Effect of nusinersen on motor, respiratory and bulbar function in early-onset spinal muscular atrophy
Astrid Pechmann, Max Behrens, Katharina Dörnbrack, Adrian Tassoni, Sabine Stein, Sibylle Emilie Vogt, Daniela Zöller, Günther Bernert, Tim Hagenacker, Ulrike Schara‐Schmidt, Inge Schwersenz, Maggie C. Walter, Matthias Baumann, Manuela Baumgärtner, Marcus Deschauer, Astrid Eisenkölbl, Marina Flotats‐Bastardas, Andreas Hahn, Veronka Horber, Ralf A. Husain, Sabine Illsinger, Jessika Johannsen, Cornelia Köhler, Heike Kölbel, Monika Müller, Arpad von Moers, Kurt Schlachter, Gudrun Schreiber, Oliver Schwartz, Martin Smitka, Elisabeth Steiner, Eva Stögmann, Regina Trollmann, Katharina Vill, Claudia Weiß, Gert Wiegand, Andreas Ziegler, Hanns Lochmüller, Janbernd Kirschner, the SMArtCARE study group, Thea Beatrice Abele, Bárbara Andres, Daniela Angelova-Toshkina, Petra Baum, Tobias Baum, Ute Baur, Benedikt Becker, Bettina Behring, Theresa Birsak, Julia Bellut, Astrid Bertsche, Markus Blankenburg, Astrid Blaschek, Nathalie Braun, Sarah Braun, Nadine Burgenmeister, Nicole Claus, Isabell Cordts, Heike de Vries, Timo Deba, Adela Della Marina, Jonas Denecke, Joenna Driemeyer, Matthias Eckenweiler, Barbara Fiedler, Michal Fischer, Maren Freigang, Johannes Friese, Philippa Gaiser, Axel Gebert, Stephanie Geitmann, Klaus Goldhahn, Michael Grässl, Kristina Gröning, Julian Großkreutz, U Gruber‐Sedlmayr, Helene Guillemot, René Günther, Maja von der Hagen, H. Hartmann, Miriam Hiebeler, Elke Hobbiebrunken, Georg F. Hoffmann, Britta Holtkamp, Dorothea Holzwarth, Eva Jansen, Angela M. Kaindl, Nadja Kaiser, Jennifer Klamroth, Jan Christoph Koch, Stefan Koelker, Kirsten Kolzter, Brigitte Korschinsky, Hanna Küpper, Thorsten Langer, Ilka Lehnert, Paul Lingor, Wolfgang N. Löscher, Dana Loudovici-Krug, Κyriakos Martakis
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 >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.