Type I SMA “new natural history”: long‐term data in nusinersen‐treated patients

Abstract

Objective The aim of this paper was to report the 2‐year follow‐up in type I patients treated with Nusinersen and to assess whether possible changes in motor function are related to the subtype, age, or SMN2 copy number. Methods Sixty‐eight patients, with ages ranging from 0.20 to 15.92 years (mean: 3.96; standard deviation: +3.90) were enrolled in the study. All patients were assessed using the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) and the developmental section of the Hammersmith Infant Neurological Examination (HINE‐2) at the time they started treatment and 12 and 24 months after that. Results For both CHOP and HINE‐2 repeated measures analysis of variance showed a significant difference (P < 0.001) between baseline and 12 months, 12 months and 24 months, and baseline and 24‐month scores for the whole group. When age subgroups (<210 days, <2 years, 2–4 years, 5–11 years, 12–18 years) were considered, on the CHOP INTEND the difference was significant between baseline and 24 months in all age subgroups. On the HINE‐2, the difference between baseline and 24 months was significant in all the subgroups before the age of 4 years. Age was predictive of changes on both scales (P < 0.05), whereas SMN2 copy number and decimal classification were not. Interpretation Our results suggest that some improvement of motor function can be observed even after the first year of treatment. This is more obvious in the infants treated in the first 2 years but some improvement can also be found in older children.

Spinal muscular atrophy: From approved therapies to future therapeutic targets for personalized medicine

“…25 Nusinersen is now available in many countries, with a wider perspective on its efficacy in a range of patient groups, [26][27][28] and some evidence that clinical improvement continues after the first year of treatment. 29 Finally, a recent study assessed the distribution of ASO and the associated SMN Review ll increase in the spinal cord of post-mortem samples from infants treated with nusinersen. This study suggests that there is variability in distribution of ASO within the CNS, with a lower concentration in the cranial portion of the spinal cord and in the brain.…”

Nusinersen: A Review in 5q Spinal Muscular Atrophy

“…Improvements in motor function may occur beyond the first year of nusinersen treatment, according to 24-month follow-up data from the Italian EAP cohort ( n = 68), with improvements more obvious in patients younger than 2 years of age [ 21 ]. For both CHOP-INTEND and HINE-2 scores, significant ( p < 0.001) improvements were seen from baseline at 12 months, from baseline at 24 months and from 12 months at 24 months.…”

Spinal muscular atrophy: from rags to riches

“…Real world data have allowed to collect real world data in patients that had not been included in the pivotal studies [37 , 43 , 63-65] . The first published results of the real world usage of Nusinersen, mainly focused on SMA-I patients but with a much wider spectrum of age than those enrolled in the ENDEAR study, confirmed that the best results were found in the younger patients treated before 6 months but significant motor function improvements could also be found in infants treated between 7 and 24 months [66] . A smaller degree of improvement could also be found in the older children.…”