Biologics in chronic rhinosinusitis with nasal polyposis

Abstract

Objective: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common and heterogeneous inflammatory condition, for which the drivers of the underlying inflammation are not yet fully understood. The use of biologic therapies to target specifically relevant effector cells or cytokines in CRSwNP is a growing field of interest. The objectives of this review are to provide an update on the existing studies of biologics in CRSwNP and to identify potential future areas for further research.

Data sources: An initial literature review of biologic therapies in CRS was performed through publications gathered from a PubMed search for title/abstract containing "biologic" and "chronic rhinosinusitis." Further manuscripts describing scientific premise for each biologic were then reviewed.

Study selections: A detailed review of all studies describing biologic therapies targeting inflammation in CRSwNP was performed.

Results: Biologic therapies targeting interleukin (IL)-4Rα, IL-5, IL-5Rα, IL-33, immunoglobulin (Ig)E, and thymic stromal lymphopoietin (TSLP) have all been developed and have been investigated for treatment in CRSwNP, or current research suggests that they may have utility in this area. Only dupilumab, which inhibits IL-4Rα, has gained Food and Drug Administration approval for the treatment of adults with inadequately controlled CRSwNP.

Conclusion: Recent advances in our understanding of the fundamental drivers of the chronic respiratory inflammation in CRSwNP has led to the identification of several potential therapeutic targets for this disease. Future clinical success will rely on the availability of biomarker-based endotyping and responder analyses so that clinicians can precisely match each patient to the appropriate biologic, thereby optimizing the proper treatment strategy.

Figure 1.. Immunopathology of CRSwNP and current therapeutic targets under investigation.

Red starbursts highlight the targets of biologics or new agents for CRSwNP.

Figure 2.. Response to dupilumab in a patient with AERD.

Representative sinus CT scan images are shown for a patient with AERD prior to starting treatment with dupilumab (left) and again after four months of every-other-week dupilumab treatment (right).