Lipton, Richard B.

Background Atogepant is an oral, small-molecule, calcitonin gene-related peptide receptor antagonist for the preventive treatment of episodic migraine. Methods In this 52-week, multicenter, randomized, open-label trial, adults with 4–14 monthly migraine days received atogepant 60 mg once-daily or standard care. Health outcome endpoints collected from participants randomized to atogepant included change from baseline in Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQ v2.1) Role Function-Restrictive (RFR), Role Function-Preventive (RFP) and Emotional Function (EF) domain scores, change in Activity Impairment in Migraine-Diary (AIM-D) Performance of Daily Activities (PDA) and Physical Impairment (PI) domain scores, and change in Headache Impact Test-6 (HIT-6) total score. Results Of 744 randomized participants, 521 received atogepant 60 mg in the modified intent-to-treat population. Least-squares mean changes from baseline in MSQ-RFR score were 30.02 (95% confidence interval = 28.16–31.87) at week 12 and 34.70 (95% confidence interval = 32.74–36.66) at week 52. Improvements were also observed in other MSQ domains, AIM-D PDA, PI and HIT-6 total scores. A ≥5-point improvement from baseline in HIT-6 score was observed in 59.9% of participants at week 4 and 80.8% of participants at week 52. Conclusion Over 52 weeks, atogepant 60 mg once-daily was associated with sustained improvements in quality of life and reductions in activity impairment and headache impact. Trial Registration: NCT03700320

Chronic migraine (CM) is a neurological disease characterized by frequent migraine attacks that prevent affected individuals from performing daily activities of living, significantly diminish quality of life, and increase familial burden. Before onabotulinumtoxinA was approved for CM, there were few treatment options for these seriously disabled patients and none had regulatory approval. The terminology and recognition of CM evolved in parallel with the onabotulinumtoxinA clinical development program. Because there were no globally accepted classification criteria for CM when onabotulinumtoxinA was in development, the patient populations for the trials conducted by Allergan were determined by the Allergan migraine team in collaboration with headache scientists and clinicians. These trials and collaborations ultimately led to improvements in CM classifications. In 2010, onabotulinumtoxinA became the first medication and first biologic approved specifically to prevent headaches in patients with CM. Approval was based on 2 similarly designed phase 3, double-blind, randomized, placebo-controlled, multicenter clinical studies. Both studies showed significantly greater improvements in mean change from baseline in headache-day frequency in patients with CM receiving onabotulinumtoxinA compared with those receiving placebo. The safety and effectiveness of onabotulinumtoxinA have been established globally in >5000 patients with CM with or without medication overuse treated in clinical and observational studies. Benefits also include improvements in quality of life, fewer psychiatric comorbidities, and reduced healthcare resource utilization. Across studies, onabotulinumtoxinA was well tolerated; adverse events tended to be mild or moderate in severity and to decline over subsequent treatment cycles.

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.