Treatment benefit among migraine patients taking fremanezumab: results from a post hoc responder analysis of two placebo-controlled trials

Abstract

Background: Monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway, including the fully humanized monoclonal antibody (IgG2Δa) fremanezumab, have demonstrated safety and efficacy for migraine prevention. Clinical trials include responders and nonresponders; efficacy outcomes describe mean values across both groups and thus provide little insight into the clinical benefit in responders. Clinicians and their patients want to understand the extent of clinical improvement in patients who respond. This post hoc analysis of fremanezumab treatment attempts to answer this question: what is the benefit in subjects who responded to treatment during the two, phase 3 HALO clinical trials?

Methods: We included subjects with episodic migraine (EM) or chronic migraine (CM) who received fremanezumab quarterly (675 mg/placebo/placebo) or monthly (EM: 225 mg/225 mg/225 mg; CM: 675 mg/225 mg/225 mg) during the 12-week randomized, double-blind, placebo-controlled HALO EM and HALO CM clinical trials. EM and CM responders were defined as participants with a reduction of ≥ 2 or ≥ 4 monthly migraine days, respectively. Treatment benefits evaluated included reductions in monthly migraine days, acute headache medication use, and headache-related disability, and changes in health-related quality of life (HRQoL).

Results: Overall, 857 participants from the HALO trials were identified as responders (EM: 429 [73.8%]; CM: 428 [56.7%]). Reductions in the monthly average number of migraine days were greater among EM (quarterly: 5.4 days; monthly: 5.5 days) and CM (quarterly: 8.7 days; monthly: 9.1 days) responders compared with the overall population. The proportion of participants achieving ≥ 50% reduction in the average monthly number of migraine days was also greater in responders (EM: quarterly, 59.8%; monthly, 63.7%; CM: quarterly, 52.8%; monthly, 59.0%) than in the overall population. Greater reductions in the average number of days of acute headache medication use, greater reductions in headache-related disability scores, and larger improvements in HRQoL were observed among EM and CM responders compared with the overall populations.

Conclusions: Fremanezumab responders achieved clinically meaningful improvements in all outcomes. The magnitude of improvements with fremanezumab across efficacy outcomes was far greater in responders than in the overall trial population, providing insight into expected treatment benefits in participants who respond to fremanezumab in clinical practice.

Trial registration: ClinicalTrials.gov identifiers: NCT02629861 (HALO EM) and NCT02621931 (HALO CM).

Keywords: Fremanezumab; Monoclonal CGRP antibody; Preventive migraine treatment; Responder analysis.

Conflict of interest statement

Stephen D. Silberstein provides consultation to Alder, Allergan, Amgen, Autonomic Technologies, Avanir, Curelator Inc., Depomed, Dr. Reddy’s Laboratories, Ensured Inc., electroCore Medical LLC, eNeura Therapeutics, Insys Therapeutics, Lilly USA LLC, Supernus Pharmaceuticals, Teva Pharmaceuticals, Theranica, and Trigemina Inc. Adelene E. Jann has served on speakers bureaus for Allergan and Lundbeck. Michael J. Marmura has been a principal investigator for Allergan, gammaCore, Teva Pharmaceuticals, and Theranica; served on advisory boards/speakers bureaus for Alder, Amgen/Novartis, Antares Pharma, Eli Lilly and Company, Promius, Supernus Pharmaceuticals, and Valeant. Joshua M. Cohen, Ronghua Yang, Sanjay K. Gandhi, and Evelyn Du are employees of Teva Pharmaceuticals.

Figures

Fig. 1

Patient disposition. CM, chronic migraine; EM, episodic migraine; MAMD, monthly average migraine days. aFor participants with EM, response was defined as a reduction of ≥2 MAMD. bFor participants with CM, response was defined as a reduction of ≥4 MAMD

Fig. 2

Mean change from baseline in the MAMD among participants with (a) EMa and (b) CMb. CM, chronic migraine; EM, episodic migraine; MAMD, monthly average migraine days; SE, standard error. aFor participants with EM, response was defined as a reduction of ≥2 MAMD. bFor participants with CM, response was defined as a reduction of ≥4 MAMD

Fig. 3

Proportion of participantsa,b with ≥ 50% (a, b) or ≥ 75% (c, d) reduction in MAMD. CM, chronic migraine; EM, episodic migraine; MAMD, monthly average migraine days; SE, standard error. aFor participants with EM, response was defined as a reduction of ≥ 2 MAMD. bFor participants with CM, response was defined as a reduction of ≥ 4 MAMD

Fig. 4

Mean change from baseline in monthly average number of days with any acute headache medication use. a, b CM, chronic migraine; EM, episodic migraine; MAMD, monthly average migraine days. aFor participants with EM, response was defined as a reduction of ≥ 2 MAMD. bFor participants with CM, response was defined as a reduction of ≥ 4 MAMD

Fig. 5

Mean change from baseline in headache-related disability, as measured by (a) MIDASa and (b) HIT-6b. CM, chronic migraine; EM, episodic migraine; HIT-6, 6-item Headache Impact Test; MAMD, monthly average migraine days; MIDAS, Migraine Disability Assessment; SE, standard error. aFor participants with EM, response was defined as a reduction of ≥ 2 MAMD. bFor participants with CM, response was defined as a reduction of ≥ 4 MAMD

Fig. 6

Mean change from baseline in MSQoL in participants with (a) EMa and (b) CMb. CM, chronic migraine; EM, episodic migraine; MAMD, monthly average migraine days; MSQoL, Migraine-Specific Quality of Life; MSQoL-EF, MSQoL emotional function; MSQoL-RFR, MSQoL role function–restrictive; MSQoL-RFP, MSQoL role function–preventive; SE, standard error. aFor participants with EM, response was defined as a reduction of ≥ 2 MAMD. bFor participants with CM, response was defined as a reduction of ≥ 4 MAMD