Biologics for the Treatment of Allergic Rhinitis, Chronic Rhinosinusitis, and Nasal Polyposis.

Allergic rhinitis (AR), most presentations of nasal polyposis (NP), and many presentations of chronic rhinosinusitis are type 2high disorders characterized by expression of interleukin (IL)-4, IL-5, and IL-13. Neutralization of IgE with anti-IgE (omalizumab) has proven efficacy in AR. Similarly, in addition to anti-IgE, blockade of IL-5/IL-5 (mepolizumab, reslizumab, benralizumab) and dual blockade of IL-4 and IL-13 with anti-IL-4R (dupilumab) have demonstrated efficacy in NP. However, these agents are expensive and future studies are essential to evaluate cost effectiveness in comparison with current medical and surgical therapies. This article reviews biologics as potential interventions in AR, chronic rhinosinusitis, and NP.

Systematic literature review of humanistic and economic burdens of chronic rhinosinusitis with nasal polyposis.

OBJECTIVES: We conducted a systematic literature review (SLR) of randomized controlled trials and real-world evidence (RWE) studies to determine the humanistic (e.g. health-related/disease-specific quality of life [QOL]) and economic (e.g. direct and indirect costs) burdens of chronic rhinosinusitis with nasal polyposis (CRSwNP). METHODS: The SLR adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Embase, MEDLINE and Evidence-Based Medicine Reviews databases were searched using OVID. Relevant studies involving adult patients with CRSwNP published between 1 January 2008 and 16 February 2019 were included, with relevant conference abstracts from 1 January 2017, onward. RESULTS: Sino-Nasal Outcomes Test (SNOT)-22 was the most frequently used disease-specific health-related QOL/patient-reported outcomes instrument for patients with CRSwNP. Baseline SNOT-22 scores ranged from 25 to 73 for surgical candidates and from 14 to 56 for medically managed patients with CRSwNP. Mean baseline EuroQol-5 Dimensions (EQ-5D) index for patients with CRSwNP ranged from 0.81 to 0.86, and mean baseline Short Form-6 Dimensions (SF-6D) ranged from 0.67 to 0.75. Three months (EQ-5D) and 5 years (SF-6D) post-endoscopic sinus surgery (ESS), rates increased from 0.81 to 0.89 and from 0.69 to 0.80, respectively. One year post-diagnosis, patients with CRSwNP had significantly more systemic prescriptions, underwent significantly more medical procedures, demonstrated greater health care resource utilization and had significantly greater mean health care costs compared with matched controls (all p < .001). Overall, for patients with initial ESS, CRSwNP was associated with higher disease-related expenditures compared with CRS without nasal polyposis (NP), even for patients who did not undergo revision surgery. CONCLUSIONS: This SLR identified substantial humanistic burden among surgery candidates. RWE shows that surgeries were used to treat relatively more severe CRSwNP patients as recommended by guidelines. Patient QOL is improved significantly after surgery; however, there is a lack of evidence on patients with revision surgery. Surgery is also associated with higher costs, and the presence of NP was a predictor of revision surgery. Patients with CRSwNP demonstrate greater health care resource utilization and costs compared to those with CRS without NP. Costs associated with different severity of CRSwNP and revision surgery need to be assessed further.

Direct and indirect costs of adult patients with chronic rhinosinusitis with nasal polyps.

BACKGROUND: European direct and indirect cost data is missing for patients with chronic rhinosinusitis with nasal polyps (CRSwNP). This study was aimed to establish the economic burden of CRSwNP based on a Dutch cohort of patients. METHODS: A cross-sectional study was performed in adult patients with CRSwNP (N=115) to calculate mean annual direct medical costs and indirect costs per patient with CRSwNP. Outpatient visits, general practitioner visits, first aid visits, hospitalisation and patient travel expenses were measured with the iMTA medical consumption questionnaire. Missed workdays (absenteeism) and decreased productivity during paid work (presenteeism) or during daily life were measured with the and the iMTA productivity cost questionnaire. RESULTS: Total direct costs were €1501 per patient/year, primarily due to outpatient department visits and hospitalisation. Indirect costs were €5659 per patient/year, with productivity losses as major cost expense. CONCLUSION: Adult patients with CRSwNP have higher indirect costs than direct costs and this forms a substantial burden to society. Total annual costs of patients with CRSwNP are estimated to be 1,9 billion/year in the Netherlands.

