Brevig, Thomas

Abstract Objective To evaluate the effect of eptinezumab on patient‐reported outcomes in patients with chronic migraine (CM) and medication‐overuse headache (MOH). Background MOH is a secondary headache disorder commonly occurring in patients with CM and associated with functional and psychological impairments. Medication overuse and monthly headache and migraine days were reduced with eptinezumab compared with placebo as published previously; however, these outcomes do not fully capture the burden of migraine and treatment effect. Methods PROMISE‐2 was a phase 3, randomized, double‐blind, placebo‐controlled trial in adults with CM. Patients were randomized (1:1:1) to receive eptinezumab 100 mg, eptinezumab 300 mg, or placebo (up to 2 doses, 12 weeks apart). Patients completed the following patient‐reported outcomes: 6‐item Headache Impact Test (HIT‐6), Patient Global Impression of Change (PGIC), patient‐identified most bothersome symptom (PI‐MBS), and 36‐item Short‐Form Health Survey (SF‐36). Results A total of 431 CM patients (139, 147, and 145 patients in the eptinezumab 100 mg, eptinezumab 300 mg, and placebo groups, respectively) had MOH diagnosed at screening (40.2% of the total PROMISE‐2 population [ n = 1072]). In CM with MOH patients, both doses of eptinezumab were associated with clinically meaningful improvements in mean HIT‐6 total scores by week 4 and remained improved throughout the 24‐week study. Responder rates for individual HIT‐6 items were greater with eptinezumab than with placebo at all time points. At week 12, almost twice as many eptinezumab‐treated patients indicated the PGIC was “much” or “very much” improved (58.5% [79/135, 100 mg] and 67.4% [95/147, 300 mg] vs. 35.8% [48/134, placebo]). Patients in the eptinezumab groups showed numerically greater improvements over placebo in the PI‐MBS and SF‐36 scores. Conclusions This subgroup analysis in patients with CM/MOH at baseline suggests that eptinezumab treatment is associated with early, sustained, and clinically meaningful improvements in patient‐reported outcomes.

Abstract Objective This post hoc analysis in patients medically diagnosed with chronic migraine (CM) and medication‐overuse headache (MOH) evaluated reductions in the use of acute headache medication (AHM) and sustained changes in the diagnostic status of CM and MOH following eptinezumab treatment in the PROMISE‐2 study. Background Eptinezumab, a monoclonal antibody that inhibits calcitonin gene‐related peptide, is approved in the United States for the preventive treatment of migraine. A previous analysis showed that eptinezumab reduced monthly migraine days and was well tolerated in the subgroup of PROMISE‐2 patients diagnosed with both CM and MOH. Methods The phase 3, double‐blind, placebo‐controlled PROMISE‐2 study (NCT02974153) randomized adults with CM to eptinezumab 100 mg, 300 mg, or placebo (administered intravenously every 12 weeks for up to two doses). MOH was prospectively diagnosed at screening by trained physicians based on 3 months of medication history and International Classification of Headache Disorders‐3β criteria. This post hoc analysis evaluated changes in total and class‐specific days of AHM usage, the percentage of patients using AHM at or above MOH diagnostic thresholds, and the percentage of patients experiencing monthly headache and migraine day frequency below diagnostic thresholds for MOH and/or CM. Results In PROMISE‐2, 431/1072 (40.2%) patients with CM were diagnosed with MOH (eptinezumab 100 mg, n = 139; 300 mg, n = 147; placebo, n = 145) and were included in this analysis. Total monthly AHM use decreased from 20.6 days/month at baseline to 10.6 days/month over 24 weeks of treatment (49% decrease) with eptinezumab 100 mg, from 20.7 to 10.5 days/month (49% decrease) with eptinezumab 300 mg, and from 19.8 to 14.0 days/month (29% decrease) with placebo. Numerically greater decreases from baseline with eptinezumab were also observed for individual drug classes. In each study month, the percentages of patients who were below MOH thresholds were numerically higher for both eptinezumab doses compared with placebo, as were the percentages of patients experiencing headache and migraine frequency below CM thresholds. Of patients with available data across the entire treatment period, 29.0% (58/200) of patients treated with eptinezumab stopped meeting and remained below diagnostic thresholds for both CM and MOH during Weeks 1–24, as well as 6.3% (6/96) of patients who received placebo. Conclusions Across 24 weeks of treatment, eptinezumab reduced AHM use in patients diagnosed with CM and MOH. More than one‐fourth (29%) of patients treated with eptinezumab did not meet the diagnostic thresholds for either CM or MOH for the entire treatment period.

Abstract Objective To evaluate the efficacy, tolerability, and safety of eptinezumab 100 and 300 mg compared with placebo in patients with the dual diagnosis of chronic migraine (CM) and medication‐overuse headache (MOH). Background Eptinezumab, a humanized monoclonal antibody targeting calcitonin gene‐related peptide, may be effective for treating patients with a dual diagnosis of CM and MOH. Methods PROMISE‐2 (NCT02974153) was a double‐blind, randomized, placebo‐controlled, phase 3 study that comprised a screening visit, a 28‐day pretreatment period, and a 32‐week study duration. Patients in this exploratory analysis of a prespecified subgroup had confirmed diagnoses of both CM and MOH at screening. Patients were randomly assigned to receive intravenous eptinezumab 100, 300 mg, or placebo every 12 weeks. Efficacy outcomes included mean changes from baseline in monthly migraine days (MMDs) during weeks 1–12, migraine responder rates at week 12, and percentages of patients below International Classification of Headache Disorders thresholds for CM and MOH over weeks 1–24. Results There were 431 patients who were diagnosed with CM and MOH as specified in the protocol and received eptinezumab 100 mg ( n = 139), 300 mg ( n = 147), or placebo ( n = 145). During the baseline period, these patients experienced an average of 16.7 migraine days across treatment arms. Over weeks 1–12, eptinezumab‐treated patients experienced greater reductions from baseline in MMDs than placebo patients (100 mg, change from baseline = −8.4, difference from placebo [95% confidence interval (CI)] = −3.0 [−4.56, −1.52], p < 0.0001 vs. placebo; 300 mg, change from baseline = −8.6, difference from placebo [95% CI] = −3.2 [−4.66, −1.78], p < 0.0001 vs. placebo; placebo, −5.4). Compared with placebo, more eptinezumab‐treated patients were ≥50% migraine responders (100 mg, 84/139 [60.4%]; 300 mg, 91/147 [61.9%]; placebo, 50/145 [34.5%]) or ≥75% responders (100 mg, 38/139 [27.3%]; 300 mg, 44/147 [29.9%]; placebo, 21/145 [14.5%]) over weeks 1–12. Therapeutic benefits with eptinezumab were observed from day 1 after dosing, and improvements were sustained with an additional dose. For the full 24‐week treatment period, 71/139 (51.1%), 80/147 (54.4%), and 47/145 (32.4%) of 100, 300 mg, and placebo‐treated patients, respectively, were below CM thresholds, and of the patients who provided sufficient acute medication data, 47/93 (50.5%), 53/107 (49.5%), and 26/96 (27.1%), respectively, were below medication‐overuse thresholds. Conclusions In patients diagnosed with both CM and MOH, eptinezumab treatment resulted in greater reductions in MMDs, higher responder rates, and fewer patients meeting CM and MOH criteria, thus demonstrating the efficacy and clinical utility of eptinezumab in this patient population.