Nusinersen safety and effects on motor function in adult spinal muscular atrophy type 2 and 3.

Abstract

OBJECTIVE:

To retrospectively investigate safety and efficacy of nusinersen in a large cohort of adult Italian patients with spinal muscular atrophy (SMA).

METHODS:

Inclusion criteria were: (1) clinical and molecular diagnosis of SMA2 or SMA3; (2) nusinersen treatment started in adult age (>18 years); (3) clinical data available at least at baseline (T0-beginning of treatment) and 6 months (T6).

RESULTS:

We included 116 patients (13 SMA2 and 103 SMA3) with median age at first administration of 34 years (range 18-72). The Hammersmith Functional Rating Scale Expanded (HFMSE) in patients with SMA3 increased significantly from baseline to T6 (median change +1 point, p<0.0001), T10 (+2, p<0.0001) and T14 (+3, p<0.0001). HFMSE changes were independently significant in SMA3 sitter and walker subgroups. The Revised Upper Limb Module (RULM) in SMA3 significantly improved between T0 and T14 (median +0.5, p=0.012), with most of the benefit observed in sitters (+2, p=0.018). Conversely, patients with SMA2 had no significant changes of median HFMSE and RULM between T0 and the following time points, although a trend for improvement of RULM was observed in those with some residual baseline function. The rate of patients showing clinically meaningful improvements (as defined during clinical trials) increased from 53% to 69% from T6 to T14.

CONCLUSIONS:

Our data provide further evidence of nusinersen safety and efficacy in adult SMA2 and SMA3, with the latter appearing to be cumulative over time. In patients with extremely advanced disease, effects on residual motor function are less clear.

• Authors: Lorenzo Maggi, Luca Bello, Silvia Bonanno, Alessandra Govoni, Claudia Caponnetto, Luigia Passamano, Marina Grandis, Francesca Trojsi, Federica Cerri, Manfredi Ferraro, Virginia Bozzoni, Luca Caumo, Rachele Piras, Raffaella Tanel, Elena Saccani, Megi Meneri, Veria Vacchiano, Giulia Ricci, Gianni Soraru', Eustachio D'Errico, Irene Tramacere, Sara Bortolani, Giovanni Pavesi, Riccardo Zanin, Mauro Silvestrini, Luisa Politano, Angelo Schenone, Stefano Carlo Previtali, Angela Berardinelli, Mara Turri, Lorenzo Verriello, Michela Coccia, Renato Mantegazza, Rocco Liguori, Massimiliano Filosto, Gianni Marrosu, Gabriele Siciliano, Isabella Laura Simone, Tiziana Mongini, Giacomo Comi, Elena Pegoraro
• Journal: Journal of neurology, neurosurgery, and psychiatry (J Neurol Neurosurg Psychiatry) Vol. 91 Issue 11 Pg. 1166-1174 (11 2020) ISSN: 1468-330X [Electronic] England
• PMID: 32917822 (Publication Type: Journal Article)
• Copyright: © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

• Oligonucleotides
• Oligonucleotides, Antisense
• nusinersen

Topics

• Adolescent
• Adult
• Age of Onset
• Aged
• Cohort Studies
• Female
• Forced Expiratory Volume
• Functional Status
• Humans
• Injections, Spinal
• Italy
• Male
• Middle Aged
• Oligonucleotides (therapeutic use)
• Oligonucleotides, Antisense (therapeutic use)
• Retrospective Studies
• Sitting Position
• Spinal Muscular Atrophies of Childhood (drug therapy, physiopathology)
• Treatment Outcome
• Vital Capacity
• Walk Test
• Walking
• Young Adult