ARISE: A Phase 3 randomized trial of erenumab for episodic migraine

Cephalalgia ◽  
2018 ◽  
Vol 38 (6) ◽  
pp. 1026-1037 ◽  
Author(s):  
David W Dodick ◽  
Messoud Ashina ◽  
Jan Lewis Brandes ◽  
David Kudrow ◽  
Michel Lanteri-Minet ◽  
...  
Keyword(s):  
Physical Function ◽  
Episodic Migraine ◽  
Physical Impairment ◽  
Acute Migraine ◽  
Phase 3 ◽  
Medication Treatment ◽  
Everyday Activities ◽  
Point Reduction ◽  
Calcitonin Gene ◽  
Specific Medication

Background Calcitonin gene-related peptide plays an important role in migraine pathophysiology. Erenumab, a human monoclonal antibody that inhibits the calcitonin gene-related peptide receptor, is being evaluated for migraine prevention. Methods In this randomized, double-blind, placebo-controlled, phase 3 study, 577 adults with episodic migraine were randomized to placebo or 70 mg erenumab; 570 patients were included in efficacy analyses. Primary endpoint was change in monthly migraine days. Secondary endpoints were ≥50% reduction in monthly migraine days, change in acute migraine-specific medication treatment days, and ≥5-point reduction in Physical Impairment and Impact on Everyday Activities domain scores measured by the Migraine Physical Function Impact Diary. All endpoints assessed change from baseline at month 3. Results Patients receiving erenumab experienced −2.9 days change in monthly migraine days, compared with −1.8 days for placebo, least-squares mean (95% CI) treatment difference of −1.0 (−1.6, −0.5) ( p < 0.001). A ≥ 50% reduction in monthly migraine days was achieved by 39.7% (erenumab) and 29.5% (placebo) of patients (OR:1.59 (95% CI: 1.12, 2.27) ( p = 0.010). Migraine-specific medication treatment days were reduced by −1.2 (erenumab) and −0.6 (placebo) days, a treatment difference of −0.6 (−1.0, −0.2) ( p = 0.002). The ≥5-point reduction rates in Migraine Physical Function Impact Diary – Physical Impairment were 33.0% and 27.1% (OR:1.33 (0.92, 1.90) ( p = 0.13) and in Migraine Physical Function Impact Diary – Everyday Activities were 40.4% and 35.8% (OR:1.22 (0.87, 1.71) ( p = 0.26). Safety and adverse event profiles of erenumab were similar to placebo. Most frequent adverse events were upper respiratory tract infection, injection site pain, and nasopharyngitis. Conclusions As a preventive treatment of episodic migraine, erenumab at a dosage of 70 mg monthly significantly reduced migraine frequency and acute migraine-specific medication use. (Funded by Amgen). Trial registration ClinicalTrials.gov, NCT02483585.

scholarly journals Randomised, controlled trial of erenumab for the prevention of episodic migraine in patients from Asia, the Middle East, and Latin America: The EMPOwER study

Cephalalgia ◽  
2021 ◽  
pp. 033310242110241
Author(s):  
Shuu-Jiun Wang ◽  
Artemio A Roxas ◽  
Bibiana Saravia ◽  
Byung-Kun Kim ◽  
Debashish Chowdhury ◽  
...  
Keyword(s):  
Latin America ◽  
Middle East ◽  
Primary Endpoint ◽  
Episodic Migraine ◽  
Acute Migraine ◽  
Efficacy And Safety ◽  
Medication Treatment ◽  
Significant Difference ◽  
Specific Medication ◽  
Secondary Endpoints

