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Objectives: This retrospective study explored the qualitative and quantitative assessment of F18-fluordeoxyglucose ([18F]-FDG) positron emission tomography and computed tomography (PET/CT) scans to assess pathophysiological muscle glucose uptake in patients with a rheumatic musculoskeletal disease (RMD). [18F]-FDG PET/CT detects metabolic activity via glucose uptake in tissues. This study aimed to determine the feasibility of quantitative assessment of [18F]-FDG uptake in muscles across three different RMDs compared to controls. Methods: In this study we analysed whole-body [18F]-FDG PET/CT scans from patients with rheumatoid arthritis (RA; n = 11), osteoarthritis (OA; n = 10), and idiopathic inflammatory myositis (IIM; n = 10), and non-RMD controls (n = 11), focusing on muscle-tracer uptake in specific muscle groups. Qualitative assessment visually identified regions with high [18F]-FDG uptake, followed by quantitative assessment using two methods: fixed volume-of-interest (VOI) and hotspot VOI. In the fixed VOI method, a VOI was placed in the respective muscle at a fixed position (50% height from proximal to distal end) on PET/CT images. In the hotspot VOI method, the VOI was placed at the site of the highest [18F]-FDG uptake observed during qualitative assessment. Standardised uptake values (SUVs) were determined for different muscle groups between RMDs and controls. Results: Qualitative assessment revealed a heterogenous uptake pattern of [18F]-FDG that was found in 93% of quadriceps and hamstring muscles, while other muscles displayed either heterogenous or homogenous patterns. A Bland–Altman analysis showed that the hotspot VOI method had a higher sensitivity in detecting differential [18F]-FDG uptake in muscles. Across all muscle groups, patients with IIM had the highest [18F]-FDG uptake, followed by patients with OA and RA, respectively. Conclusions: [18F]-FDG PET/CT enables qualitative and quantitative differentiation of muscle glucose uptake in patients with RA, OA, and IIM, at both individual muscle and patient group levels. The hotspot method and SUVpeak are recommended for quantitative assessment. High [18F]-FDG uptake in multiple muscle groups suggests pathophysiological glucose metabolism in RMD-affected muscles. [ABSTRACT FROM AUTHOR]

Background and purpose: There are concerns for safety regarding SARS‐CoV‐2 vaccines for patients with autoimmune neuromuscular disease. We compared daily functioning using disease‐specific patient‐reported outcome measures (PROMs) before and after SARS‐CoV‐2 vaccinations. Methods: In this substudy of a prospective observational cohort study (Target‐to‐B!), patients with myasthenia gravis (MG), chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN), and idiopathic inflammatory myopathy (IIM) vaccinated against SARS‐CoV‐2 were included. Surveys of daily functioning (Myasthenia Gravis Activities of Daily Living, Inflammatory Rasch‐Built Overall Disability Scale, Multifocal Motor Neuropathy Rasch‐Built Overall Disability Scale, and Health Assessment Questionnaire–Disability Index) were sent before first vaccination and every 60 days thereafter for up to 12 months. Regression models were constructed to assess differences in PROM scores related to vaccination, compared to scores unrelated to vaccination. We also assessed the proportion of patients with deterioration of at least the minimal clinically important difference (MCID) between before first vaccination and 60 days thereafter. Results: We included 325 patients (median age = 59 years, interquartile range = 47–67, 156 [48%] female sex), of whom 137 (42%) had MG, 79 (24%) had CIDP, 43 (13%) had MMN, and 66 (20%) had IIM. PROM scores related to vaccination did not differ from scores unrelated to vaccination. In paired PROMs, MCID for deterioration was observed in three of 49 (6%) MG patients, of whom none reported a treatment change. In CIDP, MCID for deterioration was observed in eight of 29 patients (28%), of whom two of eight (25%) reported a treatment change. Conclusions: SARS‐CoV‐2 vaccination had no effect on daily functioning in patients with autoimmune neuromuscular diseases, confirming its safety in these patients. [ABSTRACT FROM AUTHOR]

