Depemokimab: First Approval.

Multidisciplinary consensus on a stepwise treatment algorithm for management of chronic rhinosinusitis with nasal polyps.

Dupilumab improves patient-reported outcomes in patients with chronic rhinosinusitis with nasal polyps and comorbid asthma

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Basophils are elevated in nasal polyps of patients with chronic rhinosinusitis without aspirin sensitivity

Immunology-based recommendations for available and upcoming biologics in aspirin-exacerbated respiratory disease

Fevipiprant in CRSwNP and comorbid asthma: Wrong target population or wrong PGD2 receptor?

BackgroundA significant proportion of patients with severe asthma may also suffer from nasal polyposis, which is commonly defined as chronic rhinosinusitis with nasal polyps (CRSwNP), the presence of which may adversely affect asthma treatment outcomes. The biologic agent omalizumab is effective as add-on therapy in patients with severe allergic asthma. The aim of this post hoc analysis of the PROXIMA study was to compare the efficacy of omalizumab between patients with severe allergic asthma, with and without comorbid CRSwNP.MethodsPROXIMA was a prospective observational 2-part study conducted in Italy in adult patients with severe allergic asthma, where, in the second part, patients eligible for add-on omalizumab initiated treatment for 12 months. Patient baseline data such as comorbidities and history of exacerbations were collected. Outcomes were asthma control (Asthma Control Questionnaire [ACQ]), lung function (forced expiratory volume in 1 s [FEV1]) and exacerbation rate. The post hoc analysis compared these outcomes between the cohort with comorbid CRSwNP and the cohort without CRSwNP.ResultsOf 123 patients included in this analysis, 17 (13.8%) were in the CRSwNP cohort. There was no significant difference between cohorts in baseline clinical characteristics or in change from baseline at 12 months in ACQ values, % of predicted FEV1 or annual asthma exacerbation rate, although results were numerically in favor of the CRSwNP cohort versus the non-CRSwNP cohort. The proportion of patients who achieved an improvement in all three outcomes was numerically greater in the CRSwNP cohort (35.7% vs 23.0%).ConclusionsIn an observational real-world setting, add-on omalizumab for severe allergic asthma was effective in improving asthma control, lung function and in reducing exacerbations, including in those patients with CRSwNP.

BackgroundRespiratory multimorbidities are linked to asthma, such as allergic rhinitis (AR) with early allergic asthma and chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) with late nonallergic asthma.ObjectiveOur aim was to investigate the association of asthma severity and control with specific upper airway phenotypes.MethodPatients with asthma were prospectively recruited from 23 pulmonology and ear, nose, and throat clinics. Asthma severity and control, as well as upper airway comorbidities (AR and non-AR [NAR], CRSwNP, and CRS without nasal polyps [CRSsNP]) were assessed according to international consensus guidelines definitions.ResultsA total of 492 asthmatic patients were included. Half of the asthmatic patients (49.6%) had associated rhinitis (37.0% had AR and 12.6% had NAR) and 36.2% had CRS (16.7% had CRSsNP and 19.5% had CRSwNP), whereas 14.2% had no sinonasal symptoms. Most cases of AR (78%) and NAR (84%) were present in patients with mild-to-moderate asthma, whereas CRSwNP was more frequent in patients with severe asthma (35% [P < .001]), mainly nonatopic asthma (44% [P < .001]). Patients with severe asthma with CRSwNP had worse asthma control, which was correlated (r = 0.249 [P = .034]) with sinus occupancy. Multiple logistic regression analysis showed that late-onset asthma, intolerance of aspirin and/or nonsteroidal anti-inflammatory drugs, and CRSwNP were independently associated with severe asthma.ConclusionSevere asthma is associated with CRSwNP, with sinus occupancy affecting asthma control. This study has identified 2 main different upper airway treatable traits, AR and CRSwNP, which need further evaluation to improve management and control of patients with asthma.

Biologics for chronic rhinosinusitis with nasal polyposis: What should we do now without direct comparison trials?

