Dataset Information

Positive response to galcanezumab following treatment failure to onabotulinumtoxinA in patients with migraine: post hoc analyses of three randomized double-blind studies.

ABSTRACT:

Background and purpose

Humanized monoclonal antibody galcanezumab, which binds to calcitonin-gene-related peptide, has shown efficacy for episodic and chronic migraine prevention. These analyses evaluated galcanezumab response for migraine headache prevention in patients who previously failed onabotulinumtoxinA ('nonresponse' or 'inadequate response' or safety reasons).

Methods

Post hoc analyses included data from three double-blind, placebo-controlled, phase 3 episodic or chronic migraine studies; 2886 patients randomly received 120 or 240 mg galcanezumab or placebo. During double-blind periods the study drug was administered subcutaneously once a month for 6 months in EVOLVE-1 and -2 and for 3 months in REGAIN. The 120 mg groups received a 240 mg loading dose at month 1. Pooled analyses included 129 patients who failed onabotulinumtoxinA. Using mixed effect model repeat measurements, the least squares mean change from baseline in the number of migraine headache days (MHDs) was calculated for the first 3 months of treatment.

Results

For pooled analyses, significant decreases from baseline in the number of MHDs were observed for 120 mg (-3.91) and 240 mg (-5.27) galcanezumab overall versus placebo (-0.88) across 3-month time points for patients who failed onabotulinumtoxinA. Corresponding data for patients with chronic migraine showed significant decreases: 120 mg (-3.18) and 240 mg (-4.26) galcanezumab versus placebo (0.16). Significant reductions in the number of MHDs per month with acute medication use included 120 mg galcanezumab (-4.35) and 240 mg galcanezumab (-4.55) versus placebo (-0.83). Estimates of ?50% response during months 1-3 were 9.4% for placebo, 41.3% for 120 mg galcanezumab and 47.5% for 240 mg galcanezumab.

Conclusion

Galcanezumab is an option for prevention of migraine in patients who have previously failed onabotulinumtoxinA preventive therapy.

SUBMITTER: Ailani J

PROVIDER: S-EPMC7028018 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Publications

Positive response to galcanezumab following treatment failure to onabotulinumtoxinA in patients with migraine: post hoc analyses of three randomized double-blind studies.

Ailani J J Pearlman E E Zhang Q Q Nagy A J AJ Schuh K K Aurora S K SK

European journal of neurology 20191210 3

<h4>Background and purpose</h4>Humanized monoclonal antibody galcanezumab, which binds to calcitonin-gene-related peptide, has shown efficacy for episodic and chronic migraine prevention. These analyses evaluated galcanezumab response for migraine headache prevention in patients who previously failed onabotulinumtoxinA ('nonresponse' or 'inadequate response' or safety reasons).<h4>Methods</h4>Post hoc analyses included data from three double-blind, placebo-controlled, phase 3 episodic or chronic ...[more]

PMID: 31595600

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Project description:ObjectiveTo evaluate the efficacy and safety of galcanezumab, a humanized monoclonal antibody that selectively binds to calcitonin gene-related peptide, in the preventive treatment of chronic migraine.MethodsA phase 3, randomized, double-blind, placebo-controlled study of LY2951742 in patients with chronic migraine (Evaluation of Galcanezumab in the Prevention of Chronic Migraine [REGAIN]) was a phase 3 study with a 3-month double-blind, placebo-controlled treatment phase and a 9-month open-label extension. Eligible patients 18 to 65 years of age with chronic migraine were randomized 2:1:1 to monthly subcutaneous injections of placebo (n = 558), galcanezumab 120 mg (with a 240-mg loading dose, n = 278), or galcanezumab 240 mg (n = 277). The primary endpoint was the overall mean change from baseline in the number of monthly migraine headache days (MHDs) during the 3-month double-blind treatment phase.ResultsMean number of monthly MHDs at baseline was 19.4 for the total sample. Both galcanezumab dose groups demonstrated greater overall mean reduction in the number of monthly MHDs compared to placebo (placebo -2.7, galcanezumab 120 mg -4.8, galcanezumab 240 mg -4.6) (p < 0.001 for each dose compared to placebo). There were no clinically meaningful differences between galcanezumab doses and placebo on any safety or tolerability outcome except for a higher incidence of treatment-emergent injection-site reaction (p < 0.01), injection-site erythema (p < 0.001), injection-site pruritus (p < 0.01), and sinusitis (p < 0.05) in the galcanezumab 240-mg group relative to placebo.ConclusionsBoth doses of galcanezumab were superior to placebo in reducing the number of monthly MHDs. Galcanezumab appears efficacious, safe, and well tolerated for the preventive treatment of chronic migraine.Clinicaltrialsgov identifierNCT02614261.Classification of evidenceThis interventional study provides Class I evidence that galcanezumab is superior to placebo in the reduction of the number of monthly MHDs.

