Exhalation Delivery System With Fluticasone Research Articles

LB1581. Exhalation Delivery System with Fluticasone (EDS-FLU) Significantly Reduces Acute Exacerbations and Associated Antibiotic Use in Chronic Rhinosinusitis

Abstract Background Data suggest chronic rhinosinusitis (CRS) may be the top reason for adult outpatient antibiotic use; of ≈10 million office visits per year for CRS, ≈70% result in antibiotic use. Acute exacerbations of CRS (AECRS) are common, possibly due to persistently impaired mucociliary clearance, and drive use of antibiotics. No drugs have been shown effective for reducing AECRS. ReOpen1 and 2 are randomized controlled trials that evaluated prevention of AECRS with the exhalation delivery system with fluticasone (EDS-FLU; XHANCE®), a novel device delivering topical steroid into chronically inflamed sinonasal regions not typically accessible with standard nasal sprays (eg, past the nasal valve and above the inferior turbinate). Methods CRS patients were randomized to EDS-FLU one or two sprays per nostril or placebo twice daily (BID) for 24 weeks. Frequency of AECRS, defined as worsening of at least 1 cardinal symptom of CRS (nasal congestion/obstruction, rhinorrhea, facial pain/pressure, hyposmia/anosmia) for ≥ 3 days requiring escalation of medical care (eg, doctor visit, antibiotic or steroid prescription), was analyzed using pooled data from both trials. Results Among 555 patients enrolled, 39.4% were using standard nasal steroids at study entry and 38.8% reported prior sinus surgery. There were 76 AECRS over 24 weeks, almost all (71) resulting in antibiotic use. Patients receiving EDS-FLU had a large reduction in AECRS versus placebo (incidence rate ratio [IRR]=0.39, P=0.001, vs placebo). Reduction was greater at the higher dose (2 sprays/nostril BID) than the lower dose (1 spray/nostril BID): IRR=0.34, P=0.002; IRR=0.44, P=0.012, respectively. 9.9% of low-dose patients and 7.8% of high-dose patients had ≥ 1 AECRS (20 and 15 events, respectively) vs 15.7% receiving placebo (41 events; P=0.012 and P=0.002 vs placebo, respectively). Treatment was well tolerated: adverse events in ≥ 3% of patients and more common in one active group than placebo were epistaxis, COVID-19, headache, and nasopharyngitis. Conclusion EDS-FLU is the first and only medication shown in randomized controlled trials to significantly reduce acute exacerbations of CRS, offering potential to improve antibiotic stewardship by substantially reducing one of the most common drivers of outpatient antibiotic use. Disclosures Ramy Mahmoud, MD, MPH, OptiNose Inc.: Employee of OptiNose Inc.

RANDOMIZED, CONTROLLED TRIAL OF EXHALATION DELIVERY SYSTEM WITH FLUTICASONE FOR CHRONIC RHINOSINUSITIS WITHOUT NASAL POLYPS

<h3>Introduction</h3> There are no FDA-approved medications for the >20 million chronic rhinosinusitis patients without nasal polyps. The Exhalation Delivery System with Fluticasone (EDS-FLU) is an intranasal steroid in a device that delivers drug to regions above the inferior turbinate and behind the nasal valve. <h3>Methods</h3> In this phase 3, 24-week, randomized, controlled trial evaluating EDS-FLU versus EDS-placebo twice daily in chronic sinusitis without polyps, co-primary endpoints were combined symptom score (CSS; week 4) and average of percentages of CT-opacified volume across ethmoid/maxillary sinuses (APOV; week 24). Other outcomes included Quality-of-Life (SNOT-22, SF-36), Sleep (PSQI), and Patient-reported Global Impression of Change (PGIC). <h3>Results</h3> Baseline scores suggest moderate-severe disease: mean CSS=6.0; APOV=62.0%. Both EDS-FLU doses [186µg (n=74) and 372µg (n=74)] significantly reduced both symptoms and sinus opacification versus EDS-placebo (n=75): CSS least-square (LS) mean change, EDS-placebo, -0.81; EDS-FLU 186µg, -1.54 (p<.05); EDS-FLU 372µg, -1.74, (p<.001); APOV LS mean change +1.19, -7.00 (p<.001), -5.14 (p<.01), respectively. EDS-FLU (n=145) vs EDS-placebo (n=75) also significantly improved secondary measures at Week 24 including SNOT-22 (LS mean -17.5 vs -8.7, p=.001); SF-36v2 (LS Mean PCS 4.9 vs 1.8, p=.002); PSQI Global score (LS mean -1.54 vs -.33; p<.001); and PGIC (60% vs 25% much/very much improved; p<.001). Adverse events (≥3% of patients and >EDS-placebo) were COVID-19, epistaxis, headache, and depression. <h3>Conclusion</h3> EDS-FLU is the first and only drug to show improvement in a phase 3 trial in both symptoms and sinus opacification in chronic rhinosinusitis without nasal polyps.

