Dataset Information

Migraine Headache Day Response Rates and the Implications to Patient Functioning: An Evaluation of 3 Randomized Phase 3 Clinical Trials of Galcanezumab in Patients With Migraine.

ABSTRACT:

Objective

This post hoc study investigated the relationship between patient response in terms of migraine headache day reduction and patient-reported outcomes of health-related quality of life (HRQoL) and disability categories.

Background

Migraine causes considerable disease-related disability and negatively impacts HRQoL of patients. Calcitonin gene-related peptide inhibitors improve these outcomes and may eliminate disability due to migraine in some patients.

Methods

Analyses used data from 3 double-blind, placebo (PBO)-controlled, phase 3 studies in adults with episodic migraine (EM) (EVOLVE-1: N = 858 and EVOLVE-2: N = 915) or chronic migraine (CM) (REGAIN: N = 1113). Patients were randomized 2:1:1 to subcutaneous injection of PBO, galcanezumab (GMB) 120 mg, or GMB 240 mg once monthly for 6 months in EVOLVE-1 and -2 and for 3 months in REGAIN. Primary endpoint was overall mean change from baseline in monthly migraine headache days. Patients were divided into 4 response-level groups based on percent change from baseline (<30%, ≥30% to <50%, ≥50% to <75%, ≥75%). Patient-reported outcomes included the 14-item Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQ) and Migraine Disability Assessment (MIDAS) questionnaire.

Results

Among patients with migraine, mean improvements from baseline in MSQ domain scores increased with each successive level of migraine headache day response. On a 100-pt scale, increases in Role Function-Restrictive score in EM were 16.8 and 36.0 at the <30% and ≥75% response levels, respectively, and for CM were 10.7 and 46.5. Similar patterns in scores were observed for the Role Function-Preventive and Emotional Function domains. Examination of improvement in MSQ item score by treatment group showed that, in patients with EM, approximately 10 to 20% more GMB-treated patients (N = 796 for GMB 120 mg and GMB 240 mg) had improvements in all 14 MSQ items compared with PBO-treated patients (N = 773) (all P < .001). In patients with CM, 3 to 16% more GMB-treated patients (N = 507) had improvements in the 14 MSQ items compared with PBO (N = 494), though differences were statistically significant in only 19 of 28 comparisons. At baseline, mean MIDAS scores (EM, 33.1; CM, 67.2) indicated severe mean disability for patients with EM and very severe disability for patients with CM. Among patients with EM, 215 of 425 (50.6%) of those treated with GMB 120 mg and 212 of 413 (51.3%) treated with 240 mg had little/no disability due to migraine after 6 months (PBO: 277 of 832 (33.3%), P < .001 for both). Among patients with CM, 50 of 254 (19.7%) of those treated with GMB 120 mg and 54 of 258 (20.9%) treated with 240 mg reached the level of little/no disability after 3 months of treatment (PBO: 70 of 504 (13.9%), P = .045 for 120 mg, P = .017 for 240 mg).

Conclusions

Because migraine greatly impairs an individual's ability to participate in activities of daily living, measurements of HRQoL are essential in clinical research. This study showed that function in daily life, as measured by MSQ score, improved as migraine headache days were reduced and that GMB-treated patients were more likely to see improvement in MSQ item scores compared with PBO-treated patients. Elimination of migraine-related disability was also more frequent in GMB-treated patients compared with placebo-treated patients.

SUBMITTER: Ford JH

PROVIDER: S-EPMC7756324 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:OBJECTIVE:To evaluate changes from baseline in patient-reported outcomes for measures of functioning and disability among patients with migraine treated with galcanezumab or placebo. METHODS:Patients with episodic migraine (4-14 monthly migraine headache days) were treated with either galcanezumab (Evaluation of LY2951742 in the Prevention of Episodic Migraine [EVOLVE]-1: 120 mg n = 210, 240 mg n = 208; EVOLVE-2: 120 mg n = 226, 240 mg n = 220) or placebo (EVOLVE-1 n = 425; EVOLVE-2 n = 450) during 6 months of treatment. Migraine-Specific Quality of Life Questionnaire v2.1 (MSQv2.1) measured the effect of migraine on patient functioning (physical and emotional) in 3 domains, and the Migraine Disability Assessment (MIDAS) quantified headache-related disability associated with missed or reduced productivity at work or home and social events. Both were collected at baseline and during the treatment period (MSQv2.1 = monthly; MIDAS = months 3 and 6 only). RESULTS:Differences in MSQv2.1 total score least squares (LS) mean change from baseline (month 4-6) for galcanezumab (120 and 240 mg, respectively) were superior to placebo (EVOLVE-1 = 7.3 and 6.7 [both p < 0.001]; EVOLVE-2 = 8.5 and 7.3 [both p < 0.001]). Differences were similar for all domain scores (p < 0.001 for both galcanezumab doses compared with placebo), were observed as early as month 1, and were sustained for 6 months for most domains. Differences of MIDAS LS mean change from baseline (month 6) for galcanezumab (120 and 240 mg, respectively) compared with placebo were: EVOLVE-1 = -6.3 (p < 0.001) and -5.2 (p = 0.002); EVOLVE-2 = -9.2 and -8.2 (both p < 0.001). CONCLUSIONS:Patients with episodic migraine treated with galcanezumab reported significant and clinically meaningful improvements in daily functioning and decreased disability compared with patients who received placebo. CLASSIFICATION OF EVIDENCE:This study provides Class II evidence that for patients with migraine, galcanezumab (120 mg or 240 mg) given once monthly improved functioning and reduced disability.

