Dados do Trabalho

Título

FIVE-YEAR EXPERIENCE IN SPINAL MUSCULAR ATROPHY TREATMENT WITH NUSINERSEN: A SINGLE-CENTER EXPERIENCE

Introdução

Nusinersen is the first approved treatment for Spinal Muscular Atrophy (SMA). It 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.

Objetivo

To present long-term results (5 years of follow-up) in SMA patients under treatment with Nusinersen.

Método

We followed a total of 24 patients with SMA type 1 and 30 patients with SMA type 2 and 3. The patients were evaluated by the functional scales CHOP-INTEND (The Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders) and Hammersmith Functional Motor Scale Expanded (HFMSE), gain of motor milestones (head control, sitting with or without support, standing and walking), assessment of survival and use of continuous ventilation (CV) and feeding route.

Resultados

Among SMA type 1 patients, after five years of follow-up, 22 (91.6%) patients are 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. Thirty patients with SMA types 2 and 3 were followed for five years. In these patients, five developed severe scoliosis (Cobb angle > 45°), and six underwent spinal arthrodesis, totaling eleven patients (36.6%) with clinically significant spinal deformity. These patients began to demand greater complexity in the intrathecal application, requiring the use of imaging in subsequent applications. HFMSE assessment showed an average gain of +2.1 (±6.9) and +1.3 (±7.1) points at 36 and 48 months of follow-up, respectively. In 48 months of treatment, 21 patients (70%) remained stable or continued to gain points in long-term follow-up, and nine patients (30%) lost 2 or more points on the scale, these developed severe scoliosis or underwent arthrodesis of column.

Conclusão

Nusinersen showed continuous benefit over five years of treatment, with motor improvement mainly within the first 2 years of treatment and maintaining motor function acquired at 4 years. Among SMA type 1, 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.

Referências

Łusakowska A, Wójcik A, Frączek A, Aragon-Gawińska K, Potulska-Chromik A, Baranowski P, Nowak R, Rosiak G, Milczarek K, Konecki D, Gierlak-Wójcicka Z, Burlewicz M, Kostera-Pruszczyk A. Long-term nusinersen treatment across a wide spectrum of spinal muscular atrophy severity: a real-world experience. Orphanet J Rare Dis. 2023 Aug 4;18(1):230. doi: 10.1186/s13023-023-02769-4. PMID: 37542300; PMCID: PMC10401775.

Palavras Chave

Spinal muscular atrophy; NUSINERSEN; long-term follow up