Real-life observational cohort verifies high efficacy of dupilumab for chronic rhinosinusitis with nasal polyps.
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ABSTRACT:
SUBMITTER: van der Lans RJL
PROVIDER: S-EPMC9298295 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe human monoclonal antibody dupilumab blocks interleukin (IL)-4 andIL-13, key and central drivers of type 2 inflammation. Dupilumab, on background mometasone furoate nasal spray (MFNS), improved outcomes in the phase III SINUS-52 study (NCT02898454) in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP). This posthoc analysis of SINUS-52 examined whether eosinophilic status of CRSwNP was a predictor of dupilumab efficacy.MethodsPatients were randomized 1:1:1 to dupilumab 300 mg every 2 weeks (q2w) until week 52; dupilumab 300 mg q2w until Week 24, then 300 mg every 4 weeks until week 52; or placebo (MFNS) until week 52. Coprimary endpoints were change from baseline in nasal polyps score (NPS), nasal congestion (NC), and Lund-Mackay score assessed by CT (LMK-CT) at week 24. Patients (n = 438) were stratified by eosinophilic chronic rhinosinusitis (ECRS) status according to the Japanese Epidemiological Survey of Refractory Eosinophilic Rhinosinusitis algorithm.ResultsDupilumab significantly improved NPS, NC, and LMK-CT scores versus placebo at week 24 in all ECRS subgroups (p < 0.001), with improvements maintained or increased at week 52 (p < 0.001). There was no significant interaction between ECRS subgroup (non-/mild or moderate/severe) and dupilumab treatment effect for all endpoints at weeks 24 and 52 (p > 0.05), except LMK-CT at week 24 (p = 0.0275). Similar results were seen for the secondary endpoints. Dupilumab was well tolerated across all ECRS subgroups.ConclusionDupilumab produced consistent improvement in symptoms of severe CRSwNP irrespective of ECRS status. Therefore, blood eosinophil level may not be a suitable biomarker for dupilumab efficacy in CRSwNP.
| S-EPMC9290136 | biostudies-literature
Project description:Objectives/hypothesisDupilumab, 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.MethodsPatients 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.ResultsOf 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.ConclusionDupilumab 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 evidence2 Laryngoscope, 131:E1770-E1777, 2021.
| S-EPMC8247406 | biostudies-literature
Project description: Not available
| S-EPMC9306796 | biostudies-literature
Project description:BackgroundChronic 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.MethodsPatients 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.ResultsOf 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.ConclusionDupilumab improved CRSwNP outcomes irrespective of surgery history, with greater improvements in endoscopic outcomes in patients with shorter duration since last surgery.
| S-EPMC8359289 | biostudies-literature
Project description: Not available
| S-EPMC9544911 | biostudies-literature
Project description:Chronic rhinosinusitis without nasal polyps (CRSsNP) is more prevalent than chronic rhinosinusitis with nasal polyps (CRSwNP). Certain diseases predispose to whereas others are associated with CRSsNP. Predisposing diseases include allergic and nonallergic upper and lower airway diseases, epithelial cell disorders, immunodeficiencies, autoimmune diseases, and some infectious diseases. In addition, environmental and host factors, examples of which include smoking, a higher incidence of abnormal biofilms, and innate immune defects, play a role in the pathogenesis of this disease. CRSsNP is characterized by histologic abnormalities, including basement membrane thickening (fibrosis) and goblet cell hyperplasia. Neutrophils and several chemokines, TGF-β and C-X-C motif chemokine ligand (CXCL)-8, play a role in CRSsNP remodeling. However, there are conflicting data about CRSsNP endotypes, for example, whether it is characterized by neutrophilia or eosinophilia or both. In spite of advancements and the understanding of the pathogenesis of this disease, additional study is necessary to better comprehend its underlying mechanisms, endotypes, and evidence-based treatment strategies.
| S-EPMC4939221 | biostudies-literature
Project description:Asthmatic chronic rhinosinusitis with nasal polyps (aCRSwNP) is a common disruptive eosinophilic disease. Therefore, we sought to identify gene expression changes in nasosinus inflamed mucosa and adjacent polyp tissue from subjects with aCRSwNP.