Project description:BACKGROUND:Galcanezumab is a novel monoclonal antibody that target to calcitonin gene-related peptide (CGRP). It has been tested for the preventive treatment of migraine and episodic cluster headache by multiple randomized clinical trials (RCTs) and have been found to reduce headache frequency. METHODS:We systematically searched PubMed and Embase on Cochrane Central Register of Controlled Trials (CENTRAL) from the earliest date to August 1, 2019. Relative risk (RR) and weighted mean difference (WMD) were used to evaluate clinical outcomes. RESULTS:Seven studies were pooled with 3889 patients. Subcutaneous injection of Galcanezumab at 120?mg, 240?mg leads to a statistically significant response rate for the treatment of migraine compared with placebo (120?mg: RR?=?1.51; 95% CI, 1.33 to 1.70; P?<?0.001; 240?mg: RR?=?1.58; 95% CI, 1.43 to 1.76; P?<?0.001). Among them, 120?mg group has the same treatment efficacy with 240?mg group (50% response: RR?=?1.06; 95% CI, 0.92 to 1.22; P?=?0.425; 75% response: RR?=?1.07; 95% CI, 0.94 to 1.23; P?=?0.301; 100% response; RR?=?1.06; 95% CI, 0.81 to 1.37; P?=?0.682; MHD: RR?=?-?0.08; 95% CI, -?0.55 to -?0.40; P?=?0.748) while related to a lower risk for adverse events for the treatment of migraine (120?mg RR?=?1.06; 95% CI, 0.99 to 1.14; P?=?0.084; 240?mg: RR?=?1.17; 95% CI, 1.09 to 1.25; P?<?0.001). 300?mg per month galcanezumab is effective for the prevention of episodic cluster headache measured by at least 50% reduction of cluster headache frequency at week 3 (RR?=?1.36; 95% CI, 1.00-1.84; P?=?0.048). CONCLUSIONS:Use of galcanezumab is related to a significantly reduced monthly headache frequency compared with placebo for the treatment of migraine and episodic cluster headache, 120?mg has the same treatment efficacy with 240?mg group while related to a lower risk for adverse effects for the treatment of migraine. 300?mg per month galcanezumab is effective for the prevention of episodic cluster headache with no significantly increased adverse events.

Project description:BackgroundGalcanezumab, a humanized monoclonal antibody that binds calcitonin gene-related peptide, has demonstrated a significant reduction in monthly migraine headache days compared with placebo. Here, we analyze data from 3 randomized clinical trials (2 episodic trials [EVOLVE-1, EVOLVE-2] and 1 chronic trial [REGAIN]), to examine if galcanezumab also alleviates the severity and symptoms of migraine.MethodsThe episodic migraine trials were 6-month, double-blind studies in patients with episodic migraine (4-14 monthly migraine headache days). The chronic migraine trial was a 3-month, double-blind study in patients with chronic migraine (≥ 15 headache days per month, where ≥ 8 met criteria for migraine). Patients (18-65 years) were randomized to placebo or galcanezumab 120 mg with a 240-mg loading dose or 240 mg. Patients recorded headache characteristics, duration, severity, and presence of associated symptoms with each headache. The outcomes analyzed were changes from baseline in number of monthly migraine headache days with nausea and/or vomiting, photophobia and phonophobia, aura, and prodromal symptoms other than aura. Additional outcomes analyzed included the number of moderate-to-severe monthly migraine headache days, number of severe migraine headache days, and mean severity of remaining migraine headache days. Change from baseline in the proportion of days with nausea and/or vomiting and the proportion of days with photophobia and phonophobia among the remaining monthly migraine headache days were also analyzed.ResultsGalcanezumab was superior to placebo in reducing the frequency of migraine headache days with associated symptoms of migraine such as nausea and/or vomiting, photophobia and phonophobia, and prodromal symptoms. Galcanezumab reduced the frequency of migraine headache days with aura in the episodic migraine studies. There was a significant reduction in the proportion of remaining migraine headache days with nausea and/or vomiting for the episodic and chronic migraine studies, and with photophobia and phonophobia for the episodic migraine studies. Galcanezumab was superior to placebo in reducing the number of monthly moderate-to-severe migraine headache days and the overall and monthly severe migraine headache days.ConclusionsGalcanezumab reduces the frequency of migraine headache days and can alleviate potentially disabling non-pain symptoms on days when migraine is present in patients with episodic or chronic migraine.Trial registrationNCT, NCT02614183 (EVOLVE-1), registered 25 November 2015; NCT, NCT02614196 , (EVOLVE-2), registered 25 November 2015; NCT, NCT02614261 (REGAIN), registered 25 November 2015.

