Trial of Fingolimod versus Interferon Beta-1a in Pediatric Multiple Sclerosis
Tanuja Chitnis, Douglas L Arnold, Brenda Banwell, Wolfgang Brück, Angelo Ghezzi, Gavin Giovannoni, Benjamin Greenberg, Lauren Krupp, Kevin Rostásy, Marc Tardieu, Emmanuelle Waubant, Jerry S Wolinsky, Amit Bar-Or, Tracy Stites, Yu Chen, Norman Putzki, Martin Merschhemke, Jutta Gärtner, PARADIGMS Study Group, Andrew Kornberg, Barbara Bajer-Kornek, Sergey Likhachev, Antonio Pereira Gomes Neto, Denise Diniz, José Paz, Regina Alvarenga, Veneta Bojinova-Tchamova, Jean Mah, Sunita Venkateswaran, Krasanka Hafner, Katrin Gross-Paju, Bruno Brochet, Emmanuel Cheuret, François Rivier, Kumaran Deiva, Mathieu Milh, Astrid Blaschek, Regina Trollmann, Rudolf Korinthenberg, Thomas Luecke, Tjalf Ziemssen, Carlo Pozzilli, Francesco Patti, Giancarlo Comi, Girolama Alessandra Marfia, Luigi Maria Edoardo Grimaldi, Maria Trojano, Mauro Zaffaroni, Ruggero Capra, Vincenzo Brescia Morra, Guntis Rozentals, Jurate Laurynaitiene, Nerija Vaiciene-Magistris, Freddy Castro Farfan, Sandra Quinones, Barbara Steinborn, Barbara Ujma-Czapska, Mariusz Stasiolek, Miroslaw Jasinski, Dana Craiu, Alexey Boyko, Ekaterina Kairbekova, Farit Khabirov, Liudmila Kuzenkova, Nadezhda Malkova, Dimitrije Nikolic, Jasna Jancic, Ksenija Gebauer-Bukurov, Jaroslava Payerova, Francisco Gascon Jiménez, Guillermo Izquierdo Ayuso, Mar Mendibe Bilbao, Rogier Hintzen, Victoria Eugenia Fernandez Sanchez, Virginia Meca Lallana, Xavier Montalban Gairin, Karin Nordborg, Banu Anlar, Cengiz Yalcinkaya, Kivilcim Gucuyener, Murat Terzi, Serkan Ozakbas, Unsal Yilmaz, Iryna Makedonska, Kateryna Prokopenko, Liudmyla Tantsura, Sergii Moskovko, Tetiana Kobys, Tetiana Muratova, Tetiana Nehrych, Tetiana Prykhodko, Cheryl Hemingway, Evangeline Wassmer, Jay Shetty, Jay Desai, Amy Waldman, Angel Chinea Martinez, Jayne Ness, Kottil Rammohan, Michael Lloyd, Mitchel Williams, Ricardo Ayala, Ronald Davis, Vikram Bhise, Tanuja Chitnis, Douglas L Arnold, Brenda Banwell, Wolfgang Brück, Angelo Ghezzi, Gavin Giovannoni, Benjamin Greenberg, Lauren Krupp, Kevin Rostásy, Marc Tardieu, Emmanuelle Waubant, Jerry S Wolinsky, Amit Bar-Or, Tracy Stites, Yu Chen, Norman Putzki, Martin Merschhemke, Jutta Gärtner, PARADIGMS Study Group, Andrew Kornberg, Barbara Bajer-Kornek, Sergey Likhachev, Antonio Pereira Gomes Neto, Denise Diniz, José Paz, Regina Alvarenga, Veneta Bojinova-Tchamova, Jean Mah, Sunita Venkateswaran, Krasanka Hafner, Katrin Gross-Paju, Bruno Brochet, Emmanuel Cheuret, François Rivier, Kumaran Deiva, Mathieu Milh, Astrid Blaschek, Regina Trollmann, Rudolf Korinthenberg, Thomas Luecke, Tjalf Ziemssen, Carlo Pozzilli, Francesco Patti, Giancarlo Comi, Girolama Alessandra Marfia, Luigi Maria Edoardo Grimaldi, Maria Trojano, Mauro Zaffaroni, Ruggero Capra, Vincenzo Brescia Morra, Guntis Rozentals, Jurate Laurynaitiene, Nerija Vaiciene-Magistris, Freddy Castro Farfan, Sandra Quinones, Barbara Steinborn, Barbara Ujma-Czapska, Mariusz Stasiolek, Miroslaw Jasinski, Dana Craiu, Alexey Boyko, Ekaterina