Effect of nusinersen on motor, respiratory and bulbar function in early-onset spinal muscular atrophy
Authors: Pechmann Astrid , Behrens Max , Dörnbrack Katharina , Tassoni Adrian , Stein Sabine , Vogt Sibylle , Zöller Daniela , Bernert Günther , Hagenacker Tim , Schara-Schmidt Ulrike , Schwersenz Inge , Walter Maggie C , Baumann Matthias , Baumgartner Manuela , Deschauer Marcus , Eisenkölbl Astrid , Flotats-Bastardas Marina , Hahn Andreas , Horber Veronka , Husain Ralf A , Illsinger Sabine , Johannsen Jessika , Köhler Cornelia , Kölbel Heike , Müller Monika , von Moers Arpad , Schlachter Kurt , Schreiber Gudrun , Schwartz Oliver , Smitka Martin , Steiner Elisabeth , Stögmann Eva , Trollmann Regina , Vill Katharina , Weiß Claudia , Wiegand Gert , Ziegler Andreas , Lochmüller Hanns , Kirschner Janbernd ,   the SMArtCARE study group, Abele Thea Beatrice , Andres Barbara , Angelova-Toshkina Daniela , Baum Petra , Baum Tobias , Baur Ute , Becker Benedikt , Behring Bettina , Birsak Theresa , Bellut Julia , Bertsche Astrid , Blankenburg Markus , Blaschek Astrid , Braun Nathalie , Braun Sarah , Burgenmeister Nadine , Claus Nicole , Cordts Isabell , de Vries Heike , Deba Timo , Marina Adela Della , Denecke Jonas , Driemeyer Joenna , Eckenweiler Matthias , Fiedler Barbara , Fischer Michal , Freigang Maren , Friese Johannes , Gaiser Philippa , Gebert Axel , Geitmann Stephanie , Goldhahn Klaus , Grässl Michael , Gröning Kristina , Grosskreutz Julian , Gruber-Sedlmayr Ursula , Guillemot Helene , Günther René , von der Hagen Maja , Hartmann Hans , Hiebeler Miriam , Hobbiebrunken Elke , Hoffmann Georg Friedrich , Holtkamp Britta , Holzwarth Dorothea , Jansen Eva , Kaindl Angela , Kaiser Nadja , Klamroth Jennifer , Koch Jan Christoph , Koelker Stefan , Kolzter Kirsten , Korschinsky Brigitte , Küpper Hanna , Langer Thorsten , Lehnert Ilka , Lingor Paul , Löscher Wolfgang N , Loudovici-Krug Dana , Martakis Kyriakos , Mayer Iris , Metelmann Moritz , Meyer Sascha , Mueller-Kaempffer Katharina , Müller Petra , Müller-Felber Wolfgang , Neuwirth Christoph , Niederschweiberer Johanna , Nolte Anja , Odorfer Thorsten , Omran Heymut , Pauschek Josefine , Pickrodt Katrin , Plecko Barbara , Pühringer Manuel , Quinten Anna Lisa , Rappold Mika , Reihle Christof , Reinhardt Tabea , Rödiger Annekathrin , Roetmann Gerda , Saffari Afshin , Schimmel Mareike , Schneider Joanna , Schoene-Bake Christoph , Schorling David , Schwerin-Nagel Anette , Steinbach Robert , Steuernagel Daniela , Stolte Benjamin , Stoltenburg Corinna , Stüve Burkhard , Theophil Manuela , Thiele Simone , Topakian Raffi , Türk Matthias , van der Stam Lieske , Vollmann Peter , Warken Birgit , Weber Markus , Weiler Markus , Weiss Deike , Weiss Simone , Wenzel Franziska , Wider Sabine , Wiebe Nils , Wilichowski Ekkehard , Wilken Bernd , Wochner Katarzyna , Zeiner Fiona , Zeisler Daniela , Zeller Daniel , Zemlin Michael 
Published: July 2022

Abstract
5q-associated spinal muscular atrophy is a rare neuromuscular disorder with the leading symptom of a proximal muscle weakness. Three different drugs have been approved by the European Medicines Agency and Food and Drug Administration for the treatment of spinal muscular atrophy patients, however, long-term experience is still scarce. In contrast to clinical trial data with restricted patient populations and short observation periods, we report here real-world evidence on a broad spectrum of patients with early-onset spinal muscular atrophy treated with nusinersen focusing on effects regarding motor milestones, and respiratory and bulbar insufficiency during the first years of treatment.
Within the SMArtCARE registry, all patients under treatment with nusinersen who never had the ability to sit independently before the start of treatment were identified for data analysis. The primary outcome of this analysis was the change in motor function evaluated with the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders and motor milestones considering World Health Organization criteria. Further, we evaluated data on the need for ventilator support and tube feeding, and mortality.
In total, 143 patients with early-onset spinal muscular atrophy were included in the data analysis with a follow-up period of up to 38 months. We observed major improvements in motor function evaluated with the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders. Improvements were greater in children &gt;2 years of age at start of treatment than in older children. 24.5% of children gained the ability to sit independently. Major improvements were observed during the first 14 months of treatment. The need for intermittent ventilator support and tube feeding increased despite treatment with nusinersen.
Our findings confirm the increasing real-world evidence that treatment with nusinersen has a dramatic influence on disease progression and survival in patients with early-onset spinal muscular atrophy. Major improvements in motor function are seen in children younger than 2 years at the start of treatment. Bulbar and respiratory function needs to be closely monitored, as these functions do not improve equivalent to motor function.