The pharmacoeconomics of the state-of-the-art drug treatments for asthma: a systematic review
Keywords:
Asthma, cost-effectiveness, pharmacoeconomics, biologics, oral corticosteroids, treatmentsAbstract
Asthma is a chronic disease characterized by significant morbidities and mortality, with a large impact on socio-economic resources and a considerable burden on health-care systems. In the standard care of asthma, inhaled corticosteroids (ICS) associated with long-acting β-adrenoceptor agonists (LABA) are a reliable and often cost-effective choice, especially if based on the single inhaler therapy (SIT) strategy; however, in a subset of patients it is not possible to reach an adequate asthma control. In these cases, it is possible to resort to other pharmacologic options, including corticosteroids (OCS) or biologics. Unfortunately, OCS are associated with important side effects, whilst monoclonal antibodies (mAbs) allow excellent results, even if far more expensive. Up to now, the economic impact of asthma has not been compared with equivalent indicators in several studies. In fact, a significant heterogeneity of the cost analysis is evident in literature, for which the assessment of the real cost-effectiveness of asthma therapies is remarkably complex. To maximize the cost-effectiveness of asthma strategies, especially of biologics, attention must be paid on phenotyping and identification of predictors of response. Several studies were included, involving comparative analysis of drug treatments for asthma, comparative analysis of the costs and consequences of therapies, measurement and evaluation of direct drug costs, and the reduction of health service use. The initial research identified 389 articles, classified by titles and abstracts. A total of 311 articles were excluded as irrelevant and 78 articles were selected. Pharmacoeconomic studies on asthma therapies often report conflicting data also due to heterogeneous indicators and different populations examined. A careful evaluation of the existing literature is extremely important, because the scenario is remarkably complex, with an attempt to homogenize and interpret available data. Based on these studies, the improvement of prescriptive appropriateness and the reduction of the use of healthcare resources thanks to controller medications and to innovative therapies such as biologics partially reduce the economic burden of these treatments. A multidisciplinary stakeholder approach can also be extremely helpful in deciding between the available options and thus optimizing healthcare resources.
References
Pennington E, Yaqoob ZJ, Al-Kindi SG, Zein J. Trends in asthma mortality in the United States: 1999 to 2015. Am J Respir Crit Care Med 2019;199:1575-7.
Bahadori K, Doyle-Waters MM, Marra C, Lynd L, Alasaly K, Swiston J, et al. Economic burden of asthma: a systematic review. BMC Pulm Med 2009;9:24.
Reddel HK, Bateman ED, Becker A, Boulet LP, Cruz AA, Drazen JM, et al. A summary of the new GINA strategy: a roadmap to asthma control. Eur Respir J 2015;46:622–39.
Greenstone IR, Ni Chroinin MN, Masse V, Danish A, Magdalinos H, Zhang X, et al. Combination of inhaled long-acting beta2-agonists and inhaled steroids versus higher dose of inhaled steroids in children and adults with persistent asthma. Cochrane Database Syst Rev 2005;(4):CD005533.
Befekadu E, Onofrei C, Colice GL. Tiotropium in asthma: a systematic review. J Asthma Allergy 2014;7:11-21.
Bleecker ER, Menzies-Gow AN, Price DB, Price DB, Bourdin A, Sweet S, et al. Systematic literature review of systemic corticosteroid use for asthma management. Am J Respir Crit Care Med 2020;201:276-93.
Peters SP. Leukotriene receptor antagonists in asthma therapy. J Allergy Clin Immunol 2003;111:S62-70.
Hekking PP, Wener RR, Amelink M, Zwinderman AH, Bouvy ML, Bel EH. The prevalence of severe refractory asthma. J Allergy Clin Immunol 2015;135:896-902.
Holguin F, Cardet JC, Chung KF, Diver S, Ferreira DS, Fitzpatrick A, et al. Management of severe asthma: a European Respiratory Society/American Thoracic Society guideline. Eur Respir J 2020;55:1900588.