Project description:OBJECTIVE:To characterize adult patients with episodic migraine who achieved 100% response to galcanezumab treatment. BACKGROUND:Galcanezumab 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. METHODS:A 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. RESULTS:The 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. CONCLUSIONS:More 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.

Project description:BACKGROUND:Injection-site reactions have been reported with biologicals. In this post hoc analysis of Phase 3 studies in participants with migraine, we provide a comprehensive overview and detailed summary of injection-site reaction with galcanezumab. METHODS:Data were obtained from two randomised clinical studies in participants with episodic migraine (EVOLVE-1 and EVOLVE-2), one randomised study in participants with chronic migraine (REGAIN) and one open-label study (Study CGAJ) in participants with episodic or chronic migraine. The injection-site reactions were measured for two different cohorts: 1) six-month double-blind treatment phase in the EVOLVE-1 and EVOLVE-2 studies and three-month double-blind treatment phase in the REGAIN study, where participants received placebo and galcanezumab (placebo-controlled analysis set); 2) three month double-blind (Month 0 to Month 3; 1:1:placebo:galcanezumab)?+?9 months open-label extension phase (Month 3 to Month 12) of REGAIN and twelve month open-label phase of Study CGAJ, where participants received only galcanezumab (galcanezumab exposure analysis set). RESULTS:A total of 477 participants in the placebo-controlled analysis set (galcanezumab 240?mg, 166/730 [22.7%]; galcanezumab 120?mg, 128/705 [18.2%]; placebo, 183/1451 [12.6%]) reported at least one injection-site reaction. Most of the injection-site reactions were reported as injection-site pain, unspecified injection-site reaction, injection-site erythema, and injection-site pruritus. The incidence of injection-site pain was highest among all reported injection-site reactions and were reported with similar frequency by participants receiving galcanezumab (galcanezumab 120?mg, 10.1%; galcanezumab 240?mg, 11.6%) and placebo (9.5%) and was the most common injection-site reaction reported within 60?min of injection (~?86% of participants). The frequency of unspecified injection-site reaction, injection-site erythema and injection-site pruritus was significantly (P?<?0.001) higher in participant receiving galcanezumab versus placebo. In the galcanezumab exposure analysis set participants received up to 12 doses and the frequency of injection-site reactions reported for both doses combined was 21.8%. The reporting of injection-site reactions did not increase with the number of doses received. No ISR-related serious adverse events were reported in both the placebo-controlled and galcanezumab exposure analysis sets. CONCLUSIONS:The most common adverse event of galcanezumab is injection-site reactions. However, these events were generally mild-to-moderate in severity, non-serious, resolved spontaneously, and discontinuations due to injection-site reactions were low (1%).

