anju peters

MethodsThis was an analysis using US claims data (Optum; 2011− 2021) of CRSwNP patients undergoing FESS vs those not undergoing FESS (propensity-score matched) with available data and no post-index FESS up to 3 years post-surgery. OCS burden and costs were compared in the two groups.ResultsEach group included 3,952 patients. During the 3-year post-surgery period, substantial OCS burden was observed in both FESS (mean [SD] cumulative dose 548 [1,486] mg) and non-FESS (603 [1,567]) groups (mean difference in cumulative dose per patient− 55 mg [95% CI− 129, 19], P= 0.15). Mean (SD) total 3-year healthcare costs post-surgery were $48,317 (92,613) in the FESS and $48,593 (87,578) in the non-FESS group, a negligible difference of $275 (95% CI− 2,866, 2,316, P= 0.84) in the FESS vs non-FESS group.ConclusionsIn patients with CRSwNP undergoing FESS in real-world practice, OCS …

BackgroundChronic rhinosinusitis (CRS) is a prevalent inflammatory disease. No medications are Food and Drug Administration–approved for the most common form, CRS without nasal polyps (also called “chronic sinusitis”). Novel biomechanics of the exhalation delivery system deliver fluticasone (EDS-FLU; XHANCE) to sinonasal areas above the inferior turbinate, especially sinus drainage pathways not reached by standard-delivery nasal sprays.ObjectiveAssess EDS-FLU efficacy for CRS (irrespective of nasal polyps).MethodsTwo randomized, EDS-placebo–controlled trials in adults with CRS irrespective of polyps (ReOpen1) or exclusively without polyps (ReOpen2) were conducted at 120 sites in 13 countries. Patients received EDS-FLU 1 or 2 sprays/nostril, or EDS-placebo, twice daily for 24 weeks. Coprimary measures were composite symptom score through week 4 and ethmoid/maxillary sinus percent …

BackgroundSeasonal variability could influence asthma exacerbations. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin (IL)-4/IL-13, key and central drivers of type 2 inflammation. In the 52-week QUEST study (NCT02414854), add-on dupilumab every 2 weeks vs placebo significantly reduced exacerbations and improved prebronchodilator forced expiratory volume in 1 second in patients with uncontrolled, moderate-to-severe asthma. TRAVERSE (NCT02134028), the open-label QUEST extension study, enrolled patients with moderate-to-severe asthma to investigate long-term safety and efficacy of dupilumab, including patients who previously received placebo that initiated dupilumab therapy.ObjectiveTo investigate long-term dupilumab efficacy in reducing exacerbations across yearly seasons in patients with type 2 inflammatory asthma with and without clinical …

MethodsAROMA recruits adult patients with CRSwNP initiating dupilumab and follows them for up to 36 months. Baseline assessments include demographics, disease characteristics, medical and surgical history, including type 2 comorbidities. Primary endpoints include a descriptive summary of symptoms and health-related quality of life outcomes. This analysis evaluates baseline oral corticosteroid (OCS) use.ResultsAs of February 7, 2023, the study had recruited 303 patients. The mean (SD) age was 50.8 (13.4) years, and 49.5% of patients were male. A history of prescribed antibiotics for CRSwNP was reported by 45.2%. In the last 24 months OCS/systemic corticosteroid use was reported by 68.6% of patients. In the three months prior to screening, 21.5% of patients in AROMA received prednisone, 4.6% received methylprednisolone and 4.0% received prednisolone. At baseline 35.0% of patients self-reported …

Severe chronic rhinosinusitis with nasal polyps (CRSwNP), a form of diffuse bilateral (usually type 2) CRS, is a debilitating disease with a significant impact on quality of life (QoL). With novel knowledge and treatment options becoming available, there is a growing need to update or revise key definitions to enable communication across different specialties dealing with CRS, and to agree on novel goals of care in CRSwNP. The European Forum for Research and Education in Allergy and Airway diseases (EUFOREA) and EPOS expert members discussed how to measure treatment responses and set new treatment goals for CRSwNP. In this paper a consensus on a list of definitions related to CRSwNP is provided: control, remission, cure, recurrence/exacerbation, treatable traits, remodeling, progression, and disease modification. By providing these definitions, the involved experts hope to improve communication between all stakeholders involved in CRSwNP treatment for use in routine care, basic and clinical research and international guidelines aimed to harmonize and optimize standard of care of patients with CRSwNP in the future.