Global Initiative for Asthma. GINA Report. Accessed: 19 May 2021. Available from: https://ginasthma.org/gina-reports/
Darveaux J, Busse WW. Biologics in asthma–the next step toward personalized treatment. J Allergy Clin Immunol Pract 2015;3:152–60.
Kumar C, Zito PM. Omalizumab. Treasure Island, StatPearls Publishing; 2021.
Menzella F, Lusuardi M, Galeone C, Facciolongo N, Zucchi L. The clinical profile of benralizumab in the management of severe eosinophilic asthma. Ther Adv Respir Dis 2016;10:534-48.
Menzella F, Lusuardi M, Galeone C, Taddei S, Facciolongo N, Zucchi L. Mepolizumab for severe refractory eosinophilic asthma: evidence to date and clinical potential. Ther Adv Chronic Dis 2016;7:260-77.
Walsh GM. Reslizumab in the treatment of severe eosinophilic asthma: an update. Immunotherapy 2018;10:695-8.
Deeks ED. Dupilumab: A review in moderate to severe asthma. Drugs 2019;79:1885-95.
van Boven JFM, van de Hei SJ, Sadatsafavi M. Making sense of cost-effectiveness analyses in respiratory medicine: a practical guide for non-health economists. Eur Respir J 2019;53:1801816.
Drummond M, Brandt A, Luce B, Rovira J. Standardizing methodologies for economic evaluation in health care: practice, problems, and potential. Int J Technol Assess Health Care 1993;9:26-36.
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372:n71.
Sullivan SD, Buxton M, Andersson LF, Lamm CJ, Liljas B, Chen YZ, et al. Cost-effectiveness analysis of early intervention with budesonide in mild persistent asthma. J Allergy Clin Immunol 2003;112:1229–36.
Palmqvist M, Price MJ, Sondhi S. Cost-effectiveness analysis of salmeterol/fluticasone propionate 50/250 lg vs fluticasone propionate 250 lg in adults and adolescents with asthma IV: results. Pharmacoeconomics 1999;16:S23.
Johansson G, Price MJ, Sondhi S. Cost-effectiveness analysis of salmeterol/fluticasone propionate 50/100 lg vs fluticasone propionate 100 lg in adults and adolescents with asthma III: results. Pharmacoeconomics 1999;16:S15.
Mukhopadhyay A, Waked M, Gogtay J, Gaur V. Comparing the efficacy and safety of formoterol/budesonide pMDI versus its mono-components and other LABA/ICS in patients with asthma. Respir Med 2020;170:106055.
Rodríguez-Martínez CE, Sossa-Briceño MP, Castro-Rodriguez JA. Cost-utility analysis of the inhaled steroids available in a developing country for the management of pediatric patients with persistent asthma. J Asthma 2013;50:410-8.
Andersson F, Stahl E, Barnes PJ, Löfdahl CG, O'Byrne PM, Pauwels RA, et al. Adding formoterol to budesonide in moderate asthma–health economic results from the FACET study. Respir Med 2001;95:505-12.
Doull I, Price D, Thomas M, Hawkins N, Stamuli E, Tabberer M, et al. Cost-effectiveness of salmeterol xinafoate/fluticasone propionate combination inhaler in chronic asthma. Curr Med Res Opin 2007;23:1147-59.
Ismaila AS, Risebrough N, Li C, Corriveau D, Hawkins N, FitzGerald JM, et al. COST-effectiveness of salmeterol/fluticasone propionate combination (Advair) in uncontrolled asthma in Canada. Respir Med 2014;108:1292-302.
Lundbäck B, Jenkins C, Price MJ, Thwaites RM. Cost-effectiveness of salmeterol/fluticasone propionate combination product 50/250 microg twice daily and budesonide 800 microg twice daily in the treatment of adults and adolescents with asthma. International Study Group. Respir Med 2000;94:724-32.
Bruggenjurgen B, Ezzat N, Kardos P, Buhl R. Economic evaluation of BDP/formoterol fixed vs two single inhalers in asthma treatment. Allergy 2010;65:1108-15.
