Kudrow, David

Abstract Objective Assess the long‐term efficacy and safety of erenumab in patients with chronic migraine with acute medication overuse. Background Overuse of acute medication in patients with chronic migraine has been linked to greater pain intensity and disability and may diminish the effectiveness of preventive therapies. Methods This 52‐week open‐label extension study followed a 12‐week double‐blind placebo‐controlled study in which patients with chronic migraine were randomized 3:2:2 to placebo or once‐monthly erenumab 70 mg or 140 mg. Patients were stratified by region and medication overuse status. Patients received erenumab 70 mg or 140 mg throughout or switched from erenumab 70 to 140 mg (based on protocol amendment to augment safety data at higher dose). Efficacy was assessed in patients with and without medication overuse at parent study baseline. Results Of 609 patients enrolled in the extension study, 252/609 (41.4%) met the criteria for medication overuse at parent study baseline. At Week 52, the mean change in monthly migraine days from parent study baseline was −9.3 (95% confidence interval: −10.4, −8.1 days) in the medication overuse subgroup versus −9.3 (−10.1, −8.5 days) in the non‐medication overuse subgroup (combined erenumab doses); proportion of patients achieving ≥50% reduction in monthly migraine days at Week 52 was 55.9% (90/161; 48.2%, 63.3%) versus 61.3% (136/222; 54.7%, 67.4%), respectively. Among baseline users of acute migraine‐specific medication, the mean change in monthly migraine‐specific medication days at Week 52 was −7.4 (−8.3, −6.4 days) in the medication overuse subgroup versus −5.4 (−6.1, −4.7 days) in the non–medication overuse subgroup. Most patients (197/298; 66.1%) in the medication overuse subgroup transitioned to non‐overuse status by Week 52. Erenumab 140 mg was associated with numerically greater efficacy than erenumab 70 mg across all endpoints. No new safety signals were identified. Conclusion Long‐term erenumab treatment demonstrated sustained efficacy and safety in patients with chronic migraine with and without acute medication overuse.

Abstract Objective To assess cardiovascular (CV) safety of erenumab in clinical trial patients associated with degree of CV risk. Background Hypertension has been considered a theoretical risk associated with the inhibition of the calcitonin gene‐related peptide pathway in migraine management, particularly in a patient population with pre‐existing CV risk factors. Methods Data pooled from four double‐blind, randomized trials were used to assess blood pressure (BP) changes and CV safety in patients grouped based on 10‐year risk of cardiac, cerebrovascular, and peripheral artery disease as no‐risk‐factors, low‐risk (>0% to ≤10%), moderate‐risk (>10% to ≤20%), and high‐risk (>20%) categories. CV safety was assessed as ischemic cardiovascular and cerebrovascular adverse events (ICCAE). Results There was no apparent difference between placebo‐ ( N = 1032) and erenumab‐treatment groups (70 mg, N = 885; 140 mg, N = 504) in clinical worsening of BP category from baseline to Months 1–3 (14% [143/1032] placebo vs. 13% [114/885] and 14% [71/504] for erenumab 70 and 140 mg, respectively) regardless of baseline BP category. The adverse event (AE) profile of erenumab was similar across CV risk categories throughout the long‐term analysis. Erenumab‐treated patients with high and moderate 10‐year CV risk ( N = 107) did not experience any ICCAEs during the double‐blind treatment period; there was a single ICCAE (a cerebral dural venous sinus thrombosis) observed in the low‐risk erenumab group ( N = 273). There were no increases in AEs during the long‐term extensions of up to 5 years ( N = 2499; 3482 patient‐years of exposure to erenumab) with exposure‐adjusted incidence rates of cardio/cerebrovascular disorder AEs of 0.4, 0.5, 0.0, and 1.1 (per 100 patient‐years) for no risk factor ( N = 1805), low ( N = 492), moderate ( N = 121), and high ( N = 81) 10‐year CV risk groups, respectively. Conclusions Ischemic CV and cerebrovascular AEs were uncommon and the incidence rates were similar across the 10‐year CV risk categories. This analysis helps provide more detail on the CV safety of erenumab.

Background Erenumab (erenumab-aooe in the US) effectively reduces monthly migraine days in episodic and chronic migraine. This traditional outcome does not capture the intensity of headache pain on days with migraine. Methods This post hoc analysis of two pivotal randomized, placebo-controlled studies in patients with episodic migraine and chronic migraine examined the effect of erenumab 70 and 140 mg on migraine pain. Cumulative monthly migraine pain intensity is the sum of the peak pain intensity scores (0 = no migraine to 3 = migraine day with severe pain) on migraine days. Change from baseline in cumulative monthly migraine pain and average monthly pain intensity was assessed over months 4 to 6 for episodic migraine and month 3 for chronic migraine; change in average monthly pain intensity was assessed among monthly migraine days responders/non-responders. Results Efficacy analysis included 946 patients for the episodic migraine study and 656 patients for the chronic migraine study. Cumulative monthly migraine pain decreased significantly with erenumab versus placebo ( p < 0.001, for episodic migraine and chronic migraine). In addition, monthly average migraine pain intensity decreased significantly with erenumab versus placebo for episodic migraine ( p < 0.01); decreases were non-significant for chronic migraine. In comparison with placebo-treated patients, a greater proportion of erenumab-treated patients were pain intensity responders regardless of threshold used. Episodic migraine and chronic migraine patients with a ≥50% reduction in monthly migraine days (responders) had a greater reduction in monthly average pain intensity than non-responders. Conclusions Erenumab reduced cumulative monthly migraine pain in episodic migraine and chronic migraine patients and significantly reduced monthly average migraine pain in episodic migraine, demonstrating treatment benefit beyond reduction in migraine frequency. Clinical Trial Registration: ClinicalTrials.gov, NCT02456740; ClinicalTrials.gov, NCT02066415