Allergic rhinitis (AR) is a highly prevalent disease, affecting

Cost Efficiency of Intranasal Corticosteroid Prescribing Patterns in the Management of Allergic Rhinitis DEBI REISSMAN, PharmD; TOM PRICE, BA; and CHRISTOPHER W. LEIBMAN, PharmD, MS ABSTRACT BACKGROUND: Effective treatment of seasonal or perennial allergic rhinitis often requires use of topical intranasal corticosteroids (INSs). Despite differences in recommended starting dosages, the 4 leading INSs by market share are packaged in bottles containing 120 metered-dose sprays. OBJECTIVE: To determine the relative prescribed dosages of the leading INSs and compare economic differences resulting from these prescribing behaviors. METHODS: The IMS National Disease and Therapeutic Index (NDTI) was used to identify prescribing habits for the 4 leading INSs: fluticasone propionate nasal spray (), mometasone furoate aqueous nasal spray (), triamcinolone acetonide aqueous nasal spray (), and budesonide aqueous nasal spray (). The NDTI uses a national, randomly drawn, 2-stage stratified clustersampling methodology. Physicians are sampled during the first stage, with 2 workdays per month subsampled from each physician in the second stage. Each physician reports on all patient contacts during the 2 consecutive days, offering a continuing compilation of statistical information about patterns and treatment of disease encountered by office-based physicians. In a given month, the NDTI reports on 1,180 unique physicians. RESULTS: From January 1, 2002, to December 31, 2002, 58% of prescriptions for were for 4 sprays daily with 37% for 2 sprays daily, : 44% for 4 sprays and 52% for 2, : 65% for 4 sprays and 31% for 2, and : 29% for 4 sprays and 68% for 2. These equated to mean prescribed daily dosages of 3.47 sprays per day for, 3.33 for, 3.50 for, and 2.73 for. Because each INS is packaged in a bottle with 120 metered-dose sprays, the differences in dosage offer varying days of supply per unit filled. offered the most days of treatment (44 days), followed by (38 days) and and (means of 35 and 34 days, respectively) per single prescription filled. Cost per day of treatment was calculated by multiplying the prescribed dosage with the average wholesale price of the products. had the lowest cost per day of treatment at, with each other INS costing at least an additional $0.26 daily ( $1.80; ; $1.97). CONCLUSION: Based on physician prescribing patterns of INSs from the NDTI database, offers more days of treatment at a lower cost per day than other leading INSs. KEYWORDS: Allergic rhinitis, Intranasal corticosteroids, Budesonide, Fluticasone propionate, Mometasone furoate, Triamcinolone acetonide, Prescribing patterns, Cost-efficiency, Model simulation J Manag Care Pharm. 2004;10(1)(suppl S-a):S9-S13 Authors DEBI REISSMAN, PharmD, is president, Rxperts, Irvine, California; TOM PRICE, BA, is Business Insight leader, Respiratory and Inflammatory Therapeutic Area, and CHRISTOPHER W. LEIBMAN, PharmD, MS, is associate director, Health Economics and Outcomes Research (HECON/OR), Respiratory and Inflammation Therapeutic Area, both at AstraZeneca LP, Wilmington, Delaware. AUTHOR CORRESPONDENCE: Debi Reissman, PharmD, President, Rxperts Managed Care Consulting, 7700 Irvine Center Dr., Suite 800, Irvine, CA 92618. Tel: (949) 788-2979; Fax: (949) 788-2979; E-mail: debi@rxperts.net Copyright 2004, Academy of Managed Care Pharmacy. All rights reserved. Allergic rhinitis (AR) is a highly prevalent disease, affecting 20 to 40 million people in the United States annually. 1 The economic burden of AR is large, with estimates as high as $5.3 billion 2 and $7.7 billion 3 for total direct and indirect costs associated with this disease. Much of the direct costs are due to prescription medication use and ambulatory care. For example, prescriptions for antihistamines and intranasal corticosteroids (INSs) in 1999 exceeded $3 billion and $1 billion, respectively. 4 It has also been reported that approximately 80% of indirect costs are attributed to time lost from work, and 17% of these costs are attributed to at-work productivity loss. 5 These numbers point out the tremendous economic burden of AR and the importance of identifying the most cost-effective treatment for this condition. Currently, numerous medical treatments are available for the treatment of AR, including oral decongestants, sedating antihistamines, second-generation less-sedating antihistamines, mast cell stabilizers, INSs, leukotriene receptor antagonists (LTRAs), nasal anticholinergics, and immunotherapy. In this era of limited health care economic resources, it is vitally important to distinguish which therapy for AR is most clinically effective and cost effective. In terms of drug classes, antihistamines and INSs have been the cornerstones of therapy and are the most prevalent medications used to treat the symptoms of AR. 6 The most recent medication class to be approved for treatment of AR is the LTRAs; however, a recent review found that they were no more effective than lesssedating antihistamines and were less effective than INSs for treatment of AR. 7 Several reviews and meta-analyses 8-10 have found that INSs are more effective than oral and topical antihistamines in reducing the symptoms of AR, in particular nasal blockage. Although recently established guidelines by the World Health Organization in collaboration with the Allergic Rhinitis and Its Impact on Asthma (ARIA) Workshop have classified INSs as the most effective pharmacologic treatment of AR, 6 they still recommend antihistamines as first-line treatment for mild intermittent symptoms of AR. Antihistamines and INSs, in no preferred order, can be used as first-line treatment for moderate to severe intermittent symptoms or mild persistent symptoms of AR. For the treatment of moderate to severe persistent symptoms of AR, only INSs are recommended as first-line treatment. 