Endocrine Abstracts

Background: Recently introduced disease modifying treatments have dramatically changed the clinical course of SMA and improved survival. As a consequence, children are experiencing more complications secondary both to the disease and the new treatments. All infants and children who receive the gene therapy onasemnogene abeparvovec (OA) require a minimum of 28 days of high dose steroids to counteract common side effects, putting them at risk of steroid-induced adrenal insufficiency (SIAI) and adrenal crisis. This study aims to describe adrenal complications in the UK paediatric SMA population treated with OA and high dose steroids.

Methods: A retrospective case notes review was conducted on all paediatric patients living with SMA who received OA managed at our tertiary centre. Data on steroid duration and doses, adrenal function testing and the frequency of SIAI were collected. The risk factors for SIAI in this population were explored.

Results: Eleven children received OA and adjuvant prednisolone, 10 of whom had SMA type 1 and one was presymptomatic. Mean age at infusion was 2.6 years (range 0.5-7.3). All children were started on 1 mg/kg of prednisolone for a minimum of one month as per the OA treatment protocol and six patients (54%) required an increase to 2 mg/kg due to infusion related side effects. One child required three doses of methylprednisolone. The average duration of supra-physiological steroids was 126 days (range 52-210). The mean duration of steroid weaning was 80 days (range 19-182). Four patients (36%) developed SIAI, among whom the maximum time to full adrenal recovery was 29 months (range 6-29). There was no difference in weight and age at infusion or duration of supra-physiological steroids between children with and without SIAI.

Conclusion: A significant proportion of our cohort developed SIAI. No potential risk factors for SIAI were identified, however the sample size was small. There was wide variation in steroid weaning duration. Currently there are no specific steroid weaning guidelines for this population. We are conducting a large multi-centre UK study (SMA-ABC) to further examine adrenal complications in SMA and inform future guideline development.