Background This post hoc analysis of the international SINUS‐24/‐52 trials (NCT02912468/NCT02898454) aimed to assess dupilumab efficacy in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) according to different definitions of type 2 inflammatory signature. Methods Six definitions of type 2 inflammation were used: ≥150 eosinophils/μL or total immunoglobulin E (IgE) ≥100 IU/mL with a coexisting type 2 condition; ≥150 eosinophils/μL or total IgE ≥100 IU/mL; ≥150 eosinophils/μL; ≥250 eosinophils/μL or total IgE ≥100 IU/mL; coexisting asthma or ≥300 eosinophils/μL; presence of a coexisting type 2 condition. Odds ratios (ORs; dupilumab vs. placebo) for achieving clinically meaningful improvement (≥1 point) from baseline to week 24 (pooled SINUS‐24/‐52) and week 52 (SINUS‐52) were calculated for nasal polyp score (NPS; range 0–8), nasal congestion/obstruction score (NC …

MethodsAROMA (NCT04959448) is a prospective global registry study recruiting adult patients with CRSwNP initiating dupilumab and following them for up to 36 months. Baseline assessments include demographics, disease characteristics, and severity of type 2 comorbidities including asthma.ResultsThe study had recruited 303 patients, including 210 (69.3%) with a history of asthma. Among these patients, the mean (SD) age of asthma diagnosis was 36.6 (17.3) years. The mean (SD) number of systemic corticosteroid treatment days for severe asthma exacerbation in the year prior to screening was 2.9 (9.56) days. Baseline mean asthma control questionnaire 6 (ACQ-6) score (n= 168) was 1.36 (1.20) and fractional exhaled nitric oxide (FeNO)(n= 51) was 53.3 (63.8) ppb. The mean percent predicted Forced Expiratory Volume in 1 Second (FEV1) was 88.8% and the percentage of those above 60% predicted …

Background In the 52‐week Phase III SYNAPSE study, mepolizumab given every 4 weeks (100 mg subcutaneously) reduced nasal polyp (NP) size, improved symptoms and quality of life (QoL), and reduced corticosteroid use and number of sinus surgeries in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP), versus placebo. Because the durability of mepolizumab's efficacy after discontinuation is poorly understood in CRSwNP, the efficacy of mepolizumab after discontinuation was analyzed in severe CRSwNP, over a 24‐week follow‐up. Methods Changes from SYNAPSE baseline to end of treatment (week 52) and end of follow‐up (week 76) were assessed for total endoscopic NP score, nasal obstruction and overall symptoms visual analog scale scores, and 22‐item Sino‐Nasal Outcome Test score. Time to first sinus surgery, time to first corticosteroid use, and geometric mean blood …

MethodsThis retrospective analysis utilized electronic medical records from an academic center. CRS patients, 18 or older without asthma and BE, were identified between January 2006 and December 2013. Charts were reviewed until May 2023. New diagnoses for asthma or BE were identified in patient records following ESS before December 2018 compared to patients without ESS. Lund-Mackay (LM) scores were calculated in a random subset of patients.ResultsIn our cohort, 1,877 patients underwent ESS while 13,453 patients did not. CRS severity was higher in the ESS group (LM, 9.04) vs no ESS group (LM, 4.74). After up to 17 years of follow-up, 207/1,877 (11%) and 40/1,877 (2.1%) of patients with ESS had new asthma or BE diagnoses, respectively. 1,778/13,453 (13.2%) and 293/13,453 (2.2%) of patients without ESS had new asthma or BE diagnoses. The unadjusted odds of developing asthma were …

Rationale Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin (TSLP), thereby reducing inflammation via multiple pathways. In the phase 3 NAVIGATOR (NCT03347279) study, treatment with tezepelumab resulted in clinically meaningful improvements in asthma outcomes and sino-nasal symptoms versus placebo in patients with severe asthma and a history of nasal polyps. This post hoc analysis compared the effect of tezepelumab versus placebo on the achievement of clinically meaningful response thresholds in NAVIGATOR patients with severe, uncontrolled asthma and a history of nasal polyps. Methods NAVIGATOR was a multicenter, randomized, double-blind, placebo-controlled study. Patients (12–80 years old) were randomized to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. The proportions of patients with a history of nasal …