A Critical Look at the Efficacy and Costs of Biologic Therapy for Chronic Rhinosinusitis with Nasal Polyposis.

PURPOSE OF REVIEW: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly prevalent disease that results in significant healthcare-related costs as well as costs to society with lost productivity and time. Unfortunately, a significant percentage of patients who suffer with this disease will not find relief from current standard of care medications and surgery. With ongoing efforts to understand the pathophysiology of CRSwNP has come the introduction of monoclonal antibodies, or "biologics," targeting specific elements of the inflammatory pathway in CRSwNP. Despite efficacy, these come at significant cost and, to date, no studies on the cost-efficacy of these biologics in CRSwNP have been published. RECENT FINDINGS: Multiple studies have now demonstrated efficacy for biologics in the treatment of CRSwNP as a primary indication. However, the gains in quality of life and objective measures, while consistent, are small and, arguably, the clinical significance is still unclear. In addition, the high cost of these medications may be hard to justify when evaluated in cost-efficacy studies against standard of care therapy in CRSwNP. Furthermore, while the current literature is most robust in showing the benefit of the biologics in asthma, it does not fully support cost-efficacy for biologics. This review evaluates the current literature regarding efficacy of monoclonal antibodies for the treatment of CRSwNP and considers this efficacy in light of the cost implications to individuals and society.

A call for cost-effectiveness analysis for biologic therapies in chronic rhinosinusitis with nasal polyps.

OBJECTIVE: To identify the need for cost-effectiveness analysis of biologic therapies in the treatment of chronic rhinosinusitis (CRS). DATA SOURCES: Clinical trials of monoclonal antibodies (omalizumab, benralizumab, mepolizumab and dupilumab) for nasal polyposis or chronic rhinosinusitis published on PubMed. STUDY SELECTIONS: Clinical trials of biologic therapies in CRS and nasal polyposis. RESULTS: No cost-effectiveness analyses of biologic therapies in CRS have been performed. CONCLUSION: As more clinical trials of biologic therapies for CRS are conducted, there is a need for cost-effectiveness analysis. Future analyses should consider these therapies as part of medical therapeutic options compared with surgery. To increase generalizability, analyses should include samples from allergy and primary care clinics rather than only otolaryngology clinics.

Budget Impact of a Steroid-Eluting Sinus Implant Versus Sinus Surgery for Adult Chronic Sinusitis Patients with Nasal Polyps.

