Effect of Galcanezumab Following Treatment Cessation in Patients With Migraine: Results From 2 Randomized Phase 3 Trials

Abstract

Objective We examined the efficacy and safety of galcanezumab after treatment cessation in randomized double‐blind, placebo‐controlled, migraine prevention studies (EVOLVE‐1; EVOLVE‐2). Background Galcanezumab is indicated for migraine prevention in adults. Methods Adults with episodic migraine were enrolled into EVOLVE‐1 and EVOLVE‐2, which randomized 858 and 915 patients, respectively, to galcanezumab 120 mg (an initial 240‐mg loading dose), galcanezumab 240 mg, or placebo, administered subcutaneously once monthly for 6 months. After treatment completion or discontinuation, patients entered a 4‐month posttreatment period. Efficacy and safety from the posttreatment periods are reported. Results Overall, 740 patients (EVOLVE‐1) and 830 (EVOLVE‐2) patients entered the posttreatment periods, about 95% and 96% of patients, respectively, completed. In EVOLVE‐1, change from pre‐randomization baseline in monthly migraine headache days decreased over the posttreatment period from (mean [SE]) 5.2 (0.4) days (Month 6) to 4.1 (0.4) days (Month 10) for 120 mg and from 5.3 (0.4) days (Month 6) to 3.8 (0.4) days (Month 10) for 240 mg, and was stable for placebo (3.4 [0.3] days [Month 6] to 3.3 [0.3] days [Month 10]); differences between each galcanezumab dose group and placebo were statistically significant at each month, except for galcanezumab 240 mg at Month 10 (120 mg vs placebo: P < .001 Months 1‐6, P = .007 Month 7, P = .044 Month 8, P = .016 Month 9, and P = .042 Month 10; 240 mg vs placebo: P < .001 Months 1–7, P = .015 Month 8, P = .021 Month 9, and P = .238 Month 10). EVOLVE‐2 showed similar results. In both trials, there were no statistically significant differences between treatment groups and placebo for time‐to‐first loss of 50% response. During the posttreatment periods, 1.6% (EVOLVE‐1) and 2.3% (EVOLVE‐2) of patients initiated migraine preventive treatments. At Month 10, quality of life among galcanezumab‐treated patients was similar to those taking placebo. The most common posttreatment emergent adverse event was upper respiratory tract infections. There were no discontinuations due to adverse events during the posttreatment periods. Conclusions Galcanezumab treatment effects were reduced during the posttreatment periods, but did not return to baseline. There were no unexpected adverse events after galcanezumab cessation.

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“…In addition, during the post-treatment follow-up phase, the improvement in patient’s health-related quality of life and disability decreased over time; however, the effects did remain which is expected with the half-life of the drug. These effects during post-treatment phase were consistent with previous studies [ 29 ].…”

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“…The efficacy of galcanezumab continued post-treatment, with patients not experiencing any apparent change in the mean number of migraine headache days during the 4-month off-treatment follow-up period. This is consistent with data from previous studies, where reductions in migraine headache days compared with baseline continued for up to 4 months after termination of galcanezumab treatment [32,33]. The clinical meaningfulness of these improvements in migraine headache days in patients with EM and CM is supported by the sustained effect on HRQoL, assessed by MSQ-RFR, and PGI-S.…”

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“…EVOLVE-2 showed similar results, with both the 120 mg and 240 mg galcanezumab groups demonstrating a statistically significant long-term reduction at 10 months compared with the placebo group. This statistically significant change between the previously treated galcanezumab group and the placebo group suggests potential long-term effects even after drug cessation and warrants further study [ 35 ].…”