Rutten-van Molken MP, van Doorslaer EK, Till MD. Cost-effectiveness analysis of formoterol versus salmeterol in patients with asthma. Pharmacoeconomics 1998;14:671–84.
Gerzeli S, Rognoni C, Quaglini S, Cavallo MC, Cremonesi G, Papi A. Cost-effectiveness and cost-utility of beclomethasone/formoterol versus fluticasone propionate/salmeterol in patients with moderate to severe asthma. Clin Drug Investig 2012;32:253–65.
Johansson G, Andreasson EB, Larsson PE, Vogelmeier CF. Cost effectiveness of budesonide/formoterol for maintenance and reliever therapy versus salmeterol/fluticasone plus salbutamol in the treatment of asthma. Pharmacoeconomics 2006;24:695-708.
Miller E, Sears MR, McIvor A, Liovas A. Canadian economic evaluation of budesonide-formoterol as maintenance and reliever treatment in patients with moderate to severe asthma. Can Respir J 2007;14:269-75.
Paggiaro P, Patel S, Nicolini G, Pradelli L, Zaniolo O, Papi A. Stepping down from high dose fluticasone/salmeterol to extrafine BDP/F in asthma is cost-effective. Respir Med 2013;107:1531-7.
Chongmelaxme B, Chaiyakunapruk N, Dilokthornsakul P. Incorporating adherence in cost-effectiveness analyses of asthma: a systematic review. J Med Econ 2019;22:554-66.
Shih Y-CT, Mauskopf J, Borker R. A cost-effectiveness analysis of first-line controller therapies for persistent asthma. Pharmacoeconomics 2007;25:577–90.
Zafari Z, Lynd LD, Fitzgerald JM, Sadatsafavi M. Economic and health effect of full adherence to controller therapy in adults with uncontrolled asthma: a simulation study. J Allergy Clin Immunol 2014;134:908.
Willson J, Bateman ED, Pavord I, Lloyd A, Krivasi T, Esser D. Cost effectiveness of tiotropium in patients with asthma poorly controlled on inhaled glucocorticosteroids and long-acting beta-agonists. Appl Health Econ Health Policy 2014;12:447–59.
Hong SH, Cho JY, Kim TB, Lee EK, Kwon SH, Shin JY. Cost-effectiveness of tiotropium in elderly patients with severe asthma using real-world data. J Allergy Clin Immunol Pract 2021;9:1939-1947.e7.
Zafari Z, Sadatsafavi M, Mark FitzGerald J, Canadian Respiratory Research Network. Cost-effectiveness of tiotropium versus omalizumab for uncontrolled allergic asthma in US. Cost Eff Resour Alloc 2018;16:3.
Menendez R, Stanford RH, Edwards L, Kalberg C, Rickard K. Cost-efficacy analysis of fluticasone propionate versus zafirlukast in patients with persistent asthma. Pharmacoeconomics 2001;19:865-74.
Wang L, Hollenbeak CS, Mauger DT, Zeiger RS, Paul IM, Sorkness CA, et al. Cost-effectiveness analysis of fluticasone versus montelukast in children with mild-to-moderate persistent asthma in the Pediatric Asthma Controller Trial. J Allergy Clin Immunol 2011;127:161-6.
Price D, Musgrave S, Wilson E, Sims E, Shepstone L, Blyth A, et al. A pragmatic single-blind randomised controlled trial and economic evaluation of the use of leukotriene receptor antagonists in primary care at steps 2 and 3 of the national asthma guidelines (ELEVATE study). Health Technol Assess 2011;15:1-132.
Tan H, Sarawate C, Singer J, Elward K, Cohen RI, Smart BA, et al. Impact of asthma controller medications on clinical, economic, and patient-reported outcomes. Mayo Clin Proc 2009;84:675–84.
O’Connor RD, Nelson H, Borker R, Emmett A, Jhingran P, Rickard K, et al. Cost effectiveness of fluticasone propionate plus salmeterol versus fluticasone propionate plus montelukast in the treatment of persistent asthma. Pharmacoeconomics 2004;22:815-25.
