Abstract text (incl. figure legends and references)

OBJECTIVE: To explore impact of delivery mechanism on 12-week change from baseline in monthly migraine days (MMDs) for indirect treatment comparisons (ITCs) of eptinezumab and other aCGRP mAbs. Intravenous (IV) eptinezumab was investigated for migraine prevention in episodic (EM) and chronic migraine (CM). The comparator aCGRP mAbs are delivered subcutaneously (SC). Influence of delivery mechanism on placebo (PBO) response may bias ITCs.

METHODS: Evaluated 3 methodologies: (1) standard Bayesian network meta-analysis (NMA) of phase 3 clinical trials assuming PBOs are identical; (2) network meta-regression (NMR) regressing treatment effect on PBO response; and (3) unanchored simulated treatment comparison (STC) using only active arm data.

RESULTS: NMA results favored eptinezumab 300mg over fremanezumab in CM but favored erenumab 140mg and galcanezumab 120mg over eptinezumab 100mg in EM. NMR found all treatments were similar. Unanchored STC in EM favored eptinezumab for most comparisons, while all comparisons in CM favored eptinezumab (one-sided p<0.05). See Tables 1 and 2.

CONCLUSIONS: Assumptions about delivery mechanism have a large impact on ITCs. NMA and NMR results are mixed and rarely differentiate treatments. The unanchored STC strongly and consistently favored eptinezumab over other migraine preventive treatments. Consideration of which approach best reflects drug-placebo interactions and real-world outcomes would be beneficial to clinical and formulary decision makers.