Biologic Therapy for the Treatment of Chronic Rhinosinusitis with Nasal Polyposis: An Update and Review of the Literature

Year 2021, Volume: 4 Issue: 3, 72 - 76, 25.12.2021

Mark B. Chaskes Keonho Albert Kong Brent Senior

Abstract

Chronic rhinosinusitis (CRS) is a common inflammatory syndrome of the paranasal sinuses. CRS with nasal polyposis (CRSwNP) is one of the two major phenotypes of CRS, with an estimated prevalence of 4.2% in the United States and 4.3% in Europe. While several inflammatory pathways may mediate this condition, an estimated 85% of patients with CRSwNP exhibit Th2 (Type 2) inflammation, characterized by an increase in local eosinophilia, total IgE, interleukin (IL)-4, IL-5, and IL-13. Biologic therapies have proven successful in the treatment of related, Th2-mediated inflammatory conditions, including asthma and atopic dermatitis. As such, there has been significant interest in the role of biologics in the treatment of CRSwNP. Biologics target specific immune cells or inflammatory mediators within the cascade, thus offering treatment efficacy while limiting side effects. There has been a rapid expansion of the literature regarding the role of biologics within the treatment paradigm of patients with medically and surgically recalcitrant CRSwNP. Currently, there are five biologics under investigation or approved for the treatment of CRSwNP by the US Food and Drug Administration. As the study of biologics in the role of CRSwNP management continues to grow at a rapid pace, remaining to date on all aspects of these novel treatment modalities will be critical for the otolaryngologist. Herein, we review the current literature regarding biologic therapy options and offer perspective on the future.

