Impact of Galcanezumab on Total Pain Burden: A Post Hoc Analysis of a Phase 3, Randomized, Double-Blind, Placebo-Controlled Study in Patients with Episodic Cluster Headache

Abstract

Purpose: In a phase 3 study, galcanezumab significantly reduced the frequency of episodic cluster headache attacks across weeks 1-3 (primary endpoint) compared with placebo. However, multiple pain dimensions may contribute to the total burden of episodic cluster headache pain. This post hoc analysis assessed the impact of galcanezumab on the total pain burden of episodic cluster headache using a composite measure.

Patients and methods: Patients with episodic cluster headache were randomized 1:1 to galcanezumab 300 mg or placebo once monthly for 8 weeks. Mean weekly total pain burden was calculated (daily cluster headache attack frequency × average duration × average pain severity summed over 7 days) using data collected in an electronic patient-reported outcomes diary. Change from baseline in weekly total pain burden across weeks 1-3 was compared between galcanezumab and placebo. To explore construct validity, mean weekly total pain burden scores were stratified by Patient Global Impression of Improvement (PGI-I) responses at the week 4 clinic visit.

Results: The reduction from baseline in mean weekly total pain burden was significantly greater with galcanezumab (N=49) than with placebo (N=57): the least squares mean difference was -11.18 severity-weighted hours (p=0.035). Median weekly total pain burden decreased as PGI-I ratings improved, from 33.6 to 5.0 severity-weighted hours for patients who felt "very much worse" and "very much better," respectively.

Conclusion: Galcanezumab significantly reduced mean weekly total pain burden compared with placebo in patients with episodic cluster headache. The composite pain measure demonstrated construct validity. Total pain burden may provide a holistic measure of the pain of episodic cluster headache.

Clinical trials: ClinicalTrials.gov, NCT02397473.

Keywords: CGRP; composite pain; duration; frequency; severity.

Conflict of interest statement

M Rettiganti, T Oakes, JN Bardos, R Wenzel, DK Kuruppu, and JM Martinez are employees and stockholders of Eli Lilly and Company and/or one of its subsidiaries. JS Andrews was an employee at Eli Lilly at the time the study was conducted and is currently employed at Takeda Pharmaceuticals. D Kudrow has received personal compensation for speaking or for serving on an advisory board from Amgen, Alder Biopharmaceuticals, Biohaven Pharmaceuticals, Eli Lilly and Company, Axsome, Allergan, Lundbeck, Satsuma, Teva Pharmaceutical Industries Ltd, and Xoc Pharmaceuticals and has received research support from Amgen, Alder Biopharmaceuticals, Biogen, Biohaven Pharmaceuticals, Eli Lilly and Company, Roche-Genentech, Teva Pharmaceutical Industries Ltd, and VM Biopharma. C Gaul has received honoraria for consulting and lectures within the past 3 years from Allergan, Grünenthal, Hormosan Pharma, Eli Lilly and Company, Lundbeck, Novartis, Reckitt Benckiser, Sanofi Aventis, and Teva Pharmaceutical Industries Ltd and does not hold any stocks of pharmaceutical or medical device companies. He is honorary secretary of the German Migraine and Headache Society. The authors report no other conflicts of interest in this work.

© 2021 Andrews et al.

Figures

Figure 1

Design of the phase 3, randomized, double-blind, placebo-controlled study of galcanezumab in patients with episodic CH (NCT02397473). aProspective baseline period started on the day the patient first recorded a CH attack in their ePRO diary. Eligibility and baseline weekly CH characteristics were assessed over 7 consecutive days during the prospective baseline period.

Figure 2

LS mean change from baseline in average weekly CH attack (A) frequency (primary study endpoint), (B) duration, and (C) severity, across weeks 1–3 in patients receiving galcanezumab or placebo. Results are expressed with SE; p-values are from repeated measures analysis. N for (A) are greater than those for (B and C) because the analyses presented in (B and C) were performed in patients with at least 1 week with at least one CH attack; consequently, a few patients who had zero attacks were excluded.

Figure 3

(A) LS mean change and (B) LS mean percent change from baseline in average weekly CH attack total pain burden across weeks 1–3 in patients receiving galcanezumab or placebo. Results are expressed with SE; p-values are from repeated measures analysis.

Figure 4

Median [Q1, Q3] weekly total pain burden across weeks 1–3 according to PGI-I score at week 4 in patients with episodic CH receiving galcanezumab or placebo (N=93).