Impact of galcanezumab on total pain burden: findings from phase 3 randomized, double-blind, placebo-controlled studies in patients with episodic or chronic migraine (EVOLVE-1, EVOLVE-2, and REGAIN trials)

Jessica Ailani, J Scott Andrews, Mallikarjuna Rettiganti, Robert A Nicholson, Jessica Ailani, J Scott Andrews, Mallikarjuna Rettiganti, Robert A Nicholson

Abstract

Background: Focus on the frequency of migraine pain may undervalue the total burden of migraine as pain duration and severity may present unique, additive burden. A composite measure of total pain burden (TPB; frequency, severity, and duration) may provide a more comprehensive characterization of pain burden and treatment response in patients with episodic migraine (EM) or chronic migraine (CM). The impact of galcanezumab versus placebo on TPB among patients with EM or CM was analyzed.

Methods: Patients from randomized, double-blind, placebo-controlled episodic (two 6-month studies pooled) and chronic migraine (3-month) studies received once-monthly subcutaneous injection of galcanezumab 120 mg or placebo. A post hoc analysis of TPB for a given month was calculated as severity-weighted duration by multiplying duration (hours) and maximum pain severity (0 = none, 1 = mild, 2 = moderate, 3 = severe) of migraine for each day and summing these over the days in a month. Least square mean change from baseline in monthly TPB across Months 1-6 (EM, N = 444 galcanezumab, N = 894 placebo) and Months 1-3 (CM, N = 278 galcanezumab, N = 558 placebo) were compared using a mixed-model repeated measures model. Correlation of the Migraine Specific Quality of Life Questionnaire (MSQ) and Migraine Disability Assessment Scale (MIDAS) to TPB at baseline was assessed.

Results: At baseline, the duration of migraine on a given migraine headache day accounted for the greatest unique proportion of variability (EM, 57.4% and CM, 61.1%) to TPB after adjusting for frequency of migraine headache days and maximum pain severity. The decrease from baseline in monthly TPB was greater with galcanezumab than placebo for patients with EM (68.6 versus 36.2) and CM (102.6 versus 44.4). The average percent reduction of TPB from baseline was significantly greater with galcanezumab compared with placebo in patients with EM (50.8% versus 17.2%) and CM (29.7% versus 11.0%). In patients with EM and CM, TPB correlated with MSQ total score (r = - 0.35 and r = - 0.37) and MIDAS (r = 0.34 and r = 0.32).

Conclusions: Greater reduction in TPB was seen in patients with EM and CM treated with galcanezumab 120 mg once-monthly injection relative to placebo. Discussing TPB supports patient-centric conversations regarding treatment expectations when clinicians are evaluating options for migraine prevention.

Trial registration: ClinicalTrials.gov : # NCT02614183 (I5Q-MC-CGAG; EVOLVE-1), # NCT02614196 (I5Q-MC-CGAH; EVOLVE-2), and # NCT02614261 (I5Q-MC-CGAI; REGAIN) - all 3 trials were registered on 23 November 2015.

Keywords: Burden of illness; Chronic migraine; Clinical trial; Galcanezumab; Headache; Migraine; Pain; Prevention.

Conflict of interest statement

Jessica Alani, CME programing: Miller Communications (CME content and speaker fee), Avent (CME content and speaker fee), Peer View (CME speaker fee), Forefront (CME content and speaker fee); Consultant: (Honoraria for independent consulting) Alder, Amgen, Allergan, Electrocore, Eli Lilly and Company, Promius, Teva, Impel, Satsuma, Zosano, Revance, Alpha Sites Consulting, Neurodiem; Research Support: American Migraine Foundation, Allergan, Biohaven, Eli Lilly and Company; Speaker’s Bureau: (Honoraria for promotional speaking) Allergan, Amgen, Electrocore, Eli Lilly and Company, Promius, Teva; Other: Current pain and headache reports, section editor.

J. Scott Andrews, Employee of Eli Lilly and Company, and/or one of its subsidiaries, Indianapolis, IN, USA.

Mallikarjuna Rettiganti, Employee of Eli Lilly and Company, and/or one of its subsidiaries, Indianapolis, IN, USA.

Robert A. Nicholson, Employee of Eli Lilly and Company, and/or one of its subsidiaries, Indianapolis, IN, USA.

Figures

Fig. 1
Fig. 1
Total pain burden (monthly severity-weighted duration in hours) for patients with episodic migraine and chronic migraine. Greater decreases in total pain burden (severity-weighted hours) were observed with galcanezumab treatment Months 1 to 6 overall for patients with episodic migraine and Months 1 to 3 overall for patients with chronic migraine
Fig. 2
Fig. 2
Total pain burden sensitivity analysis: total monthly severity-weighted duration in hours adjusted for change in migraine headache days for patients with episodic migraine and chronic migraine. Greater decreases in total pain burden (severity-weighted hours) were observed with galcanezumab treatment Months 1 to 6 overall for patients with episodic migraine and Months 1 to 3 overall for patients with chronic migraine

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Source: PubMed

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