BACKGROUND: A corticosteroid-eluting sinus implant was recently approved by the FDA as a drug to treat adult patients with nasal polyps who have undergone previous endoscopic sinus surgery (ESS) of the ethmoid sinuses. ESS is performed in an operating room under general anesthesia, whereby diseased tissue and bone are removed to provide improved drainage. ESS typically involves dissection of 1 or more of the 4 paired sinus cavities (maxillary, ethmoid, sphenoid, or frontal). The implant, containing 1,350 mcg of mometasone furoate, is inserted by a physician in an office setting and offers controlled localized release of corticosteroid to the polypoid sinus tissue. The implant has demonstrated significant improvements in clinical testing; however, little research has been conducted on its economic impact. OBJECTIVE: To evaluate and quantify the budget impact to a commercial payer of using this implant instead of ESS in patients with nasal polyps after a previous ESS. Since essentially all patients with recurrent nasal polyps after ESS are patients with chronic sinusitis (CS) diagnosis, this study also identified patients with CS with nasal polyposis (CSwNP) for consistency with the patient population studied in clinical trials evaluating the implant. METHODS: A budget impact analysis was conducted from a U.S. commercial payer perspective over a 1-year time horizon with patients who received the implant or revision ESS. Primary outcomes of interest were annual total and per-member per-month (PMPM) direct health care costs. Costs were estimated using a decision analysis model, assuming 50% implant utilization as an alternative to revision ESS in eligible patients, with other levels (25%, 75%) also considered. The model utilized the results of a recently published analysis of 86,052 patients in the Blue Health Intelligence database, results from published clinical trials evaluating the implant, a literature review, and published Medicare national payment amounts. RESULTS: A commercial health plan with 1 million members could anticipate 1,000 CSwNP patients as candidates for receiving the implant or revision ESS. Estimated direct treatment costs for refractory CSwNP using only revision ESS are $11.03 million ($0.92 PMPM). If the implant replaced surgery in 50% of cases and if 63% those patients received a second treatment with the implant during the year, the estimated total cost savings would be $2.56 million ($0.21 PMPM). Cost savings associated with using the implant changed to $0.11 PMPM and $0.32 PMPM with implant adoption of 25% and 75%, respectively. CONCLUSIONS: In a large commercially insured U.S. population, annual revision ESS costs are substantial. Using the implant instead of revision ESS could result in considerable cost savings for payers at various levels of adoption. DISCLOSURES: This study was sponsored by Intersect ENT, which was involved in study design and manuscript review. Ernst and Imhoff are employed by CTI Clinical Trial and Consulting Services, which contracted with Intersect ENT to conduct this study. Ernst and Imhoff also report other financial support from Intersect ENT during the conduct of the study. DeConde reports personal fees from Intersect ENT during the conduct of the study, as well as personal fees from Optinose, Stryker Endoscopy, and Olympus, outside the submitted work. Manes reports grants from Intersect ENT during the conduct of the study, as well as grants from Optinose and Sanofi outside the submitted work.

Cost burden and resource utilization in patients with chronic rhinosinusitis and nasal polyps.

OBJECTIVES/HYPOTHESIS: Establish treatment patterns and economic burden in US patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) versus without chronic rhinosinusitis (CRS). Determine comparative costs of subgroups with high clinical burden. STUDY DESIGN: Observational, retrospective, case-control study. METHODS: This study matched patients with CRSwNP to patients without CRS (1:1) using the Truven Health MarketScan US claims database. Categorical and continuous variables were compared using McNemar test and paired t test (normal distribution) or Wilcoxon signed rank tests (non-normal distribution). Within subgroups, χ2 and Wilcoxon or t tests were used (normal distribution). RESULTS: There were 10,841 patients with CRSwNP and 10,841 patients without CRS included. Mean age in the CRSwNP cohort was 45.8 years; 56.2% were male. During follow-up, patients with CRSwNP had an increased diagnosis of asthma versus patients without CRS (20.8% vs. 8.1%, respectively; P < .001). Annual incremental costs were $11,507 higher for patients with CRSwNP versus those without CRS. Costs were higher in subgroups of patients with CRSwNP undergoing functional endoscopy sinus surgery (FESS), with a comorbid diagnosis of asthma, receiving oral corticosteroids, or macrolides versus the overall CRSwNP group. Patients with CRSwNP undergoing FESS had the highest costs of the four subgroups ($26,724, $22,456, $20,695, and $20,990, respectively). CONCLUSIONS: Annual incremental costs were higher among patients with CRSwNP versus without CRS. Patients with CRSwNP with high clinical burden had higher overall costs than CRSwNP patients without. LEVEL OF EVIDENCE: NA Laryngoscope, 129:1969-1975, 2019.

Uncharted Waters: Challenges in the Era of Biologic Therapies for Nasal Polyposis.

