The Overexposure to Steroids for Asthma Patients

The Global Initiative for Asthma (GINA), an organization working to reduce asthma prevalence, morbidity, and mortality worldwide, estimates that 334 million people are directly affected by the disease, 13 million of whom have severe, uncontrolled asthma, despite attempts at treatment optimization.¹

Asthma is a chronic condition characterized by inflammation and subsequent narrowing of the airways, leading to coughing, wheezing, breathlessness, and tightness of the chest. There are many different types of asthma, each with its distinct triggers, but all result in airway narrowing due to inflammation. (Figure 1) This inflammation then results in further symptoms such as mucus overproduction and remodeling of the airway walls.² The primary goal of asthma treatment is to reduce inflammation, often using bronchodilators, enabling control of symptoms.

Corticosteroids: An Established Treatment for Asthma

Inhaled corticosteroids (ICS) and oral corticosteroids (OCS) have been the standard-of-care for asthma for many years, providing effective relief from symptoms both in the short-term, following acute exacerbation, and for long-term management.³

ICS are commonly used as controller medications and are effective in cases of mild to moderate asthma. OCS are used to reduce airway inflammation in patients experiencing an acute asthma exacerbation, commonly referred to as an asthma attack. In these instances, OCS can reduce the need for emergency department visits and minimize hospitalizations.

International guidelines recommend limiting the use of OCS due to the side effects associated with long-term use, but evidence shows that approximately 60% of patients with severe asthma receive chronic systemic steroid treatment, with OCS-use being widespread in developed countries, and treatment regimens varying drastically worldwide.⁴ In 2024, a global, large-scale characterization study explored real-world treatment trajectories in adults with asthma and COPD. Treatment regimens included short-acting beta agonists (SABA) monotherapy such as salbutamol (UK, USA, Spain, and Netherlands), long-acting beta-agonists (LABA) ICS such as salmeterol (Europe), systemic steroid bursts (USA), LABA-ICS and ICS monotherapy (Estonia), and leukotriene receptor antagonists such as montelukast (South Korea).⁵

Steroid-Toxicity in Asthma Patients

Since their first clinical use in 1948, the adverse side effects and toxicities of steroids have been well documented, including osteoporosis, hypertension, anxiety, depression, and cardiovascular events.⁶ However, due to their effectiveness at reducing inflammation and suppressing immune responses, steroids, both inhaled and oral, continue to be a critical part of asthma management.

In 2018, researchers conducted a series of 11 cohort studies using data from the Clinical Practice Research Datalink (CPRD), a validated UK-based electronic healthcare record. There was a strong association between OCS use with bone-related conditions, cataracts, affective disorders, and cardiovascular, as well as a small association with herpes zoster and peptic ulcer, adding to existing evidence that OCS treatment for asthma carries an increased risk for many serious conditions.⁷

Cost Implications of Steroid Over-Prescribing

In addition to the detrimental impact on human health, these steroid toxicities also come with associated costs, increasing the burden on healthcare systems. A recent study in Sweden has highlighted the costly impact of OCS in asthma treatment, reviewing a cohort of 15,000 patients ranging from regular users to non-users of OCS. When compared to patients with lower steroid doses, the healthcare costs for regular OCS users were dramatically higher, primarily due to inpatient care following hospitalization. Costs associated with OCS side effects and toxicities were increased three times in regular users than in the non-users, and two times in periodic-users, reflecting the positive impact dosage tapering could have on reducing healthcare costs.⁸

Improving Education in Asthmatic Patients to Increase Shared-Decision Making

Research has shown that the majority of patients are unaware that being prescribed OCS can be an indication that their asthma is not well controlled, and that there may be alternative innovative treatments available.

In 2018, the Asthma and Allergy Foundation of America (AAFA) conducted a survey to explore the impact of OCS asthma patients, forming the basis for the Oral Corticosteroid Stewardship Statement. Results showed that nearly 85% of patients had at least one course of OCS within the previous 12 months, with 78% of patients being prescribed OCS by a non-asthma specialist. Additionally, while 70% of patients under the care of an asthma specialist were told of the risks associated with steroids, more than half were unaware that alternative treatments are available - demonstrating the distinct lack of education surrounding the detrimental impact of steroids in asthma patients.⁹

The Steroid Stewardship Statement is part of a collaborative effort to minimize OCS overreliance in asthma patients, outlining a range of initiatives to drive a shift away from corticosteroids.¹⁰

Strategies include:

• Educating patients and caregivers about the risks of OCS and alternative treatment options.
• Ensuring all patients are under the care of a trained asthma specialist.
• Supporting healthcare providers to shift to steroid-sparing treatments.
• Pushing for updated healthcare guidelines and policies that recommend steroid-sparing treatments.
• Empowering healthcare professionals to continue to educate patients about OCS alternatives.

In combination with other education platforms, and alongside developments in alternative treatments, the statement seeks to raise awareness of OCS-associated risks and side effects, enabling patients and physicians to engage in shared decision-making surrounding treatment plans.

