Aim of the study. This study aimed to evaluate the effects of nusinersen therapy in Polish children with SMA type 1.Clinical rationale of study. Spinal muscular atrophy (SMA) is a neuromuscular disorder that is characterised by the loss of motor neurons, progressive muscle weakness and atrophy, leading to increased disability and mortality. Nusinersen, an antisense oligonucleotide that promotes production of the functional survival motor neuron protein is approved for the treatment of SMA 5q in the European Union. In 2017, an early access programme (EAP) for nusinersen was launched in Poland. In this study, we present the results of nusinersen treatment in Polish patients participating in the EAP. Materials and methods.We collected prospectively clinical data including mutational analysis of SMN1 and SMN2 genes, motor function outcomes as measured on a standardized scales, ventilatory and nutritional status, on SMA type 1 patients receiving nusinersen in three EAP centres in Poland. Scores on the CHOP-INTEND scale after 18-26 months of treatment were compared to baseline. Results. We analysed data from 26 patients with SMA type 1, mean age 4.79 (2-15) years. The mutational analysis revealed two SMN2 gene copies in the majority of patients (61.54%). Three and four copies were found in 34.62% and 3.84%, respectively. Median disease duration was 21 months. Half (n = 13) of the patients required mechanical ventilation at baseline and 57.69% (n = 15) were fed by nasogastric tube or percutaneous endoscopic gastrostomy. No patient worsened during the follow-up. Mean improvement in CHOP-INTEND from baseline to the last follow-up was 7.38 points (p < 0.001). CHOP-INTEND scores did not decline for any patient. Patients with three or more SMN2 gene copies had higher scores than did the patients with two copies (p = 0.013), and they tended to show greater improvement over time, but the difference was not significant (p = 0.324). Shorter disease duration and higher CHOP-INTEND baseline score were associated with a better response (p = 0.015). Patients with a CHOP-INTEND score above the median had higher scores overall than the rest (p < 0.0013), and they improved significantly more than the rest (p = 0.037). Nusinersen was well tolerated, no new safety findings were identified.Conclusions and clinical implications. Our data indicates that nusinersen treatment might be effective in SMA type 1 patients, regardless of their age and functional status.
Nusinersen jest oligonukleotydem antysensownym wpływającym na alternatywny splicing genu SMN2, który wpływa na produkcję pełnowartościowego białka przeżycia neuronów ruchowych. W roku 2016 lek został zarejestrowany w leczeniu rdzeniowego zaniku mięśni (SMA) 5q w Stanach Zjednoczonych a w roku 2017 na obszarze Unii Europejskiej. Rdzeniowy zanik mięśni jest jedną z wiodących, genetycznych chorób będących przyczyną śmierci niemowląt. Choroba związana z dziedziczeniem autosomalnym recesywnym cechuje zapadalność na poziomie 10,3-13,5 przypadków na 100 000 żywych urodzeń. Do momentu rejestracji a później refundacji wąską grupę, 30 pacjentów leczono w Polsce, w ramach programu rozszerzonego dostępu do leku. Refundacja nusinersenu weszła w życie od 1. stycznia 2019 roku zapewniając pacjentom z SMA szeroki dostęp do leczenia, z możliwością włączenia pacjentów przedobjawowych i każdego typu SMA niezależnie od wieku i stanu funkcjonalnego. Kryteria leczenia pacjentów z SMA są ujęte w programie lekowym "Leczenie Rdzeniowego Zaniku Mięśni (B.102)", na podstawie Obwieszczenia Ministra Zdrowia z dnia 27 grudnia 2018 r. Aktualnie w programie lekowym, na dzień 31 sierpnia 2019 jest leczonych 280 pacjentów.
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