1,6,11 If INSs are chosen for treatment, the next step is to determine which INS to use and the appropriate dosing. It would be important to know which INS of the many that are currently available is the most clinically effective and most cost-efficient product. There are 6 INSs currently available for treatment of AR: fluticasone propionate nasal spray (, Flonase), mometasone furoate nasal spray (, Nasonex), triamcinolone acetonide nasal spray (, Nasacort), budesonide aqueous nasal spray (, Rhinocort Aqua), beclomethasone dipropionate (Beconase AQ), and flunisolide (Nasalide and Nasarel, generic flunisolide). www.amcp.org Vol. 10, No. 1, S-a January 2004 JMCP Supplement to Journal of Managed Care Pharmacy S9

Clinical studies and comparison trials have found that all of these INSs demonstrate approximately the same level of efficacy for treating the symptoms of AR. 8,10,12,13 They have also been found to be safe and generally well tolerated. 8,10,12,13 Of these INSs,,,, and are the leading INSs by market share (approximately 96% of the market). 14 All 4 of these INSs are dispensed in bottles containing 120 metereddose sprays. However, the recommended once-daily adult starting dosage, based on manufacturer s prescribing information, varies: is 2 sprays per nostril (200 µg total dose), is 2 sprays per nostril (200 µg total dose), is 2 sprays per nostril (220 µg total dose), and is 1 spray per nostril (64 µg total dose). Because of these differences, there may be an economic advantage of certain INSs over others based on actual prescribing patterns. Access to a centralized database containing physician-reported patient data would provide the necessary records for examination of prescription and drug utilization information as it pertained to specific products and diseases. The National Disease and Therapeutic Index (NDTI) database 15 is one such database that provides data on how products are actually being prescribed in clinical practice to help determine prescribing patterns and identify utilization. Modeling monetary units onto the data results generated from the NDTI on the 4 leading INSs can provide information about real-world prescribing patterns and treatment costs for each product. Economic differences identified between the 4 leading INSs can then be evaluated to help establish the efficiency frontier for AR (for a detailed description, see Part I of this supplement), providing a value-based strategy for the treatment of AR. The aim of this study was to determine the relative prescribed dosages of the leading INSs and to compare economic differences resulting from these prescribing behaviors. Methods NDTI, 15 a product of IMS Health, was used to identify prescribing patterns for the 4 leading INSs by market share:,,, and. Percent of Patients per Prescribed Dosage FIGURE 1 100 80 60 40 20 0 NDTI --- Prescriptions Written; Doses per Day* 8 Sprays qd 4 Sprays qd 2 Sprays qd Percent of patients receiving written prescriptions for,,, and by dosages. = budesonide aqueous nasal spray; = fluticasone propionate nasal spray; = mometasone furoate nasal spray; = triamcinolone acetonide nasal spray. *Data based on prescriber-reported dosing generated from the IMS National Disease and Therapeutic Index (NDTI) January 1, 2002, to December 31, 2002. qd = once a day. FIGURE 2 50 40 3% 29% 68% 5% 4% 4% 58% 37% 44% 52% 65% 31% Mean Days of Treatment Supply per Prescription Based on the Mean Prescribed Daily Dosage* National Disease and Therapeutic Index The NDTI database has been available since 1958 and continually updates and compiles statistical information about patterns and treatment of disease encountered by office-based physicians. Information is gathered from all primary specialties involved in direct patient care. The NDTI panel of physicians currently consists of more than 3,600 physicians in a variety of therapeutic areas. Of these physicians, there are currently 150 participating allergists who are primary specialists within allergy, allergy and immunology, immunology, and pediatric allergy. These physicians are drawn from 9 different census regions: New England and Middle Atlantic (East), East North Central and West North Central (Midwest), South Atlantic, East South Central, West South Central (South), and Mountain and Pacific (West). Mean Number of Days 30 20 10 43.61 34.56 38.21 33.57 0 *Mean days of treatment supply per prescription (one bottle) of,,, and as written most commonly by physicians. = budesonide aqueous nasal spray; = fluticasone propionate nasal spray; = mometasone furoate nasal spray; = triamcinolone acetonide nasal spray. S10Supplement to Journal of Managed Care Pharmacy JMCP January 2004 Vol. 10, No. 1, S-a www.amcp.org

