OBJECTIVES : INP104, a drug-device combination of dihydroergotamine mesylate (DHE 1.45mg) administered to the upper nasal space using Precision Olfactory Delivery technology, was evaluated in the STOP 301 open-label safety study for the acute treatment of migraine. We aimed to estimate the comparative clinical outcomes of INP104 versus gepants and DHE nasal spray via a matching-adjusted indirect comparison (MAIC).

METHODS : The analysis included individual patient data from the STOP 301 study and published aggregate data from comparator trials identified from a systematic literature review (SLR). Weights for patients in STOP 301 were estimated from a propensity score model to match key prognostic factors from the comparator trials, then pairwise comparisons were conducted using the balanced populations.

RESULTS : The SLR identified 15 unique randomized controlled trials that assessed rimegepant, ubrogepant and DHE nasal spray 4 mg/mL. The MAIC showed INP104 improved pain-related outcomes relative to the gepants, with significantly higher rates of pain freedom (PF) at 2 hours (rimegepant OR: 1.81 [95%CI: 1.37-2.41]; ubrogepant OR: 1.92 [95%CI: 1.43-2.59]), and sustained PF from 2 to 48 hours (rimegepant OR: 2.53 [95%CI: 1.86-3.44]; ubrogepant OR: 2.00 [95%CI: 1.22-3.26]). Similar findings were seen for symptom-related outcomes, with INP104 showing higher rates of freedom from most bothersome symptom at 2 hours (rimegepant OR: 1.93 [95%CI: 1.52-2.45]; ubrogepant OR: 1.83 [95%CI: 1.42-2.35]). Only 1 of the 3 DHE nasal spray studies reported PF, and none reported sustained pain- or most bothersome symptom-freedom; pain relief at 2 hours and nausea did not show statistically significant differences. Safety outcomes from the comparator trials observed either a single migraine or two migraines confounding the ability to make adequate comparisons to the STOP 301 study across multiple attacks over 24 and 52 weeks.

CONCLUSIONS : INP104 was associated with greater reductions in pain and other migraine-related symptoms in an indirect comparison with gepants.