The Effect of EDS-FLU on Objective and Patient-Reported Subjective Outcomes for Patients with Chronic Rhinosinusitis with Nasal Polyps.

Exhalation delivery system with fluticasone (EDS-FLU) delivers medication high and deep in the nasal passages and has been shown to reduce nasal polyp (NP) grade, an objective measure of efficacy, and to yield clinically meaningful improvements on subjective measures of symptoms in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). To better characterize EDS-FLU treatment, we analyzed responder rates for four outcome measures used in the EDS-FLU pivotal trials, in the overall study population as well as in subgroups of patients with or without prior sinus surgery or prior use of a standard intranasal corticosteroid spray (INS). Data were pooled from two randomized, 24-week (16-week, double-blind + 8-week, open-label), placebo-controlled studies (NAVIGATE I and II). Results for patients receiving EDS-FLU (186µg [n = 161] or 372µg [n = 160]) or EDS-placebo (n = 161) twice daily during the double-blind phase are described. Responder criteria included NP grade reduction (≥1-point), 22-item Sino-Nasal Outcome Test (SNOT-22) reduction (>12-points), Patient Global Impression of Change (PGIC) (much/very much improved), and congestion score improvement (>0.5-points). More patients in the EDS-FLU group responded to each of the four responder criteria compared with EDS-placebo. More patients receiving EDS-FLU responded to ≥ 1 criterion compared with EDS-placebo at week 4 (82.7% and 60.4%, respectively) and week 16 (95.7% and 80.3%, respectively). Patients responded similarly irrespective of prior sinus surgery or prior INS use. Patient-reported outcome measures showed earlier responses than NP scores. Meaningful improvements were seen across multiple response criteria with EDS-FLU, suggesting that the broad treatment effect of EDS-FLU includes objective reduction in polyp grade and improvements in several patient-reported outcomes. ClinicalTrials.gov (NAVIGATE I: NCT01622569 and NAVIGATE II: NCT01624662).

EDS-FLU (Exhalation Delivery System With Fluticasone) is Associated With Improved Sleep in Patients With Nasal Polyposis

Patients with CRSwNP frequently suffer from poor quality of sleep, significantly lower quality-of-life scores, and chronic depression. EDS-FLU has been shown to significantly improve symptoms of CRSwNP. This post-hoc analysis reports the effects on sleep from EDS-FLU pivotal trials.

Exhalation Delivery Systems for Application of Intranasal Corticosteroids.

Chronic rhinosinusitis (CRS) is a common sinonasal disorder which results in significant inflammation in the nasal cavity and paranasal sinuses. Topical nasal steroids play an important role in the treatment of CRS. Exhalation delivery system with fluticasone (EDS-FLU) utilizes a patient's forced exhalation to power the delivery of topical steroids to deeper areas of the nasal cavity and paranasal sinuses most affected by CRS. This review focuses on evidence surrounding the safety and efficacy of the EDS-FLU system. Literature search was conducted of articles investigating the safety and efficacy of EDS-FLU. Relevant efficacy and safety data were examined and summarized from the studies. The efficacy and safety of EDS-FLU in CRS, both with and without polyps, has been established in open-label and placebo-controlled phase 3 trials. There was significant improvement in the cardinal symptoms of CRS and subjective patient-reported outcomes scores. Additionally, there was objective improvement in sinonasal inflammation as measured by polyp grade. Recent studies have also established significant improvement in health status and general quality of life following treatment using EDS-FLU. Emerging data have also examined patients who have previously had endoscopic sinus surgery and on appropriate medical therapy and noted improvement in polyp burden and overall Lund-Kennedy scores after using EDS-FLU. Exhalation delivery system with fluticasone demonstrates significant results in both patient-oriented outcomes and objective measures of sinonasal inflammation in patients with CRS with and without polyps. Further research is needed to investigate the long-term outcomes of EDS-FLU and to compare the effects of EDS-FLU with ESS. Exhalation delivery system with fluticasone provides an additional effective treatment modality for patients suffering from CRS.

