Lasmiditan Efficacious in Patients With Insufficient Triptan Response

Investigators’ analysis of a subset of patients with insufficient response from the CENTURION study suggests that the acute agent from Eli Lilly offers potential in this population.

Data from the CENTURION study (NCT03670810) suggest that lasmiditan (Reyvow; Eli Lilly) is effective in treating acute migraine with or without aura in patients with an insufficient response to triptans.

“No standard definition for triptan insufficient responders (TIR) exists. Prior definitions have included both efficacy and tolerability considerations, and often rely on patients’ self-reports rather than prospective identification,” presenting author John Krege, MD, senior medical fellow, Eli Lilly, and colleagues wrote. Krege presented the data at the 2021 American Headache Society (AHS) Annual Scientific Meeting, June 3-6.

The phase 3, placebo-controlled CENTURION study defined patients as TIR if they were currently taking a triptan with a score of less than 5 on the Migraine Treatment Optimization Questionnaire 6 (mTOQ-6); did not achieve pain freedom at 2 hours post-dose in at least 2 of their 3 most recent attacks; or were not currently taking a triptan and had discontinued due to lack of efficacy, tolerability issues, or contraindications. These criteria were defined beforehand based on literature review and input from a migraine expert advisory board.

Krege and colleagues investigated the efficacy of lasmiditan in the subset population of 633 participants with TIR in the CENTURION study. These participants were a mean age of 42 years (standard deviation [SD], 12) and 88% were women. Most (91%) were white, and 62% had cardiovascular risk factors. The mean migraine history was 19 years (SD, 13) and participants had had a mean of 5.0 (SD, 1.6) migraines per month in the past 3 months. The participants had a mean Migraine Disability Assessment (MIDAS) score of 34 (SD, 22) and 36% took migraine preventive treatment during the study.

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Of the TIR participants, 76% had tried 1 triptan, 17% had tried 2, and 7% had tried 3 or more. Most participants (63%; n = 401) were considered TIR due to inadequate response to most recent triptan or due to a mTOQ-6 score of no more than 5 on their current triptan (61%; n = 388). The remaining TIR population (26%; n = 167) discontinued their triptan due to lack of efficacy (76%; n = 127), tolerability issues (23%; n = 39), or contraindications (1.2%; n = 2).

The investigators found that both lasmiditan 100 mg and 200 mg resulted in statistically significant improvements in the percentage of patients being pain-free beginning at 1 hour. Lasmiditan 200 mg showed statistically significant improvements in the percentage of patients with pain relief beginning at 0.5 hours and the 100-mg dose showed improvements beginning at 1 hour.

First-dose findings in the TIR population were similar for the global population in the CENTURION study when investigators excluded TIR patients categorized based on tolerability or contraindications without formal analysis.

After first dose of lasmiditan 100 mg (n = 183), patients had a 4.2 odds ratio (OR; 95% CI, 1.8-9.6) of achieving sustained pain freedom for 24 hours, a 1.9 OR (95% CI, 0.9-4.2) of achieving sustained pain freedom for 48 hours, and a 1.6 OR (95% CI, 0.8-2.9) of being disability free at 2 hours (compared to placebo; all P <.005). These patients also had a 2.3 OR (95% CI, 1.4-3.9) of having a much or very much better patient global impression of change (PGIC) score at 2 hours, a 1.6 OR (95% CI, 1.0-2.7) of a “much” or “very much” better PGIC score at 24 hours, a 1.3 OR (95% CI, 0.8-2.0) of being most bothersome symptom (MBS)-free at 2 hours, and a 0.6 OR (95% CI, 0.4-1.0) of using rescue medication at 2-24 hours (compared to placebo; all P <.005).

After first dose of lasmiditan 200 mg (n = 203), patients had a 4.4 OR (95% CI, 1.9-10.0) of achieving sustained pain freedom at 24 hours, a 2.9 OR (95% CI, 1.4-5.9) of achieving sustained pain freedom at 48 hours, and a 2.2 OR (95% CI, 1.2-4.0) of being disability free at 2 hours (all compared to placebo; P <.005). These patients also had a 2.4 OR (95% CI, 1.4-4.1) of having a much or very much better PGIC score at 2 hours, a 2.4 OR (95% CI, 1.5-4.0) of having a much or very much better PGIC score at 24 hours, a 1.3 OR (95% CI, 0.8-2.0) of being MBS-free at 2 hours, and a 0.5 OR (95% CI, 0.3-0.8) of using rescue medication at 2-24 hours (compared to placebo; all P <.005).

“Lasmiditan was efficacious across multiple clinically relevant endpoints in a pre-specified subset of patients with an insufficient response to triptans,” Krege and colleagues concluded.

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REFERENCE
Reuter U, LombardL, Krege JH, et al. Lasmiditan Is effective in the acute treatment of migraine in patients with insufficient response to triptans: Findings from the CENTURION study. Presented at 2021 AHS Annual Scientific Meeting; June 3-6. Abstract P64.