ABSTRACTBackgroundSevere asthma with an eosinophilic phenotype (SAEP) and chronic rhinosinusitis with nasal polyps (CRSwNP) are predominantly type 2‐driven diseases, characterised by eosinophilic inflammation and substantial disease burden. Mepolizumab, a humanised monoclonal antibody that targets interleukin‐5, a key cytokine in type 2 inflammation, is an effective, approved treatment both in SAEP and CRSwNP. We aimed to analyse real‐world evidence of mepolizumab effectiveness in patients with comorbid SAEP and CRSwNP.MethodsThis study pooled five existing, predominantly European cohorts to describe the impact of mepolizumab on the rate of clinically significant exacerbations (CSEs) and other outcomes in adults with SAEP without and with comorbid CRSwNP (SAEP[−]CRSwNP and SAEP[+]CRSwNP, respectively).ResultsOverall, 1037 patients were included. Baseline characteristics were similar in both cohorts. Mepolizumab was associated with a reduction from baseline in the annual rate of CSEs at 12‐months post‐initiation (SAEP[−]CRSwNP: 72.7%; SAEP[+]CRSwNP: 79.7%), irrespective of baseline blood eosinophil count (BEC). When patients with SAEP[+]CRSwNP were compared with patients with SAEP[−]CRSwNP, a 30.0% incremental benefit in the reduction of CSEs was observed. At 12‐months post‐initiation, mepolizumab was also associated with a reduction in oral corticosteroid use and BEC, and an improvement in lung function and Asthma Control Test (ACT) scores in both cohorts. Post‐mepolizumab initiation, ≥ 3 clinical remission criteria were fulfilled by 47.2% and 52.3% of patients with SAEP[−]CRSwNP and SAEP[+]CRSwNP, respectively.ConclusionsThe results provide a greater understanding of mepolizumab's effectiveness, demonstrating a substantial improvement in asthma outcomes, irrespective of baseline BEC and the presence of comorbid CRSwNP.

B cell-activating Factor of the TNF Family (BAFF) and a Proliferation-inducing Ligand (APRIL) Expression in Chronic Rhinosinusitis

