A Phase II, Multicenter, Randomized, Placebo-Controlled Study of Benralizumab, a Humanized Anti-IL-5R Alpha Monoclonal Antibody, in Patients With Eosinophilic Chronic Rhinosinusitis

Takabayashi, Tetsuji; Asaka, Daiya; Okamoto, Yoshitaka; Himi, Tetsuo; Haruna, Shinichi; Yoshida, Naohiro; Kondo, Kenji; Yoshikawa, Mamoru; Sakuma, Yasunori; Shibata, Kunihiko; Suzuki, Motohiko; Kobayashi, Masayoshi; Kawata, Ryo; Tsuzuki, Kenzo; Okano, Mitsuhiro; Higaki, Toru; Takeno, Sachio; Kodama, Satoru; Yonekura, Syuji; Saito, Hiromi; Nozaki, Akiyo; Otori, Nobuyoshi; Fujieda, Shigeharu

doi:10.1177/19458924211009429

Cited by 47 publications

(34 citation statements)

References 30 publications

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“…Peripheral eosinophil count is associated with tissue eosinophilia in CRSwNP and has been proposed as a surrogate marker thereof. 33 Reductions in NPS with benralizumab have previously been linked to baseline blood eosinophil count in patients with CRSwNP, 23,34 and eosinophils in sinonasal mucosa and peripheral blood are elevated to a greater degree in patients with CRS and asthma than in patients with CRS alone. [35][36][37] In OSTRO, patients with comorbid asthma had higher mean baseline blood eosinophil counts than patients without the disease (Table E1).…”

Section: Discussionmentioning

confidence: 97%

Efficacy and safety of benralizumab in chronic rhinosinusitis with nasal polyps: A randomized, placebo-controlled trial

Bachert

Han

Desrosiers

et al. 2022

Journal of Allergy and Clinical Immunology

178

136

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Section: Discussionmentioning

confidence: 97%

Efficacy and safety of benralizumab in chronic rhinosinusitis with nasal polyps: A randomized, placebo-controlled trial

Bachert

Han

Desrosiers

et al. 2022

Journal of Allergy and Clinical Immunology

178

136

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“…72 Therefore, the results cannot be extrapolated to the general Asian population. Recently, Takabayashi et al 73 conducted a phase 2 study on the effects of benralizumab, a humanized anti-IL-5Rα monoclonal antibody, on Japanese patients with eosinophilic chronic rhinosinusitis, 73 and found that although benralizumab did not meet the primary efficacy endpoint, patients with high blood eosinophil levels had a greater tendency to respond to benralizumab treatment. This finding further reinforces the endotype depend- Although the percentage of recurrence in CRSsNP patients is remarkably lower than that described in CRSwNP patients, approximately 12.9% of CRSsNP patients may recur within 12 years, and CRSsNP patients with T2 inflammation have higher recurrence rates.…”

Section: Current Evidence Regarding T2 Biologics In Asian Crswnp Pati...mentioning

confidence: 99%

Revisiting Asian chronic rhinosinusitis in the era of type 2 biologics

Yao

Zeng

Liu

2021

Clin Experimental Allergy

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Chronic rhinosinusitis (CRS) is defined as the inflammation of the mucosa of the nose and paranasal sinuses over 12 weeks, occurring in 11%-12% of adults in Europe and the United States, 1 and approximately 8% of adults in China and Korea. 2,3 CRS frequently presents with other inflammatory airway conditions such as asthma and allergic rhinitis (AR), and imposes huge global health and economic burdens. 1,2 CRS is a highly heterogeneous disorder with diverse inflammatory profiles. [4][5][6] Based on endoscopic examination finding, CRS is clinically subclassified into CRS without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP). 4,5 Studies in Caucasian patients have shown that CRSwNP is characterized by type 2 (T2) [high interleukin (IL)-4, IL-5, IL-13 and IgE expression] and eosinophilic inflammation, whereas CRSsNP is primarily characterized by type 1 (T1) [high interferon (IFN)γ expression] and type 3 (T3) (high IL-17A expression) inflammation. 1,4,6 Conventional anti-inflammatory treatments of CRS include intranasal and systemic corticosteroids. 1,4 Endoscopic sinus surgery is considered when medical therapy fails. 1,4 However, it has been shown that approximately 20% of CRSsNP and 40% of CRSwNP patients relapse 1-2 years after surgery. [7][8][9] Eosinophilic inflammation and T2 immune response have been identified as important risk factors for disease relapse in CRS patients, 1,4,6,10,11 thus stimulating the study of T2 biologics in Caucasian patients with severe CRSwNP. Four multicentre and international phase 3 trials have demonstrated promising effect of omalizumab (anti-IgE), dupilumab (anti-IL-4Rα), mepolizumab (anti-IL-5) and benralizumab (anti-IL-5Rα) in reducing nasal polyp (NP) size and relieving symptoms in patients with refectory and severe CRSwNP. [12][13][14][15]

