Home Support Outweighs Nusinersen Delays in Patients With SMA During COVID-19 Lockdown

A small, single-center study determined that adequate support at home affected outcomes in motor ability more so than the first COVID-19 lockdown in Italy.

The COVID-19 pandemic caused delays in medical care worldwide, including for some patients with spinal muscular atrophy (SMA) receiving intrathecal nusinersen infusions. An explorative single-center study published in Frontiers in Neurology examined the clinical and social effects of delayed infusions during the pandemic at the Pediatric Palliative Care Center of Padua in Veneto, Italy.

SMA is an inherited neuromuscular disorder caused by mutation or deletion of the SMN1 gene. The resulting lack of survival motor neuron production is leads to progressive muscle atrophy and weakness. Nusinersen is an oligonucleotide-based therapy that was approved for the treatment of SMA in 2017. It is administered intrathecally, and early treatment initiation is crucial given that patients with SMA typically become symptomatic in infancy.

At the time of the first COVID-19 lockdown, which caused nusinersen discontinuation for those on maintenance doses as of February 2, 2020, at the Pediatric Palliative Care Center of Padua, a total of 31 children on nusinersen therapy were identified. Of these patients, 5 decided not to resume therapy post lockdown and 1 was excluded due to a language barrier, so a total of 25 were included in the study.

Throughout the lockdown, the center offered support via telephone 24/7 and conducted nursing phone interventions once or twice per month. Physiotherapy was done via video call with positive results, and home visits were reserved for cases of necessity.

To gauge whether any issues arose from nusinersen treatment delays, medical records for each patient were reviewed for basic measurements and the following key data:

  • nusinersen responder or nonresponder condition according to the pivotal trials;
  • motor function scale values;
  • Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP), 0 to 64-point scale composed of 16 items used to assess motor skills;
  • Hammersmith Infant Neurological Examination (HINE), a 0- to 26-point scale to evaluate motor skills in children from 2 months to 2 years of age; and
  • Hammersmith Functional Motor Scale—Expanded (HFMSE), a 0 to 66-point scale to evaluate motor function in children.

Data were pulled from the time of first SMA diagnosis, last nusinersen administration before the first lockdown period, first nusinersen administration after the first lockdown period, and second nusinersen administration after the first lockdown period. Cross-sectional surveys were also conducted with children 6 years or older and for parents at the first nusinersen administration post lockdown.

Of the 25 patients included in the study, 11 (44%) were responders as of the last infusion before lockdown. At the first visit post lockdown, 9 patients (36%) showed lower functional scores than prior to the lockdown, but 5 patients (20%) showed improvement. None of the 9 who saw reductions in functional scores were responders, and only 3 patients saw reductions of more than 2 points.

Eight children (32%) had delayed doses due to lockdown, and only marginal changes in functional scores were reported except in 1 patient who experienced a notable worsening of scoliosis. None of the children visited the emergency department or were hospitalized during lockdown.

At the second postlockdown treatment 4 months after the prior infusion, 10 patients (40%) had lower functional scores, but 8 patients (32%) saw improvements. Again, only 3 patients saw reductions of more than 2 points.

The surveys found that 20% of 25 parents interviewed did not see a change in their child’s strength, while 48% perceived a worsening and 32% felt they saw an improvement. Additionally, 88% did not perceive a change in their child’s swallowing function, and 80% did not see a change in their child’s breathing function. Parents attributed any worsened symptoms to suspension of outpatient physiotherapy (40%), a delay in nusinersen infusion (24%), no particular identifiable cause (24%), the impossibility of changing aids (8%), and less home help (4%).

A total of 13 children were interviewed, with a median age of 10 years. Ten of them (77%) perceived no change in their strength, 2 (15%) felt a slight worsening, and 1 (8%) felt a notable improvement. Twelve of the patients felt no change in swallowing function, and 9 perceived no change in breathing function. During the lockdown, children reported missing going to school and seeing their friends (61%) or taking lessons (23%) more than they worried about delayed treatment. Two children (16%) missed physiotherapy or hydrotherapy more.

Overall, researchers concluded that the worst outcomes were due to patients’ individual family and caretaker situations, not delayed infusions. Those with robust family support actually saw improvements despite treatment delays and the lockdown. They noted that keeping up with physiotherapy at home is crucial, because worsening muscle strength leads to worsened breathing ability.

“Although a detailed statistical analysis was not possible due to the small sample size, no correlation between a delayed treatment and changes of functional scores emerged over the short-period evaluations (~2 months after the end of the first lockdown) and the immediately following months (long-term evaluations),” the authors wrote.

Reference

Agosto C, Salamon E, Giacomelli L, et al. Effect of the COVID-19 pandemic on children with SMA receiving nusinersen: what is missed and what is gained? Front Neurol. 2021;12:704928. doi:10.3389/fneur.2021.704928