Migraine is a primary headache disorder with disabling episodic attacks, affecting around 12.5 percent of Hong Kong’s population. Important gaps in local migraine management include underuse of preventive therapy, delayed specialist referral and medication overuse. In an interview with MIMS Doctor, Dr David Sing-Ngai Cheung, Specialist in Neurology and a member of the Hong Kong Headache Society, discussed how calcitonin gene-related peptide (CGRP)–targeted therapies, particularly gepants, support earlier intervention and potentially improve outcomes of patients with migraine while offering favourable tolerability and safety.
Limitations of traditional migraine Tx
Acute migraine therapy has historically focused on symptom relief. NSAIDs and nonspecific analgesics (paracetamol ± caffeine, aspirin) have been used first-line, with triptans used for patients who do not respond to simple analgesics or have severe, disabling migraine. However, triptans are ineffective in about one-third of patients. “As triptans cause vasoconstriction, they are contraindicated in patients with certain cardiovascular [CV] diseases, such as coronary artery disease, stroke and uncontrolled hypertension, rendering them unsuitable for many older patients. Consequently, triptans are not used in about one-fifth of patients owing to contraindications,” said Cheung. [Front Pain Res (Lausanne) 2022:3:873179; Adv Ther 2020;37:4765-4796; Cephalalgia 2023;43:1-13]
“Suboptimal efficacy and tolerability of acute treatments contribute to poor migraine control, progression from episodic to chronic migraine, and increased healthcare use,” he noted. “Frequent use of acute analgesics can lead to medication overuse headache [MOH], which is common in people with chronic migraine [ie, ≥15 headache days/month for >3 months, with features of migraine headache on >8 days/month] and is associated with substantial disability and reduced quality of life. In our practice, about 5–10 percent of all migraine patients and 70 percent of chronic migraine patients have MOH.” [Nat Rev Neurol 2016 ;12:455-464; https://ichd-3.org/1-migraine/1-3-chronic-migraine/; Nat Rev Dis Primers 2023;9:5]
“Given these challenges, preventive therapy is essential: it reduces attack frequency, severity and duration, limits reliance on acute treatments, and lowers the risk of MOH,” Cheung continued. Traditionally used preventive agents (β- blockers antidepressants, anticonvulsants) are non–migraine-specific and limited by variable efficacy, side effects (such as weight gain with antidepressants), tolerability issues and contraindications. [Continuum (Minneap Minn) 2024;30:364- 378; Clin Ther 2008;30:1069-1080; J Headache Pain 2023;24:56]
Together, these limitations underscore the need for mechanism-based, migraine-specific therapies with improved efficacy and tolerability.
CGRP-targeted therapies: A paradigm shift in preventive & acute Tx
CGRP is released from sensory neurons in the trigeminal ganglion during migraine attacks. It causes vasodilation of meningeal blood vessels and facilitates nociceptive pain signalling within the central nervous system. Blocking CGRP signalling can therefore abort attacks and lower migraine susceptibility. In recent years, CGRP-targeted therapies, including small‑molecule CGRP receptor antagonists (gepants) and monoclonal antibodies (mAbs) that bind the CGRP ligand or its receptor, have transformed migraine care by offering mechanism-based, migraine-specific options: mAbs for preventive treatment and gepants for both acute and preventive use. [Aust Prescr 2025;48:40-46; Nat Rev Neurol 2010;6:573-582; Nat Rev Neurol 2018;14:338-350]
Pivotal trials of mAbs and some gepants have shown statistically significant reductions in monthly migraine days in both episodic and chronic migraine, with very low discontinuation rates, reflecting their efficacy and good tolerability. As a result, the American Headache Society supports CGRP-targeting therapies as a first-line preventive option without requiring prior failure of nonspecific preventive agents. [Headache 2024;64:333-341]
Gepants for acute treatment have demonstrated efficacy and favourable tolerability in randomized and real-world studies, including in patients with inadequate response to triptans. Their safety profile, including relative CV safety compared with vasoconstrictive agents, is supported by pivotal and extension studies. Consequently, gepants are now recommended as a first-line acute option alongside triptans, particularly for patients with triptan contraindications, poor triptan response, or triptan intolerance. [Headache 2026;66:976-989]
“Consensus in the Asia Pacific region supports uptake of CGRP-targeted therapies because of their efficacy and improved safety and adherence. There is a positive move towards using gepants and other CGRP-targeted therapies in this region, although it may take time for them to be adopted as first-line therapies,” Cheung remarked. “In Hong Kong, neurologists and family physicians are starting to use gepants or other CGRP-targeted therapies as first- or second-line treatment, and these drugs are becoming more popular in both the public and private sectors.” [Front Neurol 2026:17:1770966]
Rimegepant’s tolerability & real-world efficacy
Rimegepant is currently the only gepant approved for both acute and preventive treatment. “It is available as an orally disintegrating tablet that can be taken without water, which enhances convenience and treatment onset time during an attack,” said Cheung. [Nurtec Hong Kong Prescribing Information, June 2023; CNS Drugs 2023;37:255-265]
Rimegepant has a favourable tolerability profile. In pooled analyses of phase III trials (n=3,553), adverse events (AEs) occurred in 14.2 percent of patients treated with as-needed rimegepant vs 11.7 percent with placebo; most events were mild to moderate in severity and resolved without intervention. Serious AEs were uncommon (0.2 percent in both groups). The most common AEs were nausea (1.5 vs 0.8 percent) and urinary tract infection (1.1 vs 0.6 percent). In preventive treatment trials using every-other-day dosing, tolerability was similar between rimegepant and placebo, with low discontinuation rates due to AEs (2 vs 1 percent). [CNS Drugs 2023;37:255-265]
Patient satisfaction and restoration of normal daily functioning, in addition to pain relief, are increasingly recognized as efficacy outcomes. In an interim analysis of a large observational registry of 3,000 patients from China, higher proportions of patients were extremely or very satisfied with rimegepant vs triptans for pain relief and return to normal function. (Figure) AEs were uncommon (2.4 percent) and generally nonserious. The most frequently reported AE was nausea (0.1 percent). [Ran Y, et al, AHS 2025]
Conclusion
The advent of CGRP‑targeted therapies marks a shift from repurposed, non–disease‑specific drugs to mechanism‑based treatments tailored to migraine pathophysiology. “Gepants have expanded the treatment landscape by providing effective, well-tolerated, migraine-specific options that address important unmet needs. For instance, rimegepant – currently the only gepant with both acute and preventive indications – offers flexibility across treatment settings, and may help limit MOH and reduce progression to chronic migraine,” Cheung summarized.