Objective To unravel B-cell receptor (BcR) characteristics in muscle tissues and peripheral blood and gain more insight into BcR repertoire changes in peripheral blood in idiopathic inflammatory myopathies (IIMs), and study how this correlates to the clinical response to IVIG. Methods Nineteen treatment-naive patients with newly diagnosed IIM were prospectively treated with IVIG monotherapy. RNA-based BcR repertoire sequencing was performed in muscle biopsies collected before, and in peripheral blood (PB) collected before and nine weeks after IVIG treatment. Results were correlated to patients' clinical improvement based on the total improvement score (TIS). Results Prior to IVIG treatment, BcR clones found in muscle tissue could be retrieved in peripheral blood. Nine weeks after IVIG treatment, new patient-specific dominant BcR clones appeared in peripheral blood while pre-treatment dominant BcR clones disappeared. The cumulative frequency of all dominant BcR clones before treatment was significantly higher in individuals who responded to IVIG compared with those who did not respond to IVIG, and correlated with a higher CK. During follow-up, a decrease in the cumulative frequency of all dominant clones correlated with a higher TIS. Conclusion In treatment-naive patients with newly diagnosed IIM, muscle tissue and peripheral blood share expanded BcR clones. In our study a higher cumulative frequency of dominant BcR clones in blood before treatment was associated with a higher CK and better treatment response, suggesting that response to IVIG may depend on the composition of the pre-treatment BcR repertoire. [ABSTRACT FROM AUTHOR]

Objectives To prospectively compare ultrasound (US) and whole-body MRI for detection of muscle abnormalities compatible with idiopathic inflammatory myopathies (IIM). Methods Newly diagnosed IIM patients underwent US (14 muscles) and MRI (36 muscles) at diagnosis and after nine weeks monotherapy with intravenous immunoglobulin. Muscles were compatible with IIM when quantitative US echo-intensity (EI) z scores was ≥1.5, semi-quantitative US Heckmatt score was ≥2, qualitative US was abnormal, or when MRI showed oedema on T2-weighted images. At patient level, findings were classified as abnormal when quantitative US EI z scores was >1.5 (n  = 3 muscles), >2.5 (n  = 2 muscles) or >3.5 (n  = 1 muscle), or if ≥3 muscles showed abnormalities as described above for the other diagnostic methods. Results At diagnosis, in 18 patients US of 252 muscles revealed abnormalities in 36 muscles (14%) with quantitative, in 153 (61%) with semi-quantitative and in 168 (67%) with qualitative analysis. MRI showed oedema in 476 out of 623 muscles (76%). Five patients (28%) reached abnormal classification with quantitative US, 16 (89%) with semi-quantitative and qualitative US, and all patients (100%) with MRI. Nine-week follow-up of 12 patients showed no change over time with quantitative US or MRI, and a decrease in abnormalities with semi-quantitative US (P  <0.01), and qualitative US (P  <0.01). Conclusion At diagnosis, MRI was more sensitive than US to detect muscle abnormalities compatible with IIM. Semi-quantitative US and qualitative US detected abnormalities in the majority of the patients while evaluating fewer muscles than MRI and showed change over time after nine weeks of treatment. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the clinimetric properties of the Academic Medical Centre Disability Score (ALDS) in patients with idiopathic inflammatory myopathy (IIM). Methods We used prospectively collected data of IIM patients who completed a phase-2 study with first-line IVIG monotherapy. The ALDS is a patient-reported questionnaire which contains 25 items relevant for disability in myositis. ALDS and all core set measures (CSMs) for myositis [including HAQ-Disability Index (HAQ-DI)] were evaluated at baseline and 9 weeks follow-up. In addition, the 2016 ACR/EULAR myositis response criteria outcome called Total Improvement Score (TIS) was evaluated at 9 weeks. We examined floor/ceiling effects, reliability and construct validity of the ALDS. To examine known-group validity, ALDS change scores over time were compared with TIS and physician impression of clinical response. Results Nineteen patients with IIM [median age 59 years, 12 (63%) female] were enrolled. At baseline, ALDS showed a median score of 65.4 (IQR 58.2–73.5), good Cronbach's alpha (α = 0.84) and a small ceiling effect (11%). Construct validity was confirmed by moderate to strong correlations between ALDS and HAQ-DI [rs = −0.57 (baseline); −0.86 (follow-up)]. ALDS change score correlated with TIS (rs = 0.70), discriminated between responders and non-responders (TIS ≥ 40; P  = 0.001), between groups based on physician impression of clinical response (P  = 0.03), and detected deterioration. Conclusion The ALDS showed promising clinimetric properties and detected relevant changes in disability in patients with myositis. These results warrant further investigations. [ABSTRACT FROM AUTHOR]

