Project description:ObjectivesTo describe the methodology and implications of the patient-identified most bothersome symptom (PI-MBS) measure used in the phase 3, multicenter, randomized, double-blind, placebo-controlled, and parallel-group PROMISE-2 trial and to evaluate the contribution of this measure to the assessment of the preventive migraine benefits of treatment.BackgroundAlthough freedom from MBS is a coprimary endpoint in acute migraine treatment trials, its evaluation in preventive migraine trials is limited. The PROMISE-2 study assessed a unique PI-MBS measure as a secondary endpoint.MethodsThis was a secondary analysis of data from the PROMISE-2 study. Adults with chronic migraine (CM) were randomized to receive intravenous (IV) eptinezumab 100 mg, eptinezumab 300 mg, or placebo, administered on day 0 and every 12 weeks. At the screening visit, patients were asked to verbally describe the MBS associated with their CM; the question format was open ended. At subsequent visits, patients were asked to rate the overall change in severity of their MBS from study inception to that time point, using a 7-point ordinal scale ranging from "very much worse" (-3) to "very much improved" (+3). Patients completed the Patient Global Impression of Change (PGIC) assessment during the same visits, using an identical rating scale and recall period. Endpoints were summarized descriptively; post hoc correlations using the methodologies of Pearson and Spearman were calculated to evaluate relationships between PGIC and PI-MBS and between PGIC and mean monthly migraine days (MMDs; primary efficacy endpoint in PROMISE-2).ResultsAltogether, 1072 patients received treatment (eptinezumab 100 mg, n = 356; eptinezumab 300 mg, n = 350; placebo, n = 366) and were included in the analysis. There were 23 unique MBS identified; those reported by ≥10 patients included light sensitivity (18.7%), nausea/vomiting (15.1%), pain with activity (13.7%), pain (12.4%), headache (11.2%), sound sensitivity (7.3%), throbbing/pulsating pain (4.7%), cognitive disruption (4.1%), fatigue (2.4%), mood changes (1.5%), and sensitivity to smell (0.9%). Four weeks after the first dose (week 4), the rates of much or very much improvement in PI-MBS were higher with eptinezumab 100 mg (45%) and 300 mg (57%) than with placebo (29%). Four weeks after the second dose (week 16), the proportions with much or very much improvement in PI-MBS had increased to 58%, 65%, and 36%, respectively. At each time point, the percentages of patients with PGIC ratings of much or very much improved were similar to those for patient-reported improvement in PI-MBS. Patient ratings of changes in PI-MBS and PGIC correlated strongly across time points (Pearson, r range, 0.83-0.88; Spearman, r range, 0.83-0.89); the absolute value of the correlations was greater than the correlation among changes in MMDs and PGIC (Pearson, r range, -0.49 to -0.52; Spearman, r range, -0.49 to -0.52).ConclusionsAmong patients with CM in the PROMISE-2 study, a broad range of PI-MBS was reported at baseline. Throughout the study, patients treated with eptinezumab reported greater improvement in their PI-MBS severity compared with placebo recipients, and this improvement correlated strongly with PGIC findings. Collectively, these results indicate that PI-MBS is a promising and novel outcome measure for preventive trials of CM and thus may provide a unique patient-centered approach for identifying and measuring the burden of migraine symptoms that matter most to each patient, as well as the benefits of treatment.
| S-EPMC8251621 | biostudies-literature