Objective EMPOwER, a double-blind, randomised, phase 3 study, evaluated the efficacy and safety of erenumab in adults with episodic migraine from Asia, the Middle East, and Latin America. Methods Randomised patients (N = 900) received monthly subcutaneous injections of placebo, erenumab 70 mg, or 140 mg (3:3:2) for 3 months. Primary endpoint was change from baseline in monthly migraine days at Month 3. Other endpoints included achievement of ≥50%, ≥75%, and 100% reduction in monthly migraine days, change in monthly acute migraine-specific medication treatment days, patient-reported outcomes, and safety assessment. Results At baseline, mean (standard deviation) age was 37.5 (9.9) years, 81.9% were women, and monthly migraine days was 8.2 (2.8). At Month 3, change from baseline in monthly migraine days (primary endpoint) was −3.1, −4.2, and −4.8 days for placebo, erenumab 70 mg, and erenumab 140 mg, respectively, with a statistically significant difference for erenumab versus placebo (P = 0.002 [70 mg], P < 0.001 [140 mg]). Both erenumab doses were also significantly superior to placebo on all secondary endpoints, including the proportion of patients achieving ≥50% reduction from baseline in monthly migraine days, change from baseline in monthly acute migraine-specific medication treatment days and change from baseline in the Headache Impact Test-6™ scores. The safety profile of erenumab was comparable with placebo; no new safety signals were observed. Conclusions This study of erenumab in patients with episodic migraine from Asia, the Middle East, and Latin America met all primary and secondary endpoints. A consistent numerical benefit was observed with erenumab 140 mg versus erenumab 70 mg across all efficacy endpoints. These findings extend evidence of erenumab’s efficacy and safety to patients under-represented in previous trials. ClinicalTrials.gov identifier: NCT03333109

scholarly journals Effect of erenumab on functional outcomes in patients with episodic migraine in whom 2–4 preventives were not useful: results from the LIBERTY study

2021 ◽  
pp. jnnp-2020-324396
Author(s):  
Michel Lanteri-Minet ◽  
Peter J Goadsby ◽  
Uwe Reuter ◽  
Shihua Wen ◽  
Peggy Hours-Zesiger ◽  
...  
Keyword(s):  
Functional Outcomes ◽  
Impact Test ◽  
Work Productivity ◽  
Placebo Treatment ◽  
Episodic Migraine ◽  
Activity Impairment ◽  
Everyday Activities ◽  
Point Reduction ◽  
Patient Reported ◽  
Headache Impact

ObjectiveTo evaluate the effect of erenumab on patient-reported, functional outcomes in patients with episodic migraine (EM) in whom 2–4 preventives were not useful from the Phase 3b LIBERTY study.MethodsAs previously reported, 246 patients with EM with 2–4 prior failed preventives were randomised 1:1 to subcutaneous erenumab 140 mg or placebo every 4 weeks for 12 weeks. This analysis evaluated Migraine Physical Function Impact Diary (MPFID), Headache Impact Test (HIT-6) and Work Productivity and Activity Impairment (WPAI) scores at Week 12. P values were nominal without multiplicity adjustment.ResultsErenumab significantly improved MPFID-Physical Impairment (PI) and Everyday Activities (EA) scores versus placebo (treatment difference (TD) (95% CI) MPFID-PI: −3.5 (−5.7 to –1.2) (p=0.003); MPFID-EA: −3.9 (−6.1 to –1.7)) (p<0.001) at 12 weeks. Patients on erenumab were more likely to have a ≥5-point reduction in MPFID score (OR vs placebo (95% CI) MPFID-EA: 2.1 (1.2 to 3.6); MPFID-PI: 2.5 (1.4 to 4.5)). A similar trend was observed for HIT-6 (TD: −3.0; p<0.001); significantly higher proportions of patients on erenumab reported a ≥5-point reduction (OR (95% CI): 2.4 (1.4 to 4.1)). In three out of four WPAI domains, erenumab showed improvement versus placebo.ConclusionAt 12 weeks, erenumab was efficacious on functional outcomes in patients with EM in whom 2–4 preventives were not useful.Trial registration detailsClinicalTrials.gov identifier: NCT03096834.

scholarly journals Assessment of immunogenicity from galcanezumab phase 3 trials in patients with episodic or chronic migraine

Cephalalgia ◽  
2020 ◽  
Vol 40 (9) ◽  
pp. 978-989 ◽  
Author(s):  
James M Martinez ◽  
Nada Hindiyeh ◽  
Greg Anglin ◽  
Kavita Kalidas ◽  
Michael E Hodsdon ◽  
...  
Keyword(s):  
Adverse Events ◽  
Chronic Migraine ◽  
Antibody Titer ◽  
Episodic Migraine ◽  
Calcitonin Gene Related Peptide ◽  
Phase 3 ◽  
Related Peptide ◽  
Antidrug Antibody ◽  
Calcitonin Gene ◽  
Antidrug Antibodies

