Pain freedom with celecoxib oral solution, ubrogepant, and rimegepant through 4 hours postdose: post hoc analysis in the acute treatment of migraine

Pain freedom with celecoxib oral solution, ubrogepant, and rimegepant through 4 hours postdose: post hoc analysis in the acute treatment of migraine

Background:

People with migraine consistently rank complete relief and rapid onset of relief among the most important attributes of medications used for acute treatment. Research also suggests that incomplete relief of headache and slow onset of action are among the most important reasons for dissatisfaction with medications used for acute treatment. A recent assessment of the clinical value of the small molecule calcitonin gene-related peptide (CGRP) inhibitors ubrogepant and rimegepant found that their main clinical benefits occur between 3 and 8 hours postdose. Celecoxib oral solution (Elyxyb) is a liquid formulation of the cyclooxygenase-2-selective nonsteroidal anti-inflammatory drug indicated for the acute treatment of migraine. Previously, celecoxib 120 mg oral solution demonstrated favorable pharmacokinetics, including speed of onset (tmax=42 mins) and bioavailability relative to celecoxib 400 mg oral capsules; and a single dose of celecoxib 120 mg oral solution was shown to be effective in the acute treatment of migraine.

Purpose/Objectives:

The objective of this post hoc analysis was to use data from 2 independent, randomized, double-blind, placebo-controlled, multicenter, 2-attack phase 3 trials of celecoxib 120 mg oral solution (Study 1 and Study 2) to compare the therapeutic gain of celecoxib 120 mg oral solution with that of previously published therapeutic gain for ubrogepant 50 mg (NEJM. 2019;381(23):2230-2241) and rimegepant 75 mg (NEJM. 2019;381(2):142-149) in the acute treatment of migraine pain over the first 4 hours postdose.

Methods:

The cumulative proportion of celecoxib oral solution and vehicle pain-free participants was computed at 15, 30, 45, 60, 90, 120, and 240 minutes postdose. Participants taking rescue medication after 120 minutes postdose were censored; even if achieving pain freedom at 240 minutes, their pain-free status was designated a failure. One site was removed from analysis of Study 1 because it was an influential outlier (value 2x all other sites), as evaluated by the DFBETAs influence statistics. Therapeutic gains — defined as the difference between active response and placebo response — are reported pooling data from Study 1 and Study 2.

Results:

Therapeutic gain for pooled celecoxib oral solution data ranged from −1.67% to 16.1%, achieving 12.6% at 120 minutes postdose, which exceeded ubrogepant 50 mg by 4.4% and rimegepant 75 mg by 5.6%.

Conclusions: People living with migraine consider speed of onset among the most important attributes of a medication for acute treatment. Ubrogepant and rimegepant have well documented delayed onset of pain freedom; in contrast, celecoxib oral solution has a fast onset with superior therapeutic gain at 2-hours post-dose. These data have clinical implications for treatment selection in adults with migraine.

References: NEJM. 2019;381(23):2230-2241
NEJM. 2019;381(2):142-149