Biologic Therapy for Chronic Rhinosinusitis with Nasal Polyps: Case Analysis and Proposal of a Qualification Scheme.

Rapid and sustained effects of dupilumab in severe chronic rhinosinusitis with nasal polyps.

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

BackgroundAbout one‐tenth of patients with difficult‐to‐treat chronic rhinosinusitis with nasal polyps (CRSwNP) have comorbid non‐steroidal anti‐inflammatory drug‐exacerbated respiratory disease (NSAID‐ERD). Dupilumab, a fully human monoclonal antibody that blocks the shared interleukin (IL)‐4/IL‐13 receptor component, is an approved add‐on treatment in severe CRSwNP. This post hoc analysis evaluated dupilumab efficacy and safety in patients with CRSwNP with/without NSAID‐ERD.MethodsData were pooled from the phase 3 SINUS‐24 and SINUS‐52 studies in adults with uncontrolled severe CRSwNP who received dupilumab 300 mg or placebo every 2 weeks. CRSwNP, nasal airflow, lung function, and asthma control outcomes at Week 24 were evaluated, and treatment–subgroup interactions were assessed for patients with and without NSAID‐ERD.ResultsOf 724 patients, 204 (28.2%) had a diagnosis of NSAID‐ERD. At Week 24, least squares mean treatment differences demonstrated significant improvements in nasal polyp score, nasal congestion (NC), Lund–Mackay computed tomography, 22‐item Sinonasal Outcome Test (SNOT‐22), Total Symptom Score (TSS), rhinosinusitis severity visual analog scale, peak nasal inspiratory flow (PNIF), six‐item Asthma Control Questionnaire score, and improvement in smell with dupilumab versus placebo (all p < .0001) in patients with NSAID‐ERD. Treatment comparisons demonstrated significantly greater improvements with dupilumab in patients with versus without NSAID‐ERD for NC (p = .0044), SNOT‐22 (p = .0313), TSS (p = .0425), and PNIF (p = .0123).ConclusionsIn patients with uncontrolled severe CRSwNP, dupilumab significantly improved objective measures and patient‐reported symptoms to a greater extent in the presence of comorbid NSAID‐ERD than without. Dupilumab was well tolerated in patients with/without NSAID‐ERD.

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

Patients with Non-steroidal anti-inflammatory drugs (NSAID)-Exacerbated Respiratory Disease (N-ERD) can suffer from difficult-to-treat primary diffuse type 2 chronic rhinosinusitis with nasal polyps (CRSwNP). This study evaluates dupilumab effectiveness and dose tapering in CRSwNP patients with N-ERD compared to those without. A real-world prospective cohort with CRSwNP patients, with N-ERD or without (CRSwNP-NOS; not otherwise specified), aged ≥ 18 treated with dupilumab 300 mg subcutaneously every 2 weeks. In case of clinical control, the interdose interval was prolonged every 6 months with steps of 2 weeks. (Clinical) data were collected at baseline, 24 weeks, and 2 years of treatment. Most baseline characteristics, including Nasal Polyp Score (NPS), Sino-Nasal Outcome Test-22 (SNOT-22), and Sniffin' sticks-12 test (SSIT-12) were comparable between groups (N-ERD n = 105, CRSwNP-NOS n = 293). There was a higher prevalence (91.5% vs. 71.1%, p < 0.001) but comparable control of asthma in N-ERD patients (asthma control test [ACT]: N-ERD 66.7% less controlled/uncontrolled vs. CRSwNP-NOS 58.3%, p = 0.21). All outcomes improved significantly with dupilumab treatment at 24 weeks and remained improved after 2 years, without intergroup differences (median scores at 24 weeks for N-ERD patients vs. CRSwNP-NOS, respectively: NPS: 2 vs. 1, p = 0.65; SNOT-22: 18 vs. 19, p = 0.27; SSIT-12: 7 vs. 8, p = 0.02; ACT: 21 vs. 22, p = 0.11). Dose tapering was possible in the majority of patients, with almost half at an 8-12 weeks interval in both groups after 2 years. Dupilumab shows comparable effectiveness and taper feasibility between CRSwNP N-ERD patients and CRSwNP-NOS patients.

