Benefit-Risk Assessment of Atogepant: A Post Hoc Analysis of the ADVANCE Trial
Stephanie Nahas1, Jessica Ailani2, Peter McAllister3, Rashmi Halker Singh4, Richard B. Lipton5, Julia Ma6, Pranav Gandhi6, Jonathan H. Smith6, Yingyi Liu6, Natty Chalermpalanupap6, Brett Dabruzzo6
1Thomas Jefferson University, 2Medstar Georgetown Neurology, 3New England Inst for Neurology and Headache, 4Mayo Clinic, 5Albert Einstein College of Medicine, 6AbbVie
Objective:
To determine the number needed to treat (NNT) and number needed to harm (NNH) for atogepant for the preventive treatment of episodic migraine (EM).
Background:
Atogepant is an oral calcitonin gene‒related peptide receptor antagonist approved for the preventive treatment of EM in adults. NNT and NNH are clinically relevant assessments of effect size that can inform management. The Migraine-Specific Quality of Life Questionnaire (MSQ v2.1) Role Function-Restrictive (RFR) domain assesses impacts of migraine on daily functioning that are important to people with migraine.
Design/Methods:
The ADVANCE trial (NCT02848326) was a 12-week, randomized, double-blind, placebo-controlled trial that evaluated the efficacy and safety of atogepant for the preventive treatment of EM. The NNT was calculated based on achievement of a ≥50% decrease in mean monthly migraine days (MMDs) (NNT≥50%) across 12 weeks. A second NNT was calculated based on achievement of a ≥10.9-point clinically relevant improvement from baseline in MSQ-RFR score (NNTMSQ-RFR) at week 12. NNH was calculated using the proportion of participants reporting a treatment-emergent adverse event (TEAE) leading to discontinuation.
Results:
A 50% reduction of MMDs from baseline was achieved by 56%-61% of atogepant participants versus 29% of placebo participants. The calculated NNTs≥50% for atogepant 10 mg, 30 mg, and 60 mg were 3.8, 3.4, and 3.1, respectively. The NNTsMSQ-RFR for the atogepant dose groups were 5.9, 5.7, and 6.3, respectively. TEAEs leading to discontinuation in participants treated with atogepant 10 mg, 30 mg, and 60 mg were reported by 4.1%, 1.8%, and 2.6% of participants, respectively, versus 2.7% of placebo-treated participants. The NNH was 73.0 for atogepant 10 mg. In the atogepant 30 mg and 60 mg dose groups, a lower percentage of participants discontinued versus placebo, resulting in negative NNT calculations (−105.5 and −949.7, respectively).
Conclusions:
These findings show a positive benefit-risk profile with atogepant for the preventive treatment of EM.