Trajectory of migraine-related disability following long-term treatment with lasmiditan: results of the GLADIATOR study

Abstract

Background: Migraine is recognized as the second leading cause of disability globally. Lasmiditan is a novel, selective serotonin 5-HT1F receptor agonist developed for acute treatment of migraine. Here we analyzed effects of lasmiditan on migraine disability assessed with the Migraine Disability Assessment (MIDAS) scale for interim data from a long-term safety study.

Methods: Completers of two single-attack parent studies were offered participation in the 1 year GLADIATOR study, that randomized participants to treatment with lasmiditan 100 mg or 200 mg taken as needed for migraine attacks of at least moderate severity. Changes in MIDAS were modeled using a mixed model repeated measures analysis.

Results: The sample included 1978 patients who received ≥1 lasmiditan dose and were followed for a median of 288 days. Baseline mean MIDAS scores for the lasmiditan 100-mg and 200-mg groups were 29.4 and 28.9, respectively, indicating severe migraine-related disability. Relative to baseline, MIDAS total scores were significantly lower at 3, 6, 9, and 12 months for both dose groups. At 12 months, changes in MIDAS scores were - 12.5 and - 12.2 for lasmiditan 100 mg and 200 mg, respectively, with 49% and 53% of patients, respectively, achieving at least a 50% decrease in MIDAS total score. Statistically significant improvements were also seen for work and/or school absenteeism and presenteeism, monthly headache days, and mean headache pain intensity at all time points up to 1 year. Findings for patients who completed all visits versus those dropping out early were similar. Responses were generally similar for the lasmiditan 100 mg or 200 mg doses, between subgroups defined based on the number of baseline monthly migraine attacks (≤5 vs. >5), and also between subgroups defined by pain-free response (yes/no) during initial attacks.

Conclusions: Long-term treatment with lasmiditan was associated with significant reductions in migraine-related disability, including both work or school absenteeism and presenteeism. The similarity of responses in completers and those who dropped out suggests that selective attrition does not account for the improvements. Benefits were significant at 3 months and maintained through 12 months.

Trial registration: clinicaltrials.govNCT02565186; first posted October 1, 2015.

Keywords: 5-HT1F agonist; Absenteeism; Disability; Ditan; Function; MIDAS; Migraine; Presenteeism; Serotonin.

Conflict of interest statement

Richard B Lipton has received consultant fees, honoraria, and/or research grants from Alder, Allergan, Inc., Amgen, Biohaven, Dr. Reddy’s Laboratories, eNeura, electroCore, Eli Lilly and Company, Novartis, Teva, and Trigemina. He has stock options in eNeura and Biohaven. Dawn C Buse has received grant support and honoraria from Allergan, Amgen/Novartis, Biohaven, Dr. Reddy’s Laboratories/Promeius, Eli Lilly and Company, and Teva. Louise Lombard, Dustin D Ruff, John H Krege, Li Shen Loo, and Andrew Buchanan were employees and minor stockholders of Eli Lilly and Company. Thomas E Melby was an employee of Syneos Health, Inc., under contract to Eli Lilly and Company.

Figures

Fig. 1

Completer analysis showing MIDAS total score overall and for patients who completed a maximum of 3, 6, 9, or 12 months of study for a) Lasmiditan 100 mg and b) Lasmiditan 200 mg. Abbreviations: Mo. = month. Note that N within completer subgroups remained nearly constant (within 2 patients) across relevant timepoints

Fig. 2

Decreases from baseline in MIDAS total score of (a) ≥5 points or (b) ≥50%

Fig. 3

Improvement from baseline in lost productive days of (a) ≥50% or (b) 100%

Fig. 4

Mean MIDAS score by study month in subgroups defined by monthly migraine attacks at baseline (a) ≤5 and (b) >5. **P < 0.001 vs. baseline; mixed model for repeated measures. There were no significant differences between the lasmiditan dose groups.

Fig. 5

Mean MIDAS Score by pain-free response 2 h post-dose (a) yes, first attempt, (b) no, first attempt, (c) yes, ≥2 of first 3 attempts (d) no, ≥2 of first 3 attempts (intent-to-treat population). **P < 0.001 vs. baseline; mixed model for repeated measures There were no significant differences between the lasmiditan doses.