Lasmiditan for Patients with Migraine and Contraindications to Triptans: A Post Hoc Analysis

John H Krege, Richard B Lipton, Simin K Baygani, Mika Komori, Sinéad M Ryan, Maurice Vincent, John H Krege, Richard B Lipton, Simin K Baygani, Mika Komori, Sinéad M Ryan, Maurice Vincent

Abstract

Introduction: As 5-HT1B receptor agonists, triptans produce vasoconstriction and have cardiovascular contraindications and precautions. Lasmiditan, a selective 5-HT1F receptor agonist, has a low affinity for 5-HT1B receptors, does not cause vasoconstriction, and is free of cardiovascular contraindications and precautions. The objective of this post hoc analysis was to evaluate the efficacy and safety of lasmiditan in patients with and without at least one triptan contraindication.

Methods: Patient subgroups, with and without triptan contraindications, were analyzed from pooled patient data from four randomized, double-blind, placebo-controlled clinical trials (SAMURAI, SPARTAN, CENTURION, and MONONOFU). Patients experiencing a single migraine attack of moderate or severe intensity were treated with lasmiditan 50 mg (SPARTAN and MONONOFU only), 100 mg, 200 mg, or placebo, and efficacy data were recorded in an electronic diary.

Results: Of 5704 patients, 207 (3.6%) patients had at least one contraindication to triptans. Overall subgroup analysis revealed that the effects of lasmiditan on pain freedom, pain relief, freedom from most bothersome symptom, disability freedom, and Patient Global Impression of Change at 2 h post-dose did not differ in patient groups with and without triptan contraindications. These outcomes generally showed a similar benefit pattern for lasmiditan in both subgroups, with all results being statistically significant in patients without contraindications, and pain relief being statistically significant in patients with contraindications. The safety and tolerability profiles of patients with triptan versus without triptan contraindications were similar, including dizziness in 18.3 to 22.8% and somnolence in 7.9 to 9.9% of patients at the highest dose of lasmiditan.

Conclusions: In pooled analyses from four trials, patients with and without triptan contraindications did not differ in their patterns of lasmiditan efficacy. Lasmiditan may be a treatment option in patients with contraindications to triptans.

Trial registration numbers: SAMURAI, NCT:02439320; SPARTAN, NCT:02605174; CENTURION, NCT:03670810; and MONONOFU, NCT:03962738.

Trial registration: ClinicalTrials.gov NCT02439320 NCT02605174 NCT03670810 NCT03962738.

Keywords: Cardiovascular; Contraindication; Headache; Lasmiditan; Migraine; Serotonin; Triptan.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Headache pain freedom (A) and freedom from MBS (B) in patients with and without a contraindication to triptans, 2 h following treatment with placebo, lasmiditan 100 or 200 mg. Comparisons of lasmiditan effect in the group of patients with triptan contraindications versus those without were not significant for any treatment group for either pain freedom or freedom from MBS (all interaction p values > 0.1). Odds ratio compared to patients who received placebo in the same subgroup. ***p < 0.001 vs. placebo. CI confidence interval, LTN lasmiditan, MBS most bothersome symptom, N number of patients, PBO placebo
Fig. 2
Fig. 2
Headache pain relief (A), Patient Global Impression of Change (B), and patient-reported freedom from migraine-related disability (C) in patients with and without a contraindication to triptans, 2 h following treatment with placebo, lasmiditan 100 or 200 mg. Comparisons of lasmiditan effect in the group of patients with triptan contraindications versus those without were not significant for any treatment group for either headache pain relief (percentage of patients with a reduction in pain severity from “moderate” or “severe” at baseline to “mild” or “none” at 2 h), PGIC (percentage of patients with responses “very much better” or “much better”), or freedom from migraine-related disability (percentage of patients with response option “none”) (all interaction p values > 0.1). Odds ratio compared to patients who received placebo in the same subgroup. *p < 0.05, ***p < 0.001 vs. placebo. CI confidence interval, LTN lasmiditan, N number of patients, PBO placebo, PGIC Patient Global Impression of Change

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