Background: Non-steroidal anti-inflammatory drugs (NSAIDs)-exacerbated respiratory disease (N-ERD) complicates the clinical course of chronic rhinosinusitis with nasal polyps (CRSwNP) and severe asthma. We aimed to determine the detection rate of NERD in patients with CRSwNP, asthma, and history of NSAID intolerance using nasal challenge with acetylsalicylic acid (ASA) and the relationship between the severities of response to ASA challenges and the grade of N-ERD. Materials and methods: Three groups of patients were included: CRSwNP with asthma and clinical history of analgesics intolerance (CRSwNP-AAI n = 18), CRSwNP with asthma but without a clinical history of analgesics intolerance (CRSwNP-A n = 20), and CRSwNP without asthma or analgesics intolerance (n = 18). All subjects were challenged nasally with 16 mg ASA and monitored with active anterior rhinomanometry. Rhinological (nasal polyp score), pulmonary (spirometry, Asthma Control Test (ACT), and asthma treatment), and psychometric questionnaire scores were recorded and correlated with rhinomanometric data following nasal challenges (flow depressions and symptom scores). Results: Nasal ASA challenge detected N-ERD in 96.7% of CRSwNP-AAI patients and 45% of CRSwNP-A patients. No N-ERD was seen in the CRSwNP group. The control grade of asthma measured with ACT scores was significantly lower in the groups CRSwNP-AAI (MV 18.22) and CRSwNP-A (MV 19.75) when compared to the CRSwNP group (MV 24.39) (p = 0.000). In the CRSwNP-AAI group, 11 patients had uncontrolled asthma (61%), and in the CRSwNP-A group, 9 patients had uncontrolled asthma (45%). No correlation was found between rhinology and pulmonary parameters, nasal symptoms, and the severity of nasal ASA challenges. Specific reactions were detectable under the therapy of prednisolone and omalizumab. Conclusion: N-ERD might not always be detected by screening a patient’s medical history. Nasal ASA challenges are recommended in patients with CRSwNP and asthma. The nasal challenge with ASA positively confirms the N-ERD diagnosis. Moreover, N-ERD is a differential diagnosis in patients with severe asthma with the need for prednisolone or omalizumab therapy. The severity of the reaction to the ASA challenge in controlled and uncontrolled asthma patients is independent of the grade of N-ERD.

Biologics and the treatment of chronic rhinosinusitis

Biologics for chronic rhinosinusitis with nasal polyps (CRSwNP)

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

The effectiveness of biologics in chronic rhinosinusitis with nasal polyps (CRSwNP) is well-established. However, real-world experience on the effectiveness of transitioning between two monoclonal antibodies is scarce. Therefore, we aimed to analyze the safety and efficacy of antibody switching in treatment of chronic rhinosinusitis. All patients with CRSwNP or nonsteroidal anti-inflammatory drugs-exacerbated respiratory disease (N-ERD) requiring a switch between biologics were retrospectively studied. Analysis included changes in polyp size, quality of life parameters, asthma control, and side effects. Out of 195 patients treated with biologics for CRSwNP or N-ERD in our center, 23 (11.8%) required transition to a different monoclonal antibody. The majority switched from omalizumab to dupilumab (17/23, 73.9%), mostly due to inadequate symptom control. Nine out of these 17 patients (52.9%) were switched without a washout period. All patients showed significant improvement in nasal polyp score, asthma control test and sino-nasal outcome test-22 after changing to dupilumab. Keratoconjunctivitis sicca was the side-effect (4.3%) reported after the switch from omalizumab to dupilumab, which lead to termination of therapy in one patient. Due to limited sample size, other antibody transitions were reported in a descriptive manner. The transition to dupilumab is an effective option in patients with inadequate treatment response or side-effects of omalizumab in nasal polyposis. Our preliminary results indicate that a wash-out period may not be necessary when switching between biologics, however, these findings require further investigations. Other monoclonal antibody transitions also show promising results, but warrant validations in larger cohorts due to small patient samples in our study.

