Tetsuji Takabayashi1, Daiya Asaka2, Yoshitaka Okamoto3, Tetsuo Himi4, Shinichi Haruna5, Naohiro Yoshida6, Kenji Kondo7, Mamoru Yoshikawa8, Yasunori Sakuma9,10, Kunihiko Shibata9, Motohiko Suzuki11, Masayoshi Kobayashi12, Ryo Kawata13, Kenzo Tsuzuki14, Mitsuhiro Okano15,16, Takaya Higaki16, Sachio Takeno17, Satoru Kodama18,19, Syuji Yonekura3, Hiromi Saito20, Akiyo Nozaki20, Nobuyoshi Otori2, Shigeharu Fujieda1. 1. Department of Otorhinolaryngology-Head & Neck Surgery, University of Fukui, Fukui, Japan. 2. Department of Otorhinolaryngology, Jikei University School of Medicine, Tokyo, Japan. 3. Department of Otorhinolaryngology, Head and Neck Surgery, Chiba University, Chiba, Japan. 4. Department of Otolaryngology, Sapporo Medical University, Hokkaido, Japan. 5. Department of Otorhinolaryngology, Head & Neck Surgery, Dokkyo Medical University, Tochigi, Japan. 6. Department of Otolaryngology, Jichi Medical University Saitama Medical Center, Saitama, Japan. 7. Department of Otolaryngology, University of Tokyo, Tokyo, Japan. 8. Department of Otorhinolaryngology, Toho University Ohashi Medical Center, Tokyo, Japan. 9. Department of Otorhinolaryngology, Yokohama City University Medical Center, Kanagawa, Japan. 10. Kagami-Zaitaku Clinic, Kanagawa, Japan. 11. Departments of Otorhinolaryngology, Nagoya City University, Aichi, Japan. 12. Department of Otorhinolaryngology-Head and Neck Surgery, Mie University Graduate School of Medicine, Mie, Japan. 13. Department of Otolaryngology, Head & Neck Surgery, Osaka Medical College, Osaka, Japan. 14. Department of Otolaryngology-Head and Neck Surgery, Hyogo College of Medicine, Hyogo, Japan. 15. Department of Otorhinolaryngology, International University of Health and Welfare Mita Hospital, Tokyo, Japan. 16. Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. 17. Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. 18. Kodama Jibiinkoka Clinic, Oita, Japan. 19. Oita University Faculty of Medicine, Otolaryngology, Head and Neck Surgery, Oita, Japan. 20. R&D Division, Kyowa kirin Co., Ltd., Tokyo, Japan.
Abstract
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.
RCT Entities:
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.
Authors: Elisabetta Pallara; Sergio Cotugno; Giacomo Guido; Elda De Vita; Aurelia Ricciardi; Valentina Totaro; Michele Camporeale; Luisa Frallonardo; Roberta Novara; Gianfranco G Panico; Pasquale Puzo; Giovanni Alessio; Sara Sablone; Michele Mariani; Giuseppina De Iaco; Eugenio Milano; Davide F Bavaro; Rossana Lattanzio; Giulia Patti; Roberta Papagni; Carmen Pellegrino; Annalisa Saracino; Francesco Di Gennaro Journal: Am J Trop Med Hyg Date: 2022-08-01 Impact factor: 3.707