Effect of Galcanezumab on Total Pain Burden in Patients Who Had Previously Not Benefited from Migraine Preventive Medication (CONQUER Trial): A Post Hoc Analysis

Abstract

Introduction: In evaluating therapies for migraine prevention, emphasis is placed on frequency and less attention is paid to duration or severity. Total pain burden (TPB) combines frequency, duration, and severity of migraine headache, and has the potential to further characterize the benefit of preventive treatment using a single composite measure. TPB was previously used to characterize response to galcanezumab (GMB) in patients with migraine. In this post hoc analysis we assessed the impact of GMB in lowering TPB in patients who had previously not benefited from two to four categories of migraine preventive medication.

Methods: CONQUER trial patients (N = 462), 18-75 years old who had previously not benefited from two to four categories of migraine preventive medication, were randomized (1:1) to monthly placebo or GMB 120 mg with 240 mg loading dose. For each patient, monthly TPB in severity-weighted hours was calculated by multiplying migraine headache duration (hours) by maximum severity for each migraine headache day, then summing these daily scores over the month for the monthly score. Changes from baseline in monthly TPB across months 1-3 were analyzed. Spearman correlations between TPB and scores on the Migraine-Specific Quality-of-Life Questionnaire (MSQ) total and Migraine Disability Assessment Scale (MIDAS) were assessed at baseline.

Results: Mean (SD) baseline monthly TPB was 192.1 (158.3) and 188.2 (197.4) severity-weighted hours for GMB-treated and placebo-treated patients, respectively. Across the 3-month double-blind period, GMB-treated patients experienced significantly greater mean reductions from baseline in monthly TPB compared with placebo-treated patients, both for mean change (GMB - 82.7, placebo - 15.8, p < 0.001) and percentage change (GMB - 38.6%, placebo 9.4%, p < 0.001). Furthermore, baseline TPB correlated with MSQ score (r = - 0.39) and MIDAS score (r = 0.40), suggesting good association of TPB with functional and disability outcomes.

Conclusion: GMB reduced mean TPB in patients who had previously not benefited from two to four categories of migraine preventive medication.

Trial registration: NCT03559257.

Keywords: CONQUER trial; Galcanezumab; Migraine; Prior preventive failures; Total pain burden.

© 2022. The Author(s).

Figures

Fig. 1

Effect of galcanezumab on total pain burden. LS mean change (SE) in severity-weighted hours from baseline at each month and overall across all months in patients with episodic migraine (a), chronic migraine (b), and in the overall population (c). ***p < 0.001 vs. placebo. Only patients with baseline and at least one post-baseline measurement were included in this analysis. Sample sizes are episodic migraine: placebo n = 132, GMB 120 mg n = 137; chronic migraine: placebo n = 96, GMB 120 mg n = 93; and overall: placebo n = 228, GMB 120 mg n = 230. CI confidence interval, GMB galcanezumab, LS least squares, PBO placebo, SE standard error

Fig. 2

Effect of galcanezumab on total pain burden. LS mean percentage change (SE) in total pain burden/severity-weighted hours from baseline at each month and overall across all months in patients with episodic migraine (a), chronic migraine (b), and in the overall population (c). ***p < 0.001 vs. placebo. Only patients with baseline and at least one post-baseline measurements were included in this analysis. Sample sizes are episodic migraine: placebo n = 132, GMB 120 mg n = 137; chronic migraine: placebo n = 96, GMB 120 mg n = 93; and overall: placebo n = 228, GMB 120 mg n = 230. CI confidence interval, GMB galcanezumab, LS least squares, PBO placebo, SE standard error

Fig. 3

Effect of galcanezumab on total pain burden following sensitivity analysis. LS mean change in severity-weighted hours from baseline after adjusting for change from baseline in monthly migraine headache days at each month and overall across all months in patients with episodic migraine (a), chronic migraine (b), and in the overall population (c). *p < 0.05 vs. placebo, **p < 0.01 vs. placebo. Only patients with baseline and at least one post-baseline measurements were included in this analysis. Sample sizes are episodic migraine: placebo n = 132, GMB 120 mg n = 137; chronic migraine placebo n = 96, GMB 120 mg n = 93; and overall: placebo n = 228, GMB 120 mg n = 230. CI confidence interval, GMB galcanezumab, LS least squares, PBO placebo