Innovations in Asthma Therapeutic Options

Despite the lack of awareness, there are in fact alternative therapeutic options available for asthma; as of 2023, there are six different biologics approved by the FDA. All are monoclonal antibodies that target specific immune molecules:

• Mepolizumab, reslizumab, and benralizumab target interleukin-5 (IL-5), a mediator in the induction, maintenance, and amplification of eosinophilic inflammation. While mepolizumab and reslizumab block IL-5 from communicating with eosinophils, benralizumab (FASENRA®) stops IL-5 from binding to the complementary receptor on eosinophils, preventing them from moving to the airways
• Dupilumab targets eosinophilic and OCS-dependent asthma by targeting and blocking the receptors for IL-4 and IL-13, both of which are produced in response to triggers, causing inflammation and an increase in mucus production
• Omalizumab treats allergic asthma by blocking IgE, an antibody which causes the release of histamine, narrowing the airways
• Tezepelumab can be used to treat both allergic and eosinophilic asthma by targeting TLSP, a molecule which triggers the production of proteins that contribute to inflammation in the airways^11,12

Omalizumab was the first biological drug approved for the treatment of asthma, meaning that these alternative treatments have been available for over 20 years, but only one in five eligible patients are treated with them.¹³ In order to be prescribed a biologic treatment, the patient must undergo phenotype and endotype assessment, requiring extensive and costly testing. Additionally, the biologics themselves are expensive, with no clear guidelines on the length of treatment, pushing physicians to focus on reducing OCS dosage and associated steroid-toxicities.¹¹

Biologics as a Steroid Reduction Strategy

Many patients who are prescribed biologics as a treatment remain on a lower dose of steroids; a recent study explored the use of benralizumab in patients with severe eosinophilic asthma to reduce the need for steroids, evaluating the effectiveness and safety of a rapid personalized steroid-reduction algorithm following benralizumab initiation.

Of patients on benralizumab, 20-60% of patients continued to receive OCS. Side effects include suppression of the hypothalamic pituitary-adrenal axis, which can increase eosinophil levels, further exacerbating inflammation of the airways. The PONENTE trial was a multinational, multicenter trial that aimed to address this knowledge gap by evaluating the effectiveness and safety of a tailored steroid reduction algorithm in asthma patients over a course of 8-24 weeks, depending on steroid dose, control status, and adrenal function. Nearly all patients eliminated OCS or achieved a daily dose of ≤5mg by the end of the study, demonstrating that individualized steroid-reduction protocols can enable the safe reduction of OCS use in severe asthma patients, and provides a proof-of-principle for the development of similar reduction strategies for other diseases.¹⁴

Steroid-Toxicity Quantification and Monitoring

Recognizing the need to reduce steroid use in asthma patients, researchers are continuing to raise awareness of both the adverse effects of steroid-toxicity and the existence of alternative therapeutic options. Initiatives such as the Steroid Stewardship Statement, which is focused specifically on OCS in the treatment of asthma, and The Great Taper, a public initiative that is driving a shift in steroid prescribing patterns worldwide, are educating and empowering both clinicians and patients, facilitating a reduction in OCS overreliance.

To support this movement, a team of experts developed the Glucocorticoid Toxicity Index (GTI) the first standardized, validated clinical outcome assessment (COA) which enables the quantification and monitoring of steroid-toxicity in patients – and now forms the foundations of a suite of COAs for broad indications. By considering a series of health domains (BMI, blood pressure, glucose metabolism, lipid metabolism, bone mineral density, glucocorticoid myopathy, skin toxicity, neuropsychiatric effects, and infection), the GTI derives the cumulative worsening score (CWS) and aggregate improvement score (AIS), which can be used to assess steroid toxicity in patients and evaluate the ability of new therapeutics to prevent or reverse steroid-toxicity.¹⁵ The GTI can also be deployed to determine which patients will benefit the most from switching to steroid-sparing therapeutics.

In patients with asthma, it has been shown that steroid-toxicity can vary widely between individual patients, and that GTI scores do not necessarily correlate with recent steroid exposure. Instead, the GTI scores corresponded directly with the asthma quality of life questionnaire (mini-AQLQ), with this offering a strong predictor of steroid-toxicity.

Reducing OCS Overreliance by Tapering Early

Published in the Journal of Allergy and Clinical Immunology, a recent study demonstrated the need to taper steroids early, with patients developing steroid-toxicities in the long-term that don’t improve despite dose reductions. The longitudinal study compared OCS associated toxicities in patients with severe asthma at the start of biologic treatment to levels after one and three years.¹⁶

A key takeaway is that changes in the GTI scores at year one were predictive of changes in scores at year three, demonstrating that changes in the GTI scores could be used to quickly determine which patients are unlikely to achieve steroid-toxicity reduction with reduced OCS exposure, and therefore identify where alternative treatment options and OCS-reduction protocols should be explored.

Patient Engagement is Critical in Shared Decision-Making

Understandably, asthma patients taking OCS tend to overlook the consequences of chronic steroid use, feeling that they are a necessary tool in managing their condition and immediate symptoms, not realizing that the need for OCS in the first place is a sign that their asthma is uncontrolled.

