Objectives/Hypothesis: Dupilumab, which blocks the shared receptor component for interleukin‐4 and interleukin‐13, reduced polyp size, sinus opacification, and symptom severity, and was well tolerated in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) in the SINUS‐52 study (NCT02898454). We assessed dupilumab in patients enrolled at Japanese centers.Methods: Patients on a background of mometasone furoate nasal spray, received dupilumab 300 mg every 2 weeks (q2w) for 52 weeks (Arm A); dupilumab 300 mg q2w for 24 weeks, followed by every 4 weeks (q4w) for 28 weeks (Arm B); or placebo (Arm C). Co‐primary endpoints were week 24 nasal polyp score (NPS), nasal congestion (NC) score, and sinus Lund–Mackay CT (LMK‐CT) scores. Symptoms, sense of smell, health‐related quality of life, and safety were assessed during the 52‐week treatment period.Results: Of 49 patients enrolled in Japan, 45 completed the study. Week 24 least squares (LS) mean improvement versus placebo were as follows: NPS (Arm A: −3.1, P < .0001; Arm B: −2.1, P = .0011); NC score (Arm A: −1.2, P < .0001; Arm B: −0.9, P < .0001); and LMK‐CT (Arm A: −5.1, P = .0005; Arm B: −2.8, P = .0425). The most common treatment‐emergent adverse event in dupilumab and placebo‐treated patients was nasopharyngitis.Conclusion: Dupilumab provided rapid, significant, and clinically meaningful improvements for patients with CRSwNP in Japan. Dupilumab was well tolerated, and safety and efficacy were consistent with the overall study population.Level of Evidence: 2 Laryngoscope, 131:E1770–E1777, 2021

Background: Strong eosinophil infiltration in chronic rhinosinusitis with nasal polyp (CRSwNP) is highly associated with recalcitrance and higher nasal polyp recurrence rate after surgery. The prevalence of eosinophilic CRSwNP (ECRS) is increasing in Asian countries including Japan. Benralizumab is a humanized anti-IL-5R alpha monoclonal antibody that depletes eosinophils by antibody-dependent cell-mediated cytotoxicity. Objective: To assess the efficacy and safety of benralizumab in patients with ECRS. Methods: This phase II, randomized, double-blind, placebo-controlled study was conducted in Japan. Patients were randomized 1:2:2 to placebo, a single administration of benralizumab 30 mg, or benralizumab 30 mg every 4 weeks (q4w) for a total of three doses. The primary endpoint was the change in nasal polyp score from baseline at Week 12. Results: Overall, 56 patients were enrolled (placebo, n = 11; benralizumab single dose, n = 22; benralizumab q4w, n = 23). Although the mean total nasal polyp score began to decrease after the initiation of benralizumab treatment, there were no statistically significant differences in change in nasal polyp score from baseline at Week 12 between benralizumab and placebo (placebo, −0.5 ± 0.8; benralizumab single, −0.3 ± 0.8; benralizumab q4w, −0.5 ± 1.5). Post-hoc analysis showed that the administration of benralizumab decreased nasal polyp scores ≥2 points in 42.2% of ECRS patients and that patients with high blood eosinophil levels had a greater tendency to respond to benralizumab treatment. The safety profile was similar to that in previous studies and no unexpected adverse events were noted. Conclusion: Although benralizumab did not meet the primary efficacy endpoint, reductions of nasal polyp scores were seen in the benralizumab group compared with the placebo group over the whole study period, especially in patients with high levels of blood eosinophils.

The overall pathological view of paranasal sinus inflammation in the Japanese population has profoundly changed in recent years. Eosinophilic chronic rhinosinusitis (ECRS) is a clinical entity of intractable chronic sinus inflammation accompanied by numerous infiltrations of activated eosinophils in the paranasal sinus mu- cosa and/or nasal polyps. Several pathologic processes are considered to act in concert to promote the accumulation of eosinophils in ECRS. They include infiltration of progenitor cells, increase in local IL-3, IL-5, IL-13, GM-CSF and eotaxin production, and upregulation of adhesion molecules. The role of nasal allergen sensitization and innate immunity responses in the sinus mucosa has also been proposed in the development of ECRS. Various pathogens including TLRs ligands may trigger an abnormal immune response at the mucosal surface. The objectives of ECRS management should focus directly on inhibition of local eosinophil infiltration. Surgical procedures include widely opening the bony wall septum of every affected sinus and mechanical removal of diseased mucosal lesion. The use of local and/or systemic steroids, leukotriene receptor antagonists, and Th2 cytokine antagonists is recommended. Local administration of steroids is a potent treatment strategy for preventing relapse of nasal polyposis and is considered to be the first-line treatment for ECRS patients

Background: Comprehensive understanding of frontal recess anatomy is essential for the successful treatment of patients with frontal sinus disease. This study was designed to determine the prevalence of specific frontal recess cells in Japanese subjects and the association of these cells with the development of frontal sinusitis. Methods: Frontal recess anatomy was analyzed using high-resolution spiral computed tomography images of paranasal sinuses from December 2008 through September 2011. The distribution of various frontal recess cells in patients with and without frontal sinusitis was compared by logistic regression analysis. Results: A total of 150 patients met the criteria, and 300 sides were analyzed. Agger nasi cells were present in 88.0 % of sides; frontal cell types 1 (FC1), 2 (FC2), 3 (FC3), and 4 (FC4) were present in 37.0 %, 6.3 %, 4.3 %, and 1.3 %, respectively; supraorbital ethmoid cells in 6.0 %, suprabullar cells in 37.0 %, frontal bullar cells (FBC) in 7.0 %, and interfrontal sinus septal cells in 8.6 %. Multiple logistic regression analysis showed that the presence of FBCs was significantly associated with the development of frontal sinusitis ( p = 0.043). Conclusions: The frequencies of frontal recess cells in Japanese adult patients were similar to those reported for other East Asian adult populations, including Chinese, Korean, and Taiwanese. Anatomically, FBCs may show a greater association with the development of frontal sinusitis than other frontal recess cells.