Likelihood of response with subsequent dosing for patients with migraine and initial suboptimal response with eptinezumab: A post hoc analysis of two placebo‐controlled randomized clinical trials

OBJECTIVE: To develop a multivariable model assessing factors predicting a second‐dose response to eptinezumab treatment over weeks 13–24 in patients with migraine initially reporting a suboptimal response over weeks 1–12. BACKGROUND: Eptinezumab is a monoclonal antibody used for migraine prevention, administered every 12 weeks. In the PROMISE‐1 and PROMISE‐2 studies, the first‐dose response to eptinezumab treatment (≥50% monthly migraine day [MMD] reduction over weeks 1–12) occurred in ~50–60% of patients with episodic (EM) and chronic migraine (CM), respectively. METHODS: This post hoc analysis included patients with suboptimal first‐dose response (<50% MMD reduction over weeks 1–12) with EM and CM, with patient‐reported outcome data at weeks 12 and 24. Eptinezumab 100 and 300 mg doses were pooled. RESULTS: The analysis included 416/888 patients (46.8%) from PROMISE‐1 and 479/1072 patients (44.7%) from PROMISE‐2 with suboptimal first‐dose response. The proportion of suboptimal first‐dose responders who were second‐dose responders was 37.0% (71/192; eptinezumab) and 33.9% (42/124; placebo) in PROMISE‐1 and 28.8% (79/274) and 18.5% (38/205) in PROMISE‐2. Significant first‐dose predictors of second‐dose response were percent change in MMDs across weeks 1–12 (PROMISE‐1, odds ratio [OR]: 0.97, 95% confidence interval [CI]: 0.95, 0.98, p = 0.0001; PROMISE‐2, OR: 0.94, CI: 0.92, 0.96, p < 0.0001) and change in 6‐item Headache Impact Test (HIT‐6) total score (PROMISE‐2 only, OR: 0.92; CI: 0.87, 0.98; p = 0.027). In PROMISE‐1, the probability of second‐dose response ranged from 21.7% in patients with first‐dose 0% MMD change to 56.0% in patients with first‐dose 45% MMD reduction. In PROMISE‐2, depending on HIT‐6 total score, probability of second‐dose response ranged from 5.9–12.1% in patients with first‐dose 0% MMD change to 54.2%–72.3% in patients with first‐dose 45.0% MMD reduction. CONCLUSION: Individuals with migraine not experiencing ≥50% MMD response to their first dose of eptinezumab may benefit from a second dose.