In patients with mild asthma, mometasone furoate dry powder inhaler resulted in improved adherence and fewer exacerbations than beclomethasone dipropionate hydrofluoroalkane aerosol inhaler.
To evaluate adherence to therapy and markers of asthma control among patients with mild asthma prescribed mometasone furoate dry powder inhaler or beclomethasone dipropionate hydrofluoroalkane aerosol inhaler.
Retrospective healthcare claims database analysis (2005-2008).
Included were patients with mild asthma aged 12 to 65 years (1273 matched patients in each treatment cohort) who resided in the United States and were enrolled in their health plan for at least 1 year before (ie, preindex period) and after (ie, postindex period) they initiated treatment with mometasone furoate or beclomethasone dipropionate. Patients were propensity score matched based on demographic data and preindex variables. Claims were analyzed during the postindex period for adherence to mometasone furoate or beclomethasone dipropionate, measured as the percentage of days covered and the numbers of exacerbations and short-acting ß2-agonist (SABA) claims.
Multivariate analyses indicated that the cohort receiving mometasone furoate had better outcomes than the cohort receiving beclomethansone dipropionate, including greater adherence (29.5% vs 20.2%, respectively, P <.001), fewer exacerbations (mean, 0.12 vs 0.19, P = .002), and decreased SABA canister claims (mean, 0.9 vs 1.1, respectively, P <.001).
Adherence to prescribed therapy among patients with mild asthma may be better with mometasone furoate versus beclomethasone dipropionate, as reflected in fewer exacerbations and more limited use of SABA rescue medications. Improved adherence to mometasone furoate versus beclomethasone dipropionate may be related to a simpler dosing regimen (ie, once daily vs twice daily).
(Am J Manag Care. 2010;16(7):e151-e156)
This retrospective healthcare claims database analysis provides a real-life perspective on adherence to inhaled corticosteroid therapy among patients with mild asthma.
National Asthma Education and Prevention Program (NAEPP) guidelines1 recommend inhaled corticosteroids (ICSs) as first-line treatment for mild persistent asthma. Although ICSs are often considered similar in terms of clinical efficacy and safety,2 differences between inhalers in prescribed dosing regimens or variations in the device may affect patient adherence. This has the potential to significantly affect asthma control and patient outcomes. Current NAEPP guidelines highlight the importance of assessing and encouraging patient adherence to prescribed asthma medication for optimizing asthma control. Previous studies3-5 have shown that reduced adherence to prescribed ICS therapy among patients with asthma can significantly and negatively affect asthma control scores, numbers of exacerbations, and frequency of emergency department visits.
Mometasone furoate dry powder inhaler (Asmanex; Merck & Co, Inc, Kenilworth, NJ) and beclomethasone dipropionate hydrofluoroalkane aerosol inhaler (Qvar; 3M Drug Delivery Systems, Northridge, CA) are 2 ICSs that are commonly prescribed for treating patients with mild persistent asthma. Mometasone furoate is indicated for use with a once-daily dosing regimen for most patients,6 whereas beclomethasone dipropionate is indicated for use with a twice-daily dosing regimen for all patients.7 The dosing regimen of a prescribed asthma treatment is an important component of asthma therapy and has the potential to affect patient outcomes. Previous data indicate that reducing the number of daily doses of a prescribed treatment increases patient adherence to therapy.8 Among patients with asthma, greater treatment adherence has been associated with improved patient outcomes, including better asthma control scores,3,4 reduced emergency department visits,5 and fewer oral corticosteroid prescriptions.5
In the present study, we conducted a retrospective healthcare claims database analysis to evaluate asthma-related health resource utilization among patients with mild asthma (previously receiving asthma-related therapy) who obtained prescriptions for mometasone furoate or beclomethasone dipropionate. The objectives of the study were to determine if there were differences in adherence and markers of asthma control, including asthma exacerbation rates and short-acting β2-agonist (SABA) canister claims, between cohorts of patients with mild asthma prescribed mometasone furoate versus beclomethasone dipropionate therapy.
Retrospective healthcare claims analyses were performed using an administrative claims database (Ingenix LabRx, Eden Prairie, MN). There were approximately 37 million patients in the database during the time frame analyzed, all of whom resided in the United States (43% in the South, 33% in the Midwest, 13% in the West, and 11% in the Northeast). We identified claims representing the first date of a mometasone furoate or beclomethasone dipropionate prescription (ie, index date); examined these claims between January 1, 2005, and June 30, 2008; and selected patients with mild asthma (aged 12-65 years) who were enrolled in their health plan for at least 1 year before and at least 1 year after their index date and had prior claims for asthma-related medications.
