Background Facioscapulohumeral muscular dystrophy (FSHD) is a dominantly-inherited progressive muscular dystrophy caused by de-repression of the DUX4 gene, which causes disease by a toxic-gain-of-function. As molecularly targeted drugs move from preclinical testing into human trials, it is essential that we validate clinical trial tools and methodology to facilitate the drug development process. Methods/design The primary goal of this study is to hasten drug development for FSHD by validating two novel clinical outcome assessments (COAs) and refining clinical trial strategies. We will perform an 18-month longitudinal study in 220 genetically confirmed and clinically affected participants using our FSHD Clinical Trial Research Network, comprised of 8 sites in the United States, and 3 collaborating sites in Europe. Visits occur at baseline and months 3, 12, and 18. At each visit we will collect: 1) a novel FSHD functional composite COA made up of 18 evaluator-administered motor tasks in the domains of shoulder/arm, hand, core/abdominal, leg, and balance function; and 2) electrical impedance myography as a novel muscle quality biomarker (US sites). Other COAs include 1) Domain 1 of the Motor Function Measure; 2) Reachable workspace; 3) orofacial strength using the Iowa Oral Performance Instrument; 4) lean muscle mass using dual-energy X-ray absorptiometry (DEXA); 5) strength as measured by quantitative myometry and manual muscle testing; and 6) the FSHD Health Index and other patient-reported outcomes. Plasma, DNA, RNA, and serum will be collected for future biomarker studies. We will use an industry standard multi-site training plan. We will evaluate the test-retest reliability, validity, and sensitivity to disease progression, and minimal clinically important changes of our new COAs. We will assess associations between demographic and genetic factors and the rate of disease progression to inform refinement of eligibility criteria for future clinical trials. Discussion To the best of our knowledge, this is the largest collaborative study of patients with FSHD performed in the US and Europe. The results of this study will enable more efficient clinical trial design. During the conduct of the study, relevant data will be made available for investigators or companies pursuing novel FSHD therapeutics. Trial registration clinicaltrials.gov NCT03458832; Date of registration: 1/11/2018

Introduction/Aims In this study, we examined the social and health impacts of the coronavirus disease 2019 (COVID‐19) pandemic and social guidelines on people with muscular dystrophies. Methods A prospective de‐identified electronic survey was distributed to adults with self‐reported facioscapulohumeral muscular dystrophy (FSHD), myotonic dystrophy (DM), and limb‐girdle muscular dystrophy (LGMD) enrolled in national registries or with patient advocacy groups. The COVID‐19 Impact Survey was developed by muscular dystrophy experts in association with patient collaborators and advocacy groups. The Perceived Stress Scale was used to measure perceived stress. Results Respondents (n = 774: 56% FSHD; 35% DM, and 9% LGMD) were mostly women and middle‐aged (range 19–87 y). Rates of COVID‐19 infections were low (<1%), compliance with local social distancing guidelines and policies high (98%). Major challenges reported during the pandemic included: obtaining treatment (40%), managing stress (37%), social distancing (36%), and obtaining essentials (34%). The majority reported a slight worsening in their disease state. Respondents reported moderate stress levels (stress score = 15.4; range = 0–35), with higher stress levels reported by women and those under age 30 y. Three‐quarters of participants who participated in telemedicine visits were satisfied with the encounters; however, most reported a preference for in‐person visits. Discussion People with muscular dystrophy reported moderate stress and challenges during the COVID‐19 pandemic. Interventions such as exercise and stress‐coping strategies, including strategies specific to women or individuals <30 y, may be important. Further investigation is needed into the role of telemedicine in the care of individuals with muscular dystrophy.

Introduction: In this study, we examined the long-term social and health impacts of the coronavirus disease 2019 (COVID-19) pandemic on people with muscular dystrophy. Methods: We modified our prior COVID-19 Impact Survey to assess impacts from the continuing pandemic using feedback from muscular dystrophy experts, patients, and advocacy group/registry representatives. The survey assessed COVID-19 medical history, and the effects of the pandemic on social aspects, muscle disease, and medical care. We also used the validated 10-item Perceived Stress Scale. The de-identified, electronic survey was distributed to adults with muscular dystrophy via international patient registries and advocacy group websites from February 8, 2021 to March 22, 2021. Results: Respondents (n = 1243 : 49% Facioscapulohumeral Muscular Dystrophy (FSHD); 43% Myotonic Dystrophy (DM), and 8% Limb-Girdle Muscular Dystrophy (LGMD)) were mostly women and middle-aged (range 18–90 years). Rates of COVID-19 infections were low at 8% with zero deaths. Reported recovery times were also short with only 9% reporting a recovery period greater than eight weeks, and 7% requiring hospitalization with one individual requiring a ventilator. Major challenges reported during the pandemic included: stress management, particularly for those with LGMD, (27%) and wearing a mask (24%). The majority reported a slight worsening in their disease state. Respondents reported moderate stress levels (stress score = 16.4; range = 0–39), with higher stress levels reported by women and those under age 30 years. Seventy-percent of participants who had telemedicine visits were satisfied with the encounters; however, most reported a preference for in-person visits. Conclusions: People with MD found ways to manage their stress and overcome obstacles during the COVID-19 pandemic. COVID-19 infection rates and medical complications were similar to a general population. Telemedicine visits may have a more permanent role in care.

Background and purpose Data on maintenance therapy with subcutaneous immunoglobulin (SCIg) in myasthenia gravis (MG) are limited. We report on transitioning acetylcholine receptor (AChR) antibody‐positive (Ab+) MG patients on stable intravenous immunoglobulin (IVIg) regimens as part of routine clinical care to SCIg 1:1.2. Methods This multicenter North American open‐label prospective investigator‐initiated study had two components: the IVIg Stabilization Period (ISP) enrolling patients already on IVIg as part of routine clinical care (Weeks −10 to −1), followed by transition of stable MG subjects to SCIg in the Experimental Treatment Period (ETP; Weeks 0 to 12). We hypothesized that >65% of patients entering the ETP would have a stable Quantitative Myasthenia Gravis (QMG) score from Week 0 to Week 12. Secondary outcome measures included other efficacy measures, safety, tolerability, IgG levels, and treatment satisfaction. Results We recruited 23 patients in the ISP, and 22 entered the ETP. A total of 12 subjects (54.5%) were female, and 18 (81.8%) were White, with mean age 51.4 ± 17 years. We obtained Week 12 ETP QMG data on 19 of 22; one subject withdrew from ETP owing to clinical deterioration, and two subjects withdrew due to dislike of needles. On primary analysis, 19 of 22 participants (86.4%, 95% confidence interval = 0.72–1.00) were treatment successes using last observation carried forward (p = 0.018). Secondary efficacy measures supported MG stability. SCIg was safe and well tolerated, and IgG levels were stable. Treatment satisfaction was comparable between ISP and ETP. Conclusions MG patients on IVIg as part of their routine clinical care remained stable on monthly IVIg dosage, and most maintained similar disease stability on SCIg.

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