Several new, promising, targeted therapies for nasal polyposis are being tested in large-scale clinical trials. These agents target pathways thought to be involved in the disease, including IgE, IL-5, IL-4/IL-13, and others. Designing these trials poses significant challenges: who and when to enroll is not completely clear, optimal dosing is not known, outcome measures are insufficiently robust, there are no validated biomarkers, trial regimens may not comport with how clinicians might use these drugs once approved, and cost-benefit ratios have not been assessed. Thus, there is a need to consider such questions, as trials of these novel treatments continue and these biologics become available. Despite these uncertainties about trial design, there remains a great deal of excitement in the field as we approach the dawn of a new era of therapeutic options for nasal polyposis. In this rostrum, we enumerate these issues and call for a conference that will allow stakeholders in the field to confront them as we enter this new era of opportunity to advance the treatment of nasal polyposis.

The impact of asthma on the cost effectiveness of surgery for chronic rhinosinusitis with nasal polyps.

BACKGROUND: The objective of this work was to evaluate the impact of asthma on the cost-effectiveness profile of endoscopic sinus surgery (ESS) compared to medical therapy for patients with chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: The study design consisted of a cohort-style Markov decision-tree cost utility analysis with a 35-year time horizon. Matched cohorts of CRSwNP patients with (n = 95) and without (n = 95) asthma who underwent ESS were compared with cohorts of patients from the national Medical Expenditures Survey Panel (MEPS) database who underwent medical management for chronic rhinosinusitis (CRS). Baseline, 1-year, and 2-year health utility values were calculated from responses to the EuroQol-5 Dimension (EQ-5D) instrument in both cohorts. The primary outcome measure was the incremental cost effectiveness ratio (ICER) for each cohort. RESULTS: The reference cases for CRSwNP patients with and without asthma yielded ICERs for ESS vs medical therapy alone of $12,066 per quality-adjusted life year (QALY) and $7,369 per QALY, respectively. At a willingness-to-pay threshold of $50,000/QALY, the ICER scatter plots demonstrated 86% and 99% certainty that the ESS strategy was the most cost-effective option for CRSwNP patients with and without asthma, respectively. ESS was not significantly more cost effective for CRSwNP patients without asthma (p = 0.494). CONCLUSION: ESS remains cost effective compared to medical therapy for patients both with and without asthma. While the comorbidity of asthma results in an inferior ICER result, it does not result in a statistically significant negative impact on the overall cost effectiveness of ESS.

Endoscopic sinus surgery in adult patients with chronic rhinosinusitis with nasal polyps (PolypESS): study protocol for a randomised controlled trial.

BACKGROUND: Chronic rhinosinusitis with nasal polyps is a chronic disease frequently seen in otorhinolaryngological practice. Along with its chronic disease burden it creates high societal costs. Therapy consists of long-term use of medication and, if insufficient, endoscopic sinus surgery. No consensus exists on the right timing and extent of disease that warrants surgery. Furthermore, there is lack of clinical knowledge about the benefit of surgery over medication only. The current trial evaluates the clinical effectiveness and cost-effectiveness of endoscopic sinus surgery in addition to drug treatment versus medication exclusively in the adult patient group with nasal polyps. METHODS: A prospective, multicentre, superiority, randomised controlled (PolypESS) trial in 238 patients aged 18 years or older selected for primary or revision endoscopic sinus surgery by the otorhinolaryngologist was designed. Patients will be randomised to either endoscopic sinus surgery in addition to medication or medical therapy only. Relevant data will be collected prior to randomisation, at baseline and 3, 6, 12, 18 and 24 months after start of treatment. Complete follow-up will be 24 months. Primary outcome is disease-specific Health-related Quality of Life quantified by the SNOT-22 after 12-month follow-up. Secondary outcomes are generic Health-related Quality of Life, cost-effectiveness, objective signs of disease and adverse effects of treatment. Subgroup analyses will be performed to verify whether treatment effects differ among patient phenotypes. DISCUSSION: The PolypESS trial will investigate tailored care in adult patients with chronic rhinosinusitis with nasal polyps and will result in improved clinical pathways to help to determine in which circumstances to perform surgery. TRIAL REGISTRATION: Dutch Trial Register, NTR4978 . Registered on 27 November 2014.