2010-08-12 | GSE23552 | GEO
Project description:The mechanisms underlying neutrophilic inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP) remain poorly investigated. This study aimed to examine the factors that contribute to tissue neutrophilia in CRSwNP. The numbers of neutrophils and active caspase-3-positive apoptotic neutrophils in sinonasal tissues were assessed via immunofluorescence staining. The 95th percentile of tissue neutrophil numbers in control subjects was selected as a cut-off to define neutrophil-high (Neu-high) or neutrophil-low (Neu-low) nasal polyps (NPs). The levels of 34 inflammatory mediators in sinonasal tissues were analyzed using Bio-Plex assay. Purified human peripheral blood neutrophils were incubated with nasal tissue homogenates, and the apoptotic neutrophils were assessed via flow cytometry. The cut-off for Neu-high NPs was >10 myeloperoxidase positive cells/high-power field. Compared with Neu-low NPs, Neu-high NPs had higher tissue levels of IL-1β, IL-1Ra, IL-6, IL-8, G-CSF, MCP-1, and MIP-1α, but lower levels of IL-5, IL-13, IgE, and eosinophils. Principal component and multiple correspondence analyses revealed mixed type 1, type 2, and type 3 endotypes for Neu-low NPs, and predominant type 1 and type 3 endotypes for Neu-high NPs. Neu-high NPs had lower percentages of apoptotic neutrophils than Neu-low NPs. The numbers of neutrophils and the percentages of apoptotic neutrophils correlated with G-CSF and IL-6 levels in the NPs. Tissue homogenates from Neu-high NPs, but not those from Neu-low NPs, suppressed neutrophil apoptosis in vitro, which was reversed by anti-G-CSF treatment. Tissue neutrophil numbers were associated with difficult-to-treat disease in patients with CRSwNP after surgery. We propose that G-CSF promotes neutrophilic inflammation by inhibiting neutrophil apoptosis in CRSwNP.
| S-EPMC8718617 | biostudies-literature
Project description:Chronic rhinosinusitis with nasal polyp (CRSwNP) patients are often characterized by asthma comorbidity and a type-2 inflammation of the sinonasal mucosa. The mucosal microbiota has been suggested to be implicated in the persistence of inflammation, but associations have not been well defined. To compare the bacterial communities of healthy subjects with CRSwNP patients, we collected nasal swabs from 17 healthy subjects, 21 CRSwNP patients without asthma (CRSwNP-A), and 20 CRSwNP patients with co-morbid asthma (CRSwNP+A). We analysed the microbiota using high-throughput sequencing of the bacterial 16S rRNA. Bacterial communities were different between the three groups. Haemophilus influenzae was significantly enriched in CRSwNP patients, Propionibacterium acnes in the healthy group; Staphylococcus aureus was abundant in the CRSwNP-A group, even though present in 57% of patients. Escherichia coli was found in high amounts in CRSwNP+A patients. Nasal tissues of CRSwNP+A patients expressed significantly higher concentrations of IgE, SE-IgE, and IL-5 compared to those of CRSwNP-A patients. Co-cultivation demonstrated that P. acnes growth was inhibited by H. influenzae, E. coli and S. aureus. The nasal microbiota of healthy subjects are different from those of CRSwNP-A and CRSwNP+A patients. However, the most abundant species in healthy status could not inhibit those in CRSwNP disease.
| S-EPMC5962583 | biostudies-literature
Project description:Considering the complex and multifarious features of Chronic rhinosinusitis (CRS) including immunologic patterns, novel modalities are needed to reflect clinical and pathophysiological endotypes beyond nasal polyps.We aimed to investigate the proteome of nasal secretions on filter paper from CRS patients to characterize endotypes.
2019-07-29 | PXD013330 | Pride