Online communities such as the Global Allergy and Airways Patient Platform (GAAPP) is raising global quality standards for access to treatment, diagnosis and care by addressing gaps in patient education and clinical practice. Through its Steroid Stewardship Hub, GAAPP is encouraging the cautious use of OCS where required, while pushing for a shift to steroid-sparing therapeutics where possible. As part of this, the organization has embraced technological advancements designed to optimize steroid use and enable patients to better advocate for themselves. For example, the Steroids and Me platform (Sam), a first-in-class digital companion designed to educate and equip patients to engage shared decision-making with their doctors toward a reduction in steroid exposure.

Reducing Steroid Exposure by Employing Effective Steroid-Sparing Alternatives

It is clear that even a prevalent disease such as asthma, there is little patient awareness of the adverse effects of its long-term management with OCS. While ICS and OCS are effective in the treatment of asthma, reducing airway inflammation and associated symptoms, the toxicities that come with their overreliance, including muscle weakness, osteoporosis, hypertension, and mood changes, are severe, and often out-weigh the benefits.

As such, it is critical that we continue to develop novel steroid-toxicity sparing therapeutics to be deployed in combination with personalized steroid-reduction strategies, focusing not just on reducing dosage, but also on reducing toxicity. And what is key, is intervention at the earliest point –optimizing treatment for newly diagnosed patients and optimizing treatment for long-term asthma sufferers. More research is required into broader asthma cohorts, including across all forms in larger populations, to standardize treatment approaches globally and raise awareness of alternative therapeutic options. The outlook is hopeful; innovative approaches in the field demonstrating that it is possible to successfully taper steroid dosage and reduce associated toxicities to ultimately improve patient quality of life.

References

1. Global Initiative for Asthma (GINA): https://ginasthma.org/
2. Hammad, H. and Lambrecht, B., 2021 The basic immunology of asthma. Cell. 184 (6):1469 1485
3. Alangari, A., 2014 Corticosteroids in the treatment of acute asthma. Ann Thorac Med. 9(4):187-92
4. Canonica, G. W. and Colombo, G. L., et al. 2019. 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 Organization Journal, Volume 12, Issue 1, 100007
5. Markus, A. F. and Rijnbeek, P. R., et al. 2024 Real-world treatment trajectories of adults with newly diagnosed asthma or COPD. BMJ Open Resp Res. 11: e002127
6. Schacke, H. and Docke, W., et al. 2002. Mechanisms involved in the side effects of glucocorticoids Pharmacology and Therapeutics. 96: 23–43
7. Bloechliger, M. and Reinau, et al. 2018 Adverse events profile of oral corticosteroids among asthma patients in the UK: cohort study with a nested case-control analysis Respir Res 19:75
8. Janson C., and Lisspers K., et al. 2018 Health care resource utilization and cost for asthma patients regularly treated with oral corticosteroids – a Swedish observational cohort study (PACEHR). Resp. Research 19:168-175
9. Oral corticosteroid health risks: https://ginasthma.org/wp-content/uploads/2024/05/ GINA-2024-Strategy-Report-24_05_22_WMS.pdf.
10. Oral Corticosteroid Stewardship Statement: https://aafa.org/wp-content/ uploads/2022/08/oral-corticosteroid-stewardship-statement-november-2018.pdf
11. Jin, H. J., 2020 Biological treatments for severe asthma Yeungnam Univ J Med. 37(4):262 268
12. Pelaia, C. and Paoletti, G., et al. 2019 Interleukin-5 in the pathophysiology of severe asthma Front Physiol 17(10):1514
13. Carroll, W. and Wong, E., et al. 2023. PCRS pragmatic guide to caring for patients with asthma receiving biologic therapy. Issue 26 Spring
14. Menzies-Gow A., and Corren J., et al. 2019 Corticosteroid tapering with benralizumab treatment for eosinophilic asthma: PONENTE trial ERJ Open Res 5: 00009–2019
15. Stone, J. and McDowell, J., et al. 2022 The Glucocorticoid toxicity index: measuring change in glucocorticoid toxicity over time Seminars in Arthritis and Rheumatism 55:152010
16. McDowell, J., and Busby, J. et al. 2025 Longitudinal assessment of glucocorticoid toxicity reduction in patients with severe asthma treated with biologic The Journal of Allergy and Clinical Immunology 13(2):298-307.

Author Details 

John H. Stone, MD MPH- Rheumatologist and Professor of Medicine at Harvard Medical School, The Edward A. Fox Chair in Medicine at Massachusetts General Hospital

John H Stone, MD MPH graduated from Harvard Medical School and completed his internal medicine training at Johns Hopkins Hospital. He trained in rheumatology at the University of California-San Francisco. Dr. Stone is currently a Rheumatologist and Professor of Medicine at Harvard Medical School, and the Edward A. Fox Chair in Medicine at Massachusetts General Hospital. Dr. Stone led the international group of investigators who developed the Glucocorticoid Toxicity Index (GTI) and serves as Chair of the Scientific Advisory Board at Steritas.  

Publication Details

This article appeared in American Pharmaceutical Review:

Vol. 28, No. 3
April 2025

Pages: 48-51

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