Health Care Use of Cardiac Specialty Care in Children With Muscular Dystrophy in the United States.

Background Duchenne and Becker muscular dystrophy are progressive disorders associated with cardiac mortality. Guidelines recommend routine surveillance; we assess cardiac resource use and identify gaps in care delivery. Methods and Results Male patients, aged 1 to 18 years, with Duchenne and Becker muscular dystrophy between January 2013 and December 2017 were identified in the IBM MarketScan Research Database. The cohort was divided into <10 and 10 to 18 years of age. The primary outcome was rate of annual health care resource per person year. Resource use was assessed for place of service, cardiac testing, and medications. Adjusted incidence rate ratios (IRRs) were estimated using a Poisson regression model. Medication use was measured by proportion of days covered. There were 1386 patients with a median follow-up time of 3.0 years (interquartile range, 1.9-4.7 years). Patients in the 10 to 18 years group had only 0.40 (95% CI, 0.35-0.45) cardiology visits per person year and 0.66 (95% CI, 0.62-0.70) echocardiography/magnetic resonance imaging per person year. Older patients had higher rates of inpatient admissions (IRR, 1.46; 95% CI, 1.03-2.09), outpatient cardiology visits (IRR, 2.0; 95% CI, 1.66-2.40), cardiac imaging (IRR, 1.59; 95% CI, 1.40-1.80), and Holter monitoring (IRR, 3.33; 95% CI, 2.35-4.73). A proportion of days covered >80% for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was observed in 13.6% (419/3083) of total person years among patients in the 10 to 18 years group. Conclusions Children 10 to 18 years of age have higher rates of cardiac resource use compared with those <10 years of age. However, rates in both age groups fall short of guidelines. Opportunities exist to identify barriers to resource use and optimize cardiac care for patients with Duchenne and Becker muscular dystrophy.

Clinical Experience With Gene Therapy in Older Patients With Spinal Muscular Atrophy.

BACKGROUND: Onasemnogene abeparvovec was recently approved for the treatment of spinal muscular atrophy (SMA) in children younger than two years; however, clinical trials were primarily completed in children younger than seven months, so practical experience dosing older children began in summer 2019. Here, we look at the safety and efficacy of onasemnogene in seven infants older than seven months who were treated at our center. METHODS: Seven patients were included. RESULTS: Acute viral symptoms with emesis and/or fever were seen in six of seven patients two to three days after the infusion. Thrombocytopenia occurred in four of seven patients, and six of seven patients had prolonged steroid courses due to persistently elevated liver enzymes, one of whom required escalation to intravenous steroids. All patients demonstrated motor improvements, which were apparent by three months, although with continued progress in those patients followed for longer periods of time. CONCLUSIONS: Overall, onasemnogene appears to be efficacious in children older than seven months and well tolerated. Side effects were similar to those previously reported, although more common and in some cases more severe and more prolonged than seen in the original trials. The impact of age, weight, and other confounding factors on development of side effects still needs to be elucidated.

Diagnostic Testing for Patients with Spinal Muscular Atrophy.

Diagnostic genetic testing for spinal muscular atrophy is key in establishing early diagnosis for affected individuals. Prenatal carrier testing of parents with subsequent testing of the fetus for homozygous SMN1 gene deletion in those at risk of this autosomal recessive disorder as well as newborn screening can identify the vast majority of affected individuals before the onset of symptoms. Patients presenting symptomatically must be genetically confirmed as soon as possible because targeted treatments are now available that profoundly impact symptoms and improve quality of life.

Clinical Course in a Patient With Spinal Muscular Atrophy Type 0 Treated With Nusinersen and Onasemnogene Abeparvovec.

Spinal muscular atrophy type 0 is the most severe phenotype of the disease, with patients presenting with contractures, weakness, and respiratory failure at birth, and is typically fatal within weeks. We describe the case of a patient with spinal muscular atrophy type 0 who was treated with both nusinersen and onasemnogene abeparvovec. She has made modest motor improvements since treatment initiation with a 30-point improvement in CHOP-INTEND score, and continues to make motor gains at age 13 months without regression of function, although she remains profoundly weak. Although she has had motor improvements, she has also had continued systemic complications from her spinal muscular atrophy, including chronic respiratory failure, dysphagia, congenital heart malformation, digit necrosis, and diffuse macular rash. This case highlights the challenges in treating those with more severe disease phenotypes and raises questions of how some systemic complications may respond to current SMN replacement therapies.