Nasal IL-25 predicts the response to oral corticosteroids in chronic rhinosinusitis with nasal polyps

ObjectivesThe aim was to compare the control of chronic rhinosinusitis with nasal polyps (CRSwNP) after endoscopic sinus surgery (ESS), in patients with/without nonsteroidal anti-inflammatory drug exacerbated respiratory disease (NERD).Study Desing: A retrospective hospital-based sample of CRSwNP patients with/without NERD with follow-up.SettingTertiary rhinology centers.MethodsElectronic patient record data from 116 CRSwNP patients (46 with NERD and 70 without NERD) undergoing ESS during 2001–17 were studied. Mean follow-up time was 9.9 years (range 1.1–15.3). Endpoints reflecting uncontrolled CRSwNP were revision ESS, and need for rescue/advanced therapy (e.g. antibiotics, oral corticosteroids and/or biological therapy) during follow-up. NERD was variable of interest and gender, age, asthma, allergic rhinitis (AR), smoking, Lund-Mackay (LM) score of sinus computed tomography scans previous ESS and baseline total ethmoidectomy were used as covariates.ResultsTwenty-one (49.7%) NERD patients and 18 (25.7%) non-NERD patients underwent revision ESS within a mean ± SD of 4.3 ± 2.8 and 3.7 ± 2.6 years, respectively (p = .013, by Logrank test). In Cox´s regression models, NERD, female gender, young age, asthma, AR, previous ESS, and lack of total ethmoidectomy were associated with revision-ESS. In adjusted model, only the total ethmoidectomy predicted revision-free survival. In adjusted logistic regression model, there was an insignificant trend that NERD and LM score were associated with the need for rescue/advanced therapy in the follow-up.ConclusionsPatients with NERD had higher risk of uncontrolled CRSwNP than patient group without NERD, as measured by revision ESS and/or need for rescue/advanced therapy in the follow-up. In addition, baseline total ethmoidectomy was associated with revision-free survival.

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

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Objective: The upcoming introduction of mepolizumab represents a promising treatment for chronic rhinosinusitis with nasal polyps (CRSwNP). The present study aimed to evaluate the effectiveness of mepolizumab on sinonasal outcomes of comorbid CRSwNP and severe asthma in a real-life setting. The primary endpoint was to evaluate changes in the SinoNasal Outcome Test (SNOT)-22 score, Nasal Polyp (NP) score, and blood eosinophil count during a 12-month treatment with mepolizumab. Secondary endpoints were to quantify mepolizumab’s effects on the mentioned parameters, identify clinical variables influencing the degree of response to treatment, and portray responder and nonresponder patients. Methods: A multicentric retrospective no-profit observational study on severe asthmatic patients, treated with mepolizumab, and comorbid CRSwNP was conducted. All patients were followed for at least 12 months. SNOT-22 score, NP score, and blood eosinophil count (and other CRS-specific variables) were collected at baseline and after 12 months. Results: Forty-three patients were included. A statistically significant reduction was observed for SNOT-22 score (mean t0 SNOT-22 54.8 ± 25.9; mean t12 SNOT-22 31.5 ± 21.3, p < 0.0001), NP score (median t0 NPS 3 (IQR 3); median t12 NPS 2 (IQR 4), p < 0.0001), and blood eosinophil count (mean t0 blood eosinophils 804.7 ± 461.5 cell/µL; mean t12 blood eosinophils 107.5 ± 104.6 cell/µL, p < 0.0001) after 12 months of treatment. Twenty patients (47%) gained improvement both in clinical and endoscopic outcome. Mepolizumab responder patients presented a t0 SNOT-22 significantly higher than nonresponders (p = 0.0011). Conclusions: Mepolizumab improved CRSwNP outcomes in a population of severe asthmatic patients. No clinical feature emerged to outline the profile of a “typical” responder patient, except for baseline SNOT-22 score, which seemed to affect the response to treatment. Further studies would be necessary to supplement these preliminary evaluations.