Background This analysis characterizes the immunogenicity profile of galcanezumab, a humanized monoclonal antibody that selectively binds calcitonin gene-related peptide and inhibits its activity, in phase 3 migraine trials. Methods Immunogenicity data were analyzed from baseline and double-blind, placebo-controlled phases of the 3-month chronic migraine study REGAIN, the 6-month episodic migraine studies EVOLVE-1 and EVOLVE-2, and from baseline and open-label phases of the 12-month chronic and episodic migraine Study CGAJ. The incidence of baseline antidrug antibodies, treatment-emergent antidrug antibodies, neutralizing antidrug antibodies, and the effect of antidrug antibody titer on pharmacokinetics and pharmacodynamics were assessed. The relationship between antidrug antibody status and efficacy was explored using average change in monthly migraine headache days. Safety analyses assessed the potential relationship between treatment-emergent antidrug antibodies and hypersensitivity events or adverse events related to injection sites. Findings Across studies, 5.9–11.2% of patients had baseline antidrug antibodies. The incidence of treatment-emergent antidrug antibodies was 2.6–12.4% in the galcanezumab group and 0.5–1.7% in the placebo group. The majority of treatment-emergent antidrug antibodies were detected approximately 3–6 months after first study drug dose. Overall, the observed antidrug antibody titer did not impact galcanezumab concentrations, calcitonin gene-related peptide concentrations, or galcanezumab efficacy. There was no evidence that hypersensitivity events or adverse events related to injection sites were mediated by treatment-emergent antidrug antibodies. Interpretation These data showed that immunogenicity did not impact galcanezumab concentrations, calcitonin gene-related peptide concentrations, or the efficacy and hypersensitivity profile of galcanezumab in patients with migraine.

scholarly journals Erenumab in chronic migraine with medication overuse

Neurology ◽  
2019 ◽  
Vol 92 (20) ◽  
pp. e2309-e2320 ◽  
Author(s):  
Stewart J. Tepper ◽  
Hans-Christoph Diener ◽  
Messoud Ashina ◽  
Jan Lewis Brandes ◽  
Deborah I. Friedman ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Confidence Interval ◽  
Chronic Migraine ◽  
Odds Ratio ◽  
Medication Overuse ◽  
Controlled Study ◽  
Acute Migraine ◽  
Medication Treatment ◽  
Specific Medication

ObjectiveTo determine the effect of erenumab, a human anti-calcitonin gene-related peptide receptor monoclonal antibody, in patients with chronic migraine and medication overuse.MethodsIn this double-blind, placebo-controlled study, 667 adults with chronic migraine were randomized (3:2:2) to placebo or erenumab (70 or 140 mg), stratified by region and medication overuse status. Data from patients with baseline medication overuse at baseline were used to assess changes in monthly migraine days, acute migraine-specific medication treatment days, and proportion of patients achieving ≥50% reduction from baseline in monthly migraine days.ResultsOf 667 patients randomized, 41% (n = 274) met medication overuse criteria. In the medication overuse subgroup, erenumab 70 or 140 mg groups had greater reductions than the placebo group at month 3 in monthly migraine days (mean [95% confidence interval] −6.6 [−8.0 to −5.3] and −6.6 [−8.0 to −5.3] vs −3.5 [−4.6 to −2.4]) and acute migraine-specific medication treatment days (−5.4 [−6.5 to −4.4] and −4.9 [−6.0 to −3.8] vs −2.1 [−3.0 to −1.2]). In the placebo and 70 and 140 mg groups, ≥50% reductions in monthly migraine days were achieved by 18%, 36% (odds ratio [95% confidence interval] 2.67 [1.36–5.22]) and 35% (odds ratio 2.51 [1.28–4.94]). These clinical responses paralleled improvements in patient-reported outcomes with a consistent benefit of erenumab across multiple measures of impact, disability, and health-related quality of life. The observed treatment effects were similar in the non–medication overuse subgroup.ConclusionsErenumab reduced migraine frequency and acute migraine-specific medication treatment days in patients with chronic migraine and medication overuse, improving disability and quality of life.Clinicaltrials.gov identifierNCT02066415.Classification of evidenceThis study provides Class II evidence that erenumab reduces monthly migraine days at 3 months in patients with chronic migraine and medication overuse.