Project description:PurposeTo evaluate secondary outcomes including changes in functioning and disability associated with galcanezumab, a humanized monoclonal antibody to calcitonin gene-related peptide, in patients with chronic migraine.MethodsPatients randomly received galcanezumab (120 mg n = 278, 240 mg n = 277) or placebo (n = 558) during 3 months of double-blind treatment, followed by a 9-month open-label extension. The Migraine-Specific Quality-of-Life Questionnaire v2.1 (MSQv2.1) measured the impact of migraine on patient functioning. The Migraine Disability Assessment (MIDAS) quantified headache-related disability. Changes from baseline were analyzed with mixed model repeated measures or analysis of covariance.ResultsTotal MSQ score at baseline was 44.88 ± 18.02 (mean ± SD), indicating significant functional impairment. At Month 3, least squares (LS) mean change ± SE in total MSQ for galcanezumab-treated patients were 20.51 ± 1.49 (120 mg) and 20.49 ± 1.49 (240 mg), both statistically significantly greater vs placebo-treated patients (14.55 ± 1.21; both P < 0.001). Total MIDAS score at baseline was 67.24 ± 57.31 (mean ± SD). At Month 3, LS mean change ± SE from baseline in total MIDAS for galcanezumab-treated patients was statistically significantly greater than placebo for 120 mg group (placebo: - 11.53 ± 3.38 vs 120 mg: - 20.27 ± 4.07; P < 0.05) but not for 240 mg group (- 17.02 ± 4.05). At Month 12, within-group mean changes from baseline for total MSQ (28.56 ± 1.19 previous placebo; 29.53 ± 1.51 previous 120 mg; 25.83 ± 1.49 previous 240 mg) and MIDAS scores (- 28.47 ± 2.95 previous placebo; - 31.47 ± 3.69 previous 120 mg; - 31.13 ± 3.62 previous 240 mg) were statistically significant (P < 0.001) for the open-label treatment population regardless of previous double-blind treatment assignment.ConclusionsGalcanezumab-treated patients with chronic migraine reported statistically significant improvements in functioning and disability, representing a clinically significant change.Trial registrationClinicalTrials.gov registry: NCT02614261. Registered 25 November 2015.

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:BackgroundMigraine clinical profile may change with age, making it necessary to verify that migraine treatments are equally safe and effective in older patients. These analyses evaluated the effects of patient age on the pharmacokinetics (PK), efficacy, and safety of galcanezumab for prevention of migraine.MethodsAnalyses included efficacy data from three double-blind phase 3 clinical trials: two 6-month studies in episodic migraine (EVOLVE-1, EVOLVE-2: N = 1773) and one 3-month study in chronic migraine (REGAIN:N = 1113). Patients were randomized 2:1:1 to placebo, galcanezumab 120 mg, or galcanezumab 240 mg. Safety and PK data included additional phase 2 and phase 3 trials for a larger sample size of patients > 60 years (range = 18-65 for all studies). Subgroup analyses assessed efficacy measures, adverse event (AE) occurrence, and cardiovascular measurement changes by patient age group. Galcanezumab PK were evaluated using a population analysis approach, where age was examined as a potential covariate on apparent clearance (CL/F) and apparent volume of distribution (V/F) of galcanezumab.ResultsNumbers of baseline monthly migraine headache days were similar across age groups. There were no statistically significant treatment-by-age group interactions for any efficacy measures, except in episodic migraine studies where older patients appeared to have a larger reduction than younger patients in the number of monthly migraine headache days with acute medication use. Age (18-65) had a minimal effect on CL/F, and no effect on V/F. Galcanezumab-treated patients ≥60 years experienced no clinically meaningful increases in blood pressure and no increased frequency in treatment-emergent AEs, discontinuations due to AEs, serious adverse events (SAEs) overall, or cardiovascular SAEs, compared to age-matched placebo-treated patients.ConclusionsAge (up to 65 years) does not affect efficacy in migraine prevention and has no clinically meaningful influence on galcanezumab PK to warrant dose adjustment. Furthermore, older galcanezumab-treated patients experienced no increases in frequency of AEs or increases in blood pressure compared with age-matched placebo-treated patients.Trial registrationsEVOLVE-1 (NCT02614183, registered 23 November 2015), EVOLVE-2 (NCT02614196, 23 November 2015), REGAIN (NCT02614261, 23 November 2015), ART-01 (NCT01625988, 20 June 2012, ), I5Q-MC-CGAB (NCT02163993, 12 June 2014, ), I5Q-MC-CGAJ (NCT02614287, 23 November 2015, ), all retrospectively registered.