Long-term reductions in acute headache medication use after eptinezumab treatment in patients with migraine and prior preventive treatment failures: Post hoc analysis of the DELIVER randomized trial.

Objective: To evaluate long-term reductions in acute headache medication (AHM) use with eptinezumab versus placebo in patients with prior preventive migraine treatment failures and medication overuse (MO).

Background: Preventive migraine treatment is recommended for patients for whom AHMs have failed and for those who are using excessive amounts of AHM. MO may worsen headache and migraine symptoms in people with migraine; it is a risk factor for disease chronification and/or MO headache.

Methods: DELIVER was a multicenter, parallel-group, double-blind, randomized, placebo-controlled, phase 3b clinical trial that randomized adults with migraine and two to four prior preventive failures to eptinezumab 100 mg, 300 mg, or placebo infusion every 12 weeks; patients initially given placebo received eptinezumab 100 mg or 300 mg in the extension period. MO was defined according to diagnostic criteria for MO headache in the baseline diary reports. This post hoc analysis of the DELIVER study included change from baseline in AHM days/month of use (ergotamines, triptans, simple or combination analgesics, and opioids; total and select class-specific use) in the MO population.

Results: A total of 890 patients were included in the total population, and 438/890 (49.2%) had MO at baseline. In both the total population and MO population, eptinezumab resulted in greater reductions in total AHM days/month of use during weeks 1-24 than placebo, with triptans showing the largest reduction among AHM classes. Patients switching from placebo to eptinezumab experienced reductions in AHM days/month similar to that of initial eptinezumab treatment. In the extension population, mean (standard error [SE]) changes from baseline in AHM days/month were -4.6 (0.32; 100 mg) and -4.8 (0.32; 300 mg) across weeks 1-4 in patients who received eptinezumab for the entire treatment period and were -4.8 (0.44; placebo-100 mg) and -5.5 (0.44; placebo-300 mg) across weeks 25-28 in patients who switched from placebo to eptinezumab. Mean (SE) changes from baseline in AHM days/month in the extension MO population were -6.5 (0.59; 100 mg) and -6.6 (0.57; 300 mg) across weeks 1-4 in patients who received eptinezumab for the entire treatment period and were -7.1 (0.81; 100 mg) and -8.0 (0.80; 300 mg) across weeks 25-28 in patients who were switched from placebo to eptinezumab. All treatment arms sustained or further reduced AHM use across 18 months of trial participation. Across weeks 1-4, in patients fulfilling criteria for MO at baseline, 68.0% (102/150) of patients treated with eptinezumab 100 mg and 74.7% (109/146) of patients treated with eptinezumab 300 mg reported AHM use below MO thresholds compared to 43.3% (61/141) of patients receiving placebo. In patients with MO at baseline, the proportion of patients without MO remained above 60.0% for all treatment groups during the extension period.

Conclusions: Eptinezumab reduced total AHM use more than placebo in patients with prior preventive failures and in patients with MO at baseline; largest reductions were observed for triptans. Robust reductions in AHM use after eptinezumab were sustained or further reduced with up to 18 months of treatment, and most patients no longer met thresholds for MO.