scholarly journals Efficacy and safety of erenumab in Japanese migraine patients with prior preventive treatment failure or concomitant preventive treatment: subgroup analyses of a phase 3, randomized trial

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Koichi Hirata ◽  
Fumihiko Sakai ◽  
Takao Takeshima ◽  
Noboru Imai ◽  
Yasuhiko Matsumori ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Preventive Treatment ◽  
Controlled Study ◽  
Acute Migraine ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Subgroup Analyses ◽  
Specific Medication

Abstract Background These subgroup analyses of a Phase 3, randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of erenumab 70 mg in Japanese migraine patients with/without prior preventive treatment failure(s) (“failed-yes” and “failed-no” subgroups) and with/without concomitant preventive treatment (“concomitant preventive-yes” and “concomitant preventive-no” subgroups). Methods Overall, 261 patients were randomized; 130 and 131 patients to erenumab 70 mg and placebo, respectively. Subgroup analyses evaluated the change from baseline to Months 4–6 in mean monthly migraine days (MMD) (primary endpoint), achievement of a ≥50% reduction in mean MMD, and change from baseline in mean monthly acute migraine-specific medication (MSM) treatment days. Treatment-emergent adverse events were also evaluated. Results Of the 261 patients randomized, 117 (44.8%) and 92 (35.3%) patients were in the failed-yes and concomitant preventive-yes subgroups, respectively. Erenumab 70 mg demonstrated consistent efficacy across all subgroups, with greater reductions from baseline in mean MMD versus placebo at Months 4–6 (treatment difference versus placebo [95% CI], failed-yes: − 1.9 [− 3.3, − 0.4]; failed-no: − 1.4 [− 2.6, − 0.3]; concomitant preventive-yes: − 1.7 [− 3.3, 0.0]; concomitant preventive-no: − 1.6 [− 2.6, − 0.5]). Similar results were seen for achievement of ≥50% reduction in mean MMD and change from baseline in mean monthly acute MSM treatment days. The safety profile of erenumab 70 mg was similar across subgroups, and similar to placebo in each subgroup. Conclusion Erenumab was associated with clinically relevant improvements in all efficacy endpoints and was well tolerated across all subgroups of Japanese migraine patients with/without prior preventive treatment failure(s) and with/without concomitant preventive treatment. Trial registration Clinicaltrials.gov. NCT03812224. Registered January 23, 2019.

Efficacy and safety of erenumab (AMG334) in episodic migraine patients with prior preventive treatment failure: A subgroup analysis of a randomized, double-blind, placebo-controlled study

Cephalalgia ◽  
2019 ◽  
Vol 39 (7) ◽  
pp. 817-826 ◽  
Author(s):  
Peter J Goadsby ◽  
Koen Paemeleire ◽  
Gregor Broessner ◽  
Jan Brandes ◽  
Jan Klatt ◽  
...  
Keyword(s):  
Placebo Response ◽  
Preventive Treatment ◽  
Episodic Migraine ◽  
Prior Treatment ◽  
Controlled Study ◽  
Study Phase ◽  
Acute Migraine ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Specific Medication