Efficacy of the exhalation delivery system with fluticasone in patients who remain symptomatic on standard nasal steroid sprays.

Standard nasal steroid sprays are often first-line treatment for chronic rhinosinusitis (CRS), but many patients remain symptomatic despite their use. The exhalation delivery system with fluticasone (EDS-FLU) has been shown to be efficacious in mixed populations of symptomatic patients, but the question remains whether benefits would be similar in those already on traditional steroid sprays. The goal of this study was to compare EDS-FLU treatment outcomes in patients who have previously failed nasal steroids. Using pooled data from the NAVIGATE I and II trials, EDS-FLU efficacy was compared in the subgroup treated with a conventional nasal steroid at trial entry (mean duration, ≈3 years) to efficacy in the overall study population. Sensitivity analyses were performed for more restrictive definitions of the subgroup changing from prior standard nasal steroids. Of482 total subjects, 218 (45.2%) reported using standard nasal steroid sprays at entry (mean duration, 1051 days). Across multiple outcome measures, improvements for "switchers" receiving EDS-FLU (least squares mean change from baseline vs EDS plus placebo) were comparable with improvements in the overall population. For EDS-FLU 372 μg, comparable improvements were observed in congestion (-0.73 vs -0.62), rhinorrhea (-0.71 vs -0.57), facial pain/pressure (-0.48 vs -0.41), and sense of smell (-0.35 vs -0.30) at week 4 and 22-item Sino-Nasal Outcome Test (-21.01 vs -20.52), Patient Global Impression of Change, and other outcomes at week 16. Results for EDS-FLU 186 μg were similar. EDS-FLU comparably improves symptoms, irrespective of whether patients are symptomatic while using conventional nasal steroids before treatment.

Exhalation delivery system with fluticasone improves quality of life and health status: pooled analysis of phase 3 trials NAVIGATE I and II

BackgroundChronic rhinosinusitis with or without nasal polyps (CRSwNP/CRSsNP) seriously impairs health‐related quality of life (HRQoL). This analysis describes the impact of the exhalation delivery system with fluticasone (EDS‐FLU) on HRQoL, assessed by the 36‐item Short‐Form Health Survey version 2 (SF‐36v2), and on utilities, assessed via the Short‐Form 6‐Dimension (SF‐6D), in patients with CRSwNP.MethodsPost hoc analysis of pooled randomized clinical trial data (NAVIGATE I and II; N = 643) to examine change from baseline in SF‐36v2 and SF‐6D at end‐of‐double‐blind (EODB: 16 weeks) and end‐of‐open‐label (EOOL: 24 weeks; following 8 weeks of open‐label treatment) for EDS‐FLU vs placebo (EDS‐PBO). Baseline characteristics predictive of change in SF‐36 and SF‐6D scores were assessed.ResultsMean baseline SF‐36v2 scores were below population norms. At EODB, mean improvement was greater for all SF‐36v2 domain and component scores with EDS‐FLU (range: 2.9 [physical functioning] to 5.11 [bodily pain {BP}]) vs EDS‐PBO (range: 0.81 [mental health] to 2.87 [BP]) (each comparison p < 0.01); physical and mental component score improvements within the EDS‐FLU group exceeded the minimal clinically important difference (MCID). Clinically meaningful and statistically significant improvements in SF‐6D utility scores were seen in EDS‐FLU–treated patients compared to EDS‐PBO–treated patients (0.058 vs 0.023, respectively, p < 0.001). At EOOL, SF‐36v2 and SF‐6D mean scores were at or above population norms, with clinically meaningful and statistically significant improvements from baseline.ConclusionIn this pooled analysis of 2 large pivotal EDS‐FLU trials, health domain and health utilities improvements were significantly greater with EDS‐FLU than EDS‐PBO and were comparable to population norms.

P455 EXHALATION DELIVERY SYSTEM WITH FLUTICASONE TREATMENT IN PATIENTS NOT CONTROLLED WITH CONVENTIONAL INTRANASAL STEROIDS

The exhalation delivery system with Fluticasone (EDS-FLU) delivers steroid more posteriorly and superiorly within the nasal cavity than conventional nasal sprays. Placebo-controlled efficacy studies with EDS-FLU in nasal polyps (NAVIGATE I/II) included subjects with moderate/severe congestion despite using conventional nasal steroids. This is a new analysis of change in disease activity in the subgroup of patients who reported using an INS at the time of screening.

