Multidimensional Impact of Dupilumab on Chronic Rhinosinusitis with Nasal Polyps: A Complete Health Technology Assessment of Clinical, Economic, and Non-Clinical Domains.

Chronic RhinoSinusitis with Nasal Polyps (CRSwNP) represents a condition mainly caused by the type 2 inflammation presence and marked by the existence of polyps within the nasal and paranasal sinuses. The standard of care includes intranasal steroids, additional burst of systemic steroids, if needed, and surgery. However, recurrence is common, especially among patients with comorbid type 2 inflammatory diseases. Recently, biological drugs, addressing the underlying cause of the disease, have been approved in Italy (dupilumab, omalizumab, and mepolizumab). A Health Technology Assessment was conducted to define multidimensional impact, assuming Italian NHS perspective and a 12-month time horizon. The EUnetHTA Core Model was deployed, using the following methods to analyze the domains: (i) literature evidence; (ii) administration of semi-structured questionnaires to 17 healthcare professionals; (iii) health economics tools to define the economic sustainability for the system. Evidence from NMA and ITC showed a more favorable safety profile and better efficacy for dupilumab compared with alternative biologics. All the analyses, synthesizing cost and efficacy measures, showed that dupilumab is the preferable alternative. Specifically, the cost per responder analysis for dupilumab, exhibiting a 67.0% response rate at Week 52, is notably economical at 14,209EUR per responder. This presents a more economical profile compared with the cost per responder for omalizumab (36.2% response rate) at 24,999EUR and mepolizumab (28.5% response rate) at 31,863EUR. These results underscore dupilumab's potential, not merely in terms of clinical outcomes, but also in terms of economic rationality, thereby solidifying its status as a valid and preferrable alternative in the management of CRSwNP, in the context of the Italian NHS.

Effectiveness and rapidity on olfatory fuction recovery in CRS patients treated with Dupilumab: a real life prospective controlled study.

BACKGROUND: Recovery of olfactory function plays a prominent role in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). While rates and timing of such recovery vary, monoclonal antibodies might yield better results which we aimed at evaluating with this study. METHODOLOGY: A prospective controlled study was conducted at our tertiary otolaryngological center from April 1, 2021, to October 1, 2022, in CRSwNP patients. We included an active group (n = 60 patients) performing dupilumab treatment and a control group (n = 60 patients) treated with intranasal and oral corticosteroids. Primary endpoints were changes in smell visual analogical scale (VAS) and SS-I (Sniffin' Sticks-identification) scores, and olfactory recovery rate. The secondary efficacy endpoints were nasal obstruction, rhinorrhea, headache, SNOT-22, and nasal congestion score (NCS). RESULTS: At 6 months, the active group demonstrated better outcomes than control in SS-I scores (10.23 ± 4.21 vs.3.68 ± 3.08; p < 0.001). No significant differences were found in blood eosinophil count, SNOT-22, and NPS (p > 0.05 for all). Olfactory function in the treatment arm improved in 86.66% (52/60 cases), with normal scores in 48.33% (29/60), while the control group reported a lower recovery rate (3/60; 5%), with no normal olfaction cases. Log-rank comparison for Kaplan-Meier functions was statistically significant (p < 0.001), but no differences were found in subanalysis in the active group based on blood eosinophil count at baseline, SNOT-22, and NPS scores. CONCLUSIONS: Patients who receive dupilumab treatment may experience a faster recovery of olfactory function compared to those receiving corticosteroid therapy. This result would be maintained regardless of the severity of type 2 CRSwNP inflammation, the volume of the polyps, or the patient's subjective symptomatology.

Dupilumab in chronic rhinosinusitis with nasal polyps: Real life data in a multicentric Sicilian experience.

OBJECTIVE: This study aimed to evaluate the effectiveness and safety of dupilumab during the first year of treatment in a real-life setting, focusing on improvement in nasal polyp score (NPS) as well as specific symptoms, quality of life and olfactory function. METHODOLOGY/PRINCIPAL: A multicentric observational cohort study was carried out. A total of 170 patients were enrolled in the Otorhinolaryngology Unit of the three University Hospitals and considered for dupilumab therapy. All recorder characteristics were age (at the first dupilumab application visit), sex, smoke habits, previous local and systemic corticosteroid therapy, history of endoscopic sinus surgery, number of previous endoscopic sinus surgery, concomitant asthma, history of an allergic condition, immunoglobulin E (IgE), allergy to nonsteroidal anti-inflammatory drugs (NSAIDs), Aspirin Exacerbated Respiratory Disease (AERD), other comorbidities associated, blood eosinophils, nasal polyp score, sinonasal outcome test 22 (SNOT 22), sniffin' stick test, the start date of dupilumab therapy and number of doses of dupilumab and eventually, Dupilumab's adverse events related to administration. The Wilcoxon test for dependent samples was performed to compare variables. Statistical significance was assumed for p values < 0.05. RESULTS: A statistically significant reduction in SNOT-22 and NPS was shown at the 6th and 12th month compared to baseline values (p < 0.001 for both comparisons). A statistically significant increase value at the Sniffin' sticks test was shown in the 6th and 12th month compared to baseline values (p < 0.001 for both comparisons). At the 12-month follow-up, according to EUFOREA indications, all patients were considered to remain in treatment with dupilumab and continued the treatment because of a reduced NPS, improved quality of life and a reduced need for system corticosteroids. Dupilumab seemed to be well tolerated by all patients. Any adverse effect of the drug led to the quit of biological treatment. CONCLUSIONS: This multi-centric real-life study supported the effectiveness of dupilumab as an add-on therapy to intranasal corticosteroids in patients with severe uncontrolled CRSwNP in improvement of quality of life, severity of symptoms, polyp size reduction and smell function. Furthermore, our data support the safety profile of monoclonal therapy with dupilumab.

