Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials

Bachert, Claus; Han, Joseph K.; Desrosiers, Martin; Hellings, Peter; Amin, Nikhil; Lee, Stella E.; Mullol, Joaquim; Greos, Leon S.; Bosso, John V.; Laidlaw, Tanya M.; Cervin, Anders; Máspero, Jorge; Hopkins, Claire; Olze, Heidi; Canonica, Giorgio Walter; Paggiaro, Pierluigi; Cho, Seong H.; Fokkens, Wytske J.; Fujieda, Shigeharu; Zhang, Mei; Lu, Xin; Fan, Chunpeng; Draikiwicz, Steven; Kamat, Siddhesh; Khan, Asif; Pirozzi, Gianluca; Patel, Naimish; Graham, Neil M.H.; Ruddy, Marcella; Staudinger, Heribert; Weinreich, David M.; Stahl, Neil; Yancopouloš, George D.; Mannent, Leda

doi:10.1016/s0140-6736(19)31881-1

Cited by 966 publications

(1,378 citation statements)

References 28 publications

Supporting

Mentioning

1,141

Contrasting

Unclassified

Order By: Relevance

“…70 An important recent clinical trial demonstrated that a biologic directed against IL-4/IL-13 receptor alpha chain significantly decreased NP size. 71 These data support a role of type 2 cytokines in NP pathogenesis. IL-5 is a key activation and survival factor for eosinophils in NPs.…”

Section: Nature Of Np and Fibrin Depositionsupporting

confidence: 55%

“…A recent large phase 3 clinical trial demonstrated that dupilumab, a fully human mAb that inhibits signaling of IL-4 and IL-13, significantly decreased NP size. 71 Although it was not tested, it is reasonable to speculate that dupilumab blocks IL-4/IL-13 signaling and may subsequently restore tPA production in nasal epithelial cells, which would then activate fibrinolysis and result in NP shrinkage. We do note that fibrin deposition is not restricted to NPs associated with type 2 inflammation, and are aware of studies by Z. Liu et al showing that fibrin deposition is a feature of noneosinophilic polyps in Wuhan, China (personal communication, 2020).…”

Section: Fibrinolytic Impairment Causes Abnormal Fibrin Deposition Inmentioning

confidence: 99%

See 1 more Smart Citation

Formation of nasal polyps: The roles of innate type 2 inflammation and deposition of fibrin

Takabayashi

Schleimer²

2020

Journal of Allergy and Clinical Immunology

111

View full text Add to dashboard Cite

Section: Nature Of Np and Fibrin Depositionsupporting

confidence: 55%

Section: Fibrinolytic Impairment Causes Abnormal Fibrin Deposition Inmentioning

confidence: 99%

Formation of nasal polyps: The roles of innate type 2 inflammation and deposition of fibrin

Takabayashi

Schleimer²

2020

Journal of Allergy and Clinical Immunology

111

View full text Add to dashboard Cite

“…In addition to a significant efficacy in CRSwNP (severity, nasal polyp size, nasal function, nasal symptoms, sinus occupation, QOL, and T2 inflammatory markers) and asthma (lung function and control) outcomes and up to 1 year of treatment, dupilumab has shown an outstanding and fast (2 weeks) improvement in loss of smell, the most difficult-to-treat symptom in patients with severe CRSwNP with or without asthma or aspirin/nonsteroidal anti-inflammatory drug-exacerbated respiratory disease. 9 All these findings have promoted ''loss of smell'' as one of the main criteria for indication of and response to biological treatment. 10 Olfactory training is recommended in patients with olfactory loss of postviral and posttraumatic origin, but no data are available to recommend its use in patients with CRS.…”

