PMID- 38462625 OWN - NLM STAT- MEDLINE DCOM- 20240312 LR - 20240313 IS - 1129-2377 (Electronic) IS - 1129-2369 (Print) IS - 1129-2369 (Linking) VI - 25 IP - 1 DP - 2024 Mar 11 TI - Safety and tolerability of atogepant for the preventive treatment of migraine: a post hoc analysis of pooled data from four clinical trials. PG - 35 LID - 10.1186/s10194-024-01736-z [doi] LID - 35 AB - BACKGROUND: Conventional, non-specific preventive migraine treatments often demonstrate low rates of treatment persistence due to poor efficacy or tolerability. Effective, well-tolerated preventive treatments are needed to reduce migraine symptoms, improve function, and enhance quality of life. Atogepant is a migraine-specific oral calcitonin gene-related peptide receptor antagonist that is indicated for the preventive treatment of migraine in adults. This analysis evaluated the safety and tolerability profile of atogepant for the preventive treatment of migraine, including adverse events (AEs) of interest, such as constipation, nausea, hepatic safety, weight changes, and cardiac disorders. METHODS: This post hoc analysis was performed using data pooled from 2 (12-week) randomized, double-blind, placebo-controlled trials (RCTs) and 2 (40- and 52-week) open-label long-term safety (LTS) trials of oral atogepant for episodic migraine (EM). RESULTS: The safety population included 1550 participants from the pooled RCTs (atogepant, n = 1142; placebo, n = 408) and 1424 participants from the pooled LTS trials (atogepant, n = 1228; standard care [SC], n = 196). In total, 643/1142 (56.3%) atogepant participants and 218/408 (53.4%) placebo participants experienced >/= 1 treatment-emergent AEs (TEAEs) in the RCTs. In the LTS trials, 792/1228 (64.5%) of atogepant participants and 154/196 (78.6%) of SC participants experienced >/= 1 TEAEs. The most commonly reported TEAEs (>/= 5%) in participants who received atogepant once daily were upper respiratory tract infection (5.3% in RCTs, 7.7% in LTS trials), constipation (6.1% in RCTs, 5.0% in LTS trials), nausea (6.6% in RCTs, 4.6% in LTS trials), and urinary tract infection (3.4% in RCTs, 5.2% in LTS trials). Additionally, weight loss appeared to be dose- and duration-dependent. Most TEAEs were considered unrelated to study drug and few led to discontinuation. CONCLUSIONS: Overall, atogepant is safe and well tolerated in pooled RCTs and LTS trials for the preventive treatment of EM in adults. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT02848326 (MD-01), NCT03777059 (ADVANCE), NCT03700320 (study 302), NCT03939312 (study 309). CI - (c) 2024. The Author(s). FAU - Rizzoli, Paul AU - Rizzoli P AD - Brigham and Women's Hospital, Boston, MA, USA. FAU - Marmura, Michael J AU - Marmura MJ AD - Department of Neurology, Thomas Jefferson University, Jefferson Headache Center, Philadelphia, PA, USA. FAU - Robblee, Jennifer AU - Robblee J AD - Barrow Neurological Institute, Phoenix, AZ, USA. FAU - McVige, Jennifer AU - McVige J AD - DENT Neurologic Institute, Amherst, NY, USA. FAU - Sacco, Sara AU - Sacco S AD - Carolinas Headache Clinic, Matthews, NC, USA. FAU - Nahas, Stephanie J AU - Nahas SJ AD - Department of Neurology, Thomas Jefferson University, Jefferson Headache Center, Philadelphia, PA, USA. FAU - Ailani, Jessica AU - Ailani J AD - MedStar Georgetown University Hospital, Washington, DC, USA. FAU - De Abreu Ferreira, Rosa AU - De Abreu Ferreira R AD - AbbVie, 1 N. Waukegan Rd, North Chicago, IL, 60064, USA. FAU - Ma, Julia AU - Ma J AD - AbbVie, Florham Park, NJ, USA. FAU - Smith, Jonathan H AU - Smith JH AD - AbbVie, 1 N. Waukegan Rd, North Chicago, IL, 60064, USA. FAU - Dabruzzo, Brett AU - Dabruzzo B AD - AbbVie, 1 N. Waukegan Rd, North Chicago, IL, 60064, USA. brett.dabruzzo@abbvie.com. FAU - Ashina, Messoud AU - Ashina M AD - Department of Neurology, Danish Headache Center, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark. AD - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. LA - eng SI - ClinicalTrials.gov/NCT03939312 SI - ClinicalTrials.gov/NCT03700320 SI - ClinicalTrials.gov/NCT03777059 SI - ClinicalTrials.gov/NCT02848326 PT - Journal Article PT - Randomized Controlled Trial DEP - 20240311 PL - England TA - J Headache Pain JT - The journal of headache and pain JID - 100940562 RN - 7CRV8RR151 (atogepant) RN - 0 (Piperidines) RN - 0 (Pyridines) RN - 0 (Pyrroles) RN - 0 (Spiro Compounds) SB - IM MH - Adult MH - Humans MH - *Quality of Life MH - *Migraine Disorders/drug therapy/prevention & control/diagnosis MH - Treatment Outcome MH - Nausea MH - Double-Blind Method MH - Constipation MH - *Piperidines MH - *Pyridines MH - *Pyrroles MH - *Spiro Compounds PMC - PMC10926658 OTO - NOTNLM OT - Calcitonin gene-related peptide OT - Migraine OT - Safety OT - Tolerability COIS- PR reports no relevant disclosures. MJM within the past 24 months, has received compensation for consultation from Alder/Lundbeck, Axsome, Satsuma, Supernus, and Theranica; has participated in speaker bureaus for Amgen/Novartis and Eli Lilly; has received institutional support for serving as principal investigator for Allergan/AbbVie, and Teva; and has received payments for authorship or royalties from Cambridge University Press, Demos Medical, and MedLink. JR has received grant support from Barrow Neurological Foundation and investigator support from AbbVie and Eli Lilly; has served as a speaker for Impel; has a paid editorial relationship with MedLink Neurological and Neurodiem; and discloses that a family member has partial ownership of Scottsdale Providence Recovery Center. JM has served as a speaker and/or received research support from Alder, Allergan (now AbbVie), Amgen/Novartis, Avanir, Biohaven, Eli Lilly, Lundbeck, and Teva. SS has participated in advisory boards and/or is a speaker for Allergan (now AbbVie), Amgen, BDSI, Biohaven, Eli Lilly, Impel NeuroPharma, and Teva. SJN has received honoraria for consulting from Alder/Lundbeck, Allergan/AbbVie, Axsome (ended January 2022), BioDelivery Sciences (ended February 2022), Biohaven (ended November 2021), Eli Lilly, Teva (ended October 2021), Theranica (ended September 2022); has received honoraria for speaking from Eli Lilly (ended September 2021); has received honoraria for work in education or publishing from American Academy of Neurology, American Headache Society, Evolve Med Ed, Massachusetts Medical Society, MedLink Neurology, MJH Life Sciences, NACCME, Neurology Learning Network, Pennsylvania Neurologic Society, Springer, WebMD/Medscape, Wolters-Kluwer; has received legal fees for serving as a medical expert to Jackson & Campbell. JA has served as a consultant for AbbVie, Aeon, Amgen, Biohaven, Eli Lilly, GlaxoSmithKline, Gore, Impel, Linpharma, Lundbeck, Miravo, Nesos, Neurolief, Pfizer, Satsuma, Teva, and Theranica; received stock options from Ctrl M; provided editorial services to Current Pain and Headache Reports, SELF, and Medscape; and received clinical trial support from AbbVie, Biohaven, Eli Lilly, Rehaler, Satsuma, and Zosano. RDF, JM, JHS, and BD are employees of AbbVie and may hold AbbVie stock. MA has received personal fees from AbbVie, Amgen, Eli Lilly, GlaxoSmithKline, Lundbeck, Novartis, Pfizer and Teva; has participated in clinical trials as the principal investigator for AbbVie, Amgen, Eli Lilly, Lundbeck, Novartis, Pfizer and Teva; has received research grants from Lundbeck Foundation, Novo Nordisk Foundation, and Novartis; serves as associate editor of Cephalalgia, associate editor of The Journal of Headache and Pain, and associate editor of Brain; and has no ownership interest and does not own stocks of any pharmaceutical company. EDAT- 2024/03/11 06:42 MHDA- 2024/03/12 11:44 PMCR- 2024/03/11 CRDT- 2024/03/11 00:14 PHST- 2023/12/08 00:00 [received] PHST- 2024/02/23 00:00 [accepted] PHST- 2024/03/12 11:44 [medline] PHST- 2024/03/11 06:42 [pubmed] PHST- 2024/03/11 00:14 [entrez] PHST- 2024/03/11 00:00 [pmc-release] AID - 10.1186/s10194-024-01736-z [pii] AID - 1736 [pii] AID - 10.1186/s10194-024-01736-z [doi] PST - epublish SO - J Headache Pain. 2024 Mar 11;25(1):35. doi: 10.1186/s10194-024-01736-z.