Wilson EC, Price D, Musgrave SD, Sims EJ, Shepstone L, Murdoch J, et al. Cost effectiveness of leukotriene receptor antagonists versus long-acting beta-2 agonists as add-on therapy to inhaled corticosteroids for asthma: a pragmatic trial. Pharmacoeconomics 2010;28:597-608.
Borker R, Emmett A, Jhingran P, Rickard K, Dorinsky P. Determining economic feasibility of fluticasone propionate-salmeterol vs montelukast in the treatment of persistent asthma using a net benefit approach and cost-effectiveness acceptability curves. Ann Allergy Asthma Immunol 2005;95:181-9.
Rely K, McQuire SE, Alexandre PK, Escudero GS. Cost effectiveness of treatment with salmeterol/fluticasone compared to montelukast for the control of persistent asthma in children. Value Health 2011;14:S43-7.
Sheth K, Borker R, Emmett A, Rickard K, Dorinsky P. Cost effectiveness comparison of salmeterol/fluticasone propionate versus montelukast in the treatment of adults with persistent asthma. Pharmacoeconomics 2002;20:909-18.
Borker R, Emmett A, Jhingran P, Rickard K, Dorinsky P. Determining economic feasibility of fluticasone propionate-salmeterol vs montelukast in the treatment of persistent asthma using a net benefit approach and cost-effectiveness acceptability curves. Ann Allergy Asthma Immunol 2005;95:181-9.
Pathak DS, Davis EA, Stanford RH. Economic impact of asthma therapy with fluticasone propionate, montelukast, or zafirlukast in a managed care population. Pharmacotherapy 2002;22:166-74.
Volmer T, Effenberger T, Trautner C, Buhl R. Consequences of long-term oral corticosteroid therapy and its side-effects in severe asthma in adults: a focused review of the impact data in the literature. Eur Respir J 2018;52:1800703.
Bourdin A, Molinari N, Vachier I, Pahus L, Suehs C, Chanez P. Mortality: a neglected outcome in OCS-treated severe asthma. Eur Respir J 2017;50:1701486.
Price DB, Trudo F, Voorham J, Xu X, Kerkhof M, Ling Zhi Jie J, et al. Adverse outcomes from initiation of systemic corticosteroids for asthma: long-term observational study. J Asthma Allergy 2018;11:193-204.
Sullivan PW, Ghushchyan VH, Globe G, Schatz M. Oral corticosteroid exposure and adverse effects in asthmatic patients. J Allergy Clin Immunol 2018;141:110-6.
Sweeney J, Patterson CC, Menzies-Gow A, Niven RM, Mansur AH, Bucknall C, et al. Comorbidity in severe asthma requiring systemic corticosteroid therapy: cross-sectional data from the Optimum Patient Care Research Database and the British Thoracic Difficult Asthma Registry. Thorax 2016;71:339-46.
Lefebvre P, Duh MS, Lafeuille MH, Gozalo L, Desai U, Robitaille MN, et al. Burden of systemic glucocorticoid-related complications in severe asthma. Curr Med Res Opin 2017;33:57-65.
Barry LE, Sweeney J, O'Neill C, Price D, Heaney LG. The cost of systemic corticosteroid-induced morbidity in severe asthma: a health economic analysis. Respir Res 2017;18:129.
Canonica GW, Colombo GL, Bruno GM, Bruno GM, Di Matteo S, Martinotti C, et al. Shadow cost of oral corticosteroids-related adverse events: A pharmacoeconomic evaluation applied to real-life data from the Severe Asthma Network in Italy (SANI) registry. World Allergy Organ J 2019;12:100007.
Barry LE, Sweeney J, O'Neill C, Price D, Heaney LG. The cost of systemic corticosteroid-induced morbidity in severe asthma: a health economic analysis. Respir Res 2017;18:129.
Oba Y, Salzman G. Cost-effectiveness analysis of omalizumab in adults and adolescents with moderate-to-severe allergic asthma. J Allergy Clin Immunol 2004;114:265-9.
