Efficacy of dupilumab in patients with a history of prior sinus surgery for chronic rhinosinusitis with nasal polyps

Abstract

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease treated with sinus surgery when refractory to medical intervention. However, recurrence postsurgery is common. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor for interleukin 4 (IL‐4) and IL‐13, key and central drivers of type 2 inflammation. We report the efficacy of dupilumab in patients with CRSwNP from the SINUS‐24/SINUS‐52 trials (NCT02912468/NCT02898454), by number of prior surgeries and time since last surgery. Methods Patients were randomized to placebo or dupilumab 300 mg every 2 weeks. Post hoc subgroup analyses were performed for patients with 0, ≥1, 1/2, or ≥3 prior surgeries, and for patients who had surgery within <3, 3 to <5, 5 to <10, or ≥10 years. Efficacy outcomes at 24 weeks included co‐primary endpoints nasal polyp score (NPS) and nasal congestion (NC), and Lund‐Mackay (LMK), 22‐item Sino‐Nasal Outcome Test (SNOT‐22), and smell scores. Results Of 724 patients randomized, 459 (63.4%) had ≥1 prior surgery. Baseline sinus disease (NPS, NC, LMK) and olfactory dysfunction (University of Pennsylvania Smell Identification Test [UPSIT] and loss of smell) scores were worse for patients with ≥3 prior surgeries vs no surgery. Baseline NPS and LMK were worse in patients with <3 years since last surgery than in patients with ≥5 years since last surgery. Dupilumab significantly improved all outcome measures vs placebo in all subgroups by number of surgeries and by time since last surgery. Improvements in NPS and LMK were greater in patients with <3 years since last surgery than patients with ≥5 years. Safety results were consistent with the known dupilumab safety profile. Conclusion Dupilumab improved CRSwNP outcomes irrespective of surgery history, with greater improvements in endoscopic outcomes in patients with shorter duration since last surgery.

Studies on Clinical Features, Mechanisms, and Management of Olfactory Dysfunction Secondary to Chronic Rhinosinusitis

“…The biologics dupilumab (63)(64)(65), omalizumab (66,67), and mepolizumab (68) have been shown to improve olfaction based on symptom scores and olfaction tests. Dupilumab, blocking the shared receptor component of IL-4 and IL-13, can even improve olfaction function in patients who previously underwent more than 3 surgeries (69,70). Successful treatment with biologics may imply that type 2 inflammation plays a role in the disease mechanism of olfactory dysfunction in CRS.…”

Ethical dilemmas associated with the introduction of biologic treatments in chronic rhinosinusitis with nasal polyps

“…N-ERD is associated with significantly higher risk of revision surgery (33) , research suggests that patients with N-ERD achieve greater improvements in nasal congestion, total symptom scores, radiological severity and SNOT-22 scores than those without. Patients with a history of previous surgery, particularly those that have a symptomatic recurrence that requires revision within 3 years, are at a higher risk of undergoing further surgical intervention (33) ; again a recent study has shown that while all groups benefit from dupilumab, those with a history of increasing numbers of previous surgery, or reducing time since last surgery to revision benefit the most (34) . It appears that characte-…”

Rhinology in review: from COVID-19 to biologicals

“…With the development of the biological treatments (45)(46)(47) , it is very likely from initial investigations that olfactory function can be further improved (48) without the need of recurrent systemic steroids. However more real-life studies in this field are needed to draw a more comprehensive picture of when and which biological treatment is best used for patients with treatment-refractory olfactory dysfunction (49,50) .…”