Dataset Information

Early onset of effect following galcanezumab treatment in patients with previous preventive medication failures.

ABSTRACT:

Background

Galcanezumab is a monoclonal antibody (mAb) that binds calcitonin gene-related peptide (CGRP) and is indicated for the preventive treatment of migraine. Galcanezumab demonstrated early onset of effect in patients with migraine but it is unknown whether the same holds true for patients who have not benefited from multiple prior migraine preventives.

Methods

Patients with episodic or chronic migraine from a 3-month, randomized, double-blind, placebo-controlled, phase 3b study (CONQUER) who had 2 to 4 migraine preventive medication category failures in the past 10 years were randomized 1:1 to placebo (N = 230) or galcanezumab 120 mg/month (240 mg loading dose; N = 232). In this post-hoc analysis, change from baseline in number of monthly and weekly migraine headache days was assessed. Monthly onset of effect was the earliest month at which significant improvement with galcanezumab compared to placebo was achieved and maintained at all subsequent months. Weekly onset was the initial week at which statistical separation was achieved and maintained at all subsequent weeks during that month. Proportion of patients with migraine headache days in the first week of treatment, and patients achieving ≥50%, ≥75%, and 100% response by month and week were also assessed.

Results

Galcanezumab-treated patients had a significantly greater reduction in monthly migraine headache days starting at month 1, which remained significant for all subsequent months compared to placebo (all p ≤ 0.0001, month 1 mean change from baseline: placebo - 0.7; galcanezumab - 4.0). Weekly migraine headache days was significantly reduced in galcanezumab-treated patients starting at week 1 and continued for each subsequent week of month 1 compared to placebo (all p < 0.01, week 1 mean change from baseline: placebo - 0.2; galcanezumab - 1.1). A significantly smaller percentage of patients had a migraine headache on the first day after galcanezumab treatment compared to placebo (28.4% vs 39.2%) and at each subsequent day during week 1 (all p < 0.05). A greater proportion of galcanezumab-treated patients achieved ≥50%, ≥75%, and 100% response at months 1-3 (all p < 0.05) and at weeks 1-4 of month 1 compared to placebo (all p < 0.01).

Conclusion

Galcanezumab showed early onset of effect beginning the day after treatment initiation in patients who had not previously benefited from migraine preventive treatments.

Trial registration

ClinicalTrials.gov , NCT03559257 . Registered 18 June 2018.

SUBMITTER: Schwedt TJ

PROVIDER: S-EPMC7992932 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionResults from the open-label extension of the phase 3b CONQUER trial are presented to evaluate the effectiveness and safety of galcanezumab, a monoclonal antibody targeting calcitonin gene-related peptide, for up to 6 months in patients with multiple prior migraine preventive treatment failures.MethodsPatients were 18-75 years old with episodic or chronic migraine and 2-4 standard-of-care migraine preventive medication category failures. After 3 months of randomized treatment with galcanezumab (120 mg/month with 240 mg loading dose; n = 232) or placebo (n = 230), patients entered a 3-month open-label extension (120 mg/month galcanezumab with a blinded 240 mg loading dose for previous-placebo patients). Primary efficacy measure was mean change from double-blind baseline in monthly migraine headache days.ResultsA total of 432/449 patients (96%) who entered open-label treatment completed the study. Mean change in monthly migraine headache days in the total population, which was - 1.3 for placebo and - 4.4 for galcanezumab patients at the end of double-blind treatment (p < 0.001), was - 5.2 and - 5.6, respectively, at the end of open-label treatment with galcanezumab. Among patients with episodic migraine, mean change in monthly migraine headache days had been - 0.6 for placebo and - 2.8 for galcanezumab after double-blind treatment (p < 0.001) and was - 4.5 and - 3.8, respectively, after open-label treatment. Among patients with chronic migraine, mean change in monthly migraine headache days had been - 2.5 for placebo and - 6.6 for galcanezumab after double-blind treatment (p < 0.001) and was - 6.5 and - 8.2, respectively, after open-label treatment. Adverse events were similar to those observed during double-blind placebo treatment. Review of data in elderly patients (65-75 years of age) indicated that galcanezumab was well tolerated in this age group, with no safety issues identified.ConclusionsGalcanezumab was effective and safe during open-label treatment in patients who had experienced failures of previous migraine preventives.Clinical trial registrationClinicalTrials.gov identifier NCT03559257.