NAVIGATE I: Randomized, Placebo-Controlled, Double-Blind Trial of the Exhalation Delivery System With Fluticasone for Chronic Rhinosinusitis With Nasal Polyps.

BackgroundChronic rhinosinusitis is a common, high-morbidity chronic inflammatory disease, and patients often experience suboptimal outcomes with current medical treatment. The exhalation delivery system with fluticasone (EDS-FLU) may improve care by increasing superior/posterior intranasal corticosteroid deposition.ObjectiveTo evaluate the efficacy and safety of EDS-FLU versus EDS-placebo in patients with nasal polyps (NP). Coprimary end points were change in nasal congestion and polyp grade. Key secondary end points were Sino-Nasal Outcome Test-22 (SNOT-22) and Medical Outcomes Study Sleep Scale-Revised (MOS Sleep-R). Other prespecified end points included all 4 cardinal symptoms of NP, 36-Item Short Form Health Survey (SF-36), Patient Global Impression of Change (PGIC), Rhinosinusitis Disability Index (RSDI), and key indicators for surgical intervention.DesignRandomized, double-blind, EDS-placebo-controlled, multicenter study.MethodsThree hundred twenty-three subjects with NP and moderate-severe congestion/obstruction, most with history of corticosteroid use (94.4%) and/or prior surgery (60.4%), were randomized to EDS-FLU 93 µg, 186 µg, or 372 µg or EDS-placebo twice daily (BID) for 24 weeks (16 double-blind + 8 single-arm extension with EDS-FLU 372 µg BID).ResultsAll EDS-FLU doses produced significant improvement in both coprimary end points (P < .05) and in SNOT-22 total score (P ≤ .005). EDS-FLU significantly improved all 4 cardinal symptoms of NP (P < .05), including congestion/obstruction, facial pain/pressure, rhinorrhea/post-nasal drip, and hyposmia/anosmia. Approximately 80% of subjects reported improvement with EDS-FLU, with 65% reporting “much” or “very much” improvement by week 16. Adverse events were generally local in nature and similar to other intranasal steroids studied for similar durations in similar populations, with the most common being epistaxis.ConclusionsIn patients with chronic rhinosinusitis with NP (CRSwNP) who were symptomatic despite high rates of prior intranasal steroid use and/or surgery, EDS-FLU produced statistically significant and clinically meaningful improvements compared to EDS-placebo in multiple subjective and objective outcomes (symptoms, SNOT-22, RSDI, SF-36, PGIC, and NP grade), including all 4 cardinal symptoms of CRSwNP.

EDS-FLU VERSUS TRADITIONAL NASAL STEROIDS FOR TREATING CHRONIC RHINOSINUSITIS: SUMMARIZING CURRENT EVIDENCE FOR SYMPTOM BENEFITS

