100% Response Rate to Galcanezumab in Patients With Episodic Migraine: A Post Hoc Analysis of the Results From Phase 3, Randomized, Double‐Blind, Placebo‐Controlled EVOLVE‐1 and EVOLVE‐2 Studies

Abstract

ObjectiveTo characterize adult patients with episodic migraine who achieved 100% response to galcanezumab treatment.BackgroundGalcanezumab is a humanized monoclonal antibody that selectively binds to the calcitonin gene‐related peptide (CGRP) and has demonstrated efficacy in reducing migraine headache days (MHD) in patients with episodic and chronic migraine.MethodsA post hoc analysis of the proportion of patients with 100% response (100% reduction from baseline in monthly MHD) was calculated for each month from pooled data of 2 double‐blind, 6‐month galcanezumab studies in patients with episodic migraine (4 to 14 MHD and ≥2 migraine attacks per month at baseline). The patients were randomized (1:1:2) to monthly subcutaneous galcanezumab, 120 mg (after 240 mg initial loading dose) or 240 mg, or placebo. A generalized linear mixed model with effects for baseline MHD, treatment, month, and treatment‐by‐month interaction was used to estimate the mean monthly response rate.ResultsThe analysis included 1739 patients treated with galcanezumab, 120 mg (n = 436) or 240 mg (n = 428), or placebo (n = 875). The mean monthly 100% response rate on an average month in the 6‐month double‐blind phase was greater for galcanezumab 120 mg (13.5%) and 240 mg (14.3%) groups vs placebo (5.9%) with odds ratios of 2.5 (95% confidence interval [CI] 1.9, 3.2) and 2.6 (95% CI 2.0, 3.4), respectively (P < .001). The rate of 100% monthly response increased at each month over the 6‐month double‐blind phase with higher rates for galcanezumab dose groups (9 to 21%) than placebo (2 to 10%) (P < .02). Evaluation of 100% response by the number of months showed a greater proportion of galcanezumab‐treated patients in either dose group, compared to placebo, were able to achieve a 100% response (P < .001 up to 3 months); however, though greater than placebo, few galcanezumab patients had ≥4 months of 100% response (P < .02). The proportions of patients with 100% response were greatest in the last 3 months of the treatment. Considering the average number days between nonconsecutive MHD across the 6‐month period (not just during the times of 100% response), the duration of migraine headache‐free periods in the galcanezumab groups was 29 days for those with at least 1 month of 100% response and 55 days for those with at least 3 months of 100% response. This gap was approximately 6 to 11 times greater than the mean gap of 5 days observed at baseline.ConclusionsMore than a third of the patients with episodic migraine treated with galcanezumab 120 mg or 240 mg achieved 100% response for at least 1 month. More patients had 100% monthly response in the last 3 months of the 6‐month double‐blind period. For those with 100% response for at least 1 month, the average time between nonconsecutive MHD for the entire treatment period was nearly 1 month and approached 2 months for patients with 3 or more months of 100% response.

Novel Medications for the Treatment of Migraine

“…80 Galcanezumab has also been shown to be effective in both patients who failed and patients who did not fail ≥2 prior preventives. 80 An open-label study randomized patients to receive galcanezumab either 120 mg or 240 mg monthly for 1 year. 80 An open-label study randomized patients to receive galcanezumab either 120 mg or 240 mg monthly for 1 year.…”

“…79 More than a third of patients with episodic migraine achieved 100% response for at least 1 month, and more patients had 100% response in the last 3 months of the 6-month trial period. 80 Galcanezumab has also been shown to be effective in both patients who failed and patients who did not fail ≥2 prior preventives. 81 Post-hoc analysis of combined data from the EVOLVE-1 and EVOLVE-2 studies showed that the effect of galcanezumab can be observed 1 week after the first dose, 82 and this response continued to improve over the next few months.…”

“…81 Post-hoc analysis of combined data from the EVOLVE-1 and EVOLVE-2 studies showed that the effect of galcanezumab can be observed 1 week after the first dose, 82 and this response continued to improve over the next few months. 80 An open-label study randomized patients to receive galcanezumab either 120 mg or 240 mg monthly for 1 year. 83 AEs reported with a frequency of ≥10% in either group were injection site pain, nasopharyngitis, upper respiratory tract infection, injection site reaction, back pain, and sinusitis.…”

Misused and Misleading: “100% Response Rate” to Galcanezumab in Patients With Episodic Migraine

“…Table. Proportions in Each Treatment Group Achieving 100% Response (No Attacks at All Throughout the 6 Months of Treatment) (From Authors’ Table 2 ).…”

“…What, then, did the authors expect readers to make of an article title beginning "100% response rate to galcanezumab …"? 1 Probably, most will understand that 100% of patients on galcanezumab achieved a worthwhile end point. They will be gravely misled.…”