Improved upper limb function in non-ambulant children with SMA type 2 and 3 during nusinersen treatment: a prospective 3-years SMArtCARE registry study

• DOI: 10.1186/s13023-022-02547-8
• Publication Date: 2022-10-23T19:03:14Z
• Authors: Astrid Pechmann; Max Behrens; Katharina Dörnbrack; Adrian Tassoni; Franziska Wenzel; Sabine Stein; Sibylle Vogt; Daniela Zöller; Günther Bernert; Tim Hagenacker; Ulrike Schara-Sch...; Maggie C. Walter; Astrid Bertsche; Katharina Vill; Matthias Baumann; Manuela Baumgartner; Isabell Cordts; Astrid Eisenkölbl; Marina Flotats-Ba...; Johannes Friese; René Günther; Andreas Hahn; Veronka Horber; Ralf A. Husain; Sabine Illsinger; Jörg Jahnel; Jessika Johannsen; Cornelia Köhler; Heike Kölbel; Monika Müller; Arpad von Moers; Annette Schwerin-...; Christof Reihle; Kurt Schlachter; Gudrun Schreiber; Oliver Schwartz; Martin Smitka; Elisabeth Steiner; Regina Trollmann; Markus Weiler; Claudia Weiß; Gert Wiegand; Ekkehard Wilichowski; Andreas Ziegler; Hanns Lochmüller; Janbernd Kirschner; ; Lisa Ameshofer; Barbara Andres; Daniela Angelova-...; Daniela Banholzer; Christina Bant; Petra Baum; Sandra Baumann; Ute Baur; Benedikt Becker; Bettina Behring; Julia Bellut; Andrea Bevot; Jasmin Bischofberger; Lisa Bitzan; Bogdan Bjelica; Markus Blankenburg; Sandra Böger; Friederike Bonetti; Anke Bongartz; Svenja Brakemeier; Lisa Bratka; Nathalie Braun; Sarah Braun; Brigitte Brauner; Christa Bretschne...; Nadine Burgenmeister; Bea Burke; Sebahattin Cirak; Andrea Dall; Heike de Vries; Adela Della Marina; Jonas Denecke; Marcus Deschauer; Zylfie Dibrani; Uta Diebold; Lutz Dondit; Jessica Drebes; Joenna Driemeyer; Vladimir Dukic; Matthias Eckenweiler; Mirjam Eminger; Michal Fischer; Cornelia Fischer; Maren Freigang; Philippa Gaiser; Andrea Gangfuß; Stephanie Geitmann; Annette George; Magdalena Gosk-Tomek; Susanne Grinzinger; Kristina Gröning; Martin Groß; Anne-Katrin Gütts...; Anna Hagenmeyer; Hans Hartmann; Julia Haverkamp; Miriam Hiebeler; Annegret Hoevel; Georg Friedrich H...; Britta Holtkamp; Dorothea Holzwarth; Annette Homma; Viola Horneff; Carolin Hörnig; Anna Hotter; Andrea Hubert; Peter Huppke; Eva Jansen; Lisa Jung; Nadja Kaiser; Stefan Kappel; Bolte Katharina; Johannes Koch; Stefan Kölke; Brigitte Korschinsky; Franziska Kostede; Karsten Krause; Hanna Küpper; Annina Lang; Irene Lange; Thorsten Langer; Yvonne Lechner; Helmar Lehmann; Christine Leypold; Paul Lingor; Jaqueline Lipka; Wolfgang Löscher; Antje Luiking; Gerrit Machetanz; Eva Malm; Kyriakos Martakis; Bettina Menzen; Moritz Metelmann; Gerd Meyer zu Hörste; Federica Montagnese; Kathrin Mörtlbauer; Petra Müller; Anne Müller; Anja Müller; Lars Müschen; Christoph Neuwirth; Moritz Niesert; Josefine Pauschek; Elke Pernegger; Susanne Petri; Veronika Pilshofer; Barbara Plecko; Jürgen Pollok; Martin Preisel; Manuel Pühringer; Anna Lisa Quinten; Sabine Raffler; Barbara Ramadan; Mika Rappold; Christian Rauscher; Kerstin Reckmann; Tabea Reinhardt; Melanie Röder; Doris Roland-Schäfer; Erdmute Roth; Lena Ruß; Afshin Saffari; Mareike Schimmel; Melina Schlag; Beate Schlotter-W...; Joanna Schneider; Jan-Christoph Sch...; David Schorling; Isabella Schreiner; Stephanie Schüssler; Michaela Schwarzbach; Michaela Schwippert; Luisa Semmler; Karin Smuda; Alina Sprenger-Sv...; Theresa Stadler; Paula Steffens; Daniela Steuernagel; Benjamin Stolte; Corinna Stoltenburg; Gehrke Tasch; Andreas Thimm; Elke Tiefenthaler; Raffi Topakian; Matthias Türk; Lieske van der Stam; Katia Vettori; Peter Vollmann; Matthias Vorgerd; Deike Weiss; Stephan Wenninger; Svea Werring; Maria Wessel; Ute Weyen; Sabine Wider; Nils Ole Wiebe; Anna Wiesenhofer; Sarah Wiethoff; Corinna Wirner; Camilla Wohnrade; Gilbert Wunderlich; Daniel Zeller; Michael Zemlin; Joachim Zobel
• Keywords: 0301 basic medicine; Research; Medizin; R; 610; Spinal muscular atrophy; Spinal Muscular Atrophies of Childhood; SMArtCARE; ddc:; Muscular Atrophy, Spinal; Upper Extremity; Later-onset; 03 medical and health sciences; Nusinersen; Disease Progression; Research ; Pediatric neuromuscular diseases ; Spinal muscular atrophy ; Nusinersen ; Sitter ; Later-onset ; SMArtCARE ; Medical and Health Sciences; Medicine; Humans; ddc:610; Prospective Studies; Registries; Sitter; Child

Abstract Background The development and approval of disease modifying treatments have dramatically changed disease progression in patients with spinal muscular atrophy (SMA). Nusinersen was approved in Europe in 2017 for the treatment of SMA patients irrespective of age and disease severity. Most data on therapeutic efficacy are available for the infantile-onset SMA. For patients with SMA type 2 and type 3, there is still a lack of sufficient evidence and long-term experience for nusinersen treatment. Here, we report data from the SMArtCARE registry of non-ambulant children with SMA type 2 and typen 3 under nusinersen treatment with a follow-up period of up to 38 months.

Methods SMArtCARE is a disease-specific registry with data on patients with SMA irrespective of age, treatment regime or disease severity. Data are collected during routine patient visits as real-world outcome data. This analysis included all non-ambulant patients with SMA type 2 or 3 below 18 years of age before initiation of treatment. Primary outcomes were changes in motor function evaluated with the Hammersmith Functional Motor Scale Expanded (HFMSE) and the Revised Upper Limb Module (RULM).

Results Data from 256 non-ambulant, pediatric patients with SMA were included in the data analysis. Improvements in motor function were more prominent in upper limb: 32.4% of patients experienced clinically meaningful improvements in RULM and 24.6% in HFMSE. 8.6% of patients gained a new motor milestone, whereas no motor milestones were lost. Only 4.3% of patients showed a clinically meaningful worsening in HFMSE and 1.2% in RULM score.

Conclusion Our results demonstrate clinically meaningful improvements or stabilization of disease progression in non-ambulant, pediatric patients with SMA under nusinersen treatment. Changes were most evident in upper limb function and were observed continuously over the follow-up period. Our data confirm clinical trial data, while providing longer follow-up, an increased number of treated patients, and a wider range of age and disease severity.