Emerging biologics for the treatment of chronic rhinosinusitis

Abstract

Chronic rhinosinusitis (CRS) is a prevalent chronic inflammatory disease of the nasal and paranasal cavities and is known to seriously impair quality of life in affected patients. CRS appears to be a heterogeneous group of diseases with different inflammatory and remodeling patterns, suggesting that not only different clinical phenotypes but also pathophysiological endotypes occur. CRS with nasal polyps (CRSwNP) is considered a more severe phenotype, especially when associated with comorbid asthma, as patients having this condition often do not respond to conventional treatment, including topical and systemic corticosteroids or surgery. Recently, studies with biologic agents have shown various effects in severe airway disease; specifically in Th2-biased CRSwNP, these effects were very promising. The greatest challenge for the future is to define the different endotypes of CRSwNP using easily accessible biomarkers to select the patients who have the best chance of a positive therapeutic response to innovative approaches.

Keywords:

• asthma
• biologics
• biomarkers
• chronic rhinosinusitis
• dupilumab
• endotypes
• mepolizumab
• monoclonal antibodies
• nasal polyps
• omalizumab

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory disease with a complex pathophysiology and evidence suggests that different endotypes occur.

• The biggest challenge is to define the different endotypes of CRSwNP and connect it to matching biomarkers to find the right patient for innovative treatment.

• Omalizumab (Xolair^®) is the only mAb on the market so far and research suggests a good efficacy of this treatment in CRSwNP with comorbid asthma.

• Anti-IL-5 therapy shows promising results in CRSwNP. Good responders seem to have elevated baseline levels of IL-5 in nasal secretions, which possibly may serve as a suitable biomarker for future anti-IL-5 trials.

• Targeting both IL-4 and IL-13 appears to result in a better outcome compared to inhibiting these cytokines individually. Dupilumab is the only monoclonal antibody targeting this pathway tested in CRSwNP to date and shows promising results.

• There are several possible targets in the treatment of asthma and CRSwNP and various agents against these targets are currently under investigation. Additional studies will reveal which one of these is suitable for further development.

• As treatment with biologics may be expensive, cost–effectiveness of this treatment should be kept in mind.

Notes