Biological Treatments and Surgical Interventions for Chronic Rhinosinusitis with Nasal Polyps: A Systematic Review of Clinical Outcomes

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

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

Biologics for chronic rhinosinusitis with nasal polyps (CRSwNP)

Outside of SINUS-24 (A Controlled Clinical Study of Dupilumab in Patients With Bilateral Nasal Polyps) and SINUS-52 (Controlled Clinical Study of Dupilumab in Patients With Nasal Polyps), there are limited data on the efficacy of dupilumab in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). The objective was to compare dupilumab with functional endoscopic sinus surgery (FESS) in patients with CRSwNP by assessing the change in nasal polyp and Sino-Nasal Outcome Test (SNOT-22) scores postintervention. A retrospective matched cohort study compared 54 patients who had CRSwNP treated with dupilumab with 54 patients who had CRSwNP treated with FESS; both cohorts were treated with topical corticosteroids. The primary end points were change in nasal polyp score and overall SNOT-22 score. Secondary end points were change in SNOT-22 domain scores and SNOT-22 olfaction score. Patients who underwent FESS had a greater improvement in nasal polyp score (5.18±2.01) compared with patients treated with dupilumab (4.27±1.98, p=0.02). There was no significant difference in terms of the change in overall SNOT-22 score. Patients treated with dupilumab had greater improvement in the extranasal rhinologic SNOT-22 domain scores (4.87±3.91) compared with patients treated with FESS (2.93±4.32, p=0.02). There was a greater improvement in the SNOT-22 olfaction scores for patients treated with dupilumab (2.35±2.17) compared with patients treated with FESS (1.48±2.24, p=0.04). Patients taking dupilumab were followed on average for 12.20months and patients treated with FESS were followed for 17.90months. Overall, both therapies are effective at reducing symptoms in patients with CRSwNP according to SNOT-22. Patients treated with dupilumab reported improved olfaction and decreased cough, postnasal drainage, and thick nasal drainage as compared with patients treated with FESS, while patients treated with FESS had a greater reduction in polyp burden.

Biologics and the treatment of chronic rhinosinusitis

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic upper airway disease that may involve different inflammatory endotypes, although in Western populations it is most commonly associated with type 2 inflammation. CRSwNP has a significant impact on the patient's quality of life. The recommended appropriate medical therapy is effective in controlling CRSwNP symptoms in many patients; however, a subset continues to exhibit persistent type 2 inflammation, evidenced by recurrent nasal polyps, elevated eosinophil counts, or the need for systemic corticosteroids or surgery. Monoclonal antibodies have recently become a novel and personalized treatment that can help refractory patients restore disease control. Objective: The present study aims to evaluate the effectiveness of mepolizumab in real-world settings in a diverse patient population, focusing on assessing the impact of this therapy on patient-reported outcomes after six months of treatment. Methods: This is a multicenter, observational study of CRSwNP patients treated with mepolizumab carried out in five hospitals located in Spain. Adult patients with a diagnosis of uncontrolled CRSwNP were included in the study. The change in the nasal polyp score (NPS) was the main clinical endpoint. Changes in the Sinonasal Outcome Test (SNOT-22), nasal congestion and smell impairment visual analogue scale scores, and blood and nasal polyp tissue eosinophil counts were among other endpoints included. Results: In total, 47 patients were included, and 91% were asthmatic. The nasal polyp score (0-8) was reduced significantly in the cohort (mean change: -2.56, p < 0.0001). The mean SNOT-22 score improved 25.29 points. Nasal congestion (-3.57, p < 0.0001) and smell impairment (-4.0, p < 0.0001) visual analog scale scores (0-10) showed a significant improvement. Blood and tissue eosinophil median counts showed significant reductions versus baseline of 86% and 26%, respectively. Among those patients with asthma, the asthma control test score achieved a median value of 24 points. Conclusions: This study provides real-world evidence supporting the effectiveness of mepolizumab in managing CRSwNP in patients with features suggestive of type 2 inflammation. The observed improvements in patient-reported outcomes, nasal polyp burden, and asthma control suggest that mepolizumab may be a valuable therapeutic option for this patient population.

