Migraine is a highly disabling neurological condition that profoundly affects patients’ quality of life (QoL) and productivity. Traditional first-line (1L) preventive treatments were not originally developed for migraine and are often limited by suboptimal efficacy and poor tolerability. In an interview with MIMS Doctor, Dr William Kingston of the Division of Neurology, Department of Medicine, Temerty School of Medicine, University of Toronto, Canada, discussed the emergence of calcitonin gene–related peptide (CGRP) inhibitors, including atogepant, as a significant breakthrough in migraine prevention, offering targeted, migraine-specific efficacy with improved tolerability.
Who should receive migraine prophylaxis?
Guidelines generally recommend preventive treatment for patients who meet ≥1 of the following criteria: ≥4 monthly migraine days (MMDs); significant impact on personal, social, or professional functioning; inadequate response to optimal acute treatment; frequent use/failure of acute medications; and adverse events (AEs) with acute treatments. [Cephalalgia 2024;44:1-31; Headache 2021;61:1021-1039]
“Preventive therapy should be considered for patients whose migraines significantly interfere with QoL, even if their attacks are relatively infrequent,” shared Kingston.
CGRP-targeted Tx vs traditional 1L preventive Tx
Conventional nonspecific migraine preventive medications, including antiepileptic drugs, antihypertensives, and antidepressants, are often limited by tolerability issues and suboptimal efficacy, resulting in poor adherence — estimated at 26–29 percent at 6 months and declining to 17–20 percent by 1 year. [CMAJ 2023;195:E187-xzE192; Cephalalgia 2015;35:478-488]
“CGRP inhibitors [both monoclonal antibodies (mAbs) and gepants] provide a migraine-specific therapeutic option with superior efficacy, safety, and tolerability compared with traditional 1L migraine therapies,” pointed out Kingston. [J Headache Pain 2023;24:56; Reuter U, et al, IHC 2025, abstract IHC25-LBAPO-060]
“Atogepant offers the added benefit of a fast onset of action,” he added. Atogepant can be initiated at the therapeutic dose on day 1 and typically demonstrates rapid onset of efficacy, whereas topiramate must be started at a lower dose and gradually uptitrated, which can take up to 2–3 months to establish clinical efficacy. [Cephalalgia 2022;42:3-11; J Am Osteopath Assoc 2007;107:251-258]
TEMPLE: Atogepant outperforms topiramate
The randomized, double-blind, phase III TEMPLE trial (n=540) evaluated the tolerability, safety, and efficacy of atogepant vs topiramate for preventive treatment of migraine in adult patients with a history of ≥4 MMDs. [Reuter U, et al, IHC 2025, abstract IHC25-LBAPO-060]
Atogepant demonstrated superior tolerability vs topiramate, with significantly fewer treatment discontinuations due to AEs over the 24-week treatment period, thereby meeting the study’s primary endpoint (12.1 vs 29.6 percent; relative risk [RR], 0.41; 95 percent confidence interval [CI], 0.28–0.59; p<0.0001).
TEMPLE also met its secondary clinical efficacy endpoints evaluated during months 4–6. A significantly greater proportion of participants in the atogepant group achieved a ≥50 percent reduction in mean MMDs vs those receiving topiramate (64.1 vs 39.3 percent; RR, 1.63; p<0.0001). (Figure 1) Reduction from baseline in mean MMDs was also significantly greater with atogepant vs topiramate (-6.27 vs -4.49; treatment difference [Δ], -1.78; p<0.0001). (Figure 2)
Atogepant was associated with a lower incidence of treatment-emergent adverse events (TEAEs) and treatment[1]related TEAEs over 24 weeks compared with topiramate (76.9 vs 88.8 percent and 56.0 vs 77.9 percent, respectively). [Reuter U, et al, IHC 2025, abstract IHC25-LBAPO-060] The AE profile of atogepant was consistent with its established safety profile, demonstrating favourable systemic tolerability. In clinical trials, the most commonly reported TEAEs were mild-to-moderate constipation and nausea, which were generally transient and resolved within a few weeks of treatment initiation. [J Headache Pain 2024;25:35]
“TEMPLE’s efficacy and tolerability data provide a patient-centred perspective on treatment effectiveness, offering meaningful insight into the real-world impact of treatment persistence in migraine prevention,” noted Kingston. “Since incorporating CGRP-targeted agents, including atogepant, into our clinical practice, we have observed fewer discontinuations of migraine preventive therapy and a marked reduction in patient calls related to side effects. These improvements reflect enhanced adherence, better tolerability, and greater overall patient satisfaction.”
CGRP-targeted therapy as 1L preventive Tx
“The TEMPLE trial demonstrates that targeted treatment provides superior tolerability, adherence and efficacy [compared with nonspecific therapy.] Targeted agents should be considered earlier in migraine treatment algorithms,” highlighted Kingston. “This aligns with recent statements from the American, Canadian, and other international headache societies endorsing CGRP-targeted therapies as 1L options for migraine prophylaxis.” [Headache 2024;64:333-341; Can J Neurol Sci 2025;52:450-472; Cephalalgia 2024;44:1-31; Rev Neurol (Paris) 2024;180:1087-1099; J Headache Pain 2022;23:67]
Potential benefits of atogepant in special populations
Given that most migraine sufferers are young working adults, effective migraine control with targeted agents such as atogepant can offer meaningful benefits. “We often see improvements in productivity, reduced presenteeism [being at work but underperforming], and a lower interictal burden [the impact between migraine attacks],” said Kingston. “Patients also report better mood, improved sleep, and enhanced overall functioning.” [J Headache Pain 2024;25(Suppl 1):123; Cephalalgia 2024;44:1-14]
Atogepant represents a safer alternative to CGRP mAbs in women planning pregnancy. Owing to its short elimination half-life (10 hours vs 27–31 days for CGRP mAbs), atogepant can be discontinued 1 week before conception, whereas CGRP mAbs require a washout period of about 6 months. [Can J Neurol Sci 2025;52:450-472; Lancet Neurol 2022;21:284-294]
Final thoughts
CGRP-targeted therapies are a major advancement in migraine prevention, providing improved efficacy and tolerability. Atogepant’s oral formulation adds convenience and versatility, potentially enhancing patient adherence and acceptance.
For healthcare professional use only.
AGPT-HK-00016-FM 19 Dec 2025