Keywords

Biologics , chronic rhinosinusitis , polyps

References

• Orlandi RR, Kingdom TT, Hwang PH, et al. International consensus statement on allergy and rhinology: Rhinosinusitis. Int Forum Allergy Rhinol. 2016;6(Suppl. 1):S22-S209.
• Fokkens WJ, Lund VJ, Mullol J, et al. European position paper on rhinosinusitis and nasal polyps 2012. Rhinology. 2012;50(Suppl. 23):1-298.
• Bhattacharyya N, Orlandi RR, Grebner J, et al. Cost burden of chronic rhinosinusitis: A claims-based study. Otolaryngol Head Neck Surg. 2011;144(3):440-445.
• Wahid NW, Smith R, Clark A, et al. The socioeconomic cost of chronic rhinosinusitis study. Rhinology. 2020;58(2):112-125.
• Lourijsen ES, Fokkens WJ, Reitsma S. Direct and indirect costs of adult patients with chronic rhinosinusitis with nasal polyps. Rhinology. 2020;58:3:213-217.
• Tomassen P, Vandeplas G, Van Zele T, et al. Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers. J Allergy Clin Immunol. 2016;137(5):1449-1456.
• Poetker DM, Reh DD. A comprehensive review of the adverse effects of systemic corticosteroids. Otolaryngol Clin North Am. 2010;43(4):753-768.
• Legrand F, Klion AD. Biologic therapies targeting eosinophils: Current status and future prospects. J Allergy Clin Immunol Pract. 2015;3(2):167-174.
• Bachert C, Han JK, Desrosier M, et al. Efficacy and safety of duplimab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): Results from two multicentre, randomized, double-blind, placebo-controlled, parallel-group phase 3 trials. Lancet. 2019;394:1638-1650.
• Incorvaia C, Mauro M, Makri E, Leo G, Ridolo E. Two decades with omalizumab: What we still have to learn. Biol Targets Ther. 2018;12:135-142.
• Gevaert P, Omachi TA, Corren J, et al. Efficacy and safety of omaplizumab in nasal polyposis: 2 randomized phase 3 trials. J Allergy Clin Immunol. 2020;146(3):595-695.
• Han JK, Bachert C, Fokkens W, et al. Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): A randomized, double-blind placebo-controlled, phase 3 trial. Lancet Respir Med. 2021;S2213-2600(21):00097-00097.
• Gevaert P, Lang-Loidolt D, Lackner A, et al. Nasal IL-5 levels determine the response to anti-IL-5 treatment in patients with nasal polyps. J Allergy Clin Immunol. 2006;118(5):1133-1141.
• Identifier: NCT03401229. Efficacy and Safety Study of Benralizumab for Patients with Severe Nasal Polyposis (OSTRO). Bethesda, MD: National Library of Medicine. ClinicalTrials.gov.
• Paul WE, Zhu J. How are Th2-type immune responses initiated and amplified? Nat Rev Immunol. 2010;10(4):225-235.
• Pinto JM, Mehta N, DiTineo M, et al. A randomized, double-blind, placebo controlled trial of anti-IgE for chronic rhinosinusitis. Rhinology. 2010;48(3):318-324.
• Bachert C, Sousa AR, Lund VJ, et al. Reduced need for surgery in severe nasal polyposis with mepolizumab: Randomized trial. J Allergy Clin Immunol. 2017;140(4):1024-1031.e14.
• Scangas GA, Wu AW, Ting JY, et al. Cost utility analysis of dupilumab versus endoscopic sinus surgery for chronic rhinosinusitis with nasal polyps. Laryngoscope. 2021;131(1):E26-E33.
• Yong M, Wu YQ, Howlett J, Ballreich J, Walgama E, Thamboo A. Cost-effectiveness analysis comparing dupilumab and aspirin desensitization therapy for chronic rhinosinusitis with nasal polyposis in aspirin-exacerbated respiratory disease. Int Forum Allergy Rhinol. 2021;11:1626-1636.
• Codispoti CD, Mahdavinia M. A call for cost-effectiveness analysis for biologic therapies in chronic rhinosinusitis with nasal polyps. Ann Allergy Asthma Immunol. 2019;123(3):232-239.
• Identifier NCT04959448. Study Assessing Long-Term Outcomes of Dupilumab (DUPIXENT) Treatment in Adult Patients with Chronic Rhinosinusitis with Nasal Polyposis (CRSwNP) (AROMA). Bethesda, MD: National Library of Medicine. ClinicalTrials.gov.
• Identifier NCT04157335. Efficacy and Safety Study of Benralizumab in Patient with Eosinophilic Chronic Rhinosinusitis with Nasal Polyps (ORCHID). Bethesda, MD: National Library of Medicine. ClinicalTrials.gov.
• Identifier NCT04607005. Efficacy and Safety of Mepolizumab in Adults with Chronic Rhinosinusitis with Nasal Polyps (CRSwNP)/Eosinophilic Chronic Rhinosinusitis (ECRS) (MERIT). Bethesda, MD: National Library of Medicine. ClinicalTrials.gov.
• Identifier NCT04998604. Evaluating Treatment Responses of Dupilumab versus Omalizumab in Type 2 Patients (EVEREST). Bethesda, MD: National Library of Medicine. ClinicalTrials.gov.
• Identifier NCT04583501. Preclinical Studies of Omalizumab in Chronic Rhinosinusitis with Nasal Polyposis (CRSwNP). Bethesda, MD: National Library of Medicine. ClinicalTrials.gov.
• Identifier NCT04185012. Nasal Polyps: Inflammatory & Molecular Phenotyping of Responders to Benralizumab (NAPPREB). Bethesda, MD: National Library of Medicine. ClinicalTrials.gov.
• Miller AM. Role of IL-33 in inflammation and disease. J Inflamm. 2011;8(1):22.
• Identifier NCT02170337. A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AMG 282 in Healthy Subjects and Subjects with Chronic Rhinosinusitis with Nasal Polyps. Bethesda, MD: National Library of Medicine. ClinicalTrials.gov.
• Identifier NCT03614923. Etokimab in Adult Patients with Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). Bethesda, MD: National Library of Medicine. ClinicalTrials.gov.
• Identifier NCT04684524. Dupilumab in Allergic Fungal Rhinosinusitis (AFRS). Bethesda, MD: National Library of Medicine. ClinicalTrials.gov.
• Identifier NCT04362501. Efficacy of Dupilumab for Patients with Chronic Rhinosinusitis without Nasal Polyps (CRSsNP). Bethesda, MD: National Library of Medicine. ClinicalTrials.gov.
• Identifier NCT04678856. Dupilumab in CRSsNP (Liberty CRSsNP ORION). Bethesda, MD: National Library of Medicine. ClinicalTrials.gov.
• Identifier NCT04430179. Dupilumab Severe Eosinophilic Chronic Sinusitis with out Nasal Polyposis. Bethesda, MD: National Library of Medicine. ClinicalTrials.gov.