Project description:PurposeThis study aimed to extensively evaluate the onset and maintenance effect of galcanezumab compared with placebo for the prevention of episodic migraine in Japanese patients.Patients and methodsThis was a post-hoc analysis of a Phase 2, multicenter, randomized, double-blind, placebo-controlled study conducted between December 2016 and January 2019 (ClinicalTrials.gov: NCT02959177). Patients aged between 18 and 65 years with episodic migraine were randomized to receive a monthly injection of galcanezumab (120 mg: N = 115, 240 mg: N = 114) or placebo (N = 230) for 6 months. Outcome measures included onset of effect at weekly and daily intervals-assessed by change from baseline in the number of migraine headache days and the proportion of patients with migraine headache-with galcanezumab versus placebo. To further confirm the onset and maintenance effect, the 50% response rate was also evaluated.ResultsThe mean change from baseline in weekly migraine headache days was significantly reduced with galcanezumab (-0.97 days) compared with placebo (-0.10 days) at week 1 (p ≤ 0.0001), which was maintained at all subsequent weeks up to week 4 (all p ≤ 0.0001 vs placebo). A significantly smaller proportion of galcanezumab-treated patients had migraine headache compared with placebo-treated patients at day 1 after the first injection (13.6% vs 31.4%, respectively; p ≤ 0.0001), which was also maintained at all subsequent days during the first week after the first injection. Furthermore, the 50% response rate was significantly higher with galcanezumab compared with placebo from week 1 through month 6.ConclusionThe onset of the migraine preventive effect of galcanezumab was rapid compared with placebo, starting from day 1 after the first injection in Japanese patients with episodic migraine. The effect was maintained during the first week and first month, and throughout 6 months of monthly injections of galcanezumab. Galcanezumab is a promising preventive treatment in Japanese patients with episodic migraine.

Project description:ObjectiveWe examined the efficacy and safety of galcanezumab after treatment cessation in randomized double-blind, placebo-controlled, migraine prevention studies (EVOLVE-1; EVOLVE-2).BackgroundGalcanezumab is indicated for migraine prevention in adults.MethodsAdults 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.ResultsOverall, 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.ConclusionsGalcanezumab treatment effects were reduced during the posttreatment periods, but did not return to baseline. There were no unexpected adverse events after galcanezumab cessation.

Project description:Background and objectivesPatients with migraine and prior preventive treatment failures have a significant burden on quality of life and disability. The CONQUER study evaluated the effects of galcanezumab on patient functioning, disability, and health status in episodic or chronic migraine with a previous failure of two to four migraine preventive medication categories.MethodsPatients with two to four preventive migraine treatment category failures received galcanezumab 120 mg/month (240-mg loading dose) or placebo subcutaneously, for 3 months (double-blind period). In the 3-month open-label period, all patients received galcanezumab irrespective of the treatment received in the double-blind period. Changes in Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQ), Migraine Disability Assessment (MIDAS), and European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) scores were assessed.ResultsA total of 462 patients were randomized to receive galcanezumab (N = 232) or placebo (N = 230). At month 3, improvement in the MSQ Role-Function-Restrictive score from baseline was significantly greater for galcanezumab (23.19 ± 1.34) vs placebo (10.66 ± 1.33) [p ≤ 0.0001]. Significant improvements in remaining MSQ domains and total MSQ scores were observed (p < 0.0001) during the double-blind period. MIDAS total scores were significantly (p ≤ 0.0001) reduced with galcanezumab (- 21.10 + 3.32) vs placebo (- 3.30 + 3.28). EQ-5D-5L visual analog scale scores improved for galcanezumab (3.40 + 1.31) vs placebo (- 0.09 + 1.29; p = 0.028). During the open-label period, quality of life continued to improve for galcanezumab, with patients previously assigned to placebo reaching similar results. During both study periods, similar findings were reported in subpopulations with episodic migraine and chronic migraine.ConclusionsGalcanezumab significantly improved functioning and reduced disability in patients with episodic migraine and chronic migraine and two to four migraine preventive treatment category failures.Clinical trial registrationNCT03559257, registration date: 6 June, 2018.