Patient demographics, comorbidities, and asthma resource utilization for each patient were measured for 365 days before his or her index date (preindex period) and for 365 days after his or her index date (postindex period). Comorbidities could have occurred at any time during the preindex period. Patients with mild asthma were defined as those who were assigned an International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) code of 493.0x, 493.1x, or 493.9x and who did not have claims that indicated use of more than 2 SABA canisters or experienced an asthma exacerbation within 12 months before the index date. The fact that this analysis was a retrospective claims database study precluded access to clinical information that could have been used to classify patients based on NAEPP guidelines.1 As such, the current definition of mild asthma was used and adapted from that in previous retrospective claims database studies9-11 that also categorized patients based on asthma severity.
All patients had no chronic pulmonary condition other than asthma (ie, no patient was designated as having an ICD-9-CM code of 415x, 416x, 417x, 491x, 491.2x, 492x, 493.2x, 494x, or 770.2x). Patients in the cohort receiving mometasone furoate who received beclomethasone dipropionate within 7 days of the index date or vice versa were excluded. Patients who qualified for both the cohort receiving mometasone furoate and the cohort receiving beclomethasone dipropionate or had claims for an ICS or long-acting β2-agonist combination product within 7 days of the index date were also excluded.
Postindex claims were analyzed for adherence to index drugs (mometasone furoate or beclomethasone dipropionate) and the numbers of exacerbations and SABA claims. Adherence was measured as the percentage of days covered and was defined as the percentage of days that patients had access to medication based on prescription fill frequency and assuming daily drug use as indicated. For example, patients who refilled their index drug prescription the same day the prescription was scheduled to run out throughout the postindex period had a percentage of days covered of 100%; patients who did not, had a percentage of days covered of less than 100%. An asthma exacerbation was defined as an asthma episode that required treatment in an emergency department, hospitalization, or an outpatient visit during which a patient received nebulization or a prescription for oral corticosteroids.9 The number of mean exacerbations per patient for each cohort during the postindex period was assessed. Asthma days were defined as distinct days when there was a medical record with any diagnosis of asthma.
Treatment cohorts were matched 1:1 according to preindex demographics and comorbidities using a greedy algorithm.12 Cohorts were compared using bivariate analysis (ie, c2 or Wilcoxon rank sum test) for the preindex period. The relationship between postindex outcomes variables and treatment cohorts was examined using multivariate generalized linear regression modeling to control for the effect of preindex comorbidities, demographics, and resource utilization that were not accounted for in the propensity score matching. For all analyses, 2-sided P <.05 was considered statistically significant.
Unmatched Patients. The initial selection process identified 3064 patients with mild asthma who received mometasone furoate and 1273 patients who received beclomethasone dipropionate (). On average, patients with mometasone furoate or beclomethasone dipropionate claims were approximately 40 years of age, and about 61% to 65% of patients in both drug cohorts were female (). There were no significant differences between treatment groups in the mean number of preindex SABA canister claims. Except for rhinitis, there were no significant differences between the unmatched patient cohorts in the incidences of any measured preindex comorbidities.
Propensity Score—Matched Patients. The total sample size for the matched patient population was 2546 (ie, 1273 patients in each drug cohort) (). A comparative analysis of the preindex propensity score—matched variables indicated that the cohorts receiving mometasone furoate and beclomethasone dipropionate were well matched. Comparisons between cohorts indicated that all preindex variables were associated with P >.05, except for the incidence of sinusitis (32.4% for mometasone furoate and 36.1% for beclomethasone dipropionate, P <.05).
Multivariate Generalized Linear Regression Modeling Analyses of Patient Adherence and Asthma Control Among Propensity Score—Matched Patients
Multivariate generalized linear regression modeling analyses indicated that the cohort receiving mometasone furoate had better adherence and asthma control than the cohort receiving beclomethasone dipropionate, including significantly greater postindex adherence as measured by the percentage of days covered (29.5% vs 20.2% respectively, P <.001), fewer postindex exacerbations per patient (mean, 0.12 vs 0.19, P = .002), and decreased postindex SABA canister claims per patient (mean, 0.9 vs 1.1, P <.001) (). The distribution frequency of prescriptions showed that more patients in the cohort receiving mometasone furoate had at least 2 prescriptions (indicating refills beyond the index prescription) compared with the cohort receiving beclomethasone dipropionate (). Overall, significantly more patients in the cohort receiving methasone furoate had >2 prescriptions compared with those in the cohort receiving beclomethasone dipropionate (59.6% vs 46.2%, P <.001).