Chronic rhinosinusitis with nasal polyp (CRSwNP) is a type 2 inflammatory disease frequently associated with asthma. Patients with CRSwNP are typically treated with endoscopic sinus surgery and oral corticosteroids. However, they often experience recurrence; in addition, oral corticosteroids have several adverse effects. CRSwNP is an important factor influencing asthma control, and total control of both CRSwNP and asthma is important for treatment. Dupilumab and mepolizumab, which are anti-interleukin (IL)-4R and anti-IL-5 monoclonal antibodies, respectively, have been approved for the treatment of severe asthma and CRSwNP. Here, we discuss the successful treatment of a patient with severe asthma comorbid with CRSwNP after switching from dupilumab and mepolizumab to tezepelumab. The patient was initially treated with high-dose inhaled corticosteroids/long-acting β2-agonist/long-acting muscarinic antagonist treatment, without success. Treatment with dupilumab improved asthma and CRSwNP; however, it later induced hypereosinophilia with exacerbated asthma. Although subsequent treatment with mepolizumab improved asthma, the nasal symptoms recurred. After attempting dupilumab treatment again, the nasal symptoms improved; however, the asthma symptoms worsened parallel with an increased eosinophil count. Finally, the antithymic stromal lymphopoietin monoclonal antibody tezepelumab, was selected for treatment; the worsening asthma symptoms then improved with the control of CRSwNP. This report illustrates the potential utility of tezepelumab for the treatment of asthma and CRSwNP. Tezepelumab therapy may enhance total control of comorbidities of both the upper and lower airways. Further studies are required to identify effective therapies for asthma and CRSwNP.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is often associated with asthma. This combination aggravates the course of both conditions, including the frequency and severity of asthma and CRSwNP exacerbations. Currently, the main strategy in the treatment of severe asthma is the use of biologicals, which may also impact CRSwNP symptoms, considering the similarity of pathogenic mechanisms of these diseases. The aim of our study was to evaluate the impact of biological therapy on CRSwNP in combination with severe asthma. Methods. 49 patients with CRSwNP and severe asthma were included in a single-center prospective cohort study. Patients were divided into 4 groups: dupilumab (n = 20), benralizumab (n = 15), mepolizumab (n = 7), and omalizumab (n = 7). Patients received the biologicals for at least 12 months (min – 12.0 months; max – 52.2 months). Asthma control (ACT, FEV1, the number of asthma exacerbations) and CRSwNP control (SNOT-22, the number of nasal and sinus surgeries) were evaluated at baseline and during treatment. The safety of therapy was assessed by the examination results and the reported adverse events. Results. We observed statistically significant improvements in asthma control, respiratory function, and a decrease in the number of asthma exacerbations with the use of biologicals in all groups. However, there were no statistically significant differences between the groups (p &gt; 0.05). As for CRSwNP, we found the statistically significant improvements in symptoms (ΔSNOT-22 – (–67,3) ± 23,7, p &lt; 0,001; (–26,1) ± 24,6, p &lt; 0,001; (–34,0) ± 23,5, p = 0,016; (–35,1) ± 25,1, p = 0,025) and a decrease in the number of surgeries after therapy (Δ number of surgeries – (–5,2) ± 8,6, p &lt; 0,001; (–3,7) ± 3,3, p = 0,002; (–3,6) ± 2,4, p = 0,036; (–1,6) ± 1,4, p = 0,010). in all groups. At the same time, dupilumab showed a greater improvement of CRSwNP control according to the SNOT-22 questionnaire than benralizumab (p = 0.001) and mepolizumab (p = 0.034). Conclusion. Biologicals currently used to treat severe asthma have a beneficial effect on concomitant CRSwNP. However, not all biologicals are characterized by an effect on the processes of polyposis tissue remodeling and formation. Our study confirms the relevance of searching for other potential targets for the development of the new biologicals to address the identified clinical needs.

Chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma often coexist and thus treating both with one intervention is an attractive strategy. To prospectively evaluate whether treatment with the monoclonal antibody against IgE Omalizumab for severe allergic asthma also effectively treats co-existent CRSwNP. SNOT-22 and the ACQ-7 scores were recorded at 4 and 16 weeks of treatment in a cohort of patients with both CRSwNP and severe refractory allergic asthma treated with Omalizumab (n=13) according to UK guidelines for their severe asthma. SNOT-22 in a surgery only treated CRSwNP with asthma group (n=24) was compared. Rapid improvement was seen at 4 weeks and 16 weeks of treatment in both CRSwNP and asthma control. The improvement in CRSwNP with Omalizumab was similar to that seen in a group of patients who received upper airway surgery. Omalizumab treatment for severe allergic asthma also improves co-existent CRSwNP. Further clinical studies of current and emerging biological agents for severe asthma should include upper airway outcomes. These agents may be effective for severe CRSwNP and comparative studies with surgery are warranted.

Chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma often coexist and thus treating both with one intervention is an attractive strategy. To prospectively evaluate whether treatment with the monoclonal antibody against IgE Omalizumab for severe allergic asthma also effectively treats co-existent CRSwNP. SNOT-22 and the ACQ-7 scores were recorded at 4 and 16 weeks of treatment in a cohort of patients with both CRSwNP and severe refractory allergic asthma treated with Omalizumab (n=13) according to UK guidelines for their severe asthma. SNOT-22 in a surgery only treated CRSwNP with asthma group (n=24) was compared. Rapid improvement was seen at 4 weeks and 16 weeks of treatment in both CRSwNP and asthma control. The improvement in CRSwNP with Omalizumab was similar to that seen in a group of patients who received upper airway surgery. Omalizumab treatment for severe allergic asthma also improves co-existent CRSwNP. Further clinical studies of current and emerging biological agents for severe asthma should include upper airway outcomes. These agents may be effective for severe CRSwNP and comparative studies with surgery are warranted.