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Project description:OBJECTIVE:To evaluate onset of effect of galcanezumab in patients with episodic migraine. BACKGROUND:Galcanezumab is a monoclonal antibody that binds to calcitonin gene-related peptide and is indicated for preventive treatment of migraine. DESIGN/METHODS:Data on the primary outcome measure were analyzed from 2 previously published double-blind, Phase 3 studies (EVOLVE-1 [N = 858] and EVOLVE-2 [N = 915]) wherein adult patients with episodic migraine were randomized to receive monthly subcutaneous injections of galcanezumab 120 mg (with 240-mg loading dose) or 240 mg or placebo for up to 6 months. Monthly onset of effect was defined as the earliest month at which galcanezumab achieved and subsequently maintained statistical superiority to placebo on the mean change from baseline in the number of monthly migraine headache days (MHDs). If onset occurred in Month 1, weekly onset was evaluated and defined as the earliest week at which galcanezumab statistically separated from placebo and maintained statistical separation for remaining weeks in that month. Day of onset of effect was also analyzed, as were monthly and weekly onset, for occurrence of ?50% reduction from baseline in number of MHDs. RESULTS:For both studies, change from baseline in monthly MHDs showed a statistically significant separation of galcanezumab from placebo at Month 1 and each subsequent month (each P < .001). Analysis of the first month for both studies indicated onset of effect in the first week, with galcanezumab-treated patients having significantly higher odds of having fewer MHDs in the first week (odds ratio [95% confidence interval] for EVOLVE-1, 2.71 [2.00, 3.66], and for EVOLVE-2, 2.88 [2.16, 3.86]; both P < .001) and each subsequent week compared with placebo-treated patients (P ? .004). Daily analysis showed onset of effect at Day 1 (first day after injection day). Galcanezumab also demonstrated superiority to placebo on occurrence of ?50% reduction in MHDs starting at Week 1 (percentage of patients with 50% response in galcanezumab group vs placebo group for EVOLVE-1, 54.3% vs 32.4% [P < .001], and for EVOLVE-2, 59.4% vs 38.0% [P < .001]). CONCLUSION:Rapid onset of preventive effect on the first day after injection of galcanezumab was confirmed in both studies of episodic migraine.

Project description:ObjectiveThe objective of this study was to ascertain to what extent adults with migraine value an early onset of efficacy for preventive migraine treatments.BackgroundIn placebo-controlled clinical trials, treatment with eptinezumab resulted in a lower proportion of adults with migraine on the first day following infusion (day 1; 14% point-reduction for chronic migraine [CM] in PROMISE-2 and 8% point-reduction for episodic migraine [EM] in PROMISE-1).MethodsAdults with migraine completed an online preference-elicitation thresholding exercise to ascertain to what extent they value not having a migraine on day 1 postdosing relative to a clinically relevant reduction in number of migraine days during the first month postdosing (≥2 migraine-free days for CM and ≥1 migraine-free days for EM).ResultsOne hundred and one participants (mean age, 50.6 ± 12.4 years; 81 [80%] women) were included. In participants with CM, 29 of 50 (58%) considered the eptinezumab-generated reduction in the likelihood of migraine on day 1 postdosing to be at least as important as a clinically relevant reduction in number of migraine days the first month postdosing, whereas 37 of 50 (74%) considered a clinically relevant reduction of migraine days the first month postdosing to have a value equivalent to the eptinezumab-generated reduction in the likelihood of migraine on day 1 postdosing. In participants with EM, 18 of 35 (51%) considered the eptinezumab-generated reduction in the likelihood of migraine on day 1 postdosing to be at least as important as a clinically relevant reduction in migraine days the first month postdosing, whereas 24 of 35 (69%) considered a clinically relevant reduction of migraine days the first month postdosing to have a value equivalent to the eptinezumab-generated reduction in the likelihood of migraine on day 1 postdosing.ConclusionMost participants considered the reduction in the likelihood of migraine offered by eptinezumab on day 1 postdosing to be at least as important as a clinically relevant reduction in migraine days the first month postdosing.