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:Chronic rhinosinusitis with nasal polyps (CRSwNP) is a predominantly type 2 inflammatory disease of the nasal and paranasal sinuses. Dupilumab is a monoclonal antibody that blocks the shared receptor component for interleukin-4 and interleukin-13, which are key and central drivers of type 2 inflammation. In clinical trials, dupilumab significantly improved objective and patient-reported measures of CRSwNP versus placebo and was well tolerated. Dupilumab is approved in the European Union, USA and Japan as add-on maintenance treatment for adults with inadequately controlled CRSwNP. There exists an important evidence gap between efficacy and effectiveness data for dupilumab in severe CRSwNP. In order to bridge this gap, the AROMA prospective global registry (ClinicalTrials.gov: NCT04959448) was established. AROMA will collect long-term data on the utilisation, effectiveness and safety of dupilumab for CRSwNP treatment in real-world clinical practice. AROMA will enrol approximately 1000 adults starting dupilumab for severe CRSwNP across 120 global sites. Baseline data will include patient demographics, medical/surgical history and presence of type 2 comorbidities. Effectiveness outcome assessments will include objective measures of CRSwNP assessed as part of routine clinical care and various patient-reported questionnaires. Treatment patterns, concomitant medications and long-term safety will also be recorded. Results from AROMA, the first prospective, real-world, global registry to characterise patients with severe CRSwNP starting dupilumab, will provide evidence on the real impact of dupilumab in patients with CRSwNP and complement the data from randomised clinical trials. The registry will also provide evidence on disease progression in patients with CRSwNP, including those with coexisting diseases.
| S-EPMC9703146 | biostudies-literature
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:ObjectivesTo evaluate within-patient symptom improvement in the dupilumab SINUS-24/-52 studies in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) (NCT02912468/NCT02898454).MethodsPatients received dupilumab 300 mg or placebo every 2 weeks for 24 (SINUS-24) or 52 weeks (SINUS-52) on background intranasal corticosteroids. Patients daily reported symptoms of nasal congestion (NC), loss of smell (LoS) and rhinorrhoea on a scale of 0-3 (0 - no symptoms, 1 - mild, 2 - moderate, 3 - severe symptoms). The proportions of patients with moderate-to-severe symptoms (score ≥ 2) at baseline who improved to no-to-mild symptoms (score ≤ 1) were determined at Weeks 2, 24 (pooled studies) and 52 (SINUS-52). Subgroups with prior sinonasal surgery and coexisting asthma were analysed.ResultsAt baseline in the pooled intention-to-treat population (n = 724), the proportions of patients with scores ≥ 2 for NC, LoS and rhinorrhoea were 87, 94 and 64%, respectively. Significantly, more patients achieved scores ≤ 1 (no/mild symptoms) with dupilumab vs placebo for each symptom at each time point {Week 2 NC 12% vs 2% [odds ratio 8.9 (95% CI 3.0-26.3)], LoS 5% vs 1% [4.6 (1.3-16.8)], rhinorrhoea 9% vs 2% [4.8 (1.5-15.4)], all P < 0.05; Week 24 NC 54% vs 14% [8.7 (5.6-13.5)], LoS 43% vs 6% [14.4 (7.9-26.0)], rhinorrhoea 53% vs 16% [6.6 (4.1-10.9)], all P < 0.0001}. Results were similar in subgroups with prior surgery and coexisting asthma.ConclusionSignificantly, more patients achieved improvement from moderate-to-severe symptoms to no-to-mild symptoms with dupilumab than placebo, regardless of prior surgery or coexisting asthma. Improvement was observed as early as Week 2 and continued through to Week 52.
| S-EPMC9881398 | biostudies-literature
Project description:Objective Nasal Polyp Score (NPS) and Nasal Congestion Score (NCS) are commonly used clinical trial endpoints to determine improvements in response to treatment in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). However, limited information is available on within-patient meaningful change thresholds (MCTs) and between-group minimal important differences (MIDs) for NPS and NCS, which would aid interpretation of results. Methods Data from phase 3 placebo-controlled trials of omalizumab in patients with CRSwNP (POLYP 1 and POLYP 2) were used to estimate MCTs and MIDs for both NPS and NCS using anchor-based methods. Sino-Nasal Outcome Test-22 (SNOT-22) and SNOT-22 Sino-Nasal Symptoms Subscale (SNSS) scores were used as anchors (≥0.35 correlation with NPS and NCS). Within- and between-group differences in NPS and NCS change scores were used to estimate MCTs and MIDs, respectively. Identified MCTs were used in unblinded responder analyses to compare the proportions of patients per treatment group achieving a meaningful improvement. Results MCTs and MIDs were estimated at −1.0 and −0.5 for NPS and −0.50 and −0.35 for NCS, respectively, and were consistent across studies. Overall, 57.0% of patients achieved the MCT in NPS with omalizumab vs 29.9% with placebo (p < 0.0001). Similarly, 58.9% of patients achieved the MCT in NCS with omalizumab vs 30.7% with placebo (p < 0.0001). Group differences in mean change were statistically significant and exceeded the estimated MIDs. Conclusions Meaningful change estimates for NPS and NCS could be used to assess response to treatment for patients with chronic rhinosinusitis with nasal polyps. Trial registration: POLYP1: clinicaltrails.gov NCT03280550; registered September 12, 2017; https://clinicaltrials.gov/ct2/show/NCT03280550). POLYP2 (clinicaltrials.gov NCT03280537; registered September 12, 2017; https://clinicaltrials.gov/ct2/show/NCT03280537).
| S-EPMC10197100 | biostudies-literature
Project description:(1) Background: Factors influencing the quality of life (QoL) of patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) are poorly understood. We set out to determine the predictive factors on patients' QoL using the Sino-Nasal Outcome Test-22 (SNOT-22); (2) Methods: An ambispective analysis of data from patients diagnosed with CRSwNP in our institution. All the patients underwent a nasal polyp biopsy and completed the SNOT-22 questionnaire. Demographic and molecular data as well as the SNOT-22 scores were collected. Patients were classified in six subgroups considering the presence of asthma, non-steroidal drugs (NSAID) intolerance and corticosteroid resistance; (3) Results: The mean SNOT-22 score was 39. Considering the clinical parameters, the SNOT-22 value was significantly associated with NSAID intolerance (p = 0.04) and the endoscopic polyp score (p = 0.04). A high SNOT-22 value was also correlated with high tissue eosinophilia (p = 0.01) and high IL-8 expression; (4) Conclusions: Eosinophilia, IL-8 expression and NSAID intolerance can be used as predictors of worse QoL in patients with CRSwNP.
| S-EPMC9965377 | biostudies-literature