FIGURE 3 LEGEND Mean Cost-per-Day Calculations Using as an Example: 68% of patients prescribed received 2 sprays per day. 29% of patients were prescribed 4 sprays per day. 3% of patients were prescribed 8 sprays per day. AWP for = $67.29 per 120 metered-dose bottle. Cost of per spray = $0.56. mean cost/day = (0.68 $1.12) + (0.29 $2.24) + (0.03 $4.49). mean cost/day =. All calculations used the AWP of the INSs based on prices reported by First Data Bank as of January 15, 2003. = budesonide aqueous nasal spray; = fluticasone propionate nasal spray; = mometasone furoate nasal spray; = triamcinolone acetonide nasal spray. AWP = average wholesale price. INSs = intranasal corticosteroids. FIGURE 3.D Model Scenario Comparing With $1.80 $1.97 0.307 0.645 0.048 $1.10 $2.21 $4.41 FIGURE 3.A FIGURE 3.B Cost-per-Day Calculations Using as an Example 0.679 $1.12 $2.24 0.293 0.028 Model Scenario Comparing With 0.369 0.578 0.053 $4.49 $1.08 $2.17 $4.33 The NDTI database uses a national, randomly drawn, 2-stage stratified cluster-sampling methodology. During the first stage, a sample population of physicians is generated from American Medical Association and American Osteopathic Association physicians who are recruited for participation based on location and therapeutic specialty. In the second stage, 2 workdays per month are sampled from each physician. All patient contact during the 2 consecutive days is reported by each physician. In a given month, the NDTI database reports on 1,180 unique physicians, and data are collected on at least 2,454 workdays. Some of the information this database provides includes information about current and long-term trends in drug therapy/utilization, medical conditions for which they are prescribed, and drug profiles, patient profiles, and physician profiles. The NDTI database also has the capacity to estimate the actual number of patients using a precise product for a specific disease. Prescribed Dosage Analysis The number of days of treatment was calculated by taking the number of metered sprays in each INS bottle (120 for all 4 INSs) divided by the actual NDTI provider data from prescriptions written to evaluate the mean number of days of treatment per prescription by product. FIGURE 3.C Model Scenario Comparing With $1.80 0.516 0.441 0.043 $1.15 $2.29 $4.58 Model Simulation A model simulation was run based on prescriber-reported dosing generated from the IMS NDTI from January 1, 2002, to December 31, 2002. The scenario run used the average wholesale price (AWP) of the INSs based on prices reported by First Data Bank as of January 15, 2003. 16 The model scenario reports results in cost per product per day. Since the 4 leading INSs are indicated for treatment of both perennial and seasonal AR, treatment lengths vary by patient and by disease severity. For this reason, a more accurate population cost metric is cost per treated day. The models are based on cost only and do not provide information on the efficacy and safety of the INS products evaluated. www.amcp.org Vol. 10, No. 1, S-a January 2004 JMCP Supplement to Journal of Managed Care Pharmacy S11

The efficacy and safety of these products have been reviewed in the literature and found to be similar. 8,10,12,13 Key model assumptions were that (1) results from the NDTI can be generalized to the target population and (2) utilization of products is equal to prescribed doses. Cost Analysis The cost per day per dosage (cost per 2, 4, and 8 sprays daily) was calculated from the AWP for INS dosages per spray bottle. For example, the cost per day for a 2-sprays-per-day dosage = AWP/(sprays per bottle/2). The cost per day of each INS (calculated from the patients in which the prescribed dosage was known [>90% of patients]) = (percentage of patients prescribed 2 sprays daily x cost per day for 2 sprays) + (percentage of patients prescribed 4 sprays daily x cost per day for 4 sprays) + (percentage of patients prescribed 8 sprays daily x cost per day for 8 sprays). Dollars Per Day FIGURE 4 $ 2.00 $ 1.50 $1.00 $ 0.50 Mean Cost per Day of Treatment Based on the Mean Prescribed Daily Dosage $ 1.54 $ 1.88 $ 1.80 $ 1.97 Results Prescriptions Written The actual provider data from prescriptions written examines realworld prescribing habits. The percent of patients who received written prescriptions for,,, and by dosages are shown in Figure 1. The mean prescribed sprays per day for (2.75) was less than for (3.47), (3.14), and (3.57). patients were prescribed the lowest starting dosage of 1 spray per nostril each day more often than the other leading INSs. Evaluation of the mean days of treatment supply per prescription showed that provided the greatest number of treatment days, as written most commonly by physicians in the NDTI database, per bottle compared with,, and (Figure 2). Cost Analysis The AWP of each of the 4 leading INSs as of January 15, 2003, was $65.01 for, $68.73 for, $66.21 for, and $67.29 for. The cost per