Rimegepant, Ubrogepant, and Lasmiditan in the Acute Treatment of Migraine Examining the Benefit-Risk Profile Using Number Needed to Treat/Harm

Karissa M Johnston, Lauren Powell, Evan Popoff, Linda Harris, Robert Croop, Vladimir Coric, Gilbert L'Italien, Karissa M Johnston, Lauren Powell, Evan Popoff, Linda Harris, Robert Croop, Vladimir Coric, Gilbert L'Italien

Abstract

Objectives: To develop and compare benefit-risk profiles for rimegepant, ubrogepant, and lasmiditan based on a network meta-analysis (NMA) of published clinical trials.

Methods: A fixed-effects Bayesian NMA of randomized controlled trials of lasmiditan, rimegepant, and ubrogepant for the acute treatment of adults with migraine were used to determine risk differences for efficacy and safety outcomes of the 3 treatments compared with pooled placebo. Risk differences were used to calculate number needed to treat (NNT) for pain relief and pain freedom at 2 and 2 to 24 hours and freedom from most bothersome symptoms at 2 hours; and number needed to harm (NNH) for dizziness and nausea, relative to placebo.

Results: Results were based on 5 randomized controlled trials (NCT03461757, NCT02828020, NCT02867709, NCT02439320, and NCT02605174). NNT to achieve sustained pain relief at 2 to 24 hours was lowest for rimegepant 75 mg (5; 95% credible interval [Crl]: 4, 7) and ubrogepant 100 mg (5; 95% Crl: 4, 8) and highest for ubrogepant 25 mg (8; 95% Crl: 5, 16). Rimegepant had the lowest NNT to achieve sustained pain freedom at 2 to 24 hours and lasmiditan 50 mg had the highest (7; 95% Crl: 5, 12 vs. 26; 95% Crl: 13, 95). NNH for dizziness and nausea was highest for ubrogepant 25 mg (28; 95% Crl: 15, 62 and 99; 95% Crl: -2580, 2378, respectively). Lasmiditan 200 mg had the lowest NNH for dizziness and rimegepant 75 mg had the lowest NNH for nausea.

Conclusions: The benefit-risk profiles of lasmiditan, rimegepant, and ubrogepant may improve clinical decision-making.

Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.

Figures

FIGURE 1
FIGURE 1
Network diagram.
FIGURE 2
FIGURE 2
Number Needed to Treat for (A) pain freedom at 2 hours, (B) sustained pain freedom, 2 to 24 hours.