BackgroundPatients with chronic rhinosinusitis with nasal polyps (CRSwNP) often have atopic comorbidities, including elevated IgE levels and comorbid asthma. Omalizumab, an IgE monoclonal antibody, is an effective treatment for CRSwNP, but the impact of allergy or asthma status on response to omalizumab in patients with CRSwNP has not been well studied. ObjectiveTo evaluate the impact of allergy and asthma status on omalizumab treatment in patients with CRSwNP, this posthoc exploratory analysis assessed sinonasal outcomes from subgroups of patients included in POLYP 1 and POLYP 2 and the open-label extension (OLE) trials. MethodsPatients (N = 249) were grouped by the presence/absence of comorbid allergy (≥ 1 physician-reported allergic rhinitis, allergic sinusitis, food allergy, or atopic dermatitis), presence/absence of comorbid asthma, baseline serum total IgE (≥ 150 or <150 IU/mL), and baseline blood eosinophil levels (>300 or ≤ 300 cells/µL). Sinonasal outcomes were the nasal polyps score, nasal congestion score, and sino-nasal outcome test-22. ResultsDuring POLYP 1 and POLYP 2 and the OLE, omalizumab treatment improved the nasal polyps score, nasal congestion score, and sino-nasal outcome test-22 score in patients with/without physician-reported allergic comorbidities, with/without asthma, with higher/lower total IgE levels, and with higher/lower blood eosinophil counts. In the OLE, the pattern of improvement was similar in patients who continued or switched to omalizumab. ConclusionIn patients with CRSwNP, omalizumab improved sinonasal outcomes independent of allergic status, which suggests that a wide range of patients with different endotypes and phenotypes of CRSwNP may benefit from omalizumab treatment. Trial RegistrationClinicaltrials.gov Identifier: NCT03280550, NCT03280537, NCT03478930.

Eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) is a refractory subtype of chronic rhinosinusitis with nasal polyps (CRSwNP), with clinical characteristics differing from those of non-ECRSwNP. We aimed to explore the predictive value of clinical characteristics, including medical history, symptoms, and signs, prior to ECRSwNP diagnosis, and to develop a nomogram for use in clinical practice. A total of 502 patients with CRSwNP were enrolled. Based on the degree of eosinophilic infiltration in nasal polyps (NPs), patients were classified as ECRSwNP or non-ECRSwNP group. Participants' demographic characteristics, asthma history, severity of nasal symptoms (nasal obstruction, rhinorrhea, hyposmia, and facial pain/headache) according to the visual analog scale, and nasal polyp scores based on polyp scoring system were recorded. Logistic regression analysis was performed to screen for independent risk factors, and a model nomogram was constructed. The percentage of asthmatic patients and the hyposmia, rhinorrhea, and total nasal symptom scores were significantly higher in ECRSwNP patients than that in non-ECRSwNP patients. The nasal polyp score was lower in the eosinophilic group than that in the non-eosinophilic group. Logistic regression analysis revealed that asthma history and hyposmia, rhinorrhea and nasal polyp scores were independent predictors of ECRSwNP. A nomogram consisting of these four independent risk factors was constructed, and its C-index was 0.808 (95% CI, 0.771 to 0.846). The nomogram based on asthma history and olfactory, rhinorrhea, and nasal polyp scores could help predict ECRSwNP, providing a simple, fast, and practical way to distinguish ECRSwNP from non-ECRSwNP cases in clinical practice.

Impact of residual ethmoidal laminae on dupilumab efficacy following endoscopic sinus surgery in patients with chronic rhinosinusitis: A STROBE analysis.

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

Efficacy of buffered hypertonic seawater in different phenotypes of chronic rhinosinusitis with nasal polyps after endoscopic sinus surgery: a randomized double-blind study.

