The argument against the use of dupilumab in patients with limited polyp burden in chronic rhinosinusitis with nasal polyposis (CRSwNP)

Abstract

Dupilumab and other biologics have revolutionized the management of recalcitrant polyps in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). Despite strong evidence for the efficacy of dupilumab in treating polyps, factors such as cost and uncertain efficacy over surgery have limited its use to patients who have failed the use of topical nasal steroids and initial surgical management. Likewise, the use of this drug is often directed towards patients with greater polyp burdens. Recent studies, however, have investigated the use of dupilumab and other biologics in expanded patient populations, including those with limited polyp burden. The overall trend in the literature suggests a future move towards the use of biologics as first-line therapy for all patients with CRSwNP. The arguments against widespread, routine use of dupilumab and biologics in all patients with CRSwNP are threefold. First, endoscopic sinus surgery has been found to provide similar symptomatic benefit to dupilumab in the treatment of these patient populations. The surgical improvement of patients' sinonasal anatomy offers a rapid elimination of sources of ongoing inflammation that contribute to long-term polyp formation and symptoms. Medical non-compliance in this specific patient population is known to be an issue, with surgery offering a much greater long-term prospect of symptomatic relief in non-compliant patients. The second concern revolves around the potential for side effects of dupilumab and other biologics. Initial studies have shown an acceptable safety profile, but trials assessing the use of dupilumab for a separate indication revealed a higher rate of conjunctivitis. Long-term safety data is limited for biologics, and we must be prepared for the possibility of severe, unanticipated adverse events in the future. Our third and most profound concern is the significant cost of dupilumab. This medication is enormously expensive, and all current literature suggests that treatment would need to be life-long to remain effective. Studies comparing endoscopic sinus surgery to various biologics, including dupilumab, have shown comparable overall quality of life metrics with biologics, all while delivering considerably higher anticipated lifetime costs. As our knowledge progresses regarding the efficacy of dupilumab and other biologics in a variety of clinic situations, it is important to understand the context in which these advances are being made. While dupilumab and other biologics offer undeniable efficacy in the treatment of chronic rhinosinusitis with nasal polyposis which has failed to respond to standard therapies, we argue that biologics remain only a component of effective management in this patient population. Endoscopic sinus surgery and topical nasal steroids offer equal efficacy and substantially lower costs than biologics, and these factors should be considered when selecting treatment options for patients.

Keywords: Chronic rhinosinusitis; Endoscopic sinus surgery; Eosinophilic rhinitis; Nasal polyposis; Quality of life; Sinusitis.