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“…202 It also has a specific license from the EMA, for patients with severe T2 asthma who have co-existent severe eczema or CRSwNP. 202 Similarly, anti-IL-5 and IL-5R drugs, following successful clinical trials, are also currently under assessment for approval by multiple regulatory bodies for use in other eosinophilic conditions such as Eosinophilic Granulomatosis with Polyangiitis, 248,274 CRSwNP [275][276][277] and Eosinophilic oesophagitis. 278 Mepolizumab specifically has been approved by the Food and Drug Administration for Eosinophilic Granulomatosis with Polyangiitis 278 Finally, Omalizumab is also licensed for use in treatment-resistant chronic spontaneous urticaria and CRSwNP.…”

Section: Monoclonal Antibody Selection For Asthma and Comorbiditiesmentioning

confidence: 99%

Recent Insights into the Management of Inflammation in Asthma

Rupani¹,

Fong²,

Kyyaly³

et al. 2021

JIR

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The present prevailing inflammatory paradigm in asthma is of T2-high inflammation orchestrated by key inflammatory cells like Type 2 helper lymphocytes, innate lymphoid cells group 2 and associated cytokines. Eosinophils are key components of this T2 inflammatory pathway and have become key therapeutic targets. Real-world evidence on the predominant T2-high nature of severe asthma is emerging. Various inflammatory biomarkers have been adopted in clinical practice to aid asthma characterization including airway measures such as bronchoscopic biopsy and lavage, induced sputum analysis, and fractional exhaled nitric oxide. Blood measures like eosinophil counts have also gained widespread usage and multicomponent algorithms combining different parameters are now appearing. There is also growing interest in potential future biomarkers including exhaled volatile organic compounds, micro RNAs and urinary biomarkers. Additionally, there is a growing realisation that asthma is a heterogeneous state with numerous phenotypes and associated treatable traits. These may show particular inflammatory patterns and merit-specific management approaches that could improve asthma patient outcomes. Inhaled corticosteroids (ICS) remain the mainstay of asthma management but their use earlier in the course of disease is being advocated. Recent evidence suggests potential roles for ICS in combination with long-acting beta-agonists (LABA) for as needed use in mild asthma whilst maintenance and reliever therapy regimes have gained widespread acceptance. Other anti-inflammatory strategies including ultra-fine particle ICS, leukotriene receptor antagonists and macrolide antibiotics may show efficacy in particular phenotypes too. Monoclonal antibody biologic therapies have recently entered clinical practice with significant impacts on asthma outcomes. Understanding of the efficacy and use of those agents is becoming clearer with a growing body of real-world evidence as is their potential applicability to other treatable comorbid traits. In conclusion, the evolving understanding of T2 driven inflammation alongside a treatable traits disease model is enhancing therapeutic approaches to address inflammation in asthma.

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A Phase II, Multicenter, Randomized, Placebo-Controlled Study of Benralizumab, a Humanized Anti-IL-5R Alpha Monoclonal Antibody, in Patients With Eosinophilic Chronic Rhinosinusitis

Cited by 47 publications

References 30 publications

Efficacy and safety of benralizumab in chronic rhinosinusitis with nasal polyps: A randomized, placebo-controlled trial

Efficacy and safety of benralizumab in chronic rhinosinusitis with nasal polyps: A randomized, placebo-controlled trial

Revisiting Asian chronic rhinosinusitis in the era of type 2 biologics

Recent Insights into the Management of Inflammation in Asthma

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