Campbell JD, Spackman DE, Sullivan SD. The costs and consequences of omalizumab in uncontrolled asthma from a USA payer perspective. Allergy 2010;65:1141-8.
Dal Negro RW, Tognella S, Pradelli L. A 36-month study on the cost/utility of add-on omalizumab in persistent difficult-to-treat atopic asthma in Italy. J Asthma 2012;49:843-8.
Menzella F, Facciolongo N, Piro R, Formisano D, Roggeri A, Simonazzi A, et al. Clinical and pharmacoeconomic aspects of omalizumab: a 4-year follow-up. Ther Adv Respir Dis 2012;6:87-95.
Tan LE, Tan WHG, Aziz MIA, Koh MS, Tay TR, Pearce F, et al. Assessing the cost-effectiveness of mepolizumab as add-on therapy to standard of care for severe eosinophilic asthma in Singapore. J Asthma 2020;1-11. Online ahead of print.
Andersson M, Janson C, Kristensen T, Szende A, Golam S. Cost effectiveness of benralizumab for severe, uncontrolled oral corticosteroid-dependent asthma in Sweden. J Med Econ 2020;23:877-84.
Canadian Agency for Drugs and Technologies in Health. Pharmacoeconomic Review Report: Benralizumab (Fasenra): (AstraZeneca Canada Inc.). 2018. CADTH Common Drug Reviews. Accessed: 24 December 2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK541600/
Anderson WC 3rd, Szefler SJ. Cost-effectiveness and comparative effectiveness of biologic therapy for asthma: To biologic or not to biologic? Ann Allergy Asthma Immunol 2019;122:367-72.
Institute for Clinical and Economic Review, Midwest Comparative Effectiveness Public. Biologic therapies for treatment of asthma associated with type 2 inflammation: effectiveness, value, and value-based price benchmarks: final evidence report. Boston: Institute for Clinical and Economic Review; 2018. Available from: http://resource.nlm.nih.gov/101745064
Shaker M, Briggs A, Dbouk A, Dutille E, Oppenheimer J, Greenhawt M. Estimation of health and economic benefits of clinic versus home administration of omalizumab and mepolizumab. J Allergy Clin Immunol Pract 2020;8:565-72.
Rhyou HI, Nam YH. Predictive factors of response to inhaled corticosteroids in newly diagnosed asthma: A real-world observational study. Ann Allergy Asthma Immunol 2020;125:177-81.
Lehtimäki L, Csonka P, Mäkinen E, Isojärvi J, Hovi SL, Ahovuo-Saloranta A. Predictive value of exhaled nitric oxide in the management of asthma: a systematic review. Eur Respir J 2016;48:706-14.
Rodriguez-Martinez CE, Sossa-Briceño MP, Castro-Rodriguez JA. Predictors of response to medications for asthma in pediatric patients: A systematic review of the literature. Pediatr Pulmonol 2020;55:1320-31.
Kupczyk M, Haque S, Middelveld RJ, Dahlén B, Dahlén SE; BIOAIR Investigators. Phenotypic predictors of response to oral glucocorticosteroids in severe asthma. Respir Med 2013;107:1521-30.
Gao J, Wu F. Association between fractional exhaled nitric oxide, sputum induction and peripheral blood eosinophil in uncontrolled asthma. Allergy Asthma Clin Immunol 2018;14:21.
Kim CH, Dilokthornsakul P, Campbell JD, van Boven JFM. Asthma cost-effectiveness analyses: Are we using the recommended outcomes in estimating value? J Allergy Clin Immunol Pract 2018;6:619-32.
Rodriguez-Martinez CE, Sossa-Briceño MP, Castro-Rodriguez JA. Cost effectiveness of pharmacological treatments for asthma: A systematic review. Pharmacoeconomics 2018;36:1165-200.
Dal Negro RW, Distante C, Bonadiman L, Turco P, Iannazzo S. Cost of persistent asthma in Italy. Multidiscip Respir Med 2016;11:44.
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