Introduction: Research into novel therapies for rare, immune-mediated inflammatory diseases (IMIDs) faces significant challenges, including small patient populations, complex clinical trial design and difficulties in patient recruitment. Patients with Behçet's disease (BD), idiopathic inflammatory myopathies (IIM) and IgG4-related disease (IgG4-RD) typically undergo treatment involving prolonged administration of high-dose glucocorticoids and immunosuppressants. Both are associated with an increased risk of infection. Additionally, glucocorticoids carry long-term toxicity risks. Thus, there is an urgent need to develop more targeted and effective anti-inflammatory treatments. Given the activation of the type 1 interferon pathway in BD, IIM and IgG4-RD, inhibition of the Janus kinase (JAK) STAT pathway emerges as a promising therapeutic strategy. The Drug Rediscovery in IMIDs (DRIMID) consortium aims to conduct a prospective pilot basket trial to investigate the effects of filgotinib, a JAK1 preferential inhibitor approved for ulcerative colitis and rheumatoid arthritis, on disease activity, quality of life and safety in patients with refractory BD, IIM and IgG4-RD., Methods and Analysis: In this investigator-initiated, multicentre, open-label phase 2 study, up to 60 patients with rare IMIDs will be enrolled for a 26-week treatment period with filgotinib 200 mg once daily. The trial consists of two stages, each involving a consecutively treated cohort of up to 20 patients per disease. An interim analysis is conducted between these stages, where the trial will proceed only in diseases showing potential effectiveness. Baseline, 3-month and 6-month assessments will include data on quality of life, disease activity, corticosteroid toxicity and biomarkers. The coprimary endpoints are disease activity and quality of life across and within each disease., Ethics and Dissemination: The study received approval from the Medical Research Ethics Committee in Utrecht, Netherlands. A Data Safety Monitoring Board has been established to monitor the trial's safety and progress., Trial Registration Number: NCT06285539., Competing Interests: Competing interests: NHR and EP are employees of Alfasigma S.p.A. and were formerly employed by Galápagos NV. JMvL has received consultancy honoraria from Galápagos NV. RJG has received a speaker fee, and the pharmacy of his institution has received an institutional grant from Galápagos NV. BCG-H, JAMvL, JR, SWT, PMJW, CMC and RMT declare no competing interests., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Objectives: Novel biomarkers are needed to guide therapy in idiopathic inflammatory myopathies (IIM). Expression of Siglec-1, a type I interferon biomarker, was examined in adult patients with IIM in relation to disease activity and treatment response., Methods: We analysed PBMC samples from 19 newly diagnosed adult IIM patients who participated in a phase-2 pilot study on efficacy of intravenous immunoglobulin (IVIG) monotherapy, and from 9 healthy controls. Siglec-1 expression on monocytes was measured by flow cytometry before and after treatment, and was evaluated in relation to IIM subtype, physician global activity (PhGA) scores, manual muscle strength (MMT) and the Total Improvement Score (TIS)., Results: Diagnoses included dermatomyositis (DM; n = 9), immune-mediated necrotizing myopathy (IMNM; n = 5), non-specific/overlap myositis (NSM/OM; n = 4), and antisynthetase syndrome (ASyS; n = 1). All patients showed increased Siglec-1 expression at baseline. Relative median fluorescence intensity of Siglec-1 was highest in patients with DM. After 9 weeks, follow-up samples were available for 15 patients of whom 10 patients showed a decline in Siglec-1 expression. In DM, Siglec-1 correlated with disease activity (MMT; rs = -0.603, p= 0.013 and PhGA; rs = 0.783, p< 0.001) and with the TIS (rs = -0.786, p= 