Bleecker ER, Menzies-Gow A, Price D, Bourdin A, Sweet S, Martin A, Alacqua M, Tran TN. Systematic Literature Review of Systemic Corticosteroid Use for Asthma Management. Am J Respir Crit Care Med. 2020;201:276–93.
Steroids, either in the form of tablets or injectables, have been very useful in saving people’s lives during acute asthma attacks and in treating severe asthma. However, they also carry the risk of several serious side effects. This literature review summarized what we currently know about steroid use in asthma management and quantified the effects of these side effects. Its findings, to which OPRI’s research contributed, highlight the importance of finding strategies to reduce the use of steroids to minimize the risk of these side effects, as just one course of steroids can trigger them. People needing more than 2 courses of steroids per year should speak to their doctor about whether there are any better strategies to help them manage their asthma.
Research from one of the most extensive contributors to the global understanding of asthma, the Observational Pragmatic Research Institute (OPRI), provided a major contribution to a recent systematic literature review of systemic corticosteroid use for asthma management1. Professor David Price, the founder of OPRI, was a co-author of this paper.
Systemic corticosteroids (SCS) are typically used as a form of rescue therapy for asthmatics, as well as maintenance treatment for those with severe asthma. While they are effective in treating the symptoms of asthma, they are associated with many adverse events, the extent of which has yet to be fully quantified. This systematic literature review, therefore, highlights the important literature on this subject to characterize the extent and nature of real-world SCS use in children, adolescents and adults with asthma, as well as the clinical and economic impact it has.
Inhaled corticosteroids (ICS) are currently used to treat mild to moderate asthma, with oral corticosteroids (OCS) – a form of SCS – being primarily used as an add-on treatment for severe uncontrolled asthma. Adverse events that arise due to short or long-term exposure to SCS are due to the fact that SCS are transported via the bloodstream and therefore has the potential to affect many organs in the body. On the other hand, while ICS are present in the bloodstream in small quantities, they are typically broken down by the liver into inactive compounds before entering the bloodstream.
Of the 139 studies identified by this systematic review, 11 were studies conducted by OPRI. As one of Singapore’s leading research and development organizations, OPRI has over a decade of experience in real-world respiratory research, with a specific focus on asthma and COPD. Observational studies on SCS use, economic analyses of the impact of various therapies on the healthcare system and retrospective studies on the clinical and cost-effectiveness of different ICS therapies were featured among the identified studies.
“Steroids are often overused in the management of severe asthma,” said Professor Price. “There’s a ton of research that shows the burden it places on the patient as well as the healthcare system, and yet, it is still overprescribed at doses higher than what is recommended by the guidelines.”
With OCS being considered the be-all and end-all of severe asthma management, steroid resistance in these individuals is often overlooked. This systematic review found that most severe asthma patients were actually steroid-resistant to some degree, as characterized by their lack of response to ICS treatment.
“Steroids don’t work for everyone, and even when they do work, they put patients at risk of a whole host of acute and chronic complications. Just four courses of oral steroids over an entire lifetime puts you at a higher risk for diabetes and osteoporosis – and this risk increases with cumulative doses. It’s therefore imperative that alternative, effective treatments be found, especially for the management of severe asthma,” said Professor Price.
Some of OPRI’s research featured in this systematic literature review found that long-term OCS use put patients at 3.6x the risk of experiencing steroid-related adverse events when compared to patients who had never used OCS. Furthermore, there exists a gap in the understanding of the short-term effects of OCS use, as although acute complications such as infections and gastrointestinal events are common among OCS users, they are poorly documented in research.
The burden of steroid use extends beyond the patient to the healthcare system. Steroid-related adverse events can lead to hospitalizations and emergency department visits as well as an overall higher rate of healthcare resource use. In fact, intermittent or long-term SCS use is associated with 42% greater overall healthcare-related costs.
The advent of new biologic therapies presents as an interesting replacement to SCS use, as it has been observed to reduce OCS use in other diseases. Preliminary results in asthma also show an OCS-tapering effect. This presents as an exciting avenue for research into better asthma management.