day by dosage is similar for all 4 INSs; however, when the actual percentage of patients who were prescribed each dosage is factored into the model scenario (Figure 3), at per day, was found to have the lowest cost per day of treatment compared with,, and (Figure 4). The mean cost per day for,, and was at least $0.26 more than for. Discussion Although all 4 leading INSs come in a bottle containing 120 metered-dose sprays, prescription duration varies because the prescribed daily dosage of these products varies. While the acquisition cost of these bottles are similar, when actual prescribed dosages and percentage of patients actually prescribed these dosages were factored into the model scenario analysis, differences in the costs per treated day were revealed. patients were prescribed the lowest possible dosage of 1 spray per nostril more $ 0.00 The mean cost per day of treatment with,,, and. = budesonide aqueous nasal spray; = fluticasone propionate nasal spray; = mometasone furoate nasal spray; = triamcinolone acetonide nasal spray. often than the other 3 INSs investigated. Because all 4 INS bottles contain the same number of metered-dose sprays (120), provides more days of treatment supply per prescription than the other INSs, which leads to a lower cost per day of treatment. This is an important result since patients and physicians are faced with numerous options for treating AR; however, in the current economic climate, where health care resources are limited, there is a need to evaluate the best option for maximizing benefit per unit cost. The results of this cost analysis, or cost-minimization analysis (analysis to determine lowest cost alternative when the consequences of treatment, efficacy and safety, are equivalent), 17 show that even for products with similar efficacy and safety profiles, potential economic differences do exist. As described in Part I of this supplement, the information from this cost-minimization analysis can be applied to develop an efficiency frontier for AR to help in making value-based treatment decisions. This is of particular importance given that the 4 leading INSs have been shown repeatedly to have similar safety and efficacy profiles and differ primarily on sensory attributes (i.e., taste, scent). 18-21 Awareness of the economic differences of these products in addition to patient preference could lead to more cost-efficient prescribing patterns for the management of AR. It is important to note that the model scenarios in this study were based solely on the prescribing behaviors reported through the NDTI and on AWP prescription costs as reported by First Data Bank. Although we were able to successfully identify prescribing patterns, we did not have any patient-level data on the rationale for S12 Supplement to Journal of Managed Care Pharmacy JMCP January 2004 Vol. 10, No. 1, S-a www.amcp.org

treatment selection, patient history, or diagnosis. This study also used cost per day as the economic unit of comparison among products versus other cost-unit measures. This study evaluated INS prescriptions for all patients with AR and did not separate patients into subgroups by type of symptoms, disease severity, or duration. Thus, the cost-per-day unit of measure appeared most appropriate. For future comparisons of products, depending on the patient population and other pertinent variables of the products, a different economic unit of measure may be more appropriate. Conclusion Evaluation of INS prescribing patterns shows that patients are prescribed the lowest starting dosage of (1 spray per nostril daily) more often than the other 3 leading INSs. In addition, results of the model scenario show that had the lowest daily cost for the treatment of AR compared with,, and. DISCLOSURES Funding for this research was provided by AstraZeneca LP and was obtained by author Christopher Leibman. Authors Leibman and Tom Price are employed by AstraZeneca LP. Author Debi Reissman is a paid consultant with several pharmaceutical companies, including AstraZeneca. Reissman served as principal author of the study. Study concept and design, analysis and interpretation of data, and statistical expertise were the work of Leibman and Price. Drafting of the manuscript was primarily the work of Leibman, and its critical revision was the work of Reissman and Leibman. REFERENCES 1. Dykewicz MS, Fineman S, Skoner DP, et al. Diagnosis and management of rhinitis: complete guidelines of the Joint Task Force on Practice Parameters in Allergy, Asthma and Immunology. American Academy of Allergy, Asthma, and Immunology. Ann Allergy Asthma Immunol. 1998;81:478-518. 2. Ross RN. The cost of allergic rhinitis. Am J Manag Care. 1996;2:285-90. 3. 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Gerson I, Green L, Fishken D. Patient preference and sensory comparisons of nasal spray allergy medications. J Sens Stud. 1999;14:491-96. 21. Bachert C, El-Akkad T. Patient preferences and sensory comparisons of three intranasal corticosteroids for the treatment of allergic rhinitis. Ann Allergy Asthma Immunol. 2002;89:292-97. www.amcp.org Vol. 10, No. 1, S-a January 2004 JMCP Supplement to Journal of Managed Care Pharmacy S13