In adults with migraine and multiple prior preventive treatment failures, eptinezumab 100 mg and 300 mg administered via IV infusion every 12 weeks led to improved self-reported work productivity and reduced activity impairment compared to placebo. Benefits were observed as early as Week 4, the first post-baseline assessment. This early response is consistent with the early (within the first 4 weeks) onset of improvements in MMDs [17, 24], well-being (EQ-5D-5L) , symptoms (PI-MBS) [25,26,27], headache impact (6-item Headache Impact Test [HIT-6]) [10, 17, 25], and disease status (Patient Global Impression of Change [PGIC]) [10, 25] previously reported. Changes from baseline in MMDs in the DELIVER study showed that changes were largest during the first 4 weeks of treatment, with some patients further responding after a second dose (Weeks 13–24) .
Throughout its clinical development, eptinezumab has consistently demonstrated early and sustained reductions in headache/migraine frequency [10,11,12,13,14,15, 28,29,30] and severity , both characteristics of which can contribute to reduced work productivity. Results of the large National Health and Wellness Survey (NHWS) provide insight into the subjectively assessed benefit of reduced frequency on productivity. In the US NHWS (2016), each incremental increase in monthly headache-free days (0–10, 11–20, 21–26) was associated with a 5% reduction in work days missed and days of household activities missed . In the European NHWS (2017), even an increase of a single headache-free day was associated with reduced absenteeism (− 3.9%), presenteeism (− 2.1%), total work impairment (− 2.1%), and activity impairment (− 1.8%); an increase of 5 headache-free days was associated with greater improvements (− 18.2%, − 10.3%, − 10.1%, and − 8.7%, respectively) .
The analysis population of DELIVER consisted of patients for whom migraine severity was a key factor, as the study included patients with 2–4 prior preventive treatment failures at baseline. Eptinezumab treatment previously led to sustained and consistent reductions in PI-MBS severity in the PROMISE-2 study in chronic migraine, with 45–66% of eptinezumab-treated patients reporting much or very much improvement in their PI-MBS as early as Week 4 relative to placebo recipients (29–41%) . In DELIVER, 50–56% of eptinezumab-treated patients reported much or very much improvement in their PI-MBS at the Week 12 and Week 24 time points, compared with 19–23% of patients receiving placebo . Additionally, a higher percentage of the patients in the placebo group of the PROMISE-2 study were responsive to treatment (~ 30% and higher)  compared to patients in the placebo group of DELIVER (~ 20% and higher) . The differences in placebo response between these two populations may be indicative of the patients’ lowering expectations for treatment success as the number of prior treatment failures increases, providing further context for the improvements in scores reported in this work. Finally, severity as scored by the PI-MBS measure was found to correlate strongly with PGIC scores, the latter of which measured patients’ overall quality of life . Interestingly, correlation coefficients in the current study suggest that improvements for all domains were most strongly correlated with changes in PI-MBS, closely followed by changes in MMDs and both more than changes in migraine attacks with severe intensity, underscoring the need to address additional migraine symptoms beyond headache pain.
The current findings of improved WPAI scores after eptinezumab treatment are consistent with those reported in studies of other CGRP inhibitors but were numerically greater in magnitude than the other studies. In LIBERTY, the change from baseline in WPAI scores relative to placebo varied from − 2.6 to − 13.1 (P < 0.05) after treatment with erenumab 140 mg, reflecting improvements in 3 of the 4 WPAI subscores . In FOCUS, fremanezumab administered quarterly or monthly improved all 4 WPAI subscores, with changes from baseline ranging from − 4.7 to − 20.0, during the last 4 weeks of the 12-week double-blind treatment period (all P < 0.05 vs placebo except absenteeism with quarterly fremanezumab) . Lastly, in the HALO-CM study, quarterly or monthly fremanezumab improved all 4 WPAI subscores during the last 4 weeks of the 12-week double-blind treatment period, with changes from baseline ranging from − 12.9 to − 16.6 (all except absenteeism with both regimens and activity impairment with monthly fremanezumab being greater than changes in the placebo group [P < 0.05]) . In all of these studies, the benefit of CGRP inhibition on presenteeism was of greater magnitude than the benefit on absenteeism. This likely reflects the fact that many patients with migraine continue to work while experiencing symptoms [3, 5].
The duration of the placebo-controlled portion of DELIVER was 24 weeks, with not all patients completing the WPAI:M at baseline or every prespecified endpoint. WPAI:M was not included in the testing hierarchy and the P-values reported here have not been controlled for multiplicity. While changes in WPAI:M subscores during this time period suggest an early onset and short-term maintenance of beneficial effects on work productivity and activity, results from longer-term evaluations are needed to assess the extent of the durability of this positive response. Future work may provide insight on the change from baseline in WPAI scores over weeks 37–72. Additionally, while there were moderate correlations between MMDs and changes in WPAI:M scores, the analysis is not comprehensive and factors beyond MMDs are likely to impact scores. The DELIVER population was not diverse. Patients were predominantly female (89.9%) and white (96.0%), and most patients had two prior preventive treatment failures (61.8%). Thus, the findings reported here may not be generalizable to the broader migraine population, but subjects did hold a variety of occupational roles, including salesperson, manager, administrator, working professional, and skilled laborer. As a self-reported measure, the WPAI:M captures patients’ perceptions of improvements made and does not objectively measure changes in absenteeism or presenteeism. While the results may or may not reflect changes in actual job performance, changes in WPAI scores were found to be stable measurements, as evidenced by the plateauing of scores from Weeks 4–12.
In adults with migraine and prior preventive treatment failure, eptinezumab 100 mg and 300 mg IV every 12 weeks improved absenteeism and presenteeism and decreased work productivity loss and activity impairment more than placebo, as captured by the WPAI:M. These results indicate that eptinezumab treatment, and anti-CGRP therapies in general, can improve patient work productivity and ultimately quality of life. Reductions in migraine frequency and severity were observed early on (4 weeks post-baseline) in eptinezumab-treated patients in the DELIVER clinical trial and were sustained throughout the placebo-controlled portion of the trial.