Dados do Trabalho

Título

Long-term follow-up of SMA type 1 treatment with Nusinersen: a single-center experience

Resumo

Introduction. Spinal Muscular Atrophy (SMA) is a genetic motor neuron disease caused by mutations in the SMN1 (Survival Motor Neuron) gene, which leads to hypotonia, muscle weakness and respiratory involvement. Its most severe form, SMA type 1, starts before 6 months of life and has a high mortality due to ventilatory failure. Nusinersen, the first approved treatment for SMA, is an antisense oligonucleotide for intrathecal use, which leads to greater survival and gain in motor acquisitions. Studies on the safety and efficacy of long-term treatment are still scarce.
Objective. To present long-term results (4 years of follow-up) in SMA type 1 patients under treatment with Nusinersen.
Methods. We followed a total of 24 patients, all with SMA type 1 (20 patients with 2 copies of SMN2). The patients were evaluated by the functional scale CHOP-INTEND (The Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders) and in relation to gain of motor milestones (head control, sitting with or without support, standing and walking), in addition to assessment of survival and use of permanent ventilation (PV) and feeding route.
Results. Twelve patients were female, only 11 patients (45.8%) started treatment before 12 months of illness. 22 patients (91.6%) were already using gastrostomy at the beginning of treatment. After 4 years of follow-up, 22 (91.6%) patients were alive, two deaths occurred: one after gene therapy and the other after respiratory failure. Two patients received gene therapy but continued to use Nusinersen (combined therapy). Eight patients gained some motor milestone, all of them started treatment before 12 months disease. The greatest gains in CHOP-INTEND occurred up to 24 months of treatment, and after this period, the scores tended to stabilize, without further gains. 19 patients (79.1%) were already using PV (>16h/day) at the beginning of treatment and 15 patients were using PV after 4 years of treatment. Even in those patients who were on PV, there was a reduction in the duration of ventilation use and an improvement in the management of airway secretion. Conclusions. Nusinersen showed continuous benefit over 4 years of treatment, bringing motor improvement mainly within the first 2 years of treatment and maintaining motor function acquired at 4 years. Only patients who started treatment before 12 months of illness gained some motor milestone. No new adverse events were reported in this long-term follow-up.