Introduction Standard intranasal steroids (INS) are first-line therapy, but yield limited benefit, in treating defining symptoms of CRSw/sNP (congestion, rhinorrhea, facial pain/pressure, anosmia). We compared symptom relief with traditional INS, as summarized in a 2016 Cochrane review, with symptom relief reported in pooled trials with EDS-FLU (exhalation delivery system with fluticasone). Methods The Cochrane systematic review assessed 18 RCTs of 3-6-month duration in CRSw/sNP (N=2738). EDS-FLU data were from two 24-week (16 double-blind+8 open-label), RCTs (NAVIGATE I/II) in CRSwNP (N=643). Effects on all 4 cardinal symptoms were compared. Results Cochrane data for congestion, rhinorrhea, facial pain/pressure, and sense of smell came from 6, 6, 2, and 4 RCTs, respectively. Facial pain/pressure evidence was deemed low quality; the remainder were moderate quality. Mean difference for INS from placebo (95% CI) was -0.4 (-0.52 to -0.29), -0.25 (-0.33 to -0.17), -0.27 (-0.56 to 0.02), and -0.19 (-0.28 to -0.11) for congestion, rhinorrhea, facial pain/pressure, and sense of smell, respectively. EDS-FLU studies demonstrated a larger mean benefit on all 4 cardinal symptoms (for 186/372µg: congestion -0.46/-0.55, rhinorrhea -0.43/-0.47, facial pain/pressure -0.36/-0.33 and sense of smell -0.25/-0.38). (Table) The magnitude of effect of EDS-FLU 372 mcg on congestion, rhinorrhea and anosmia was higher than the upper 95%CI for other INS reported in the Cochrane review. Pain/pressure benefits were numerically greater, but prior data was low quality and the 95% CI was very wide. Conclusions Current evidence suggests that EDS-FLU produces a larger mean benefit on cardinal symptoms of CRS than standard INS. Standard intranasal steroids (INS) are first-line therapy, but yield limited benefit, in treating defining symptoms of CRSw/sNP (congestion, rhinorrhea, facial pain/pressure, anosmia). We compared symptom relief with traditional INS, as summarized in a 2016 Cochrane review, with symptom relief reported in pooled trials with EDS-FLU (exhalation delivery system with fluticasone). The Cochrane systematic review assessed 18 RCTs of 3-6-month duration in CRSw/sNP (N=2738). EDS-FLU data were from two 24-week (16 double-blind+8 open-label), RCTs (NAVIGATE I/II) in CRSwNP (N=643). Effects on all 4 cardinal symptoms were compared. Cochrane data for congestion, rhinorrhea, facial pain/pressure, and sense of smell came from 6, 6, 2, and 4 RCTs, respectively. Facial pain/pressure evidence was deemed low quality; the remainder were moderate quality. Mean difference for INS from placebo (95% CI) was -0.4 (-0.52 to -0.29), -0.25 (-0.33 to -0.17), -0.27 (-0.56 to 0.02), and -0.19 (-0.28 to -0.11) for congestion, rhinorrhea, facial pain/pressure, and sense of smell, respectively. EDS-FLU studies demonstrated a larger mean benefit on all 4 cardinal symptoms (for 186/372µg: congestion -0.46/-0.55, rhinorrhea -0.43/-0.47, facial pain/pressure -0.36/-0.33 and sense of smell -0.25/-0.38). (Table) The magnitude of effect of EDS-FLU 372 mcg on congestion, rhinorrhea and anosmia was higher than the upper 95%CI for other INS reported in the Cochrane review. Pain/pressure benefits were numerically greater, but prior data was low quality and the 95% CI was very wide. Current evidence suggests that EDS-FLU produces a larger mean benefit on cardinal symptoms of CRS than standard INS.

COST-EFFECTIVENESS OF EDS-FLU IN SINUS SURGERY CANDIDATES WHO HAVE CHRONIC RHINOSINUSITIS WITH NASAL POLYPS

Introduction Approximately 8% of patients with CRSwNP undergo surgery annually. Endoscopic sinus surgery (ESS) has been shown to be cost-effective compared to coventional medical therapy. A novel medical option, the exhalation delivery system with fluticasone (EDS-FLU) was recently approved by FDA for the treatment of nasal polyps in adults, and has shown potential in clinical trials (NAVIGATE I/II) to reduce need for ESS by ∼60% after 24 weeks. This study compared the modeled costs and quality adjusted life year (QALY) gains with surgery vs. EDS-FLU over a five-year time horizon in a pooled population of trial participants defined a priori as ESS candidates. Methods A Markov decision tree model was developed that incorporated health state costs, treatment costs, and ESS complication rates derived from claims data and the medical literature. Health utilities and transition probabilities were obtained from literature (Rudmik 2015) and clinical trials (Navigate I/II), respectively. A probabilistic sensitivity analysis was performed to examine the robustness of the findings. Results The analysis found that EDS-FLU was a dominant choice, producing 0.19 additional QALYs vs. ESS with 19.5% lower total cost ($19,815 vs $24,625) (Figure). Probabilistic sensitivity analysis found this conclusion to be robust, with 56.6% of simulations showing EDS-FLU to be dominant, and 84.9% of simulations showing EDS-FLU to be the preferred choice at a cost-effectiveness threshold of $50,000/QALY. Conclusions In this cost-utility model, EDS-FLU produced greater QALY gains at lower cost than surgery. Economic analysis supports EDS-FLU as a preferred strategy in this population prior to surgery.