Section: Therapeutic Optionsmentioning

confidence: 99%

The sense of smell in chronic rhinosinusitis

Mullol

Mariño‐Sánchez

Valls

et al. 2020

Journal of Allergy and Clinical Immunology

Self Cite

View full text Add to dashboard Cite

“…In eosinophil-dominant severe asthma, anti-IL-4Rα mAb, which blocks both IL-4 and IL-13 signaling, strongly reduced acute exacerbations and increased lung function [61]. Furthermore, in severe chronic rhinosinusitis with nasal polyps, anti-IL-4Rα mAb reduced polyp sizes, sinus opacification, and the severity of symptoms [62]. Considering the role of IL-4/IL-13 in the development of eosinophilic airway inflammation, anti-IL-4/IL-13 treatment likely suppresses the accumulation of eosinophils in tissues in vivo, although it has not yet been established.…”

Section: Role Of Type 2 Cytokines (Il-4 and Il-13) In The Developmentmentioning

confidence: 99%

Possible Mechanisms of Eosinophil Accumulation in Eosinophilic Pneumonia

Nakagome

Nagata

2020

Biomolecules

View full text Add to dashboard Cite

Eosinophilic pneumonia (EP), including acute EP and chronic EP, is characterized by the massive pulmonary infiltration of eosinophils into the lung. However, the mechanisms underlying the selective accumulation of eosinophils in EP have not yet been fully elucidated. We reported that bronchoalveolar lavage fluid (BALF) from EP patients induced the transmigration of eosinophils across endothelial cells in vitro. The concentrations of eotaxin-2 (CCL24) and monocyte chemotactic protein (MCP)-4 (CCL13), which are CC chemokine receptor (CCR) 3 ligands, were elevated in the BALF of EP patients, and anti-CCR3 monoclonal antibody inhibited the eosinophil transmigration induced by the BALF of EP patients. The concentration of macrophage inflammatory protein 1β (CCL4), a CCR5 ligand that induces eosinophil migration, was increased in the BALF of EP patients. Furthermore, the concentration of interleukin (IL) 5 was increased in the BALF of EP patients, and it has been reported that anti-IL-5 antibody treatment resulted in remission and the reduction of glucocorticoid use in some cases of chronic EP. The concentrations of lipid mediators, such as leukotriene (LT) B 4 , damage-associated molecular pattern molecules (DAMPs), such as uric acid, or extracellular matrix proteins, such as periostin, were also increased in the BALF of EP patients. These findings suggest that chemokines, such as CCR3/CCR5 ligands, cytokines, such as IL-5, lipid mediators, such as LTB 4 , DAMPs, and extracellular matrix proteins may play roles in the accumulation or activation of eosinophils in EP.Biomolecules 2020, 10, 638 2 of 12 mechanisms of eosinophil accumulation in the airway of EP patients are discussed. The aim of this review is to better understand the mechanisms of eosinophil accumulation and activation in EP. AEP and CEPAEP is characterized by acute febrile illness with diffuse pulmonary infiltrates, severe hypoxemia, and increased eosinophils in bronchoalveolar lavage fluid (BALF) [3]. AEP is diagnosed based on the following: acute onset of respiratory failure, diffuse pulmonary infiltrates on chest roentgenogram, and increased numbers of eosinophils in BALF (more than 25% of total cells) [3]. Although the mechanisms of AEP have not yet been fully established, inhaled agents, such as cigarette smoke or chemical agents, are known causes of AEP [1,2,[5][6][7][8][9]. For example, a relationship was observed between the recent onset of cigarette smoking and the development of AEP [5][6][7]. Even short-term passive smoking can induce AEP [7]. The collapse of the World Trade Center towers [8] and the desert of the Middle East [9] have also been reported to induce AEP.

show abstract

Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials

Cited by 966 publications

References 28 publications

Formation of nasal polyps: The roles of innate type 2 inflammation and deposition of fibrin

Formation of nasal polyps: The roles of innate type 2 inflammation and deposition of fibrin

The sense of smell in chronic rhinosinusitis

Possible Mechanisms of Eosinophil Accumulation in Eosinophilic Pneumonia

Contact Info

Product

Resources

About