Project description:IntroductionChronic migraine (CM) patients commonly take acute headache medications, often resulting in medication overuse (MO). This post hoc analysis evaluated the efficacy of fremanezumab in CM patients from Japan with and without MO, which is not yet established.MethodsA multicenter, double-blind, parallel-group, phase 2b/3 trial randomized patients (1:1:1) to monthly fremanezumab via subcutaneous injection (initial dose: 675 mg, second/third doses: 225 mg), quarterly fremanezumab (initial dose: 675 mg, second/third doses: placebo), or placebo for 3 months. This post hoc analysis analyzed data from Japanese patients with and without MO (monthly use of acute headache medication ≥ 15 days, migraine-specific acute medication ≥ 10 days, or combination medication ≥ 10 days). Outcomes included the original primary endpoint of average headache days of moderate or greater severity per month (HDs), the proportion of patients with ≥ 50% reduction in HDs and the proportion of patients changing status from with to without MO.ResultsOf 479 patients enrolled, 320 (66.8%) had baseline MO. Monthly average HDs were significantly reduced versus placebo with fremanezumab in both patients with MO (mean [standard error] difference vs. placebo: monthly - 2.0 [0.6], p = 0.0012; quarterly - 1.8 [0.6], p = 0.0042) and without MO (- 1.6 [0.8], p = 0.0437; - 1.5 [0.8], p = 0.0441). Significantly more fremanezumab-treated patients with MO (monthly 28/108 [25.9%], p = 0.0040 quarterly 25/99 [25.3%], p = 0.0070) or without MO (18/50 [36.0%], p = 0.0132; and 21/60 [35.0%], p = 0.0126) had ≥ 50% reduction in HDs versus placebo (12/111 [10.8%] and 7/49 [14.3%], respectively). A significantly greater proportion of fremanezumab-treated patients reverted to no MO (monthly 50/108 [46.3%], p = 0.0115; quarterly 44/99 [44.4%], p = 0.0272) vs. placebo (33/111 [29.7%]).ConclusionFremanezumab appears effective as preventive migraine treatment in Japanese CM patients with or without MO while also being beneficial in reducing MO.

Project description:To evaluate suicidal thoughts in relationship to depressive symptom severity and reasons for living in patients hospitalized for major depressive disorder (MDD).A post hoc analysis was conducted of a randomized, double-blind, parallel-group trial involving hospitalized patients with MDD (DSM-IV criteria) who received duloxetine 60 mg once daily or duloxetine 60 mg twice daily for 8 weeks. After 4 weeks, the dose for nonresponders receiving 60 mg once daily could be increased to 60 mg twice daily (double-blind). The study was conducted between February 9, 2007, and August 26, 2008 at 43 centers in 4 countries across Europe and South Africa. Suicidal thoughts were assessed with Montgomery-Asberg Depression Rating Scale (MADRS) item 10, depression severity was assessed with the 6-item Hamilton Depression Rating Scale and the Clinical Global Impressions-Severity of Illness scale, and protective factors were assessed with the patient-rated Reasons for Living Inventory (RFL) assessing 6 domains. Descriptive statistics, correlation, and linear regression analysis were performed.At baseline, patients (N = 336) had varying severity of suicidal thoughts: 18% had a score ? 4. The proportion of patients with a score ? 4 decreased to 7% at week 1 and 1% at week 8 of treatment. The RFL scores at baseline were lower in patients with higher baseline suicidal thoughts and increased significantly during treatment (P < .0001). A regression model revealed that only 16% of variance in baseline total RFL score is explained by the different MADRS items. Eight patients had suicidal behavior or ideation recorded as an adverse event during the study; no consistent pattern was found in the different psychometric scores either at baseline or at the visit preceding the suicidal behavior/ideation.Suicidality rapidly decreased in hospitalized patients with severe depression treated with duloxetine. The RFL scores were low at baseline but increased during treatment, suggesting that they are at least partially state rather than trait variables. Since RFL scores are lower in depressed inpatients, these scores lose the predictive value that they have in a general population sample.ClinicalTrials.gov identifier: NCT00422162.

Dataset Information

Positive response to galcanezumab following treatment failure to onabotulinumtoxinA in patients with migraine: post hoc analyses of three randomized double-blind studies.

Background and purpose

Methods

Results

Conclusion

Publications

Positive response to galcanezumab following treatment failure to onabotulinumtoxinA in patients with migraine: post hoc analyses of three randomized double-blind studies.

Similar Datasets

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