The usefulness of routine histopathology of bilateral nasal polyps - a systematic review, meta-analysis, and cost evaluation.

BACKGROUND: Controversy regarding the usefulness of routine histopathological examination of bilateral nasal polyps removed during endoscopic sinus surgery to identify occult diagnoses still exists. There is a paucity of high-level evidence in the literature. METHODS: A systematic review and meta-analysis was conducted. Two independent reviewers were used. Pooled proportions and numbers needed to screen were calculated. A cost per life year model was generated based on varying survival benefits and compared to other Canadian screening programs to provide financial context. RESULTS: Six studies (n = 3772 patients) were included. Of the 3772 patients, 3751 had a pre-operative clinical and post-operative pathological diagnosis of inflammatory nasal polyps. Agreement proportion was 99.44 %. There were 18 unexpected benign and three unexpected malignant diagnoses identified. This translated to a proportion of 0.48 and 0.08 % respectively. Number needed to screen was 210 and 1258 respectively. Pooled proportion for expected findings using a random effect model was 0.99 (95 % CI = 0.99-1). Pooled proportion for unexpected benign findings using a random effect model was 0.00522 (95 % CI = 0.00133-0.01). Pooled proportion for unexpected malignant findings using a random effect model was 0.00107 (95 % CI = 0.000147-0.00283). The cost to pick up one unexpected benign diagnosis was $14557.2. The cost to pick up 1 unexpected malignant diagnosis was $87204.56. Cost per quality life year calculated ranged from 3211.83 to $64677.58 based on varying assumptions on the survival benefits of identifying an unexpected malignancy. CONCLUSIONS: Routine pathological examination in screening for neoplasia may be low yield, however, no compelling evidence was found to cease such practice. Surgeons should exercise individual judgment in requesting routine examination.

The utility of routine polyp histopathology after endoscopic sinus surgery.

BACKGROUND: Routine histopathological assessment is standard practice for nasal polyp specimens obtained during endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS). Retrospective studies suggest that routine histopathology of nasal polyps shows few unexpected diagnoses that alter patient management. Our objective was to study the use of routine pathological analysis, and its cost to the healthcare system, in a prospective manner. METHODS: A multicenter prospective assessment was performed from data collected between 2007 and 2013. Only cases of patients undergoing ESS for bilateral CRS were included. We excluded unilateral disease cases, and cases in which diagnoses other than polyps were suspected either preoperatively or intraoperatively. We then compared the preoperative diagnosis with the final histopathology and identified the rate of unexpected pathologies. A cost analysis was performed. RESULTS: Only 4 of 866 pathological specimens were identified as having a clinically significant unexpected diagnosis. All unexpected pathologies in this series were benign. These 4 cases account for 0.46% of all specimens reviewed. This translates to a number needed to screen of 217 cases of bilateral CRS to discover 1 unexpected pathology. The associated cost for making an unexpected diagnosis was $19,192.73. CONCLUSION: Routine histopathology of nasal polyps in ESS for bilateral CRS with polyps yields few unexpected and management-altering diagnoses. It carries a significant cost to the healthcare system. In cases of bilateral CRS with no other concerning clinical features, clinicians should exercise judgment in submitting polyp specimens for pathology rather than routinely sending polyps for histopathologic analysis.

When do the risks of repeated courses of corticosteroids exceed the risks of surgery?

BACKGROUND: The management of chronic rhinosinusitis with nasal polyposis (CRSwNP) becomes unclear when patients require multiple courses of corticosteroids to maintain quality of life. Repeated courses of corticosteroids carry increased risks to patients. Although endoscopic sinus surgery (ESS) is an effective therapeutic modality, it also carries inherent risks. This study aims to identify the threshold at which the risks of repeated courses of corticosteroid exceed the risks of surgery. METHODS: An evidence-based risk analysis was simulated using literature-reported complication rates, quality of life changes, and Medicare costs. Simulations were performed from the Medicare patient perspective, societal perspective, and the universal healthcare patient perspective. RESULTS: All 3 simulations demonstrate a breakeven threshold favoring surgery over medical therapy when patients require oral corticosteroids (OCS) more often than once every 2 years in CRSwNP, once per year in CRSwNP/asthma, or twice per year for Samter's triad patients. CONCLUSION: This represents the first rationalized evidence-based analysis for when surgery should be considered in place of repeated courses of oral corticosteroids. This threshold provides a guide for otolaryngologists to use when making clinical decisions with patients.

