Tolerability and Safety of Lasmiditan Treatment in Elderly Patients With Migraine: Post Hoc Analyses From Randomized Studies.

Purpose: Limited information is available on acute treatments for migraine in elderly patients. Our objective was to evaluate the tolerability and safety of lasmiditan, a serotonin 1F agonist, for the acute treatment of migraine in elderly compared with nonelderly patients, with special emphasis on cardiovascular-related issues because cardiovascular comorbidities are more common in the elderly population.

Methods: These post hoc analyses evaluated the incidence of treatment-emergent adverse events (TEAEs) in elderly (≥65 years of age) versus nonelderly (<65 years of age) lasmiditan-treated patients. Two clinical trials entitled A Study of Two Doses of LAsMiditan (100 mg and 200 mg) Compared to Placebo in the AcUte Treatment of MigRAIne (SAMURAI) and A Study of Three Doses of Lasmiditan (50 mg, 100 mg and 200 mg) Compared to Placebo in the Acute TReaTment of MigrAiNe (SPARTAN) were randomized, double-blind, placebo-controlled, Phase III studies in adults (no upper age limit) who took placebo or lasmiditan 50 (SPARTAN only), 100, or 200 mg for a single migraine attack within 4 hours of the onset of moderate or severe pain. Patients who completed SAMURAI or SPARTAN were eligible to enroll in An Open-label, LonG-term, Safety Study of LAsmiDItan (100 mg and 200 mg) in the Acute Treatment Of MigRaine (GLADIATOR), a Phase III, randomized, open-label, multiattack study of lasmiditan 100 or 200 mg. For pooled SAMURAI+SPARTAN data, treatment × age subgroup interactions were examined using logistic regression analyses. In addition, common cardiovascular event rates were assessed from GLADIATOR during 3 periods: treatment-emergent (<48 hours after dosing), intermediate (48 hours to 1 week after dosing), and remote (>1 week after dosing).

Findings: Of 3177 lasmiditan-treated patients in SAMURAI or SPARTAN, 132 (4.2%) were elderly, and of 1262 placebo-treated patients, 54 (4.3%) were elderly. Of 2030 lasmiditan-treated patients in GLADIATOR, 85 (4.2%) were elderly. The incidences of at least 1 TEAE with lasmiditan in nonelderly and elderly patients with migraine were 36% and 35% in pooled SAMURAI+SPARTAN, respectively, and 49% and 38% in GLADIATOR, respectively. No significant treatment × age subgroup interactions were observed in patients with ≥1 TEAE overall or for any individual TEAE in pooled SPARTAN+SAMURAI; however, numerical differences in the incidence of some specific TEAEs were seen. No treatment × age subgroup interactions and no tolerability concerns for individual TEAEs were detected. Cardiovascular TEAEs were much more frequent in the nonelderly population than the elderly population. Cardiovascular events were not reported in the elderly population during the treatment-emergent period or intermediate period. There were 2 cases of increased blood pressure in elderly patients during the remote period.

Implications: The incidence of TEAEs was similar for elderly and nonelderly patients, and cardiovascular safety of lasmiditan was generally consistent with that in single-attack studies. No safety signals were observed with the limited number of patients in the elderly population. ClinicalTrials.gov identifiers: NCT02565186 (GLADIATOR), NCT02439320 (SAMURAI), and NCT02605174 (SPARTAN).