Multivariate analyses indicated that patients with mild asthma and prior medication use who began mometasone furoate treatment had better adherence, fewer exacerbations, and decreased SABA canister claims in the postindex period than patients who began beclomethasone dipropionate treatment. It is possible that the reduction in exacerbations and SABA canister claims observed in the cohort receiving mometasone furoate compared with the cohort receiving beclomethasone dipropionate may have been driven by improved adherence. The reason for improved adherence among patients who received mometasone furoate versus those who received beclomethasone dipropionate was most likely due to differences in dosing regimen convenience (ie, once daily vs twice daily). Mometasone furoate is indicated for twice-daily dosing only in patients with severe asthma receiving chronic oral corticosteroids. The patients selected for this study were categorized as having mild asthma and likely were prescribed a once-daily dosing regimen, although we were unable to determine this information. Previous studies have shown that adherence to prescribed therapy increases with fewer daily doses of medication among patients with various chronic diseases,8 including asthma.13 Current NAEPP guidelines1 encourage physicians to assess and promote patient adherence to prescribed asthma treatment and state that adherence is optimized when the number of daily medication doses is limited. In a review of 29 qualitative articles in which perspectives of patients with asthma about treatment were assessed, one of the “high emphasis factors” among adult patients with asthma that influenced their nonadherence to prescribed asthma medication was inconvenience of medication use, which included having to take multiple medication doses per day.14 Although adherence herein was significantly better in the cohort receiving mometasone furoate versus the cohort receiving beclomethasone dipropionate, nonadherence was still common in both groups (70.5% vs 79.8% of days). This is not unexpected, as adherence in real-world situations is generally much lower than that in a clinical trial setting.
It is clear that enhanced patient adherence correlates with improved asthma outcomes.3-5 The present analysis suggests that patient adherence to prescribed ICS treatment may be associated with reduced asthma exacerbations in patients with mild asthma. This finding is supported by a previous large retrospective study15 of a managed care database (n = 97,743), which found that patients with asthma who were more compliant to their prescribed asthma medication (including ICSs, which were noted as the index asthma medication prescription in 53.2% of all patients) had a reduced incidence of asthma-related exacerbations compared with less compliant patients (P <.001). Limiting asthma exacerbations is a key component of achieving optimal asthma control. Patients with a history of experiencing asthma exacerbations are at higher risk for more exacerbations in the future16 and may experience a decline in long-term lung function.17 Furthermore, patients with a history of asthma-related hospital admissions or intensive care unit admissions are at significantly increased risk of near-fatal and fatal asthma.18 Although the present study assessed patients with mild asthma having low asthma exacerbation rates, current NAEPP guidelines1 note that the frequency and severity of exacerbations may fluctuate for patients in any severity category and that preventing recurrent exacerbations and minimizing the need for emergency department visits or hospitalizations are goals of therapy for achieving optimal asthma control in all patients.
The presence of sinusitis may also have had a role in the exacerbation differences. After propensity score matching, sinusitis was the only covariate that was significantly different between the cohorts (greater in the cohort receiving beclomethasone dipropionate). Dixon et al19 reported post hoc analysis results of 2 clinical trials that examined the relationship between the presence of allergic rhinitis, sinusitis, and asthma. In the first trial with a patient population (n = 488) that had poorly controlled asthma, subjects with sinusitis had a significantly increased exacerbation rate compared with subjects without sinusitis (P <.01). However, in the second trial among patients (n = 1994) with mild asthma, there was no significant difference in exacerbation rates between subjects with and without sinusitis. The patients in the present study had mild asthma; based on the results by Dixon et al, their exacerbation rate would not be affected by the presence of sinusitis. However, this possibility cannot be ruled out.
