PMID- 29707040 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220317 IS - 1756-2856 (Print) IS - 1756-2864 (Electronic) IS - 1756-2856 (Linking) VI - 11 DP - 2018 TI - Incidence and mitigation of gastrointestinal events in patients with relapsing-remitting multiple sclerosis receiving delayed-release dimethyl fumarate: a German phase IV study (TOLERATE). PG - 1756286418768775 LID - 10.1177/1756286418768775 [doi] LID - 1756286418768775 AB - BACKGROUND: Gastrointestinal (GI) events are common adverse events (AEs) associated with delayed-release dimethyl fumarate (DMF), an approved treatment for relapsing-remitting multiple sclerosis (RRMS). The objective of the TOLERATE study was to evaluate GI tolerability and GI mitigation via symptomatic therapies in patients initiating DMF in a real-world clinical setting in Germany. METHODS: TOLERATE was a multicentre, open-label, single-arm study performed at 25 German sites. Endpoints were frequency, severity, duration (all primary) and mitigation of GI-related events (secondary). Patients were instructed to take DMF according to the prescribing information for up to 12 weeks and to document GI events and intake of GI-symptomatic therapy on numerical rating scales, using eDiaries. RESULTS: A total of 211 patients were included in the safety population (71% female; mean age 40 +/- 11 years). Of these, 185 patients (87.7%) reported GI-related events, out of which nearly half received GI-symptomatic therapy (84/185; 45.4%). The most frequently reported GI events were upper abdominal pain, flatulence and nausea. GI-related events peaked during the first 3 weeks of therapy and rapidly decreased thereafter. The severity of GI events over 12 weeks according to the Modified Overall Gastrointestinal Symptom Scale were mild to moderate in the majority of patients reporting GI-related events and taking symptomatic GI medication (53.6%). Only 10% of all patients discontinued study treatment due to AEs in general, while 6.6% discontinued due to GI-related events. The severity of GI-related events decreased over time in patients who received symptomatic treatment with one or more medications (e.g. acid secretion blockers, antidiarrhoeals or antiemetics). CONCLUSION: Gastrointestinal events associated with delayed-release DMF were mainly mild to moderate in severity. Prevalence of GI events peaked during the first 3 weeks of therapy and rapidly faded thereafter. Although 44.9% of patients experiencing GI events used common GI symptomatic therapies, only 6.6% of patients discontinued DMF because of GI events, suggesting that GI events could be managed well with common symptomatic therapy. FAU - Gold, Ralf AU - Gold R AD - Katholisches Klinikum Bochum St. Josef-Hospital, Neurological Clinic, Bochum University, Gudrunstrasse 56, 44791 Bochum, Germany. FAU - Schlegel, Eugen AU - Schlegel E AD - Centre for Neurological Studies, Siegen, Germany. FAU - Elias-Hamp, Birte AU - Elias-Hamp B AD - Institute for Clinical Studies, Hamburg, Germany. FAU - Albert, Christian AU - Albert C AD - Neurological Clinic, St. Josef Hospital, Potsdam, Germany. FAU - Schmidt, Stephan AU - Schmidt S AD - Neurological Study Centre, Bonn, Germany. FAU - Tackenberg, Bjorn AU - Tackenberg B AD - Department of Neurology, Marburg University, Marburg, Germany. FAU - Xiao, James AU - Xiao J AD - Biogen, Cambridge, MA, USA. FAU - Schaak, Tom AU - Schaak T AD - Biogen, Ismaning, Germany. FAU - Salmen, Hans Christian AU - Salmen HC AD - Biogen, Ismaning, Germany. LA - eng PT - Journal Article DEP - 20180418 PL - England TA - Ther Adv Neurol Disord JT - Therapeutic advances in neurological disorders JID - 101480242 PMC - PMC5912264 OTO - NOTNLM OT - dimethyl fumarate OT - gastrointestinal events OT - multiple sclerosis COIS- Conflict of interest statement: RG received speaker's and board honoraria from Baxter, Bayer Schering, Biogen, CLB Behring, Genzyme, Merck Serono, Novartis, Talecris, Teva and Wyeth. His department received grant support from Bayer Schering, Biogen, Genzyme, Merck Serono, Novartis and Teva. ES received travel expenses and grants from Biogen, Novartis, Roche, Icon and Takeda. BEH received research support and personal compensation for activities with Biogen, Merck Serono, Bayer Healthcare, Almirall, Novartis, Teva and Genzyme as a speaker. CA received travel/congress grants from Biogen, Novartis, Teva and Genzyme. SS received travel expenses, grants and honoraria from Biogen, Merck, Bayer Vital, Novartis, Genzyme, Roche and Teva. BT received speaker and consultancy honoraria as well as research grants and travel reimbursements from Bayer Healthcare, Biogen, CSL Behring, GRIFOLS, Merck Serono, Novartis, Octapharma, Roche, Sanofi Genzyme and Teva. JX, TS and HCS are employees of Biogen. RG receives lecturing honoraria and advisory boards' honoraria from Biogen. His institution got IIT funding from Biogen. EDAT- 2018/05/01 06:00 MHDA- 2018/05/01 06:01 PMCR- 2018/04/18 CRDT- 2018/05/01 06:00 PHST- 2017/11/22 00:00 [received] PHST- 2018/02/26 00:00 [accepted] PHST- 2018/05/01 06:00 [entrez] PHST- 2018/05/01 06:00 [pubmed] PHST- 2018/05/01 06:01 [medline] PHST- 2018/04/18 00:00 [pmc-release] AID - 10.1177_1756286418768775 [pii] AID - 10.1177/1756286418768775 [doi] PST - epublish SO - Ther Adv Neurol Disord. 2018 Apr 18;11:1756286418768775. doi: 10.1177/1756286418768775. eCollection 2018.