Sensibility, specificity, and accuracy of the Sinonasal Outcome Test 8 (SNOT-8) in patients with chronic rhinosinusitis (CRS): a cross-sectional cohort study.

PURPOSE: To analyze as the primary endpoint the accuracy, sensitivity, and specificity of the SNOT-22 assessing CRS severity and to compare the results with a version of the SNOT-8 obtained from the nasal domain items. METHODS: Data were obtained from a prospective multicenter controlled study of dupilumab in adults with moderate-severe CRSwNP. EQUATOR and STROBE network guidelines were adopted. A multivariate logistic regression model was used to evaluate the accuracy of the model with the full (SNOT-22) and reduced (SNOT-8) item set to predict the severity outcome. RESULTS: SNOT-22 demonstrated an AUC of 0.885 (95% CI 0.825, - 0.945), and sensitivity and specificity of 91.49% (83.92-96.25%) and 69.23% (48.21-85.67%), respectively. Interestingly, after stepwise items elimination good outcomes were reported for SNOT-8, with an AUC of 0.818 (95% CI 0.744-0.892), achieving a sensitivity of 93.51% (85.49-97.86%) and specificity of 57.14% (40.96-72.28%). CONCLUSION: Psychometric analyses support the accuracy, sensitivity, and specificity of the nasal domains of SNOT-22 to assess the impact on HRQoL in patients with CRSwNP.

When rhinosinusitis is not just rhinosinusitis: Clinical characteristics and phenotypes of patients with type 2 chronic rhinosinusitis with nasal polyps.

BACKGROUND AND AIM: Chronic rhinosinusitis (CRS) is a chronic and recurrent disease that negatively affects patients' quality of life. CRS has two main phenotypes: CRS with nasal polyps (CRSwNP) and CRS without polyps (CRSsNP). Minimal research has been conducted to study the variability in patients' characteristics. Therefore, we conducted this study to examine these differences. METHODS: A retrospective cohort study included patients with both CRSwNP and CRSsNP. Outcomes included symptom severity, radiographic severity, and number of sinus surgeries. Symptom severity was assessed using the Sino-nasal Outcome Test and the Lund-Mackay CT score was used to determine radiographic severity. Further subgroup analysis was done based on the presence or absence of comorbid asthma. RESULTS: A total of 110 and 106 patients were included in the CRSwNP and CRSsNP groups, respectively. The mean age in the CRSwNP and CRSsNP groups was 50.2 and 48.7, and the proportion of female patients was 40.9% and 58.5%, respectively. No significant difference in symptom severity was noted between CRSwNP and CRSsNP group (68.1±18.6 vs. 73.2±21.27; P=0.097), while the Lund-Mackay score was significantly lower in the CRSsNP group (7.4±2.3 vs. 11.9±3.6; P=0.016). Also, the number of surgeries was significantly lower in the CRSsNP group as compared to the CRSwNP group (P=0.023). Subgroup analysis revealed statistically significant differences between those with and without asthma in patients with CRSwNP in terms of Lund-Mackay scores and number of surgeries (P=0.038 and 0.043), respectively. However, no significant differences were noted in the CRSsNP group (P>0.05). CONCLUSIONS: There is a clear variability in the characteristics of patients with CRSsNP and CRSwNP. A similar difference was noted in the CRSwNP group when patients were stratified based on the presence of absence of asthma. This warrants further investigation of potential correlation with the prognosis and optimum treatment strategies of this patient population.

Influence of cigarette smoking on allergic rhinitis: a comparative study on smokers and non-smokers.

It has been described that exposure to tobacco smoke causes worsening of allergic rhinitis symptoms. Otherwise, some studies have demonstrated a negative association between cigarette smoke and allergic rhinitis (AR). Given this inconsistency, this study evaluated the quality of life and immuno-inflammatory parameters in current smokers and nonsmokers suffering from AR. A comparative cross-sectional study was conducted in patients who presented symptoms of AR. Patients were categorized into two groups: current smokers and non-smokers based on salivary cotinine measurements. Primary outcomes were the levels of immuno-inflammatory biomarkers (IgE, IL-4, IL-5, IL-13, IL-17, and IL-33) in serum and nasal lavage and the quality of life assessed by the Mini Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ). Secondary outcomes included salivary cotinine levels, and pulmonary function parameters, such as forced vital capacity (FVC), forced expiratory volume in 1s (FEV1), and FEV1/FVC ratio. Twenty-two patients per group were included in the analysis, with no significant difference regarding demographic characteristics. Statistically significant higher values in salivary cotinine levels (p<0.001) and lower lung function FEV1 (p=0.044) and FEV1/FVC (p=0.047) were found in smokers than in nonsmokers. Only serum IL-33 was significantly different in the 2 groups (p<0.001): smokers had higher values compared to non-smokers. There were no significant differences in MiniRQLQ parameters. Although cigarette smoking was not associated with more severe symptoms, smoking could be associated with increased risk of developing airway remodeling and decreased lung function in AR patients, thus appropriate treatment should be prescribed if smoke avoidance is unfeasible.