Effectiveness and tolerability of lasmiditan in the acute treatment of migraine: a real-world, prospective, multicentric study (DART study)

Background: Lasmiditan, an oral 5-HT1F receptor agonist, has been recently approved for acute migraine treatment. While its efficacy was confirmed in randomized clinical trials, scarce data is available regarding effectiveness and tolerability in the real-world setting. Objectives: To evaluate lasmiditan effectiveness and tolerability in the real-world setting in 16 Italian headache centers. Design: LasmiDitan as Acute migRaine Treatment (DART) study is a prospective, multicentric, observational study. Methods: We enrolled 58 participants with migraine (84.5% females, age 49.0 (45.2–52.9) years, 24.1% with chronic migraine) reporting 9.4 (7.4–11.3) monthly migraine days. Participants were instructed to treat their migraine attacks with oral lasmiditan 50 or 100 mg. Using an ad hoc electronic diary, participants prospectively collected migraine attack features at baseline and every 30 min after lasmiditan administration, up to 2 h post-dose. The primary outcome was 2-h pain freedom for the first-treated attack after lasmiditan intake. We also collected the occurrence of treatment-emergent adverse events (AE) after administration. Results: Overall, participants treated 100 attacks, of which 58 first-treated attacks. Regarding first-treated attacks, 44.8% of subjects rated migraine intensity as severe at lasmiditan intake. Pain freedom 2-h post-dosing was reported in 32.8% (19/58) of individuals and was associated with baseline pain intensity, being higher in subjects treating a mild/moderate attack (p = 0.044). Conversely, it was not influenced by timing of intake (p = 0.375), dosage (p = 0.727), or previous triptan failure (p = 0.351). Regarding all-treated attacks, pain freedom 2-h post-dosing was 37.0% (37/100). At least one AE was reported by 53.4% of participants (31/58), predominantly asthenia, dizziness, somnolence, anxiety or agitation, and paresthesia. Tolerability was rated as good-to-excellent by 51.8% of subjects. Conclusion: Our study supports clinical effectiveness of oral lasmiditan 50 and 100 mg for the treatment of acute migraine attacks. Lasmiditan effectiveness was not associated with the previous triptan failure and may therefore represent a valuable therapeutic option in subjects who did not benefit from, or have contraindications to, triptans. Trail registration: The study was preregistered on clinicaltrial.gov, NCT05903040 (https://clinicaltrials.gov/study/NCT05903040?cond=migraine&intr=lasmiditan&rank=5).