Jonathan Calkwood1, Timothy Vollmer1, Robert J Fox1, Ray Zhang1, Mark Novas1, Sarah I Sheikh1, Vissia Viglietta1. 1. Schapiro Center for Multiple Sclerosis, Minneapolis Clinic of Neurology, Golden Valley, MN, USA (JC); Department of Neurology, University of Colorado School of Medicine, RMMSC at Anschutz, Aurora, CO, USA (TV); Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, OH, USA (RJF); and Biogen, Cambridge, MA, USA (RZ, MN, SIS, VV).
Abstract
BACKGROUND: Delayed-release dimethyl fumarate (DMF; also known as gastroresistant DMF) is indicated for relapsing multiple sclerosis (MS). The objective of this study was to explore the safety and tolerability of DMF when administered with interferon beta (IFNβ) or glatiramer acetate (GA). METHODS: Patients with relapsing-remitting MS receiving established therapy with the same dose of IFNβ or GA for at least 12 months continued their prescribed therapy for 2 months (monotherapy period) and then received DMF 240 mg three times daily in addition to their prescribed MS therapy for 6 months (add-on therapy period). Safety and magnetic resonance imaging outcomes were monitored monthly. RESULTS: During the add-on therapy period, in the DMF+IFNβ (n = 57) and DMF+GA (n = 47) groups, the overall incidence of adverse events was 95% and 100%, respectively; the most common adverse events were flushing, diarrhea, and abdominal pain. In both groups, mean lymphocyte counts decreased but remained within normal limits, and hepatic transaminase levels increased transiently; no case met Hy's law criteria. There was no overall increased risk of infection. In both groups, gadolinium-enhancing lesion activity and new/enlarging T2 lesions decreased compared with the monotherapy period (exploratory endpoints). CONCLUSIONS: The safety profile of DMF taken with IFNβ or GA was acceptable and consistent with the known safety profile of DMF monotherapy.
BACKGROUND: Delayed-release dimethyl fumarate (DMF; also known as gastroresistant DMF) is indicated for relapsing multiple sclerosis (MS). The objective of this study was to explore the safety and tolerability of DMF when administered with interferon beta (IFNβ) or glatiramer acetate (GA). METHODS:Patients with relapsing-remitting MS receiving established therapy with the same dose of IFNβ or GA for at least 12 months continued their prescribed therapy for 2 months (monotherapy period) and then received DMF 240 mg three times daily in addition to their prescribed MS therapy for 6 months (add-on therapy period). Safety and magnetic resonance imaging outcomes were monitored monthly. RESULTS: During the add-on therapy period, in the DMF+IFNβ (n = 57) and DMF+GA (n = 47) groups, the overall incidence of adverse events was 95% and 100%, respectively; the most common adverse events were flushing, diarrhea, and abdominal pain. In both groups, mean lymphocyte counts decreased but remained within normal limits, and hepatic transaminase levels increased transiently; no case met Hy's law criteria. There was no overall increased risk of infection. In both groups, gadolinium-enhancing lesion activity and new/enlarging T2 lesions decreased compared with the monotherapy period (exploratory endpoints). CONCLUSIONS: The safety profile of DMF taken with IFNβ or GA was acceptable and consistent with the known safety profile of DMF monotherapy.
Authors: J Theodore Phillips; Krzysztof Selmaj; Ralf Gold; Robert J Fox; Eva Havrdova; Gavin Giovannoni; Heather Abourjaily; Amy Pace; Mark Novas; Christophe Hotermans; Vissia Viglietta; Leslie Meltzer Journal: Int J MS Care Date: 2015 Sep-Oct
Authors: Vilija G Jokubaitis; Vivien Li; Tomas Kalincik; Guillermo Izquierdo; Suzanne Hodgkinson; Raed Alroughani; Jeannette Lechner-Scott; Alessandra Lugaresi; Pierre Duquette; Marc Girard; Michael Barnett; Francois Grand'Maison; Maria Trojano; Mark Slee; Giorgio Giuliani; Cameron Shaw; Cavit Boz; Daniele L A Spitaleri; Freek Verheul; Jodi Haartsen; Danny Liew; Helmut Butzkueven Journal: Neurology Date: 2014-03-07 Impact factor: 9.910
Authors: Robert J Fox; David H Miller; J Theodore Phillips; Michael Hutchinson; Eva Havrdova; Mariko Kita; Minhua Yang; Kartik Raghupathi; Mark Novas; Marianne T Sweetser; Vissia Viglietta; Katherine T Dawson Journal: N Engl J Med Date: 2012-09-20 Impact factor: 91.245
Authors: Ralf Gold; Ludwig Kappos; Douglas L Arnold; Amit Bar-Or; Gavin Giovannoni; Krzysztof Selmaj; Carlo Tornatore; Marianne T Sweetser; Minhua Yang; Sarah I Sheikh; Katherine T Dawson Journal: N Engl J Med Date: 2012-09-20 Impact factor: 91.245
Authors: Richard A Rudick; William H Stuart; Peter A Calabresi; Christian Confavreux; Steven L Galetta; Ernst-Wilhelm Radue; Fred D Lublin; Bianca Weinstock-Guttman; Daniel R Wynn; Frances Lynn; Michael A Panzara; Alfred W Sandrock Journal: N Engl J Med Date: 2006-03-02 Impact factor: 91.245
Authors: Chris H Polman; Stephen C Reingold; Gilles Edan; Massimo Filippi; Hans-Peter Hartung; Ludwig Kappos; Fred D Lublin; Luanne M Metz; Henry F McFarland; Paul W O'Connor; Magnhild Sandberg-Wollheim; Alan J Thompson; Brian G Weinshenker; Jerry S Wolinsky Journal: Ann Neurol Date: 2005-12 Impact factor: 10.422
Authors: Tamara Castillo-Trivino; Ellen M Mowry; Alberto Gajofatto; Dorothee Chabas; Elizabeth Crabtree-Hartman; Bruce A Cree; Douglas S Goodin; Ari J Green; Darin T Okuda; Daniel Pelletier; Scott S Zamvil; Eric Vittinghoff; Emmanuelle Waubant Journal: PLoS One Date: 2011-02-03 Impact factor: 3.240
Authors: L Kappos; G Giovannoni; R Gold; J T Phillips; D L Arnold; C Hotermans; A Zhang; V Viglietta; R J Fox Journal: Eur J Neurol Date: 2015-01-02 Impact factor: 6.089