Kairbekova, Farit Khabirov, Liudmila Kuzenkova, Nadezhda Malkova, Dimitrije Nikolic, Jasna Jancic, Ksenija Gebauer-Bukurov, Jaroslava Payerova, Francisco Gascon Jiménez, Guillermo Izquierdo Ayuso, Mar Mendibe Bilbao, Rogier Hintzen, Victoria Eugenia Fernandez Sanchez, Virginia Meca Lallana, Xavier Montalban Gairin, Karin Nordborg, Banu Anlar, Cengiz Yalcinkaya, Kivilcim Gucuyener, Murat Terzi, Serkan Ozakbas, Unsal Yilmaz, Iryna Makedonska, Kateryna Prokopenko, Liudmyla Tantsura, Sergii Moskovko, Tetiana Kobys, Tetiana Muratova, Tetiana Nehrych, Tetiana Prykhodko, Cheryl Hemingway, Evangeline Wassmer, Jay Shetty, Jay Desai, Amy Waldman, Angel Chinea Martinez, Jayne Ness, Kottil Rammohan, Michael Lloyd, Mitchel Williams, Ricardo Ayala, Ronald Davis, Vikram Bhise
Abstract
Background: Treatment of patients younger than 18 years of age with multiple sclerosis has not been adequately examined in randomized trials. We compared fingolimod with interferon beta-1a in this population.
Methods: In this phase 3 trial, we randomly assigned patients 10 to 17 years of age with relapsing multiple sclerosis in a 1:1 ratio to receive oral fingolimod at a dose of 0.5 mg per day (0.25 mg per day for patients with a body weight of ≤40 kg) or intramuscular interferon beta-1a at a dose of 30 μg per week for up to 2 years. The primary end point was the annualized relapse rate.
Results: Of a total of 215 patients, 107 were assigned to fingolimod and 108 to interferon beta-1a. The mean age of the patients was 15.3 years. Among all patients, there was a mean of 2.4 relapses during the preceding 2 years. The adjusted annualized relapse rate was 0.12 with fingolimod and 0.67 with interferon beta-1a (absolute difference, 0.55 relapses; relative difference, 82%; P<0.001). The key secondary end point of the annualized rate of new or newly enlarged lesions on T2-weighted magnetic resonance imaging (MRI) was 4.39 with fingolimod and 9.27 with interferon beta-1a (absolute difference, 4.88 lesions; relative difference, 53%; P<0.001). Adverse events, excluding relapses of multiple sclerosis, occurred in 88.8% of patients who received fingolimod and 95.3% of those who received interferon beta-1a. Serious adverse events occurred in 18 patients (16.8%) in the fingolimod group and included seizures (in 4 patients), infection (in 4 patients), and leukopenia (in 2 patients). Serious adverse events occurred in 7 patients (6.5%) in the interferon beta-1a group and included infection (in 2 patients) and supraventricular tachycardia (in 1 patient).
Conclusions: Among pediatric patients with relapsing multiple sclerosis, fingolimod was associated with a lower rate of relapse and less accumulation of lesions on MRI over a 2-year period than interferon beta-1a but was associated with a higher rate of serious adverse events. Longer studies are required to determine the durability and safety of fingolimod in pediatric multiple sclerosis. (Funded by Novartis Pharma; PARADIGMS ClinicalTrials.gov number, NCT01892722 .).
Source: PubMed