Limiting SABA rescue medication use is another important component of asthma control. Current NAEPP guidelines1 state that infrequent SABA rescue medication use (<2 days/week) is a goal of asthma therapy for reducing asthma-related impairment, and prolonged SABA use is associated with increased risk of serious adverse events.20 The NAEPP guidelines also note that the use of more than 1 SABA canister every 1 to 2 months may suggest an overreliance on SABA rescue medications and inadequate asthma control21 that is associated with an increased risk of emergency department visits or hospitalization.22-24 Increased SABA rescue medication use also has important pharmacoeconomic implications. The mandatory conversion from chlorofluorocarbon to hydrofluoroalkane aerosol propellants in SABA metered dose aerosols has added significant cost to SABA rescue medications,25 which is underscored by the large global economic burden of asthma.26 Data from the present analysis indicate that mometasone furoate is associated with fewer postindex SABA canister claims than beclomethasone dipropionate, which could correlate with improved patient outcomes and reduced asthma-related healthcare charges. Further prospective clinical trials are necessary to test this hypothesis.
Several limitations may be considered with these study data, including difficulty in categorizing asthma severity without using predefined clinical variables, potential for errors in a claims database, and uncertainty in assessing how prescribed medication was used (eg, dosing regimen, compliance). Such limitations are a part of all retrospective claims database analyses and should not preclude the development of important conclusions using these data.
In conclusion, results of multivariate analyses from the present study collectively suggest that adherence may be better with mometasone furoate versus beclomethasone dipropionate, which may result in fewer exacerbations and more limited use of SABA rescue medications. Further clinical trials are necessary to more conclusively explore this hypothesis. However, adherence is often closely regulated in a prospective clinical trial. As such, retrospective analyses such as those herein are valuable tools for garnering reallife perspectives on adherence to controller therapy among patients with asthma.
Author Affiliations: From Analytic Solutions, LLC (HSF), New York, NY; Schering-Plough Corporation (EU), Kenilworth, NJ; Informagenics, LLC (JMM), Worthington, OH; Division of Epidemiology (JMM), Ohio State University, Columbus, OH; and Eympres Research, LLC (PN), Hilliard, OH.
Funding Source: Medical writing assistance was provided by Brett D. Mahon, PhD, at Complete Publication Solutions, LLC; this support was funded by Schering-Plough Corporation (now Merck & Co).
Author Disclosures: Dr Friedman is the owner of Analytic Consulting, LLC, which performs consulting work in the pharmaceutical industry, including Schering-Plough Corporation. He also reports serving as a paid consultant for Merck & Co, Inc. Dr Urdaneta was an employee of Schering-Plough Corporation when this study was conducted and reports owning stock in the company. Dr McLaughlin is a paid consultant for Schering-Plough Corporation and reports receiving payment for his involvement in the preparation of this manuscript. He is also employed as a research scientist at Informagenics, LLC. Dr Navaratnam is a paid consultant for Schering-Plough Corporation and reports attending meetings and conferences on their behalf. Portions of this work were previously presented at the 2009 American College of Chest Physicians (CHEST) Conference; October 31-November 5, 2009; San Diego, CA.
Authorship Information: Concept and design (HSF, EU, PN); analysis and interpretation of data (HSF, JMM, PN); drafting of the manuscript (HSF, JMM); critical revision of the manuscript for important intellectual content (HSF, EU, JMM, PN); statistical analysis (HSF, JMM); administrative, technical, or logistic support (PN); and supervision (HSF, EU).
Address correspondence to: Prakash Navaratnam, RPh, MPH, PhD, Eympres Research, LLC, 4660 Stonehill St, Hilliard, OH 43026. E-mail: email@example.com.
1. National Asthma Education and Prevention Program. Expert Panel Report 3: guidelines for the diagnosis and management of asthma (EPR-3): full report. 2007. http://www.nhlbi.nih.gov/guidelines/asthma/ index.htm. Accessed January 19, 2010.
2. Kelly HW. Comparison of inhaled corticosteroids: an update. Ann Pharmacother. 2009;43(3):519-527.
3. Krishnan JA, Riekert KA, McCoy JV, et al. Corticosteroid use after hospital discharge among high-risk adults with asthma. Am J Respir Crit Care Med. 2004;170(12):1281-1285.
4. Molimard M, Le Gros V. Impact of patient-related factors on asthma control. J Asthma. 2008;45(2):109-113.
5. Williams LK, Pladevall M, Xi H, et al. Relationship between adherence to inhaled corticosteroids and poor outcomes among adults with asthma. J Allergy Clin Immunol. 2004;114(6):1288-1293.
