Improved upper limb function in non-ambulant children with SMA type 2 and 3 during nusinersen treatment: a prospective 3-years SMArtCARE registry study
Authors: Pechmann Astrid , Behrens Max , Dörnbrack Katharina , Tassoni Adrian , Wenzel Franziska , Stein Sabine , Vogt Sibylle , Zöller Daniela , Bernert Günther , Hagenacker Tim , Schara-Schmidt Ulrike , Walter Maggie C. , Bertsche Astrid , Vill Katharina , Baumann Matthias , Baumgartner Manuela , Cordts Isabell , Eisenkölbl Astrid , Flotats-Bastardas Marina , Friese Johannes , Günther René , Hahn Andreas , Horber Veronka , Husain Ralf A. , Illsinger Sabine , Jahnel Jörg , Johannsen Jessika , Köhler Cornelia , Kölbel Heike , Müller Monika , von Moers Arpad , Schwerin-Nagel Annette , Reihle Christof , Schlachter Kurt , Schreiber Gudrun , Schwartz Oliver , Smitka Martin , Steiner Elisabeth , Trollmann Regina , Weiler Markus , Weiß Claudia , Wiegand Gert , Wilichowski Ekkehard , Ziegler Andreas , Lochmüller Hanns , Kirschner Janbernd ,   SMArtCARE study group, Ameshofer Lisa , Andres Barbara , Angelova-Toshkina Daniela , Banholzer Daniela , Bant Christina , Baum Petra , Baumann Sandra , Baur Ute , Becker Benedikt , Behring Bettina , Bellut Julia , Bevot Andrea , Bischofberger Jasmin , Bitzan Lisa , Bjelica Bogdan , Blankenburg Markus , Böger Sandra , Bonetti Friederike , Bongartz Anke , Brakemeier Svenja , Bratka Lisa , Braun Nathalie , Braun Sarah , Brauner Brigitte , Bretschneider Christa , Burgenmeister Nadine , Burke Bea , Cirak Sebahattin , Dall Andrea , de Vries Heike , Marina Adela Della , Denecke Jonas , Deschauer Marcus , Dibrani Zylfie , Diebold Uta , Dondit Lutz , Drebes Jessica , Driemeyer Joenna , Dukic Vladimir , Eckenweiler Matthias , Eminger Mirjam , Fischer Michal , Fischer Cornelia , Freigang Maren , Gaiser Philippa , Gangfuß Andrea , Geitmann Stephanie , George Annette , Gosk-Tomek Magdalena , Grinzinger Susanne , Gröning Kristina , Groß Martin , Güttsches Anne-Katrin , Hagenmeyer Anna , Hartmann Hans , Haverkamp Julia , Hiebeler Miriam , Hoevel Annegret , Hoffmann Georg Friedrich , Holtkamp Britta , Holzwarth Dorothea , Homma Annette , Horneff Viola , Hörnig Carolin , Hotter Anna , Hubert Andrea , Huppke Peter , Jansen Eva , Jung Lisa , Kaiser Nadja , Kappel Stefan , Katharina Bolte , Koch Johannes , Kölke Stefan , Korschinsky Brigitte , Kostede Franziska , Krause Karsten , Küpper Hanna , Lang Annina , Lange Irene , Langer Thorsten , Lechner Yvonne , Lehmann Helmar , Leypold Christine , Lingor Paul , Lipka Jaqueline , Löscher Wolfgang , Luiking Antje , Machetanz Gerrit , Malm Eva , Martakis Kyriakos , Menzen Bettina , Metelmann Moritz , Meyer zu Hörste Gerd , Montagnese Federica , Mörtlbauer Kathrin , Müller Petra , Müller Anne , Müller Anja , Müschen Lars , Neuwirth Christoph , Niesert Moritz , Pauschek Josefine , Pernegger Elke , Petri Susanne , Pilshofer Veronika , Plecko Barbara , Pollok Jürgen , Preisel Martin , Pühringer Manuel , Quinten Anna Lisa , Raffler Sabine , Ramadan Barbara , Rappold Mika , Rauscher Christian , Reckmann Kerstin , Reinhardt Tabea , Röder Melanie , Roland-Schäfer Doris , Roth Erdmute , Ruß Lena , Saffari Afshin , Schimmel Mareike , Schlag Melina , Schlotter-Weigel Beate , Schneider Joanna , Schöne-Bake Jan-Christoph , Schorling David , Schreiner Isabella , Schüssler Stephanie , Schwarzbach Michaela , Schwippert Michaela , Semmler Luisa , Smuda Karin , Sprenger-Svacina Alina , Stadler Theresa , Steffens Paula , Steuernagel Daniela , Stolte Benjamin , Stoltenburg Corinna , Tasch Gehrke , Thimm Andreas , Tiefenthaler Elke , Topakian Raffi , Türk Matthias , van der Stam Lieske , Vettori Katia , Vollmann Peter , Vorgerd Matthias , Weiss Deike , Wenninger Stephan , Werring Svea , Wessel Maria , Weyen Ute , Wider Sabine , Wiebe Nils Ole , Wiesenhofer Anna , Wiethoff Sarah , Wirner Corinna , Wohnrade Camilla , Wunderlich Gilbert , Zeller Daniel , Zemlin Michael , Zobel Joachim 
Published: October 2022

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.