Long-term efficacy and safety of nusinersen in adults with 5q spinal muscular atrophy: a prospective European multinational observational studyResearch in context

• Main Authors: René Günther (Author), Claudia Diana Wurster (Author), Svenja Brakemeier (Author), Alma Osmanovic (Author), Olivia Schreiber-Katz (Author), Susanne Petri (Author), Zeljko Uzelac (Author), Miriam Hiebeler (Author), Simone Thiele (Author), Maggie C. Walter (Author), Markus Weiler (Author), Tobias Kessler (Author), Maren Freigang (Author), Hanna Sophie Lapp (Author), Isabell Cordts (Author), Paul Lingor (Author), Marcus Deschauer (Author), Andreas Hahn (Author), Kyriakos Martakis (Author), Robert Steinbach (Author), Benjamin Ilse (Author), Annekathrin Rödiger (Author), Julia Bellut (Author), Julia Nentwich (Author), Daniel Zeller (Author), Mohamad Tareq Muhandes (Author), Tobias Baum (Author), Jan Christoph Koch (Author), Bertold Schrank (Author), Sophie Fischer (Author), Andreas Hermann (Author), Christoph Kamm (Author), Steffen Naegel (Author), Alexander Mensch (Author), Markus Weber (Author), Christoph Neuwirth (Author), Helmar C. Lehmann (Author), Gilbert Wunderlich (Author), Christian Stadler (Author), Maike Tomforde (Author), Annette George (Author), Martin Groß (Author), Astrid Pechmann (Author), Janbernd Kirschner (Author), Matthias Türk (Author), Mareike Schimmel (Author), Günther Bernert (Author), Pascal Martin (Author), Christian Rauscher (Author), Gerd Meyer zu Hörste (Author), Petra Baum (Author), Wolfgang Löscher (Author), Marina Flotats-Bastardas (Author), Cornelia Köhler (Author), Kristina Probst-Schendzielorz (Author), Susanne Goldbach (Author), Ulrike Schara-Schmidt (Author), Wolfgang Müller-Felber (Author), Hanns Lochmüller (Author), Otgonzul von Velsen (Author), Christoph Kleinschnitz (Author), Albert C. Ludolph (Author), Tim Hagenacker (Author)
• Format: Book
• Published: Elsevier, 2024-04-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 2666-7762; 10.1016/j.lanepe.2024.100862
• Keywords: Antisense oligonucleotide; Intrathecal therapy; Motor neuron disease; Nusinersen; Spinal muscular atrophy; Public aspects of medicine; RA1-1270
• Source: The Lancet Regional Health. Europe, Vol 39, Iss , Pp 100862- (2024)

Summary: Background: Evidence for the efficacy of nusinersen in adults with 5q-associated spinal muscular atrophy (SMA) has been demonstrated up to a period of 16 months in relatively large cohorts but whereas patients reach a plateau over time is still to be demonstrated. We investigated the efficacy and safety of nusinersen in adults with SMA over 38 months, the longest time period to date in a large cohort of patients from multiple clinical sites. Methods: Our prospective, observational study included adult patients with SMA from Germany, Switzerland, and Austria (July 2017 to May 2022). All participants had genetically-confirmed, 5q-associated SMA and were treated with nusinersen according to the label. The total Hammersmith Functional Motor Scale Expanded (HFMSE) and Revised Upper Limb Module (RULM) scores, and 6-min walk test (6 MWT; metres), were recorded at baseline and 14, 26, and 38 months after treatment initiation, and pre and post values were compared. Adverse events were also recorded. Findings: Overall, 389 patients were screened for eligibility and 237 were included. There were significant increases in all outcome measures compared with baseline, including mean HFMSE scores at 14 months (mean difference 1.72 [95% CI 1.19-2.25]), 26 months (1.20 [95% CI 0.48-1.91]), and 38 months (1.52 [95% CI 0.74-2.30]); mean RULM scores at 14 months (mean difference 0.75 [95% CI 0.43-1.07]), 26 months (mean difference 0.65 [95% CI 0.27-1.03]), and 38 months (mean difference 0.72 [95% CI 0.25-1.18]), and 6 MWT at 14 months (mean difference 30.86 m [95% CI 18.34-43.38]), 26 months (mean difference 29.26 m [95% CI 14.87-43.65]), and 38 months (mean difference 32.20 m [95% CI 10.32-54.09]). No new safety signals were identified. Interpretation: Our prospective, observational, long-term (38 months) data provides further real-world evidence for the continuous efficacy and safety of nusinersen in a large proportion of adult patients with SMA. Funding: Financial support for the registry from Biogen, Novartis and Roche.