<b>Background:</b> Chronic rhinosinusitis with nasal polyps (CRSwNP) is a high-prevalence comorbidity in severe eosinophilic asthma (SEA) and could significantly contribute to the loss of asthma control. Since CRSwNP and SEA share a T2-mediated mechanism, the use of some anti-asthma monoclonal antibodies has recently been extended to CRSwNP. While dupilumab and omalizumab are already approved for CRSwNP, mepolizumab and benralizumab are still under investigation. <b>Aim:</b> To evaluate, in a real life setting, benralizumab efficacy on SEA and CRSwNP in patients affected by both pathologies. <b>Methods:</b> We enrolled 18 patients with SEA and CRSwNP. Spirometry, FeNO test, Asthma Control Test (ACT), fiber laryngoscopy with Nasal Polyp Score (NPS), nasal cytology, Sino-Nasal Outcome Test 22 (SNOT 22) were performed at baseline (T0) and at one year after benralizumab initiation (T1). The continuous oral corticosteroid therapy (OCS), the number of year exacerbations and the need for NP surgery were also evaluated. We compared T1 with T0. Statistical significance: p&lt;0.05. <b>Results:</b> At T1 ACT underwent a sensible increase (p &lt; 0.05) and FeNO values (p &lt; 0.05), year exacerbation number (p &lt; 0.05) and mean OCS dosage (p &lt; 0.01) experienced a significative reduction. Regarding CRSwNP, in T1 patients showed a marked reduction of&nbsp;SNOT-22 (p &lt; 0.01), NPS (p &lt; 0.05), nasal eosinophilia (p &lt; 0.01) and neutrophilia (p &lt; 0.05). Only 1 patient required post benralizumab NP surgery. <b>Conclusions:</b> Our study demonstrates the efficacy of benralizumab not only on SEA but also on clinic, volumetric and cytologic traits of NP, confirming that patients affected by both SEA and CRSwNP may benefit from benralizumab.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease with variable underlying pathophysiologies. Numerous patient factors have been linked to differences in disease severity, control, and response to treatment, including asthma status, aspirin sensitivity, previous sinonasal surgery, and blood eosinophil levels. The present study examines the efficacy of the anti-immunoglobulin E therapy, omalizumab, versus placebo in patients with CRSwNP from the replicate POLYP 1 (NCT03280550) and POLYP 2 (NCT03280537) trials, grouped by inherent patient characteristics to determine the response to therapy. Patients in prespecified subgroups from POLYP 1 and POLYP 2 (studies pooled for analysis) were examined. Subgroups included blood eosinophil count at baseline (>300 or ≤300cells/μL), previous sinonasal surgery (yes or no), asthma status (yes or no), and aspirin sensitivity status (yes or no). Subgroups were examined for subgroup-specific adjusted mean difference (95% confidence interval [CI]) (omalizumab-placebo) in change from baseline at week 24 in Nasal Congestion Score (NCS), Nasal Polyp Score (NPS), Sino-Nasal Outcome Test-22 (SNOT-22), Total Nasal Symptom Score (TNSS), and University of Pennsylvania Smell Identification Test (UPSIT). Adjusted mean difference (95% CI) (omalizumab-placebo) in NCS, NPS, SNOT-22, TNSS, and UPSIT change from baseline at week 24 consistently favored omalizumab treatment over placebo in patients with blood eosinophil count >300 and ≤300cells/μL, with or without previous sinonasal surgery, asthma, and aspirin sensitivity. Together, these data suggest broad efficacy of omalizumab across clinical and patient-reported outcomes in patients with CRSwNP, independent of the underlying patient factors examined, including those with high eosinophil levels and those who have undergone previous surgery, which are associated with high recurrence. ClinicalTrials.gov identifiers: POLYP 1: ClinicalTrials.gov identifier NCT03280550 (https://clinicaltrials.gov/ct2/show/NCT03280550); POLYP 2: ClinicalTrials.gov identifier NCT03280537 (https://clinicaltrials.gov/ct2/show/NCT03280537).