6. Asmanex Twisthaler (Mometasone Furoate). Full Prescribing Information. Kenilworth, NJ: Merck & Co Inc; 2008.
7. Qvar (Beclomethasone Dipropionate). Full Prescribing Information. Horsham, PA: Teva Specialty Pharmaceuticals; 2008.
8. Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther. 2001;23(8):1296-1310.
9. Friedman HS, Yawn BP. Resource utilization in asthma: combined fluticasone propionate/salmeterol compared with inhaled corticosteroids. Curr Med Res Opin. 2007;23(2):427-434.
10. Allen-Ramey FC, Bukstein D, Luskin A, Sajjan SG, Markson LE. Administrative claims analysis of asthma-related health care utilization for patients who received inhaled corticosteroids with either montelukast or salmeterol as combination therapy. J Manag Care Pharm. 2006;12(4):310-321.
11. Colice G, Wu EQ, Birnbaum H, Daher M, Marynchenko MB, Varghese S. Healthcare and workloss costs associated with patients with persistent asthma in a privately insured population. J Occup Environ Med. 2006;48(8):794-802.
12. Black PE. Greedy algorithm. In: Black PE, ed. Dictionary of Algorithms and Data Structures [online]. Gaithersburg, MD: US National Institute of Standards and Technology; February 2, 2005. http://www. itl.nist.gov/div897/sqg/dads/HTML/greedyalgo.html. Accessed May 15, 2010.
13. Guest JF, Davie AM, Ruiz FJ, Greener MJ. Switching asthma patients to a once-daily inhaled steroid improves compliance and reduces healthcare costs. Prim Care Respir J. 2005;14(2):88-98.
14. Bender BG, Bender SE. Patient-identified barriers to asthma treatment adherence: responses to interviews, focus groups, and questionnaires. Immunol Allergy Clin North Am. 2005;25(1):107-130.
15. Stern L, Berman J, Lumry W, et al. Medication compliance and disease exacerbation in patients with asthma: a retrospective study of managed care data. Ann Allergy Asthma Immunol. 2006;97(3): 402-408.
16. Emerman CL, Woodruff PG, Cydulka RK, Gibbs MA, Pollack CV Jr, Camargo CA Jr; MARC Investigators. Prospective multicenter study of relapse following treatment for acute asthma among adults presenting to the emergency department: MARC investigators: Multicenter Asthma Research Collaboration. Chest. 1999;115(4):919-927.
17. Bai TR, Vonk JM, Postma DS, Boezen HM. Severe exacerbations predict excess lung function decline in asthma. Eur Respir J. 2007; 30(3):452-456.
18. Alvarez GG, Schulzer M, Jung D, Fitzgerald JM. A systematic review of risk factors associated with near-fatal and fatal asthma. Can Respir J. 2005;12(5):265-270.
19. Dixon AE, Kaminsky DA, Holbrook JT, Wise RA, Shade DM, Irvin CG. Allergic rhinitis and sinusitis in asthma: differential effects on symptoms and pulmonary function. Chest. 2006;130(2):429-435.
20. Donohue JF. Safety and efficacy of beta agonists. Respir Care. 2008;53(5):618-624.
21. Spitzer WO, Suissa S, Ernst P, et al. The use of beta-agonists and the risk of death and near death from asthma. N Engl J Med. 1992;326(8):501-506.
22. Crystal-Peters J, Neslusan C, Crown WH, Torres A. Treating allergic rhinitis in patients with comorbid asthma: the risk of asthma-related hospitalizations and emergency department visits. J Allergy Clin Immunol. 2002;109(1):57-62.
23. Lieu TA, Quesenberry CP, Sorel ME, Mendoza GR, Leong AB. Computer-based models to identify high-risk children with asthma. Am J Respir Crit Care Med. 1998;157(4, pt 1):1173-1180.
24. Schatz M, Nakahiro R, Crawford W, Mendoza G, Mosen D, Stibolt TB. Asthma quality-of-care markers using administrative data. Chest. 2005;128(4):1968-1973.
25. US Food and Drug Administration. Use of ozone-depleting substances: removal of essential-use designations: final rule. Fed Regist. 2005;70(63):17168-17192.
26. Masoli M, Fabian D, Holt S, Beasley R; Global Initiative for Asthma (GINA) Program. The global burden of asthma: executive summary of the GINA Dissemination Committee Report. Allergy. 2004;59(5): 469-478.