Is there a future for biologics in the management of chronic rhinosinusitis?

Abstract

Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory condition of the sinonasal mucosa consisting of poorly defined subtypes and characterized by variable clinical manifestations, responses to therapy, and underlying pathophysiologies. In the related disorder of asthma, progress has been made in defining disease subtypes on both clinical and pathophysiologic levels, facilitating the development of targeted biologic pharmacotherapy. The potential role of these drugs for the management of CRS will be reviewed. The objective of this work is to highlight the emerging therapeutic targets in CRS in light of evolving treatment options for asthma and enhanced understandings of the clinical manifestations and pathophysiology of CRS. This article is a review of recent studies regarding current and future advances in biomarker-directed therapies in the medical treatment of CRS. Various biologic therapies used in the management of asthma have demonstrated clinical promise for CRS, particularly within the CRS with nasal polyposis (CRSwNP) phenotype. Several randomized, double-blind, placebo-controlled studies increasingly support the targeting of immunoglobulin E (IgE) and interleukin (IL)-5 pathways to improve outcome measures in CRSwNP patients. The IL-4/IL-13 pathway and other type 2 inflammatory pathways have also shown potential as targets for CRSwNP, but all pathways require further investigation. Recalcitrant CRS in the United States and Europe is most commonly associated with nasal polyposis and a type 2 cytokine skewing in the tissue, resulting in tissue infiltration of eosinophils, mast cells, and basophils. Targeting biomarkers of the associated type 2 pathways may be a practical treatment option for recalcitrant CRSwNP in the future.