MethodsA systematic literature search was performed in PubMed and Cochrane to identify published data from phase 3, randomized controlled trials of US FDA-approved biologics in patients with moderate-to-severe asthma with NP. Data extracted were AAER reductions and mean absolute changes in SNOT-22 scores versus placebo.ResultsData for four biologics (mepolizumab, benralizumab, dupilumab, tezepelumab) were available across nine publications. Mepolizumab reduced AAER over 24 weeks by 80%(95% confidence interval [CI]: 65, 89) and improved SNOT-22 score by− 11.8 (95% CI:− 19.8,− 3.9) versus placebo. Benralizumab reduced AAER over 24 weeks by 69%(95% CI: 50, 81) and improved SNOT-22 score by− 8.91 (95% CI:− 16.4,− 1.4) versus placebo. Dupilumab reduced AAER over 52 weeks by 67% and improved SNOT-22 score by− 10.3 and− 11.9 (across doses) versus placebo (95% CIs …

MethodsRAPID enrolled patients≥ 12 years initiating dupilumab for asthma (primary indication) according to country-specific prescribing information. Outcomes assessed were AR prevalence and characteristics of patients with/without AR.ResultsOf 205 patients included in this analysis, 166 (81%) reported history of AR, 165 (80%) ongoing AR, and 39 (19%) no AR. In patients with vs without AR, 115 (69%) vs 19 (49%) were female. Mean (SD) age was 48.1 (17.5) vs 58.5 (14.2) years, time since first asthma diagnosis was 21.9 (18.6) vs 16.8 (13.9) years, and asthma control (6-item Asthma Control Questionnaire [ACQ-6]) score was 2.4 (1.20) vs 2.2 (1.09). 60 (36.1%) patients with AR reported having AR for a mean (SD) duration of 12.5 (18.9) years. Allergic Rhinitis Visual Analog Scale (AR-VAS) score was 48.0 (29.2)(scale: 0–100). 63 (38%) patients used nasal steroids, 9 (5%) allergen immunotherapy, and 8 (5 …

Chronic rhinosinusitis with nasal polyps (CRSwNP) is predominantly a type 2 inflammatory disease associated with type 2 (T2) cell responses and epithelial barrier, mucociliary, and olfactory dysfunction. The inflammatory cytokines interleukin (IL)-4, IL-13, and IL-5 are key mediators driving and perpetuating type 2 inflammation. The inflammatory responses driven by these cytokines include the recruitment and activation of eosinophils, basophils, mast cells, goblet cells, M2 macrophages, and B cells. The activation of these immune cells results in a range of pathologic effects including immunoglobulin E production, an increase in the number of smooth muscle cells within the nasal mucosa and a reduction in their contractility, increased deposition of fibrinogen, mucus hyperproduction, and local edema. The cytokine-driven structural changes include nasal polyp formation and nasal epithelial tissue remodeling, which perpetuate barrier dysfunction. Type 2 inflammation may also alter the availability or function of olfactory sensory neurons contributing to loss of sense of smell. Targeting these key cytokine pathways has emerged as an effective approach for the treatment of type 2 inflammatory airway diseases, and a number of biologic agents are now available or in development for CRSwNP. In this review, we provide an overview of the inflammatory pathways involved in CRSwNP and describe how targeting key drivers of type 2 inflammation is an effective therapeutic option for patients.

MethodsAROMA (NCT04959448) is a prospective global registry study, recruiting adult patients with CRSwNP initiating dupilumab. Baseline assessments included patient demographics, disease characteristics and type 2 comorbidities such as NSAID-ERD.ResultsAs of February 7, 2023, the study had recruited 303 patients, 78 (25.7%) of which self-reported a history of NSAID-ERD. The mean (SD) age of NSAID-ERD diagnosis was 39.3 (11.8) years. Of the patients with previous surgery (n= 188), 52 (66.7%) had NSAID-ERD. Among all patients with coexisting NSAID-ERD, 11 (14.1%) had undergone a confirmatory aspirin challenge, 11 (14.1%) had undergone an aspirin desensitization, and 15 (19.2%) reported experiencing an adverse reaction to alcohol consumption.ConclusionsA quarter of adult patients with CRSwNP initiating dupilumab in AROMA report having coexisting NSAID-ERD, though most have not …

