Nusinersen versus sham control in later-onset spinal muscular atrophy
<p><strong>Background:</strong><br /> 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).</p><br /> <p&g...
| প্রধান লেখক: | , , , , , , , , , , , , , , , , , , , , , , |
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| বিন্যাস: | Journal article |
| ভাষা: | English |
| প্রকাশিত: |
Massachusetts Medical Society
2018
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| _version_ | 1826256452178673664 |
|---|---|
| author | Mercuri, E Darras, BT Chiriboga, CA Day, JW Campbell, C Connolly, AM Iannaccone, ST Kirschner, J Kuntz, NL Saito, K Shieh, PB Tulinius, M Mazzone, ES Montes, J Bishop, KM Yang, Q Foster, R Gheuens, S Bennett, CF Farwell, W Schneider, E De Vivo, DC Finkel, RS |
| author_facet | Mercuri, E Darras, BT Chiriboga, CA Day, JW Campbell, C Connolly, AM Iannaccone, ST Kirschner, J Kuntz, NL Saito, K Shieh, PB Tulinius, M Mazzone, ES Montes, J Bishop, KM Yang, Q Foster, R Gheuens, S Bennett, CF Farwell, W Schneider, E De Vivo, DC Finkel, RS |
| author_sort | Mercuri, E |
| collection | OXFORD |
| description | <p><strong>Background:</strong><br />
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).</p><br />
<p><strong>Methods:</strong><br />
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.</p><br />
<p><strong>Results:</strong><br />
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).</p><br />
<p><strong>Conclusions:</strong><br />
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. (Funded by Biogen and Ionis Pharmaceuticals; CHERISH ClinicalTrials.gov number, NCT02292537. opens in new tab.)</p><br /> |
| first_indexed | 2024-03-06T18:02:29Z |
| format | Journal article |
| id | oxford-uuid:0047dffc-9c18-4a23-9f2a-3d3d519e4833 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:02:29Z |
| publishDate | 2018 |
| publisher | Massachusetts Medical Society |
| record_format | dspace |
| spelling | oxford-uuid:0047dffc-9c18-4a23-9f2a-3d3d519e48332022-03-26T08:28:45ZNusinersen versus sham control in later-onset spinal muscular atrophyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:0047dffc-9c18-4a23-9f2a-3d3d519e4833EnglishSymplectic ElementsMassachusetts Medical Society2018Mercuri, EDarras, BTChiriboga, CADay, JWCampbell, CConnolly, AMIannaccone, STKirschner, JKuntz, NLSaito, KShieh, PBTulinius, MMazzone, ESMontes, JBishop, KMYang, QFoster, RGheuens, SBennett, CFFarwell, WSchneider, EDe Vivo, DCFinkel, RS<p><strong>Background:</strong><br /> 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).</p><br /> <p><strong>Methods:</strong><br /> 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.</p><br /> <p><strong>Results:</strong><br /> 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).</p><br /> <p><strong>Conclusions:</strong><br /> 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. (Funded by Biogen and Ionis Pharmaceuticals; CHERISH ClinicalTrials.gov number, NCT02292537. opens in new tab.)</p><br /> |
| spellingShingle | Mercuri, E Darras, BT Chiriboga, CA Day, JW Campbell, C Connolly, AM Iannaccone, ST Kirschner, J Kuntz, NL Saito, K Shieh, PB Tulinius, M Mazzone, ES Montes, J Bishop, KM Yang, Q Foster, R Gheuens, S Bennett, CF Farwell, W Schneider, E De Vivo, DC Finkel, RS Nusinersen versus sham control in later-onset spinal muscular atrophy |
| title | Nusinersen versus sham control in later-onset spinal muscular atrophy |
| title_full | Nusinersen versus sham control in later-onset spinal muscular atrophy |
| title_fullStr | Nusinersen versus sham control in later-onset spinal muscular atrophy |
| title_full_unstemmed | Nusinersen versus sham control in later-onset spinal muscular atrophy |
| title_short | Nusinersen versus sham control in later-onset spinal muscular atrophy |
| title_sort | nusinersen versus sham control in later onset spinal muscular atrophy |
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