Assessing the additional disease burden of polyps in chronic rhinosinusitis.

OBJECTIVES: This study was undertaken to determine the differential disease burden between chronic rhinosinusitis (CRS) cases with and without nasal polyposis (NP). METHODS: A consecutive series of adult patients who met clinical and radiographic criteria for CRS was assessed with the Rhinosinusitis Symptom Inventory, nasal endoscopy, and computed tomography. Three clinical groups were examined: 1) CRS without NP, 2) CRS with primary NP (no prior surgery), and 3) CRS with recurrent NP (prior surgery). The groups were compared with respect to symptom presentation, medical resource utilization, and medication costs. RESULTS: Two hundred eighty-six CRS cases without NP, 131 CRS cases with primary NP, and 45 CRS cases with recurrent NP were studied; their mean Lund scores were 8.8, 13.2, and 16.3, respectively (p < 0.001). Statistically significant differences in severity for nasal (p = 0.002), facial (p = 0.025), oropharyngeal (p = 0.017), and systemic symptoms (p = 0.042) between groups were noted, whereas total symptoms did not differ between groups (p = 0.339). Medication use and physician visits were similar between groups (p = 0.335 and p = 0.951, respectively). The aggregate yearly medication costs were significantly greater for the recurrent polyp group ($866) than for either the non-polyp group ($570; p = 0.013) or the primary polyp group ($565; p = 0.020). CONCLUSIONS: Patients with non-polyp CRS and those with primary polyp CRS present with different symptom phenotypes, but exhibit similar total symptom burdens and medical resource consumption. The presence of polyps does not necessarily confer a dramatic additional disease burden in CRS.

Cost effectiveness of nasal budesonide versus surgical treatment for nasal polyps.

OBJECTIVE: To conduct a cost-effectiveness study of nasal budesonide versus surgical treatment in the management of nasal polyps. DESIGN AND METHODS: A decision-tree model reflecting two different treatment strategies for nasal polyps in Sweden was developed. The first strategy was initial polypectomy, performed under three different sets of circumstances: inpatient functional endoscopic surgery, outpatient evulsion with sedation, or outpatient evulsion with local anaesthesia; all treatments were followed by intranasal treatment with budesonide (Rhinocort) 128 microg twice daily. The second strategy was initial intranasal treatment with budesonide 128 microg twice daily. PERSPECTIVE: Healthcare provider perspective. OUTCOME MEASURES AND RESULTS: After 1 month, treatment with nasal budesonide was classified as a success (82.5%) or a failure (17.5%) based on clinical study data. In cases of success, the treatment was continued, and in cases of failure, polypectomy was undertaken, followed by budesonide 128 microg twice daily. Treatments were evaluated after 4 months using prices from the Central Hospital in Skövde, Sweden. The expected reduction in cost from using initial nasal budesonide treatment compared with the different alternatives of polypectomy were 9760 Swedish kronors (SEK) for inpatient functional endoscopic surgery, SEK2747 for outpatient evulsion with sedation, and SEK672 for outpatient evulsion with anaesthesia (1998 values). Nasal budesonide 128 microg twice daily treatment for nasal polyps revealed a potential reduction in costs of 53% compared with the primary surgery approach. CONCLUSION: Initial treatment of nasal polyps with nasal budesonide provides lower costs than treatment with initial polypectomy with maintained effectiveness.

All nasal polyps need histological examination: an audit-based appraisal of clinical practice.