“Perhaps a new treatment paradigm for the management of asthma across all severities is required,” shared Professor Price. “What we’re currently doing isn’t working as well as we’d like, but biologic therapy seems promising thus far.”
While steroids can alleviate some of the symptoms of asthma, their risk-to-benefit ratio must be carefully considered due to the risk of acute and chronic complications. Biologic therapy remains an attractive avenue for exploration and will hopefully reduce the widespread use of SCS in asthma management.
The full list of OPRI’s research that has contributed to this systematic literature review is as follows:
- Price DB, Trudo F, Voorham J, Xu X, Kerkhof M, Ling Zhi Jie J, Tran TN. Adverse outcomes from initiation of systemic corticosteroids for asthma: long-term observational study. J Asthma Allergy 2018;11:193–204. [PubMed] [Full Text]
- Price D, Kaplan A, Jones R, Freeman D, Burden A, Gould S, von Ziegenweidt J, Ali M, King C, Thomas M. Long-acting muscarinic antagonist use in adults with asthma: real-life prescribing and outcomes of add-on therapy with tiotropium bromide. J Asthma Allergy 2015;8:1–13. [PubMed] [Full Text]
- Smith JR, Noble MJ, Musgrave S, Murdoch J, Price GM, Barton GR, Windley J, Holland R, Harrison BD, Howe A, Price DB, Harvey I, Wilson AM. The At-Risk Registers in Severe Asthma (ARRISA) study: a cluster-randomised controlled trial examining effectiveness and costs in primary care. Thorax 2012;67:1052–1060. [PubMed] [Full Text]
- Martin RJ, Price D, Roche N, Israel E, van Aalderen WMC, Grigg J, Postma DS, Guilbert TW, Hillyer EV, Burden A, von Ziegenweidt J, Colice G. Cost-effectiveness of initiating extrafine- or standard size-particle inhaled corticosteroid for asthma in two health-care systems: a retrospective matched cohort study. NPJ Prim Care Respir Med 2014;24:14081. [PubMed] [Full Text]
- Price D, Small I, Haughney J, Ryan D, Gruffydd-Jones K, Lavorini F, Harris T, Burden A, Brockman J, King C, Papi A. Clinical and cost effectiveness of switching asthma patients from fluticasone-salmeterol to extra-fine particle beclomethasone-formoterol: a retrospective matched observational study of real-world patients. Prim Care Respir J 2013;22:439–448. [PubMed] [Full Text]
- Price D, Thomas M, Haughney J, Lewis RA, Burden A, von Ziegenweidt J, Chisholm A, Hillyer EV, Corrigan CJ. Real-life comparison of beclometasone dipropionate as an extrafine- or larger-particle formulation for asthma. Respir Med 2013; 107:987–1000. [PubMed] [Full Text]
- Price D, Wilson AM, Chisholm A, Rigazio A, Burden A, Thomas M, King C. Predicting frequent asthma exacerbations using blood eosinophil count and other patient data routinely available in clinical practice. J Asthma Allergy 2016;9:1–12 [PubMed] [Full Text]
- 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;18:26. [Full Text]
- Sweeney J, Patterson CC, Menzies-Gow A, Niven RM, Mansur AH, Bucknall C, Chaudhuri R, Price D, Brightling CE, Heaney LG; British Thoracic Society Difficult Asthma Network. 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;71:339–346 [PubMed] [Full Text]
- Voorham J, Xu X, Price D, Golam S, Davis J, Ling Zhi Jie J, Kerkhof M, Ow M, Tran TN. Healthcare resource utilization and costs associated with incremental systemic corticosteroid exposure in asthma. Allergy 2019;74:273–283. [PubMed] [Full Text]
- Turner S, Richardson K, Murray C, Thomas M, Hillyer EV, Burden A, Price DB; Respiratory Effectiveness Group. Long-acting b-agonist in combination or separate inhaler as step-up therapy for children with uncontrolled asthma receiving inhaled corticosteroids. J Allergy Clin Immunol Pract 2017;5:99–106, e3. [PubMed] [Full Text]