Benefit-risk assessment based on number needed to treat and number needed to harm: Atogepant vs. calcitonin gene-related peptide monoclonal antibodies.

Background: To evaluate the benefit-risk assessment of atogepant and calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) vs. placebo based on the number needed to treat (NNT) and the number needed to harm (NNH) in a blended episodic migraine and chronic migraine (EM + CM) population.
Methods: The NNT was calculated based on achievement of a ≥ 50% reduction in mean monthly migraine days (MMDs) from baseline across 12 weeks. The NNH was calculated using the proportion of participants reporting a discontinuation due to adverse events (AEs). The primary analysis included data from studies of atogepant, erenumab, galcanezumab, eptinezumab and fremanezumab.
Results: In the primary analysis, the calculated NNT for atogepant 60 mg vs. placebo was 4.2 (95% credible interval (CrI) = 3.1-6.7), which was the lowest relative to the CGRP mAbs in the blended EM + CM population. Participants who received atogepant 60 mg or fremanezumab showed the most favorable NNH values (-1010 (95% Crl = 44 to ∞ to number needed to benefit 80) for atogepant) resulting from lower rates of discontinuation due to AEs compared with those receiving placebo.
Conclusions: Atogepant demonstrated a favorable benefit-risk profile, with NNT and NNH values comparable (not statistically significant) with those of CGRP mAbs across all analyses.
Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: Jessica Ailani, MD, has served as a consultant for AbbVie, Aeon, Amgen, Axsome, BioDelivery Sciences International, Biohaven, Eli Lilly and Company, GlaxoSmithKline, Gore, Impel, Ipsen, Linpharma, Lundbeck, Merz, Miravo, Nesos, Neurolief, Pfizer, Satsuma, Teva, and Theranica. She has owned stock shares in Ctrl M, has provided editorial services for SELF magazine, and has received clinical trial grants from AbbVie, Biohaven, Eli Lilly and Company, Ipsen, Parema, Satsuma and Zosano. Anjana Lalla, MS, Pranav Gandhi, PhD, and Krisztian Nagy, MD, are employees of AbbVie and may hold AbbVie stock. Rashmi B. Halker Singh, MD, serves on the editorial board of Current Neurology and Neuroscience Reports, serves as deputy editor for Headache, and previously received grants for research support from Amgen and Eli Lilly. In the past 3 years, she has received consulting fees from AbbVie and Pfizer. Dagny Holle-Lee, MD, PhD, has received honoraria for consulting from AbbVie/Allergan, Amgen, Eli Lilly, Hormosan, Lundbeck, Novartis, Teva and Zuellig Pharma. Patricia Pozo-Rosich, MD, PhD, has received, in the past 3 years, personal fees for advisory boards and speaker panels from AbbVie, Amgen, Chiesi, Eli Lilly, Lundbeck, Medscape, Novartis, Pfizer and Teva Pharmaceuticals, and for serving on a scientific advisory or data safety monitoring board for Lilly Foundation Spain; is the principal investigator for clinical trials sponsored by AbbVie, Eli Lilly, Lundbeck, Novartis and Teva; has received (through her group) grants from AbbVie, EraNet Neuron, Instituto de Salud Carlos III, Novartis and Teva; and serves as an associate editor for Cephalalgia, Headache, Neurologia, The Journal of Headache and Pain, and Revista de Neurologia. Kari Kelton, PhD, and Cristiano Piron, MPH, are employees of Medical Decision Modeling Inc., which received payment from AbbVie for the analysis.