Case details were reviewed from 2021 patients treated surgically for nasal polyposis between 1991 and 1999, seen by six surgeons serving a catchment population of 805,000. The aim of this study was to determine the incidence of discrepancies between clinical and histological diagnosis. Twenty-two patients (1.1 per cent) were identified as having a lesion that differed histologically from the clinical diagnosis made at the time of surgery and which altered their further management. Amongst them were 11 cases of inverted papilloma, two of Wegener's granulomatosis; and two of sarcoid. The rest of the cases comprised three of squamous cell carcinoma, one of adenocarcinoma, one of myeloma, one of angiofibroma and one of microcystic papillary adenoma. In this series, the occurrence of malignancy, inverted papilloma, or other clinically significant pathology among the group of patients with otherwise clinically unsuspected histology justifies sending nasal polyps for routine pathologic examination. A cost-benefit analysis showed that, on the basis of 250 cases per year, the cost of laboratory and pathological services would be 12,000 Pounds, in comparison with the estimated average medicolegal cost of 51,000 Pounds per year incurred as a result of a delay in diagnosis together with the pain and suffering which would result given the case mix in this series.

Healthcare expenditures for sinusitis in 1996: contributions of asthma, rhinitis, and other airway disorders.

BACKGROUND: There have been no recent assessments of the economic burden of sinusitis in the peer-reviewed literature. OBJECTIVE: We sought to estimate the 1996 total direct health care expenditures for the treatment of sinusitis. METHODS: This study determined (1) direct expenditures of medical and surgical encounters in which sinusitis was the primary diagnosis and (2) attributable expenditures when related airway diseases were the primary diagnosis and sinusitis was a comorbid condition. An expert panel used the Delphi consensus-building technique to determine the proportions for the latter. RESULTS: Overall health care expenditures attributable to sinusitis in 1996 were estimated at $5.8 billion, of which $1.8 billion (30.6%) was for children 12 years or younger. A primary diagnosis of acute or chronic sinusitis accounted for 58.7% of all expenditures ($3.5 billion). About 12% each of the costs for asthma and chronic otitis media and eustachian tube disorders were attributed to diagnosis and treatment of comorbid sinusitis. Nearly 90% of all expenditures ($5.1 billion) were associated with ambulatory or emergency department services. CONCLUSION: The economic burden of sinusitis in the United States is significant. However, the limitations of this type of evaluation suggest the $5.8 billion amount may be an underestimate of the true direct costs.

Intranasal fluticasone propionate. A reappraisal of its pharmacology and clinical efficacy in the treatment of rhinitis.

The intranasal corticosteroid fluticasone propionate is an effective agent for the treatment of rhinitis, demonstrating potent local anti-inflammatory activity and little, if any, systemic activity. Intranasal fluticasone propionate has shown clinical efficacy similar to that of other intranasal corticosteroids, including beclomethasone (administered at up to a 2-fold higher dosage than fluticasone), budesonide, flunisolide and triamcinolone acetonide, and provides greater relief from nasal symptoms (including nasal blockage) than antihistamine agents and intranasal sodium cromoglycate. Its efficacy in the treatment of seasonal allergic rhinitis and perennial allergic and nonallergic rhinitis has been demonstrated in large well-controlled studies in which the drug maintained adequate control of symptoms when administered in a once daily dose of 200 micrograms. In addition, fluticasone propionate has shown similar efficacy to that of beclomethasone in the treatment of nasal polyps; however, its use in the postoperative setting requires further investigation. Intranasal fluticasone propionate is well tolerated in the majority of patients, the incidence of adverse events being similar to that seen with placebo. Pharmacoeconomic analyses indicate that intranasal fluticasone propionate is significantly more cost-effective than the antihistamines terfenadine and loratadine. Overall quality of life was improved to a similar extent by fluticasone propionate and beclomethasone. In conclusion, recent clinical experience has confirmed that intranasal fluticasone propionate is a convenient, effective and well tolerated alternative to other intranasal corticosteroids and antihistamines for the treatment of rhinitis when administered once daily.