Safety review of current systemic treatments for severe chronic rhinosinusitis with nasal polyps and future directions

ABSTRACT

Introduction: Chronic rhinosinusitis is a common condition characterized by inflammation of the nasal and sinus linings, rhinorrhea, nasal blockage, facial pain, and loss of sense of smell for longer than 12 weeks. CRS can occur with or without nasal polyps.

Areas covered: First-line treatment in chronic rhinosinusitis with nasal polyps is long-term intranasal corticosteroids, which have few adverse events associated with their use, as second-generation intranasal corticosteroids having a bioavailability of <0.5%. Systemic corticosteroids are used when intranasal steroids fail to achieve symptom control. However, the repeated use of oral corticosteroids is associated with numerous adverse events and the benefit from a course of oral corticosteroids is lost within three to six months.

Expert opinion: Antibiotics are commonly prescribed in nasal polyposis although there is also very little evidence for their use outside of acute infection. Macrolide antibiotics are also associated with a transient increase in the risk of arrhythmias. Biologics offer a steroid-sparing alternative to the treatment of severe nasal polyposis. They have shown to be relatively well tolerated in studies to date; however, studies suggest that there is no disease modifying effect and that any benefit is lost within weeks of finishing treatment.

KEYWORDS:

• Antibiotics
• biologics
• chronic rhinosinusitis
• corticosteroids
• monoclonal antibodies
• nasal polyps

Article highlights

• There is high-quality evidence demonstrating the safety of second-generation intranasal corticosteroids in the treatment of nasal polyps.

• There is evidence that as few as four short courses of oral corticosteroids lead to significant increases in adverse events such as diabetes, with a positive dose–response relationship.

• Despite the theoretical benefit of antibiotics in treating nasal polyps, there is very little evidence for their use outside of the treatment of acute infective exacerbations

• Biologics added to intranasal corticosteroids have been shown to be effective and well tolerated in patients who fail to achieve adequate long-term symptom control on the standard treatment pathway of intranasal corticosteroids, oral corticosteroids, and surgery.

• Trials in the use of biologics suggest that there is no disease modifying effect and that benefit is lost within weeks of discontinuing treatment.

This box summarizes key points contained in the article.

Declaration of interest

C Hopkins has received honoraria for serving on advisory boards for GlaxoSmithKline, Sanofi, Regeneron, and AstraZeneca. The authors have no other 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.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they are a shareholder in OptiNose, Inc., an employee of the company and is also involved with the exhalation delivery system (EDS) technology utilized by OptiNose’s product (EDS-FLU/Xhance®) to deliver a topical steroid to the nose and sinuses. Full disclosures were provided to the editorial team, but to maintain referee anonymity in line with the double-blind peer review model of the journal, some of the details have not been included here. All other peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.