Background Erenumab was effective and well tolerated in a pivotal clinical trial of episodic migraine that included subjects both naïve to, and those who had failed, previous preventives. Here we evaluated the efficacy and safety of erenumab (70 mg or 140 mg) versus placebo in the subgroup of patients who had previously failed preventive treatment(s): ≥1 or ≥2 prior failed migraine preventive categories, and in patients who had never failed. Methods Prespecified subgroup analyses evaluated change from baseline to months 4–6 (the primary endpoint of the blinded study phase) in monthly migraine days, achievement of ≥50% and ≥75% reduction in monthly migraine days, and change from baseline in acute migraine-specific medication days. Adverse events were also evaluated. Results Treatment with both doses of erenumab resulted in greater reductions in monthly migraine days at months 4–6 (treatment difference versus placebo [95% CI], never failed subgroup: −0.9 [−1.5, −0.3] for 70 mg and −1.3 [−1.9, −0.7] for 140 mg; ≥1 prior failed medication categories subgroup: −2.0 [−2.8, −1.2] for 70 mg and −2.5 [−3.4, −1.7] for 140 mg; ≥2 prior failed medication categories subgroup: −1.3 [−2.6, 0.0] for 70 mg and −2.7 [−4.0, −1.4] for 140 mg). Similar results were observed in the monthly acute migraine-specific medication days endpoint, and in the achievement of ≥50% and ≥75% reduction in monthly migraine days. For the ≥50% reduction in monthly migraine day endpoint, placebo response in the no prior treatment failed group was 32.6%, in the ≥1 failed treatment 17.5%, and in the ≥2 failed treatments 11.1%. Conclusion Erenumab showed consistent efficacy in episodic migraine patients who had failed prior preventive treatments and was well tolerated across subgroups. The data suggest prior patients with prior treatment failures have lower placebo response rates.

scholarly journals Acute migraine medication adherence, migraine disability and patient satisfaction: A naturalistic daily diary study

Cephalalgia ◽  
2016 ◽  
Vol 37 (10) ◽  
pp. 955-964 ◽  
Author(s):  
Elizabeth K Seng ◽  
Matthew S Robbins ◽  
Robert A Nicholson
Keyword(s):  
Medication Adherence ◽  
Repeated Measures ◽  
Episodic Migraine ◽  
Acute Migraine ◽  
Over The Counter ◽  
Daily Diary Study ◽  
Acute Medication ◽  
Specific Medication ◽  
Migraine Medication ◽  
Initial Medication

Objective To examine the influence of acute migraine medication adherence on migraine disability and acute medication satisfaction. Methods Adults with migraine completed three months of daily electronic diaries assessing headache symptoms, acute medication taken, acute medication satisfaction, and daily migraine disability. Repeated measures mixed-effects models examined the effect of initial medication type [migraine-specific medication (MSM) vs. over-the-counter analgesic (OTC) vs. an opiate/barbiturate], the severity of pain at dosing, and their interaction with daily migraine disability and satisfaction with acute medication. Results Participants (N = 337; 92.5% female; 91.1% Caucasian, non-Hispanic; 84.0% with episodic migraine) recorded 29,722 diary days. Participants took acute medication on 96.5% of 8090 migraine days. MSM was most frequently taken first (58%), followed by OTC (29.9%) and an opiate/barbiturate (12.1%). Acute medication was most frequently taken when pain was mild (41.2%), followed by moderate (37.7%) and severe pain (11.4%). Initially dosing with MSM while pain was mild was associated with the lowest daily disability [medication × pain at dosing F (4, 6336.12) = 58.73, p < .001] and highest acute medication satisfaction [medication × pain at dosing F (4, 3867.36) = 24.00, p < .001]. Conclusion Using an MSM (triptan or ergot) first was associated with the lowest migraine disability and highest acute medication satisfaction.

Effects of fremanezumab on the use of acute headache medication and associated symptoms of migraine in patients with episodic migraine

Cephalalgia ◽  
2019 ◽  
Vol 40 (5) ◽  
pp. 470-477 ◽  
Author(s):  
Jan Lewis Brandes ◽  
David Kudrow ◽  
Paul P Yeung ◽  
Fumihiko Sakai ◽  
Ernesto Aycardi ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Medication Use ◽  
Preventive Treatment ◽  
Episodic Migraine ◽  
Phase 3 ◽  
Humanized Monoclonal Antibody ◽  
Calcitonin Gene ◽  
Associated Symptoms ◽  
Acute Headache ◽  
To Receive

