Effects of nusinersen after one year of treatment in 123 children with SMA type 1 or 2: a French real-life observational study

被引：69

作者：

Audic, Frederique ^{[1
]}

de la Banda, Marta Gomez Garcia ^{[2
]}

Bernoux, Delphine ^{[1
]}

Ramirez-Garcia, Paola ^{[1
]}

Durigneux, Julien ^{[3
]}

Barnerias, Christine ^{[4
]}

Isapof, Arnaud ^{[5
]}

Cuisset, Jean-Marie ^{[6
]}

Cances, Claude ^{[7
]}

Richelme, Christian ^{[8
]}

Vuillerot, Carole ^{[9
]}

Laugel, Vincent ^{[10
]}

Ropars, Juliette ^{[11
]}

Altuzarra, Cecilia ^{[12
]}

Espil-Taris, Caroline ^{[13
]}

Walther-Louvier, Ulrike ^{[14
]}

Sabouraud, Pascal ^{[15
]}

Chouchane, Mondher ^{[16
]}

Vanhulle, Catherine ^{[17
]}

Trommsdorff, Valerie ^{[18
]}

Perville, Anne ^{[19
]}

Testard, Herve ^{[20
]}

Lagrue, Emmanuelle ^{[21
]}

Sarret, Catherine ^{[22
]}

Avice, Anne-Laude ^{[23
]}

Beze-Beyrie, Pierre ^{[24
]}

Pauly, Vanessa ^{[25
]}

Quijano-Roy, Susana ^{[2
]}

Chabrol, Brigitte ^{[1
]}

Desguerre, Isabelle ^{[4
]}

机构：

[1] Hop Timone Enfants, Ctr Reference Malad Neuromusculaires Enfant PACAR, Serv Neuropediat, 264 Rue St Pierre, F-13385 Marseille 5, France

[2] Hop Raymond Poincare, AP HP, Ctr Reference Malad Neuromusculaires Nord Ile Fra, Garches, France

[3] CHU Angers, Ctr Reference Malad Neuromusculaires AOC, Angers, France

[4] Hop Necker Enfants Malad, AP HP, Ctr Reference Malad Neuromusculaires Nord Ile Fra, Serv Neurol Pediat, Paris, France

[5] Hop Trousseau, AP HP, Ctr Reference Malad Neuromusculaires Nord Ile Fra, Serv Neuropediat, Paris, France

[6] Hop Salengro, CHU Lille, Ctr Reference Malad Neuromusculaires Nord Ile Fra, Serv Neuropediat, Lille, France

[7] Hop Enfants, CHU Toulouse, Ctr Reference Malad Neuromusculaires AOC, Unite Neurol Pediat, Toulouse, France

[8] Hop Pediat Nice, CHU Lenval, Ctr Reference Malad Neuromusculaires PACARARE, Nice, France

[9] Hosp Civils Lyon, Ctr Reference Malad Neuromusculaires Enfant PACAR, Serv MPR Pediat Escale, Hop Femme Mere Enfant, Bron, France

[10] Hop Hautepierre, CHU Strasbourg, Ctr Reference Malad Neuromusculaires Nord Ile Fra, Pediat Med Chirurg, Strasbourg, France

[11] CHRU Brest, Ctr Reference Malad Neuromusculaires AOC, Serv Pediatrie, Brest, France

[12] CHU Besancon, Hop Minjoz, Ctr Competences Malad Neuromusculaires Nord Ile F, Unite Neuropediat & Med Pediat, Besancon, France

[13] CHU Pellegrin, Unite Neurol Pediat, Ctr Reference Malad Neuromusculaires AOC, Bordeaux, France

[14] CHU Montpellier, Ctr Reference Malad Neuromusculaires AOC, Serv Neuropediat, Montpellier, France

[15] CHU Reims, Ctr Reference Malad Neuromusculaires Nord Ile Fra, Site Reims Enfant AMH, Reims, France

[16] CHU Dijon Bourgogne, Hop Enfants, Ctr Competence Malad Neuromusculaires Nord Ile Fr, Serv Pediat 1, Dijon, France

[17] CHU Rouen Charles Nicolle, Ctr Competence Malad Neuromusculaires Nord Ile Fr, Rouen, France

[18] CHU La Reunion, Ctr Reference Malad Neuromusculaires PACARARE, Serv Pediat, St Pierre, France

[19] CHU La Reunion, Ctr Competence Malad Neuromusculaires PACARARE, Serv Pediat, St Denis, France

[20] CHU Grenoble, Hop Couple Enfant, Clin Univ Pediat, Ctr Competence Malad Neuromusculaires PACARARE,Ne, Grenoble, France

[21] Hop Clocheville, Ctr Competence Malad Neuromusculaires AOC, Serv Neuropediat & Handicaps, Tours, France

[22] Ctr Hosp Univ Clermont Ferrand, Ctr Reference Malad Neuromusculaires PACARARE, Clermont Ferrand, France

[23] Hop Brabois, Ctr Reference Malad Neuromusculaires Nord Ile Fra, Nancy, France

[24] Ctr Hosp Pau, Serv Pediat, Pau, France

[25] Aix Marseille Univ, Ctr Etud & Rech Serv Sante & Qualite Vie CEReSS, EA 3279, Fac Med, Marseille, France

来源：

ORPHANET JOURNAL OF RARE DISEASES | 2020年 / 15卷 / 01期

关键词：

Spinal muscular atrophy type I; Spinal muscular atrophy type II; Nusinersen; Motor function measure; MFM; SPINAL MUSCULAR-ATROPHY; SHAM CONTROL; VALIDATION; EXPERIENCE;

D O I：

10.1186/s13023-020-01414-8

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Background Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord. Nusinersen has been covered by public healthcare in France since May 2017. The aim of this article is to report results after 1 year of treatment with intrathecal nusinersen in children with SMA types 1 and 2 in France. Comparisons between treatment onset (T0) and after 1 year of treatment (Y1) were made in terms of motor function and need for nutritional and ventilatory support. Motor development milestone achievements were evaluated using the modified Hammersmith Infant Neurologic Examination-Part 2 (HINE-2) for patients under 2 years of age and Motor Function Measure (MFM) scores for patients over 2 years of age. Results Data on 204 SMA patients (type 1 or 2) were retrospectively collected from the 23 French centers for neuromuscular diseases. One hundred and twenty three patients had been treated for at least 1 year and were included, 34 of whom were classified as type 1 (10 as type 1a/b and 24 as type 1c) and 89 as type 2.Survival motor Neuron 2(SMN2)copy numbers were available for all but 6 patients. Patients under 2 years of age (n = 30), had significantly higher HINE-2 scores at year 1 than at treatment onset but used more nutritional and ventilatory support. The 68 patients over 2 years of age evaluated with the Motor Function Measure test had significantly higher overall scores after 1 year, indicating that their motor function had improved. The scores were higher in the axial and proximal motor function (D2) and distal motor function (D3) parts of the MFM scale, but there was no significant difference for standing and transfer scores (D1). No child in either of the two groups achieved walking. Conclusion Nusinersen offers life-changing benefits for children with SMA, particularly those with more severe forms of the disorder. Caregiver assessments are positive. Nevertheless, patients remain severely disabled and still require intensive support care. This new treatment raises new ethical challenges.

引用

页数：10

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