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ObjectiveTo better characterize adult myotubularin 1 (MTM1)-related myopathy carriers and recommend a phenotypic classification.MethodsThis cohort study was performed at the NIH Clinical Center. Participants were required to carry a confirmed MTM1 mutation and were recruited via the Congenital Muscle Disease International Registry (n = 8), a traveling local clinic of the Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, NIH and Cure CMD (n = 1), and direct physician referral (n = 1). Neuromuscular examinations, muscle MRI, dynamic breathing MRI, cardiac MRI, pulmonary function tests (PFTs), physical therapy assessments including the Motor Function Measure 32 (MFM-32) scale, and X chromosome inactivation (XCI) studies were performed.ResultsPhenotypic categories were proposed based on ambulatory status and muscle weakness. Carriers were categorized as severe (nonambulatory; n = 1), moderate (minimal independent ambulation/assisted ambulation; n = 3), mild (independent ambulation but with evidence of muscle weakness; n = 4), and nonmanifesting (no evidence of muscle weakness; n = 2). Carriers with more severe muscle weakness exhibited greater degrees of respiratory insufficiency and abnormal signal on muscle imaging. Skeletal asymmetries were evident in both manifesting and nonmanifesting carriers. Skewed XCI did not explain phenotypic severity.ConclusionThis work illustrates the phenotypic range of MTM1-related myopathy carriers in adulthood and recommends a phenotypic classification. This classification, defined by ambulatory status and muscle weakness, is supported by muscle MRI, PFT, and MFM-32 scale composite score findings, which may serve as markers of disease progression and outcome measures in future gene therapy or other clinical trials.

Introduction/Aims: Up to 25% of patients with myasthenia gravis (MG) have refractory disease despite trials of multiple immunosuppressants. Several case series describe acetylcholine receptor antibody‐positive (AChR) MG patients treated with autologous hematopoietic stem cell transplant (HSCT). In this report, we describe three patients with anti‐muscle‐specific kinase (MuSK) MG treated with HSCT. Methods: We included all patients who had undergone HSCT with anti‐MuSK myasthenia gravis identified through the records of the Alberta Blood and Marrow Transplant Program. We collected demographic and clinical data including validated MG scales as well as questionnaire data. Results: All 3 patients had severe disease (Myasthenia Gravis Foundation of America score IVb‐V) and were refractory to multiple treatments, including rituximab. All patients improved with no clinical manifestations or mild symptoms and remained as such for 2, 3.5, and 5.5 y. Adverse events ranged from treatable infections and transient dyspnea to persistent fatigue and premature menopause. The average worst Myasthenia Gravis Activities of Daily Living (MG‐ADL) scores improved from 14.7 before to 0.3 after HSCT. The mean worst Myasthenia Gravis Quality of Life Questionnaire (MG‐QoL15) scores improved from 26.7 to 0. All patients reported they would undergo transplant again for their MG. Discussion: We describe three patients with anti‐MuSK MG treated with HSCT, all of whom became symptom free from MG with a tolerable side effect profile. In patients with severe refractory anti‐MuSK MG, it may be reasonable to consider HSCT. [ABSTRACT FROM AUTHOR]

Objective: To describe the real‐world treatment persistence (defined as the continuation of medication for the prescribed treatment duration), demographics and clinical characteristics, and treatment patterns for patients prescribed erenumab for migraine prevention in Canada. Background: The effectiveness of prophylactic migraine treatments is often undermined by poor treatment persistence. In clinical trials, erenumab has demonstrated efficacy and tolerability as a preventive treatment, but less is known about the longer term treatment persistence with erenumab. Methods: This is a real‐world retrospective cohort study where a descriptive analysis of secondary patient data was conducted. Enrollment and prescription data were extracted from a patient support program for a cohort of patients prescribed erenumab in Canada between September 2018 and December 2019 and analyzed for persistence, baseline demographics, clinical characteristics, and treatment patterns. Descriptive analyses and unadjusted Kaplan–Meier (KM) curves were used to summarize the persistence and dose escalation/de‐escalation at different timepoints. Results: Data were analyzed for 14,282 patients. Median patient age was 47 years, 11,852 (83.0%) of patients were female, and 9443 (66.1%) had chronic migraine at treatment initiation. Based on KM methods, 71.0% of patients overall were persistent to erenumab 360 days after treatment initiation. Within 360 days of treatment initiation, it is estimated that 59.3% (KM‐derived) of patients who initiated erenumab at 70 mg escalated to 140 mg, and 4.4% (KM‐derived) of patients who initiated at 140 mg de‐escalated to 70 mg. Conclusions: The majority of patients prescribed erenumab remained persistent for at least a year after treatment initiation, and most patients initiated or escalated to a 140 mg dose. These results suggest that erenumab is well tolerated, and its uptake as a new class of prophylactic treatment for migraine in real‐world clinical practice is not likely to be undermined by poor persistence when coverage for erenumab is easily available. [ABSTRACT FROM AUTHOR]