Background Fremanezumab, a fully humanized monoclonal antibody targeting calcitonin gene-related peptide, has demonstrated efficacy for the preventive treatment of migraine in adults. Objective To evaluate the effect of fremanezumab treatment on acute headache medication use and migraine-associated symptoms in patients with episodic migraine. Methods In the Phase 3 HALO trial, patients with episodic migraine were randomized to receive subcutaneous fremanezumab monthly (225 mg at baseline, weeks 4 and 8), fremanezumab quarterly (675 mg at baseline, placebo at weeks 4 and 8), or placebo over a 12-week period. The secondary endpoint was change from baseline in the monthly number of days with use of any acute headache mediation or migraine-specific acute headache medication; exploratory endpoints were change from baseline in the monthly number of days with nausea or vomiting, photophobia, or phonophobia. Results Of 875 patients randomized, 865 were included in the analysis (monthly, n = 287; quarterly, n = 288; placebo, n = 290). Baseline mean ± standard deviation days with: Any acute headache medication use (monthly: 7.7 ± 3.4; quarterly: 7.8 ± 3.7; placebo: 7.7 ± 3.6), migraine-specific acute headache medication use (6.1 ± 3.1; 6.6 ± 3.1; 7.1 ± 3.0), nausea or vomiting (4.5 ± 3.6; 4.9 ± 3.7; 4.5 ± 3.3) and photophobia and phonophobia (5.5 ± 4.1; 6.3 ± 4.1; 6.0 ± 3.9) were similar among treatment arms. Fremanezumab reduced the number of days of acute headache medication use ([least-squares mean change vs. placebo] monthly: −1.4 [95% confidence interval: −1.84, −0.89], p < 0.001; quarterly: −1.3 [−1.76, −0.82], p < 0.001) and migraine-specific acute headache medication use (monthly: −2.2 [−2.80, −1.56], p < 0.001; quarterly: −2.2 [−2.81, −1.58], p < 0.001) compared with placebo. Fremanezumab also reduced nausea or vomiting, photophobia, and phonophobia compared with placebo. Conclusions Fremanezumab reduced the need for acute headache medications, including migraine-specific medications, while treating migraine-associated symptoms in patients with episodic migraine. Trial registration Clinicaltrials.gov NCT02629861

scholarly journals Effectiveness and safety of erenumab and galcanezumab in the prevention of chronic and episodic migraine: a retrospective cohort study

2021 ◽  
Author(s):  
Adrián Viudez-Martinez ◽  
Angela Pascual-Carrasco ◽  
Isabel Beltrán Blasco ◽  
Raquel Hernandez-Lorido ◽  
Rosa Fuster-Ruiz-de-Apodaca
Keyword(s):  
Chronic Migraine ◽  
Real World ◽  
Test Score ◽  
Daily Practice ◽  
Episodic Migraine ◽  
Migraine Prevention ◽  
Acute Migraine ◽  
Inclusion Criteria ◽  
Patient Reported ◽  
Specific Medication

Aim and Methods: Erenumab and galcanezumab have shown great results for migraine prevention in several clinical trials. However, strict inclusion criteria, absence of concomitant medication and selective outcome report may sometimes be barely representative of the real-world daily practice. Therefore, this observational, retrospective, non-comparative study was aimed to evaluate the effectiveness and safety of erenumab 140 mg and galcanezumab 120 mg in real-world patients with difficult-to-treat episodic or chronic migraine, who previously did not respond to up to three well-stablished pharmacological alternatives for migraine prevention. A combination of objective well-defined tools and vastly used patient reported outcome measurements were evaluated at baseline and after the administration of 3 and 6 doses. Results: from 180 patients, 142 matched inclusion criteria for the present study. Data here reported shows that erenumab and galcanezumab reduced mean headache days, acute migraine specific medication days, Headache Impact Test score, Migraine Disability Assessment Test score and Visual Analogue Scale score after 3 and 6 doses in real-world patients diagnosed with difficult to treat chronic or episodic migraine (p<0.01). Moreover, acute migraine specific medication days were reduced by a half in, at least, a 50% of the patients enrolled in each of the groups of the study. Both treatments exhibited a great safety profile, rarely leading to discontinuation because of poor tolerance. Conclusions: Erenumab and galcanezumab seem effective and well tolerated for migraine prevention in real-world patients with episodic or chronic migraine who previously failed to oral preventive therapies.

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