the repeated-measures mixed model analysis of CDASI-a across visits of the combined IMO-8400 group compared to that of placebo showed a least squares mean difference of −1.9 (P = .238). The average changes in MMT8 between the end of trial and baseline were as follows: +3.8 for placebo, +1.8 for 0.6 mg/kg, and +2.8 for 1.8 mg/kg. Across visits, in comparison to the placebo, the least squares mean difference of MMT8 in the 0.6 mg/kg group and 1.8 mg/kg group was +0.4 (P = .846) and +2.3 (P = .250), respectively. IMO-8400 did not show clinical efficacy over placebo in treating DM skin or muscle disease. IMO-8400 may not have achieved high enough doses for the pharmacologic blockade of TLR7/9, or there may be roles for pathways outside of TLR7/9 in DM. Limitations of the study include the small sample size and patient use of concomitant medications. The authors would like to thank Dr Kristin Lynn Sainani and the members of the Sarin Lab for their critical review and feedback of the manuscript.

AB0567 CHARACTERIZATION OF PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHY AND MYOCARDIAL INVOLVEMENT: A MONO-CENTRIC EXPERIENCE.

Background:Idiopathic inflammatory myopathies (IIM) are immune-mediated disorders of the skeletal muscle, with dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM) and immune-mediated necrotizing myopathy (IMNM) representing major subtypes. Beyond skeletal muscle, other organs may be affected and myocardial involvement may lead to severe life-threatening complications. The exact prevalence of myocardial involvement among IIM patients and its impact on other disease characteristics remain unclear.Objectives:To investigate the prevalence of myocarditis in patients affected by IIM in and to determine whether the presence and extent of myocardial involvement identify a distinct disease phenotype.Methods:42 longitudinally followed IIM patients were routinely screened for myocardial involvement during a median [IQR] follow-up time of 4.2 [2-8.5] years. Patients with secondary causes of myocardial dysfunction were not included. Patients were considered to have myocarditis in case of:i) abnormal elevation of both circulating troponin T and troponin I,ii) signs of myocardial inflammation or necrosis/fibrosis at cardiac MRI, oriii) positive myocardial tissue histology. Demographic, clinical and serologic features of patients with myocarditis were compared to those with no sign of myocardial involvement. Moreover, we determined whether the extent of myocardial involvement based on troponin levels predicts skeletal muscle disease severity.Results:57.1% (24 of 42) of patients had myocarditis. The frequency of myocardial dysfunction was similar among patients with DM, PM, IBM or IMNM and was not related to autoantibody positivity. Myocarditis was not associated with sex or ethnicity. Patients with or without myocarditis were similar in terms of age at disease onset and extra-muscular manifestations including dysphonia, dysphagia, arthralgias or arthritis, Raynaud phenomenon or interstitial lung disease. Independent of the IIM subtype, the presence of perimysial macrophages at skeletal muscle biopsy seems to protect from myocarditis development (p=0.04). Patients with myocarditis had higher median [IQR] levels of aldolase (10.9 [7.8-15.8] vs. 5.6 [4.9-8.6], p=0.014) and creatine kinase (1785 [966-5852] vs. 685 [168-2255], p=0.04) compared to patients with no myocardial dysfunction. Among patients with myocarditis, levels of troponin I negatively correlated with manual muscle testing 8 (MMT8) score (r=-1, p=0.01), strength in biceps (r=-0.95, p=0.014) and wrist extensors (r=-0.95, p=0.014) at last visit. Troponin T and troponin I titers were similar among patients with different IIM subtypes. C-reactive protein (p&lt;0.04) but not erythrocyte sedimentation rate was found to predict myocardial involvement.Conclusion:Our findings suggest that myocarditis is a frequent occurrence among patients with IIM and should be routinely ruled out. A more severe skeletal muscle disease is associated with an increased likelihood of myocarditis development, presumably due to higher systemic disease activity or inefficient disease control. The extent of myocardial damage faithfully reflects the severity of skeletal muscle dysfunction.

Quality of life correlates with muscle strength in patients with dermato- or polymyositis.

The aim of this study was to compare health-related quality of life (HQoL) in adults with dermatomyositis (DM) or polymyositis (PM) with a healthy control group and to assess whether muscle strength was associated with HQoL in patients with DM or PM. A cross-sectional study was performed and included 75 patients with DM or PM and 48 healthy controls. HQoL was assessed by the Short Form 36 questionnaire (SF-36). Muscle strength of the patients was assessed using the Manual Muscle Test-8 (MMT8). Covariables and possible confounding factors were collected by validated tools. Associations were determined in multiple linear regression models. The patients had significantly lower HQoL than the control group in both the physical component summary score (PCS) and the mental component summary score (MCS). Thus, the PCS-difference between groups was 32% (p<0.001), whereas the MCS-difference was 14% (p<0.001). Muscle strength was associated with one domain in the patients; Physical Function (β=1.2; 95% confidence interval 0.37 to 2.1). No statistically significant associations were found between muscle strength and HQoL in the remaining domains. Patients with DM or PM have reduced HQoL compared to healthy controls. Notably, muscle strength was associated with scores of the domain reflecting perceived physical function in patients. These findings corroborate the validity of including selected patient reported outcomes in the evaluation and monitoring of patients with DM or PM.