TY - JOUR
T1 - Long-term efficacy and safety of nusinersen in adults with 5q spinal muscular atrophy
T2 - a prospective European multinational observational study
AU - SMArtCARE study group
AU - Günther, René
AU - Wurster, Claudia Diana
AU - Brakemeier, Svenja
AU - Osmanovic, Alma
AU - Schreiber-Katz, Olivia
AU - Petri, Susanne
AU - Uzelac, Zeljko
AU - Hiebeler, Miriam
AU - Thiele, Simone
AU - Walter, Maggie C.
AU - Weiler, Markus
AU - Kessler, Tobias
AU - Freigang, Maren
AU - Lapp, Hanna Sophie
AU - Cordts, Isabell
AU - Lingor, Paul
AU - Deschauer, Marcus
AU - Hahn, Andreas
AU - Martakis, Kyriakos
AU - Steinbach, Robert
AU - Ilse, Benjamin
AU - Rödiger, Annekathrin
AU - Bellut, Julia
AU - Nentwich, Julia
AU - Zeller, Daniel
AU - Muhandes, Mohamad Tareq
AU - Baum, Tobias
AU - Christoph Koch, Jan
AU - Schrank, Bertold
AU - Fischer, Sophie
AU - Hermann, Andreas
AU - Kamm, Christoph
AU - Naegel, Steffen
AU - Mensch, Alexander
AU - Weber, Markus
AU - Neuwirth, Christoph
AU - Lehmann, Helmar C.
AU - Wunderlich, Gilbert
AU - Stadler, Christian
AU - Tomforde, Maike
AU - George, Annette
AU - Groß, Martin
AU - Pechmann, Astrid
AU - Kirschner, Janbernd
AU - Türk, Matthias
AU - Schimmel, Mareike
AU - Bernert, Günther
AU - Martin, Pascal
AU - Rauscher, Christian
AU - Meyer zu Hörste, Gerd
N1 - Publisher Copyright:
© 2024 The Author(s)
PY - 2024/4
Y1 - 2024/4
N2 - 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.
AB - 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.
KW - Antisense oligonucleotide
KW - Intrathecal therapy
KW - Motor neuron disease
KW - Nusinersen
KW - Spinal muscular atrophy
UR - https://www.scopus.com/pages/publications/85183951276
U2 - 10.1016/j.lanepe.2024.100862
DO - 10.1016/j.lanepe.2024.100862
M3 - Article
AN - SCOPUS:85183951276
SN - 2666-7762
VL - 39
JO - The Lancet Regional Health - Europe
JF - The Lancet Regional Health - Europe
M1 - 100862
ER -
SDG 3 Good Health and Well-being