EVALUATION OF THE RISK OF OCULAR EFFECTS ASSOCIATED WITH EDS-FLU

Introduction Increased intraocular pressure (IOP) and cataracts are known risks of systemic steroid exposure. EDS-FLU (exhalation delivery system with fluticasone) 372mcg produces higher systemic exposure than fluticasone nasal spray 400mcg, but lower systemic exposure than orally inhaled fluticasone 440mcg. Ocular effects were extensively studied in EDS-FLU clinical trials. Methods Ocular safety of EDS-FLU 186mcg and 372mcg twice-daily in chronic rhinosinusitis with or without nasal polyps (CRSw/sNP) was assessed in two studies in CRSwNP, each 24-weeks in duration (16 double-blind [DB]+8 open-label [OL]) and placebo-controlled (N=643). Additionally, two 12- and 52-week OL studies evaluated 372mcg in CRS patients (N=898). Ophthalmologists performed tonometry and slit-lamp exams to assess IOP and cataracts. Results Mean change from screening in average IOP (mmHg) in right/left eyes ranged from 0.0 to -0.2 (Figure). During the DB phase, 1.2%, 1.2%, and 0.4% of subjects developed increased IOP (>21), cataract, or subcapsular cataract, respectively (placebo EDS [n=2 IOP >21; n=3 cataract; n=0 subcapsular]; 186mcg [3, 2, 1]; and, 372mcg [1, 1, 1]). All subcapsular cataracts were 6 mmHg from screening in 0.6%/0.6%, 0%/0%, and 0.6%/0% right/left eyes in EDS-placebo, EDS-FLU 186mcg, and EDS-FLU 372mcg groups, respectively. OL studies reported similar IOP changes, with 3- and 12-month cataract rates of 0.6% and 1.3% and no subcapsular cataracts. Conclusions No increased risk of elevated IOP was detected with EDS-FLU, and the rate of cataract development was similar to that reported with other INS. Mean Change in IOP from Baseline at End of Double-Blind Phase

NAVIGATE II: Randomized, double-blind trial of the exhalation delivery system with fluticasone for nasal polyposis

Chronic rhinosinusitis is common and sometimes complicated by nasal polyps (NPs). Corticosteroid nasal sprays are often unsatisfactory because they are ineffective at delivering medication to high/deep sites of inflammation. We sought to assess whether an exhalation delivery system with fluticasone (EDS-FLU) capable of high/deep drug deposition improves outcomes. Patients (n=323) 18years and older with moderate-to-severe congestion and NPs were randomized to twice-daily EDS-FLU (93, 186, or 372μg) or exhalation delivery system (EDS)-placebo for 24weeks (16 double-blind plus 8 open-label when all received 372μg). Coprimary end points were change in nasal congestion/obstruction at 4weeks and summed bilateral polyp grade at 16weeks. Secondary end points included symptoms, polyp elimination, and functioning. EDS-FLU was superior on both coprimary end points (P<.001 vs EDS-placebo, all doses). Mean polyp grade improved continuously through week 24 (P<.009, all comparisons), with polyps eliminated on at least 1 side in approximately 25% of patients at week 24 versus 8.7% with EDS-placebo (P≤.014, all comparisons). Sino-Nasal Outcomes Test scores also improved significantly versus those in patients receiving EDS-placebo (-21.1 to -21.4 vs -11.7 at week 16, P<.05 all doses). At the end of the double-blind period, EDS-FLU (all doses) significantly improved all 4 defining disease symptoms. In most patients (68%), those receiving EDS-FLU reported "much" or "very much" improvement. The number of patients eligible for surgery decreased by 62%-67%. The safety profile was similar to that reported in prior trials evaluating conventional corticosteroid nasal sprays in comparable populations. EDS-FLU produces clinically and statistically significant improvement in all 4 diagnostically defining disease symptoms, polyp grade, and quality of life in patients with chronic rhinosinusitis with NPs.

EXHANCE-12: 1-year study of the exhalation delivery system with fluticasone (EDS-FLU) in chronic rhinosinusitis.

