Abstract
BackgroundWhile pain freedom at 2 h is a key primary outcome for current trials for acute treatment of migraine, the relationship between the degree of head pain and other efficacy measures at 2 h has rarely been explored. Following lasmiditan treatment of a migraine attack with moderate or severe head pain, we contrast those who achieve pain freedom with those who achieve mild pain but not pain freedom 2 h post dosing.MethodsPatient-level data were pooled across studies and treatment arms from two Phase 3 trials comparing lasmiditan and placebo, SAMURAI and SPARTAN. This post hoc analysis assessed freedom from the most bothersome symptom (MBS), freedom from migraine-related functional disability (disability), and improved patient global impression of change (PGIC) in patients who achieved 2 h pain freedom compared to those who experienced 2 h mild pain. Mild pain differs from pain relief which is defined as either mild pain or pain freedom.ResultsPatients who achieved 2 h pain freedom (N = 913), in comparison with those with 2 h mild pain (N = 864), were significantly more likely to experience MBS freedom (91.9% vs. 44.9%), disability freedom (87.1% and 13.4%), and improved PGIC (86.5% and 31.5%) (p < 0.001 for all combinations). In addition, more patients who were pain free experienced both 2 h MBS freedom and 2 h functional disability freedom (83.6%) compared to those with mild pain (10.8%; p < 0.001). The proportion of patients with pain freedom who did not achieve either MBS or disability freedom (4.6%) was lower than in patients with mild pain (52.4%). Lastly, 55.2% of patients experienced mild pain before disability freedom compared to 72.1% who experienced pain freedom and disability freedom at the same time.ConclusionsThis study demonstrated that, at 2 h post treatment, patients who were pain free were more likely to achieve other outcomes including freedom from their MBS, freedom from migraine-related functional disability, and improved PGIC compared to those with mild pain, confirming that 2 h pain freedom is more robustly associated with other clinical outcomes than the 2 h mild pain endpoint.Trial RegistrationSAMURAI (NCT02439320); SPARTAN (NCT02605174).
Highlights
While pain freedom at 2 h is a key primary outcome for current trials for acute treatment of migraine, the relationship between the degree of head pain and other efficacy measures at 2 h has rarely been explored
The recommended primary endpoint for acute treatment of migraine attacks was revised by the International Headache Society (IHS) and Food Drug Administration (FDA) guidelines to pain freedom at 2 h post-dose for the following reasons: 1) placebo rates for pain relief at 2 h are variable and may exceed 50% [1], 2) the pain relief endpoint defines some patients with incomplete response as achieving success, and 3) judgements about mild pain may be more subjective than judgements about no pain [2]
For the subset of patients who achieved both a successful pain outcome and most bothersome symptom (MBS) freedom or functional disability freedom at 2 h, we examined the order of occurrence for those outcomes: outcome A before outcome B, or outcome B before outcome A, or both outcomes at the same assessment time point
Summary
Study design Pooled patient-level data from double-blind, multicenter Phase 3 trials, SAMURAI (NCT02439320) and SPARTAN (NCT02605174), were included in this post hoc analysis. The pain efficacy outcome responses were compared with other clinically relevant efficacy outcomes of freedom from MBS (defined as the absence of MBS) and freedom from migraine-related functional disability. PGIC was assessed with the question “How do you feel after taking study medication?” with responses recorded using a 7-point Likert scale, ranging from “very much better” to “very much worse”. The modified intent-to-treat (mITT) population was used and included patients who took the randomly assigned treatment within 4 h of migraine onset and provided post-treatment data on headache severity or symptoms. Outcomes reported through 2 h post-dose were included in this analysis; patients were considered to fail outcomes at each time point if they used rescue medication at or before that time point. Patients were indicated as unsustained if they moved into and out of the dual positive outcome group within the interval from dosing to 2 h post-dose
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