Onset of Efficacy Following Oral Treatment With Lasmiditan for the Acute Treatment of Migraine: Integrated Results From 2 Randomized Double‐Blind Placebo‐Controlled Phase 3 Clinical Studies

摘要

Objective To expand on available information on the efficacy of oral lasmiditan for the acute treatment of migraine with particular focus on the timing of the effect and on its impact on migraine‐associated symptoms. Background Lasmiditan is a novel selective 5‐hydroxytryptamine 1F receptor agonist that lacks vasoconstrictive activity. In 2 phase 3 studies, SAMURAI and SPARTAN, lasmiditan met primary and key secondary efficacy endpoints at 2 hours following initial dose. Methods Integrated analyses were completed from 2 phase 3 clinical trials, SPARTAN and SAMURAI. Baseline data and data collected every 30?minutes up to 2?hours after taking lasmiditan (50, 100, or 200?mg) or placebo were analyzed to determine the onset of efficacy. A total of 5236 patients were randomized to be treated with placebo (N?=?1493), lasmiditan 50?mg (N?=?750), lasmiditan 100?mg (N?=?1498), or lasmiditan 200?mg (N?=?1495). Data were analyzed to determine the onset of improvement for the following efficacy measures: pain freedom, most bothersome symptom freedom, pain relief, freedom from associated individual symptoms (photophobia, phonophobia, or nausea), total migraine freedom (defined as pain freedom and freedom from associated symptoms), and freedom from migraine‐related functional disability. Time to meaningful headache relief and time to first become pain free were also analyzed. Results Significantly higher rates of pain freedom (100?mg, 10.0%, P ?=?.012; 200?mg, 15.5%, P ??.001; Placebo, 7.0%) and total migraine freedom (100?mg, 8.9%, P ?=?.017; 200?mg, 12.4%, P ??.001; Placebo, 6.1%) were achieved starting at 60?minutes in 100‐ and 200‐mg lasmiditan‐treated groups compared with placebo group. Rates of freedom from most bothersome symptom (100?mg, 11.1%, P ?=?.015; 200?mg, 13.0%, P ??.001; Placebo, 7.9%), and pain relief (100?mg, 17.5%, P ?=?.007; 200?mg, 19.1%, P ??.001; Placebo, 13.4%) were significantly higher starting as early as 30?minutes in lasmiditan 100‐ and 200‐mg lasmiditan‐treated groups. A significantly higher percentage of patients in the 200‐mg lasmiditan‐treated group achieved freedom from photophobia (13.7%, P ?=?.005; Placebo, 9.2%) and phonophobia (17.4%, P ?=?.042; Placebo, 13.4%) starting at 30?minutes. A significantly greater proportion of patients in the 200‐mg lasmiditan‐treated group achieved freedom from migraine‐related functional disability starting at 60?minutes (16.4%, P ??.001; Placebo, 11.1%). All efficacy measures, except for freedom from nausea, were statistically significant after lasmiditan treatment (50, 100, or 200?mg) compared with placebo at 90 and 120?minutes. Finally, patients taking lasmiditan had a higher likelihood of achieving meaningful headache relief and becoming headache pain free within 24?hours compared with those taking placebo ( P ??.001). Conclusions Patients treated with lasmiditan for a migraine attack reported an earlier onset of efficacy compared with those treated with placebo. Some of the efficacy measures such as pain relief demonstrated improvement as early as the first assessment at 30?minutes after 100‐ or 200‐mg lasmiditan treatment.