title: Gastrointestinal Tolerability of Delayed-Release Dimethyl Fumarate in a Multicenter, Open-Label Study of Patients with Relapsing Forms of Multiple Sclerosis (MANAGE).
abstract: BACKGROUND
  In phase 3 trials, delayed-release dimethyl fumarate (DMF; also known as gastroresistant DMF) demonstrated efficacy in relapsing-remitting multiple sclerosis (MS). Gastrointestinal (GI) events were associated with DMF treatment. The single-arm, open-label MANAGE study examined the incidence, severity, duration, and management of GI events in adults with relapsing MS initiating DMF treatment in clinical practice in the United States shortly after marketing approval.
  
  
  METHODS
  Patients (N = 233) took DMF for up to 12 weeks and recorded information regarding GI events using an eDiary and numerical rating scales.
  
  
  RESULTS
  Overall, 54.1% of patients used symptomatic therapy and had GI symptoms. The incidence of GI events was highest in the first month of treatment. The duration of GI events varied by event type, and severity was generally mild to moderate. Decreased severity was seen in patients treated with antacids, bismuth subsalicylate, acid-secretion blockers, antidiarrheals, and antiemetics. Less than 10% of patients were using symptomatic therapy for GI events by week 12 of DMF treatment. A modest reduction in severe GI events was observed in patients who regularly took DMF with food compared with patients who did not. The incidence of GI-related events was comparable in patients with or without a history of GI abnormalities and in patients who did or did not use alcohol or tobacco.
  
  
  CONCLUSIONS
  Gastrointestinal events associated with DMF are generally transient, mild to moderate in severity, and manageable. Symptomatic therapy and dosing with food may mitigate these events.
authors.affiliation: University of Texas Medical Branch, Central Texas Neurology Consultants, Round Rock, TX, USA (EJF); Suncoast Neuroscience Associates, St. Petersburg, FL, USA (AV); Neurological Physicians of Arizona, Gilbert, AZ, USA (WG); PharmStats, Ltd, Escondido, CA, USA (TSM); and Biogen Inc, Cambridge, MA, USA (CvH, JW, JL, JZ).
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Fox
authors.affiliation: University of Texas Medical Branch, Central Texas Neurology Consultants, Round Rock, TX, USA (EJF); Suncoast Neuroscience Associates, St. Petersburg, FL, USA (AV); Neurological Physicians of Arizona, Gilbert, AZ, USA (WG); PharmStats, Ltd, Escondido, CA, USA (TSM); and Biogen Inc, Cambridge, MA, USA (CvH, JW, JL, JZ).
authors.forename: Alberto
authors.initials: A
authors.lastname: Vasquez
authors.affiliation: University of Texas Medical Branch, Central Texas Neurology Consultants, Round Rock, TX, USA (EJF); Suncoast Neuroscience Associates, St. Petersburg, FL, USA (AV); Neurological Physicians of Arizona, Gilbert, AZ, USA (WG); PharmStats, Ltd, Escondido, CA, USA (TSM); and Biogen Inc, Cambridge, MA, USA (CvH, JW, JL, JZ).
authors.forename: William
authors.initials: W
authors.lastname: Grainger
authors.affiliation: University of Texas Medical Branch, Central Texas Neurology Consultants, Round Rock, TX, USA (EJF); Suncoast Neuroscience Associates, St. Petersburg, FL, USA (AV); Neurological Physicians of Arizona, Gilbert, AZ, USA (WG); PharmStats, Ltd, Escondido, CA, USA (TSM); and Biogen Inc, Cambridge, MA, USA (CvH, JW, JL, JZ).
authors.forename: Tina S
authors.initials: TS
authors.lastname: Ma
authors.affiliation: University of Texas Medical Branch, Central Texas Neurology Consultants, Round Rock, TX, USA (EJF); Suncoast Neuroscience Associates, St. Petersburg, FL, USA (AV); Neurological Physicians of Arizona, Gilbert, AZ, USA (WG); PharmStats, Ltd, Escondido, CA, USA (TSM); and Biogen Inc, Cambridge, MA, USA (CvH, JW, JL, JZ).
authors.forename: Christian
authors.initials: C
authors.lastname: von Hehn
authors.affiliation: University of Texas Medical Branch, Central Texas Neurology Consultants, Round Rock, TX, USA (EJF); Suncoast Neuroscience Associates, St. Petersburg, FL, USA (AV); Neurological Physicians of Arizona, Gilbert, AZ, USA (WG); PharmStats, Ltd, Escondido, CA, USA (TSM); and Biogen Inc, Cambridge, MA, USA (CvH, JW, JL, JZ).
authors.forename: John
authors.initials: J
authors.lastname: Walsh
authors.affiliation: University of Texas Medical Branch, Central Texas Neurology Consultants, Round Rock, TX, USA (EJF); Suncoast Neuroscience Associates, St. Petersburg, FL, USA (AV); Neurological Physicians of Arizona, Gilbert, AZ, USA (WG); PharmStats, Ltd, Escondido, CA, USA (TSM); and Biogen Inc, Cambridge, MA, USA (CvH, JW, JL, JZ).
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: University of Texas Medical Branch, Central Texas Neurology Consultants, Round Rock, TX, USA (EJF); Suncoast Neuroscience Associates, St. Petersburg, FL, USA (AV); Neurological Physicians of Arizona, Gilbert, AZ, USA (WG); PharmStats, Ltd, Escondido, CA, USA (TSM); and Biogen Inc, Cambridge, MA, USA (CvH, JW, JL, JZ).
authors.forename: Javier
authors.initials: J
authors.lastname: Zambrano