0.036)., Conclusion: Siglec-1 was increased in treatment-naive IIM patients and showed a decline after IVIG monotherapy. In DM, Siglec-1 expression correlated with relevant clinical measures. This underlines the dynamic role of type I IFN in IIM and the biomarker potential of Siglec-1, in particular in DM. These findings should be further validated in larger cohorts with longer follow-up., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Introduction: For idiopathic inflammatory myopathies (IIM) ('myositis') standard initial treatment is high-dosed glucocorticoids, which results in relatively slow improvement of muscle strength. Early immunosuppression or modulation by intensive treatment ('hit-early, hit-hard') may induce faster reduction of disease activity and prevent chronic disability due to disease-induced structural muscle damage. Intravenous immunoglobulin (IVIg) in addition to standard glucocorticoid treatment may be promising in this regard as was shown in various studies: add-on IVIg improved symptoms and muscle strength in refractory myositis patients and monotherapy IVIg improved outcomes after 9 weeks, in about half of treatment-naive patients., Hypothesis: We hypothesise that early add-on IVIg leads to a greater clinical response after 12 weeks in patients with newly diagnosed myositis, in comparison to prednisone monotherapy. Second, we expect that early treatment with add-on IVIg leads to a faster time to improvement and sustained positive effects on multiple secondary outcomes., Methods: The Time Is Muscle trial is a phase-2 double-blind placebo-controlled randomised trial. Forty-eight patients with IIM will be treated with IVIg or placebo at baseline (within 1 week after diagnosis) and after 4 and 8 weeks, in addition to standard therapy with prednisone. The primary outcome is the Total Improvement Score (TIS) of the myositis response criteria at 12 weeks. At baseline, and after 4, 8, 12, 26 and 52 weeks, relevant secondary outcomes will be assessed, including time to moderate improvement (TIS≥40), mean daily prednisone dosage, physical activity, health-related quality of life, fatigue and MRI muscle imaging parameters., Ethics and Dissemination: Ethical approval was obtained from the medical ethics committee of the Academic Medical Centre, University of Amsterdam, the Netherlands (2020&#95;180; including a first amendment approval at the 12 April 2023; A2020&#95;180&#95;0001). The results will be distributed through conference presentations and peer-reviewed publications., Trial Registration Number: EU Clinical trials register (2020-001710-37)., Competing Interests: Competing interests: RGK, JAB, SWE, HAWW, CdB, JCACdK, CV and MM report no competing interests. MdV is a member of the Data Monitoring Committee of Novartis Pharma AG and chair of the Independent Data Monitoring Committee of Dynacure. FE reports grants from ZonMw (Dutch Governmental Agency) and Prinses Beatrix Spierfonds. He also reports grants from CSL Behring, Kedrion, Terumo BCT and Takeda Pharmaceutical Company. INvS chaired a steering committee for a CSL-Behring study investigating the safety and efficacy of SCIg in CIDP and received departmental honoraria for serving on scientific advisory boards for CSL-Behring and Kedrion. He received departmental research support from The Netherlands Organisation for Scientific Research, and from the Dutch Prinses Beatrix Spierfonds. All lecturing and consulting fees for I.S were donated to the Stichting Klinische Neurologie, a local foundation that supports research in the field of neurological disorders. He served on the editorial board of the Cochrane Neuromuscular Disease Group, was a member of the organising committee of the Inflammatory Neuropathy Consortium (INC), a standing committee of the Peripheral Nerve Society and was a member of the Scientific Board of the Kreuth III meeting on the optimal use of plasma-derived medicinal products, especially coagulation factors and normal immunoglobulins organised under the auspices of the European Directorate for the Quality of Medicines & HealthCare (EDQM). AJvdK received departmental honoraria for serving on a scientific advisory board for ArgenX. JR received departmental research support from the Dutch Prinses Beatrix Spierfonds, Dutch ALS foundation, Sanquin Plasma Products and Top Sector Life Science and Health., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)