BackgroundInadequate efficacy of current intranasal steroids in chronic rhinosinusitis (CRS) is attributable to ineffective and/or inconsistent drug delivery to target anatomic sites. A new exhalation delivery system with fluticasone (EDS‐FLU) may improve outcomes by significantly increasing superior/posterior corticosteroid delivery. A study was conducted to assess the long‐term efficacy and safety outcomes of EDS‐FLU in individuals with CRS.MethodsThis was a 12‐month, multicenter, single‐arm study evaluating the safety and efficacy of EDS‐FLU 372 μg twice daily in CRS patients (with [n = 34] or without [n = 189] nasal polyps [NP]). Efficacy assessments by serial nasal endoscopy and patient report included: 22‐item Sino‐Nasal Outcome Test (SNOT‐22), NP grade, standardized surgical indicator assessment, Lund‐Kennedy score, and Patient Global Impression of Change. Adverse event (AE) evaluations included nasal endoscopy. Additional safety and efficacy outcomes were assessed.ResultsOf 223 patients who received EDS‐FLU, 96% reported prior corticosteroid use and 29% prior sinus surgery. The EDS‐FLU AE profile was similar to conventional intranasal steroids studied in similar populations. Most patients (87%) reported symptom improvement. Through 12 months, mean SNOT‐22 scores improved by −21.5 and −21.1 for CRS with and without NP, respectively. Among patients with NP, 54.2% had polyp elimination in at least 1 nostril and 83.3% had ≥1‐point improvement in polyp grade.ConclusionOver 1 year of treatment in CRS with and without NP, EDS‐FLU 372 μg twice daily was well tolerated and produced improvements across a broad range of objective and subjective measures. EDS‐FLU may be a desirable new option for patients with this condition.

Exhalation Delivery System with Fluticasone (EDS-FLU) Improves Outcomes in Chronic Rhinosinusitis without Nasal Polyps (CRSsNP) in Patients With or Without Recent Intranasal Steroid Use

Systemic steroids significantly reduce inflammation and symptoms in CRSsNP, but have a poor safety profile. Multiple guidelines recommend topical intranasal steroids (INS), but efficacy is frequently unsatisfactory with currently available steroid nasal sprays (regardless of steroid molecule). EDS-FLU is different because it delivers steroid to sites high/deep in the nose, including where sinus ostia drain/ventilate. We report EDS-FLU treatment outcomes for CRSsNP patients with and without a recent INS. We analyzed CRSsNP data from two, multicenter, single-arm studies (n=898), EXHANCE-3 (12 weeks) and EXHANCE-12 (52 weeks) where patients received EDS-FLU 372μg BID. Multiple objective, subjective, quality of life and safety outcomes were examined. Sinonasal Outcomes Test (SNOT-22), Lund-Kennedy endoscopic edema assessment and Patient Global Impression of Change (PGIC) are reported by prior INS use (+INS=use ≤30 days before randomization or -INS=no use within 30 days). At study end, SNOT-22 improved by 22.1 and 19.5 (+INS) and 28.4 and 18.8 (-INS) in EXHANCE- 3 and -12, respectively. Among patients with nasal edema at baseline, 53% and 58.6% (+INS) and 50% and 41.2% (-INS) achieved resolution of edema by end-of-study in EXHANCE-3 and -12, respectively. In EXHANCE-3/12, 68.1%/74.5% +INS compared with 70.7%/66.7% -INS, respectively, reported being ‘much’ or very much improved on PGIC. EDS-FLU improved objective and subjective measures of disease and quality-of-life similarly in CRSsNP who had or had not recently used currently available INS. These data suggest EDS-FLU could play an important role in patients who do not adequately respond to currently available INS.

Exhalation Delivery System with Fluticasone (EDS-FLU) Improves Health-Related Quality of Life (HRQoL) in Patients with Chronic Rhinosinusitis with Nasal Polyps: Results from NAVIGATE II

Exhalation Delivery System with Fluticasone (EDS-FLU) Improves Health-Related Quality of Life (HRQoL) in Patients with Chronic Rhinosinusitis with Nasal Polyps: Results from NAVIGATE II

P440 Exhalation delivery system with fluticasone (EDS-FLU) improves sleep in patients with CRS with nasal polyps

The majority of patients with CRS have poor quality of sleep which is associated with significantly worse quality of life scores and comorbid depression. EDS-FLU delivers intranasal steroid to superior/posterior sites of chronic rhinosinusitis inflammation where sinus ostia normally drain/ventilate and where polyps originate. EDS-FLU has recently been shown to improve primary symptoms, including nasal congestion and obstruction. This analysis examines the effect of EDS-FLU on sleep.

P441 Exhalation delivery system with fluticasone (EDS-FLU) improves peak nasal inspiratory flow (PNIF) in CRSWNP

P441 Exhalation delivery system with fluticasone (EDS-FLU) improves peak nasal inspiratory flow (PNIF) in CRSWNP