MethodsData was collected at three time points: pre-, 6-12 months post-(V1), and 18-60 months post-(V2) ESS. Middle meatal (MM) nasal secretions were analyzed pre-ESS and V1. Outcomes, including endoscopic Modified Lund Kennedy (MLK), radiographic Lund-Mackay (LM) scores, patient reported SNOT 22 and CRS PRO, and the Brief Smell Identification Test-(BSIT), were collected pre-ESS, V1 and V2. 25 biomarkers in MM secretions were measured with Luminex and ELISA. 93 CRS patients were clustered using a K-Means algorithm that identified higher order organization of patients using their MM biomarkers. Outcomes were compared between clusters.ResultsUsing constituent biomarkers, patients organized into five clusters: severe Type2, severe Type1+ 3, mild Type2, mild Type1+ 3, and untypable. Type 2 clusters were separated by IL-5 and CCL26 (p< 0.0001) whereas Type1+ 3 clusters were …

BackgroundPrevious clinical trials have demonstrated dupilumab efficacy and safety in adults and adolescents with moderate to severe asthma for up to 3 years.ObjectiveThe TRAVERSE continuation study (NCT03620747), a single-arm, open-label study, assessed safety and tolerability of dupilumab 300 mg every 2 weeks up to an additional 144 weeks (∼3 years) in patients with moderate to severe asthma who previously completed TRAVERSE (NCT02134028).MethodsPrimary end points were incidence and event rates per 100 patient-years of treatment-emergent adverse events (TEAEs). Secondary end points included adverse events (AEs) of special interest, serious AEs, and AEs leading to study discontinuation.ResultsA total of 393 patients participated in the TRAVERSE continuation study (cumulative dupilumab exposure, 431.7 patient-years; median treatment duration, 309 days). A total of 29 patients (7.4 …

MethodsRetrospective cohort study of CRSwNP patients undergoing FESS vs not undergoing FESS, using US claims data (Optum; 2012− 2020). Groups were propensity score matched to adjust for confounding. Intervention/follow-up periods were defined as Day 0− 44/45− 365, respectively. OCS burden (cumulative dose in mg prednisone equivalents), other medications, HCRU, and costs were compared in FESS vs non-FESS patients in the 1 year post-surgery.Results17,818 patients were included (n= 8,909 in each group). During follow-up, OCS use was lower in FESS vs non-FESS patients (mean difference in cumulative dose/patient/year− 40 mg [95% CI− 64,− 16]), however substantial OCS burden was observed in both groups with the mean (SD) cumulative dose among these patients: 521 (786) mg and 612 (906) mg, respectively. The proportion of patients with an OCS prescription fill was 35%(FESS group …

Methods: Participants from the UK Biobank study baseline assessment with no previous cardiometabolic disease diagnosis, and with information on fish intake (reported by food frequency questionnaire) and FADS-genotype, were included (n= 189,683). The incidence of MI was defined based on linked data from hospital admissions and death registries. The effects of oily and non-oily fish intake frequency per week (< once, once, twice or more) on MI incidence were assessed separately, using Cox proportional-hazards regression adjusting for covariates. Interactions with 18 single nucleotide polymorphisms (SNP) of the FADS gene cluster were tested, and if significant, analyses were stratified by genotype.Results: The median age was 56 years, 58% were female. 2088 MIs occurred during a mean follow-up time of 12.2 years. Oily fish intake once per week was inversely associated with MI incidence (hazard ratio …

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is a predominantly type 2 inflammatory disease, which often coexists with allergic rhinitis (AR). Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key and central drivers of type 2 inflammation. Objective This post hoc analysis investigated the efficacy and safety of dupilumab in patients with severe CRSwNP with or without coexisting AR in the pooled phase III SINUS-24/SINUS-52 studies. Methods Patients randomized to subcutaneous dupilumab 300 mg (n = 438) or placebo (n = 286) every 2 weeks for 24 (SINUS-24) or 52 weeks (SINUS-52) were analyzed. Pooled data from the first 24 weeks of treatment are presented. Changes from baseline in disease outcome measures and biomarker levels were analyzed by the patient-reported history of AR status. Results Overall, 338 of …

IntroductionDupilumab has proven efficacy and safety in randomized controlled trials, leading to its approval as a treatment for patients with uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP). This observational study will further characterize real-world use of dupilumab for CRSwNP patients.MethodsAROMA (NCT04959448) is a phase 4, prospective, global registry study being conducted in the USA, Canada, Germany, Italy, Japan, and The Netherlands. The study recruits adult patients with CRSwNP initiating dupilumab and follows them for ≤36 months, collecting all treatments including usage of dupilumab per standard of care. Baseline assessments include demographics, disease characteristics, medical and surgical history, including type 2 comorbidities. Primary endpoints include a descriptive summary of symptoms and health-related quality of life outcomes.ResultsAs of February 7, 2023, the …