<p>Therapeutic Potential of Dupilumab in the Treatment of Chronic Rhinosinusitis with Nasal Polyps: Evidence to Date</p>

Abstract

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is one of the most severe forms of chronic rhinosinusitis. CRSwNP is characterized by nasal and facial congestion, loss of sense of smell, rhinorrhea, and post-nasal drip. Treatments have been ineffective at controlling disease recurrence, despite multiple courses of medical and surgical therapies. Oral glucocorticoid therapy is often used to control exacerbations leaving the patient exposed to steroid-induced adverse effects. Thus, there is a clear unmet need for new treatments to achieve better control of the disease. Advances in understanding Type 2 inflammatory processes that occur in about 80% of the Western world patients with CRSwNP have resulted in new avenues for disease control. Biologics in the form of monoclonal antibodies, which target Type 2 inflammation, have helped control the severest forms of atopic dermatitis and asthma. Treatment regimes for CRSwNP now include biologics. In July 2019, dupilumab was the first monoclonal antibody to gain FDA approval for the treatment of CRSwNP. In this review, we summarize the proof of concept clinical trials and Phase 3 trials leading to approval of dupilumab, an anti-IL4 alpha receptor antagonist that blocks the actions of both IL4 and IL13. These studies show that dupilumab is a proven treatment option to control disease. Collective studies demonstrate a high safety profile. Questions arise as to the best use of dupilumab in the context of current treatment paradigms, and for which subpopulation of the varied heterogeneous endotypes of CRSwNP patients. Recognizing the high cost of biologics forces the need for cost-effectiveness analysis.

Biologics for severe uncontrolled chronic rhinosinusitis with nasal polyps: a change management approach. Consensus of the Joint Committee of Italian Society of Otorhinolaryngology on biologics in rhinology

“…Dupilumab is a fully human monoclonal antibody targeting the α-chain subunit of IL-4 receptors (Type 1 and type 2 IL-4Rα) and inhibiting IL-4/IL-13 signaling 35 . Literature data [42][43][44] have demonstrated that the dual inhibition of IL-4 and IL-13 signaling may represent an important strategy for the treatment of type 2 CRSwNP. Bachert et al 35 dupilumab had a significant reduction in polyp size (primary endpoint), which was clinically observable from the 4th week of treatment.…”

Systematic literature review of the epidemiology and clinical burden of chronic rhinosinusitis with nasal polyposis

“…Patients with serious disease or who have failed medical management may be eligible for sinus surgery. Functional endoscopic sinus surgery (FESS) can improve sinonasal symptoms and inflammation, but NP may still recur 9 , with rates as high as 50% (for patients observed over a period of 3 years) 10 .…”

Systematic literature review of humanistic and economic burdens of chronic rhinosinusitis with nasal polyposis

“…Patients with serious disease or who have failed medical management may be eligible for sinus surgery. Functional endoscopic sinus surgery (FESS) can improve sinonasal symptoms and inflammation, but NP can still recur 8 , with rates as high as 50% (for patients followed over a period of 3 years) 9 .…”

“…Given the unmet need in recalcitrant CRSwNP, biologics have emerged as a novel treatment option owing to recent advancements in our understanding of the disease, particularly inflammation 9,10 . Studies have demonstrated efficacy for biologics in the treatment of CRSwNP; therefore, biologics are anticipated to reduce the clinical, humanistic and economic burden of CRSwNP.…”