TY - JOUR
T1 - Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy.
AU - Mercuri, Eugenio Maria
AU - Mazzone, Elena Stacy
AU - Schneider-Moser, Elisabeth Margarete Ute
AU - 33186,
AU - FACOLTA', DI MEDICINA E CHIRURGIA "A.GEMELLI"
AU - pubblica, ROMA - Dipartimento di Scienze della vita e sanità
AU - Darras, BT
AU - Chiriboga, CA
AU - Day, JW
AU - Campbell, C
AU - Connolly, AM
AU - Iannaccone, ST
AU - Kirschner, J
AU - Kuntz, NL
AU - Saito, K
AU - Shieh, PB
AU - Tulinius, M
AU - Montes, J
AU - Bishop, KM
AU - Yang, Q
AU - Foster, R
AU - Gheuens, S
AU - Bennett, CF
AU - Farwell, W
AU - De, Vivo DC
AU - Finkel, RS
AU - Group, CHERISH Study
PY - 2018
Y1 - 2018
N2 - BACKGROUND:
Nusinersen is an antisense oligonucleotide drug that modulates pre-messenger RNA splicing of the survival motor neuron 2 ( SMN2) gene. It has been developed for the treatment of spinal muscular atrophy (SMA).
METHODS:
We conducted a multicenter, double-blind, sham-controlled, phase 3 trial of nusinersen in 126 children with SMA who had symptom onset after 6 months of age. The children were randomly assigned, in a 2:1 ratio, to undergo intrathecal administration of nusinersen at a dose of 12 mg (nusinersen group) or a sham procedure (control group) on days 1, 29, 85, and 274. The primary end point was the least-squares mean change from baseline in the Hammersmith Functional Motor Scale-Expanded (HFMSE) score at 15 months of treatment; HFMSE scores range from 0 to 66, with higher scores indicating better motor function. Secondary end points included the percentage of children with a clinically meaningful increase from baseline in the HFMSE score (≥3 points), an outcome that indicates improvement in at least two motor skills.
RESULTS:
In the prespecified interim analysis, there was a least-squares mean increase from baseline to month 15 in the HFMSE score in the nusinersen group (by 4.0 points) and a least-squares mean decrease in the control group (by -1.9 points), with a significant between-group difference favoring nusinersen (least-squares mean difference in change, 5.9 points; 95% confidence interval, 3.7 to 8.1; P<0.001). This result prompted early termination of the trial. Results of the final analysis were consistent with results of the interim analysis. In the final analysis, 57% of the children in the nusinersen group as compared with 26% in the control group had an increase from baseline to month 15 in the HFMSE score of at least 3 points (P<0.001), and the overall incidence of adverse events was similar in the nusinersen group and the control group (93% and 100%, respectively).
CONCLUSIONS:
Among children with later-onset SMA, those who received nusinersen had significant and clinically meaningful improvement in motor function as compared with those in the control group.
AB - BACKGROUND:
Nusinersen is an antisense oligonucleotide drug that modulates pre-messenger RNA splicing of the survival motor neuron 2 ( SMN2) gene. It has been developed for the treatment of spinal muscular atrophy (SMA).
METHODS:
We conducted a multicenter, double-blind, sham-controlled, phase 3 trial of nusinersen in 126 children with SMA who had symptom onset after 6 months of age. The children were randomly assigned, in a 2:1 ratio, to undergo intrathecal administration of nusinersen at a dose of 12 mg (nusinersen group) or a sham procedure (control group) on days 1, 29, 85, and 274. The primary end point was the least-squares mean change from baseline in the Hammersmith Functional Motor Scale-Expanded (HFMSE) score at 15 months of treatment; HFMSE scores range from 0 to 66, with higher scores indicating better motor function. Secondary end points included the percentage of children with a clinically meaningful increase from baseline in the HFMSE score (≥3 points), an outcome that indicates improvement in at least two motor skills.
RESULTS:
In the prespecified interim analysis, there was a least-squares mean increase from baseline to month 15 in the HFMSE score in the nusinersen group (by 4.0 points) and a least-squares mean decrease in the control group (by -1.9 points), with a significant between-group difference favoring nusinersen (least-squares mean difference in change, 5.9 points; 95% confidence interval, 3.7 to 8.1; P<0.001). This result prompted early termination of the trial. Results of the final analysis were consistent with results of the interim analysis. In the final analysis, 57% of the children in the nusinersen group as compared with 26% in the control group had an increase from baseline to month 15 in the HFMSE score of at least 3 points (P<0.001), and the overall incidence of adverse events was similar in the nusinersen group and the control group (93% and 100%, respectively).
CONCLUSIONS:
Among children with later-onset SMA, those who received nusinersen had significant and clinically meaningful improvement in motor function as compared with those in the control group.
KW - inglese
KW - inglese
UR - http://hdl.handle.net/10807/122573
M3 - Article
SP - 625
EP - 635
JO - New England Journal of Medicine
JF - New England Journal of Medicine
SN - 0028-4793
ER -