References

    1. Buse D, Fanning K, Reed M, et al. . Life with migraine: effects on relationships, career, and finances from the Chronic Migraine Epidemiology and Outcomes (CaMEO) study. Headache. 2019;59:1286–1299.
    1. Messali A, Sanderson J, Blumenfeld A, et al. . Direct and indirect costs of chronic and episodic migraine in the United States: a web-based survey. Headache. 2016;56:306–322.
    1. Raval A, Shah A. National trends in direct health care expenditures among US adults with migraine: 2004 to 2013. J Pain. 2017;18:96–107.
    1. Ford J, Ye W, Nichols R, et al. . Treatment patterns and predictors of costs among patients with migraine: evidence from the United States medical expenditure panel survey. J Med Econ. 2017;22:849–858.
    1. Ailani J, Burch RC, Robbins MS. The American Headache Society Consensus Statement: update on integrating new migraine treatments into clinical practice. Headache. 2021;61:1021–1039.
    1. Marcus SC, Shewale AR, Silberstein SD, et al. . Comparison of healthcare resource utilization and costs among patients with migraine with potentially adequate and insufficient triptan response. Cephalalgia. 2020;40:639–649.
    1. Harris L, L’Italien G, O’Connell T, et al. . A framework for estimating the eligible patient population for new migraine acute therapies in the United States. Adv Ther. 2021;38:5098–5099.
    1. De Matteis E, Guglielmetti M, Ornello R, et al. . Targeting CGRP for migraine treatment: mechanisms, antibodies, small molecules, perspectives. Expert Rev Neurother. 2020;20:627–641.
    1. Edvinsson L, Haanes K, Warfvinge K, et al. . CGRP as the target of new migraine therapies—successful translation from bench to clinic. Nat Rev Neurol. 2018;14:338–350.
    1. Peters G. Migraine overview and summary of current and merging treatment options. Am J Manag Care. 2019;25:S23–S34.
    1. Allergan USA. UBRELVY (ubrogepant) tablets prescribing information. Madison, NJ: FDA; 2021.
    1. Biohaven Pharmaceutical Inc. NURTEC ODT (rimegepant) Prescribing Information. FDA. 2021. Available at: .
    1. Croop R, Goadsby P, Stock D, et al. . Efficacy, safety, and tolerability of rimegepant orally disintegrating tablet for the acute treatment of migraine: a randomised, phase 3, double-blind, placebo-controlled trial. Lancet. 2019;394:737–745.
    1. Croop R, Lipton RB, Kudrow D, et al. . Oral rimegepant for preventive treatment of migraine: a phase 2/3, randomised, double-blind, placebo-controlled trial. Lancet. 2020;397:51–60.
    1. Eli Lilly and Company. REYVOW (lasmiditan) tablets prescribing information. Indianapolis, IN: FDA; 2019.
    1. Hou M, Xing H, Li C, et al. . Short-term efficacy and safety of lasmiditan, a novel 5-HT(1F) receptor agonist, for the acute treatment of migraine: a systematic review and meta-analysis. J Headache Pain. 2020;21:66.
    1. Lipton R, Lombard L, Ruff D, et al. . Trajectory of migraine-related disability following long-term treatment with lasmiditan: results of the GLADIATOR study. J Headache Pain. 2020;21:20.
    1. . Efficacy, Safety, and Tolerability Study of Oral Ubrogepant in the Acute Treatment of Migraine (ACHIEVE I). NCT02828020. 2019. Available at: . Accessed August 6, 2020.
    1. . Efficacy, Safety, and Tolerability of Oral Ubrogepant in the Acute Treatment of Migraine (ACHIEVE II). NCT02867709. 2019. Available at: . Accessed August 6, 2020.
    1. . Lasmiditan Compared to Placebo in the Acute Treatment of Migraine: (SAMURAI). NCT02439320. 2019. Available at: . Accessed August 6, 2020
    1. . Three doses of lasmiditan (50 mg, 100 mg and 200 mg) compared to placebo in the acute treatment of migraine (SPARTAN). NCT02605174. 2019. Available at: . Accessed August 6, 2020.
    1. . BHV3000-303: phase 3, double-blind, randomized, placebo controlled, safety and efficacy trial of BHV-3000 (rimegepant) orally disintegrating tablet (ODT) for the acute treatment of migraine. NCT03461757. 2020. Available at: 2020. Accessed August 6, 2020.
    1. Dodick D, Lipton R, Ailani J, et al. . Ubrogepant for the treatment of migraine. N Engl J Med. 2019;381:2230–2241.
    1. Goadsby P, Wietecha L, Dennehy E, et al. . Phase 3 randomized, placebo-controlled, double-blind study of lasmiditan for acute treatment of migraine. Brain. 2019;142:1894–1904.
    1. Kuca B, Silberstein S, Wietecha L, et al. . Lasmiditan is an effective acute treatment for migraine: a phase 3 randomized study. Neurology. 2018;91:e2222–e2232.
    1. Lipton R, Dodick D, Ailani J, et al. . Effect of ubrogepant vs placebo on pain and the most bothersome associated symptom in the acute treatment of migraine the ACHIEVE II Randomized Clinical Trial. JAMA. 2019;322:1887–1898.
    1. Atlas S, Touchette D, Agboola F, et al. . Acute treatments for migraine: effectiveness and value. Institute for Clinical and Economic Review. 2020. Available at: . Accessed August 5, 2020.
    1. Johnston K, Popoff E, Deighton A, et al. . Comparative efficacy and safety of rimegepant, ubrogepant and lasmiditan for acute treatment of migraine: a network meta-analysis. Expert Rev Pharmacoecon Out Res. 2021;22:155–166.
    1. Johnston K, Powell L, Popoff E, et al. . Rimegepant 75 mg, Ubrogepant, and Lasmiditan in the acute treatment of migraine examining the benefit-risk profile using number needed to treat/harm American Headache Society 2021 Virtual Annual Scientific Meeting; 2021.
    1. Cook RJ, Sackett DL. The number needed to treat: a clinically useful measure of treatment effect. BMJ (Clin Res ed). 1995;310:452–454.
    1. Citrome L, Ketter T. When does a difference make a difference? Interpretation of number needed to treat, number needed to harm, and likelihood to be helped or harmed. Int J Clin Pract. 2013;67:407–411.
    1. Moher D, Liberati A, Tetzlaff J, et al. . Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ (Clin Res ed). 2009;339:b2535.
    1. Diener HC, Tassorelli C, Dodick DW, et al. . Guidelines of the International Headache Society for controlled trials of acute treatment of migraine attacks in adults: fourth edition. Cephalalgia. 2019;39:687–710.
    1. Higgins J, Altman D, Gotzche P, et al. . The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ (Clin Res ed). 2011;343:d5928.
    1. Bruce N, Pope D, Stanistreet D. Quantitative Methods for Health Research: A Practical Interactive Guide to Epidemiology and Statistics, 2nd ed. John Wiley & Sons; 2018.
    1. Andrade C. The numbers needed to treat and harm (NNT, NNH) statistics: what they tell us and what they do not. J Clin Psychiatry. 2015;76:e330–e333.
    1. Dias S, Welton N, Sutton A, et al. . NICE DSU Technical Support Document 2: A Generalised Linear Modelling Framework For Pairwise and Network Meta-Analysis of Randomised Controlled Trials. 2011. Available at: . Accessed August 5, 2020.
    1. Serrano D, Lipton R, Scher A, et al. . Fluctuations in episodic and chronic migraine status over the course of 1 year: implications for diagnosis, treatment and clinical trial design. J Headache Pain. 2017;18:101.
    1. Derry CJ, Derry S, Moore RA. Sumatriptan (oral route of administration) for acute migraine attacks in adults. Cochrane Database Syst Rev. 2012;2012:Cd008615.
    1. VA/DOD. Clinical Practice Guideline for the Primary Care Management of Headache. Department of Veterans Affairs, Department of Defense, editions. VA/DoD; 2020:1–150. Available at: . Accessed April 9, 2021.
    1. Yeung J, Mierzwinski-Urban M. Lasmiditan for the Acute Treatment of Migraine. CADTH; 2020.
    1. Pant S, Mierzwinski-Urban M. Small Molecule Calcitonin Gene-Related Peptide Receptor Antagonists for the Acute Treatment of Migraine. CADTH; 2020.
    1. de Vries T, Villalón CM, MaassenVanDenBrink A. Pharmacological treatment of migraine: CGRP and 5-HT beyond the triptans. Pharmacol Ther. 2020;211:107528.

Source: PubMed

3
Suscribir