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Article dans une revue

Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy

Sibylle Vogt Marcus Krueger Astrid Pechmann Bianca Rippberger Matthias Eckenweiler Ulrike Schara 1 Heike Koelbel Barbara Andres Katrin Rupprich Andrea Gangfuss Philipp Jachertz Adela Della Marina Nina Sponemann Markia Pane Concetta Palermo Marco Piastra Lavinia Fanelli Roberto de Sanctis Orazio Genovese 2 Laura Antonaci Maria Carmela Pera Priscilla Lamendola Sonia Messina Gianluca Vita Vincenzo Di Bella Maria Sframeli Matteo Rosa Costanza Barcellona Maria Grazia Distefano Filippo Cavallaro Antonio Versaci Francesco de Luca Giuseppe Vita Andres Nacimento Osorio Eduardo Tizzano 3 Carlos Ignacio Ortez Gonzalez Juan Dario Ortigoza Escobar 4 Juame Colomer Oferil Julita Medina Cantillo Anna Febrer Rotger Meritxell Vigo Morancho Johanneh Eldblom Niklas Darin 5 Anna Karin Kroksmark Asa Lindstedt Eva Michael Eva Kimber Lisa Wahlgren Sophelia Hoi-Shan Chan Stella Chim Joseph Chiu Alvin Chi Chung Ho Jing Kun Janice Ip Wendy Wai Man Lam Maggie Chui-San Ng Connie Wan Virginia Chun Nei Wong Yvonne Yue Reiko Arakawa Akemi Yamauchi Satoru Nagata Yasushi Ito Hidetsugu Nakatsukasa Akiko Takeshita Kyoko Hirasawa Tetsuo Ikai Kaoru Eto Yui Otamni Yasuhiro Takeshima Noroki Fukuda Yasuhiro Tanaka Hideki Shimomura Tomoko Lee Takayuki Shibano E. Mercuri Tomohiro Tachikawa B. T. Darras Jong-Hee Chae 6 C. A. Chiriboga Byung Chan Lim J. W. Day Hyung-Ik Shin C. Campbell Soo Yeon Kim A. M. Connolly Sun Ah Choi S. T. Iannaccone Woo Sung Son J. Kirschner 7 Hyemi Jo N. L. Kuntz Seong Min Chun K. Saito 8 Hyuna Kim 9 P. B. Shieh M. Tulinius E. S. Mazzone J. Montes K. M. Bishop Q. Yang 10 R. Foster S. Gheuens C. F. Bennett W. Farwell E. Schneider 11 D. C. de Vivo R. S. Finkel Walter G. Bradley Petra Kaufmann Patricia I. Dickson Stephen C. Reingold Charles S. Davis Kristen Arredondo Diana Castro Margaret Cowie Alan Farrow-Gillespie Andrew Hebert Melissa Kauk Nancy Miller Leslie Nelson Thomas Spain Joshua Cappell Andrei Constantinescu 12 Rosangel Cruz 13 Jahannaz Dastgir Darryl de Vivo Sally Dunaway Kristin Engelstad Alexander G. Khandji Samantha Kramer Jonathan Marra Molly Popolizio Rachel Salazar Louis H. Weimer Sonya Aziz-Zaman Nicole Lamarca Partha Ghosh Fouad Al-Ghamdi Wendy Liew Robert Graham Charles Berde 14 Navil Sethna Anjali Koka Luke Wang Regina Laine Michelle Souris Grace Ordonez Timothy Harrington Heather Szelag Amy Pasternak Elizabeth Mirek Janet Quigley Richard Finkel Debbie Berry Matthew Civitello Julie Duke Endsley Candace Eden Wendy Leon Kathleen O'Reardon Laufey Sigurdardottir Craig Johnson 15 Jenna Turner Melisa Vega Fabiola Weber-Guzman Matthias Zinn Ana Carolina Tesi Rocha Karolina Watson Genevieve d'Souza R. J. Ramamurthi Richard Gee Janis Kitsuwa-Lowe Katharine Hagerman 16, 17 Sheela Crasta Lesly Welsh Shirley Paulose Danielle Mcfall Jennifer Perez Swetapadma Patnaik Bharati Sanjanwala Sarada Sakamuri Crystal Proud Bona Park Purse Trinh Tina Duong Jacinda Sampson Gihan Tennekoon John Brandsema Allan Glanzman Jean Flickinger Michele Toms Laura Adang Delores Stanford Oscar Mayer Joshua Zigmont Madeline Chadehumbe Elizabeth Kichula Erika Finanger Barry Russman Colin Roberts Andrea Frank Danielle Benjamin Kirsten Zilke Paul T. Golumbek Craig M. Zaidman Pallavi Anand 18 Rebecca Gadeken Catherine Siener Nancy Kuntz 19 Leon Epstein Jena Krueger Stewart Goldman Kristin Krosschell Colleen Blomgren Hyoung Won Choi Jonathan Kurz Julie Parsons Joanne Janas Michele Yang Alison Ballard Terri Carry Stephanie Shea Alan Bielsky Kaylee Booker Alicia Camuto Sierra Lord-Halvorson Melissa Gibbons Carl Zimmerman Victoria Allen Peter Fuhr 20 Hannah Johnson Vi Tran Gina Vanderveen Perry Shieh Eileen Fowler Nicholas Parziale Lekha Rao Christy Skura Carolyn Kelley Francy Shu Maryam Oskoui David Zielinski Chantal Poulin Pablo Mauricio Ingelmo Sarah Turgeon Desilets Pamela Dinunzio Gonzalo Rivera Myriam Srour 21 Stephanie Arpin 22 Sharan Goobie Paul Gibson Cheryl Scholtes Wendy Mcdonald Eugenio Zapata Cam-Tu Emilie Nguyen Laurent Servais 23 Elena Gargaun 24 Anne-Gaelle Le Moing 25, 26 Teresa Gidaro 27 Raphael Vialle 27 Marie-Laurence Guye Charlotte Lilien 24, 28 Gwenn Olliver Stephanie Gilabert Sabine Borell Sabine Wider Sabine Stein
Abstract : 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. (Funded by Biogen and Ionis Pharmaceuticals; CHERISH ClinicalTrials. gov number, NCT02292537.)
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https://hal-u-picardie.archives-ouvertes.fr/hal-03604455
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Soumis le : jeudi 10 mars 2022 - 14:27:57
Dernière modification le : mardi 3 mai 2022 - 15:14:05

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Sibylle Vogt, Marcus Krueger, Astrid Pechmann, Bianca Rippberger, Matthias Eckenweiler, et al.. Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy. NEW ENGLAND JOURNAL OF MEDICINE, 2018, 378 (7), pp.625-635. ⟨10.1056/NEJMoa1710504⟩. ⟨hal-03604455⟩

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