ABSTRACTBackgroundDirect comparative efficacy data for biologics in chronic rhinosinusitis with nasal polyps (CRSwNP) remain limited, particularly for novel agents like tezepelumab, underscoring the need to identify optimal therapies for precision management.ObjectiveTo rank the comparative efficacy and safety of dupilumab, tezepelumab, omalizumab, and mepolizumab versus placebo for CRSwNP using network meta‐analysis.MethodsPubMed, Embase, Web of Science, and Cochrane Library were searched from inception through April 1, 2025. Randomized controlled trials (RCTs) in adults with CRSwNP comparing biologics against placebo were eligible. PRISMA‐NMA guidelines were followed. GRADE methodology was employed for evidence certainty assessment. Two investigators independently extracted data. Fixed‐effect model network meta‐analysis was performed, with treatments ranked via surface under the cumulative ranking curve (SUCRA). The primary outcomes were Nasal Polyp Score (NPS) and safety metrics (proportion of participants with ≥ 1 adverse event). Secondary outcomes included Sino‐Nasal Outcome Test‐22 (SNOT‐22), University of Pennsylvania Smell Identification Test (UPSIT), and Nasal Congestion Score (NCS).ResultsThirteen RCTs (n = 2304) evaluating four biologics versus placebo were included. Compared to placebo, NPS was significantly improved by dupilumab (WMD: −2.16, 95% CI [−2.44, −1.89]), omalizumab (WMD: 1.25, 95% CI [−1.52, −0.97]), mepolizumab (WMD: 0.90, 95% CI [−1.19, −0.62]), and tezepelumab (WMD: −1.50, 95% CI [−1.81, −1.19]). Dupilumab ranked first in efficacy outcomes (NPS, SNOT‐22, UPSIT, and NCS, SUCRA ≥ 0.900, respectively). Tezepelumab ranked second in NPS (SUCRA: 0.720) and UPSIT (SUCRA: 0.749), while omalizumab ranked first in safety (SUCRA of adverse events: 0.064). GRADE assessments indicated that the certainty of the evidence was predominantly high for these key efficacy comparisons.ConclusionsDupilumab demonstrated the highest efficacy and safety profile. Tezepelumab showed comparable efficacy in NPS with omalizumab.

BackgroundThe alignment between objective scores and patient-reported outcome measures (PROMs) is underexplored. This study aimed to assess changes in Nasal Polyp Score (NPS) and Sino-Nasal Outcome Test (SNOT) scores in chronic rhinosinusitis with nasal polyps (CRSwNP) patients undergoing dupilumab treatment and explore correlations between these scores.MethodsCRSwNP patients received dupilumab therapy for six months. SNOT-20 German Adapted Version (GAV)/SNOT-22 scores were assessed weekly, and NPS was measured at baseline and after one, three, and six months. Correlations were analyzed using Spearman’s rank correlation and regression analysis.Results69 patients were included. After one, three and six months of dupilumab therapy, SNOT and NPS scores improved significantly. Correlation analysis of SNOT and NPS showed significant correlations only within the nasal subscores, along with a weak trend for SNOT-20. Absolute changes over time lacked significance. However, correlation analysis revealed significant associations between relative changes in SNOT score and NPS, irrespective of timing, and when stratified by baseline NPS of 8, 6, and 4 (r = -0.54, p = 0.01; r = -0.44, p < 0.001; r = -0.7, p < 0.001). This was supported by linear regression modeling, suggesting potential predictive capability of NPS reduction on relative SNOT score improvement.ConclusionDupilumab therapy significantly improved subjective and objective CRSwNP scores, exhibiting weak correlations in absolute values for nasal subscores. Furthermore, evidence indicated a correlation between relative changes in SNOT score and NPS, substantiated by predictive capability. This might be due to subjective perception variability, highlighting the suitability of relative change correlation analysis.