Worldwide, more than 50 million people – 1% of the adult population – are on long-term glucocorticoids (GC) [Fardet]. They are widely used as an inexpensive and readily available treatment for a variety of conditions, even though long-term use is associated with a range of toxicities - these include an increased risk of costly adverse events such as fractures, infections, and gastrointestinal bleeding [Rice].

Key side effects of steroids that incur cost

A systematic literature review of long-term systemic corticosteroid exposure by Rice et al. [Rice] uncovered a whole range of commonly-cited associated adverse effects (AEs), including:

• hypertension (prevalence >30%);
• bone fracture (21%–30%);
• cataract (1%–3%);
• nausea, vomiting other gastrointestinal conditions (1%–5%);
• and metabolic issues such as weight gain, hyperglycemia, and type 2 diabetes.

Not surprisingly, the costs to the health care system are very significant.

Economic impact on healthcare systems

Assessments of the economic impact of corticosteroid use and their side effects clearly show a dose-dependent increase in health care resources used and costs.

The annual incremental cost of steroid-toxicity ranges from $5700 for low-dose users (<7.5 mg/d) to as much as $29,000 for high-dose users (>15 mg/d).

It must be noted that treatment guidelines to avoid side effects (e.g., prescribing oral bisphosphonates, calcium, and vitamin D) are still rarely followed [Rice].

The shadow cost of oral corticosteroid-related adverse events in asthma

A major area of application in which corticosteroids are frequently used is asthma, which affects about 6% of the general population – more than 300 million people around the world. The prevalence of asthma appears to be increasing, and this is responsible for high and increasing health-related direct and indirect costs, especially in patients with suboptimal asthma control [Canonica].

Calculation of the shadow cost of oral corticosteroid-related adverse events in asthma shows the initial cost of oral corticosteroids (OCS) may be low, but they come with high shadow costs associated with steroid toxicity-related morbidity.

A study by Barry et al. aimed to estimate the additional healthcare costs associated with steroid-induced morbidity by comparing three patient groups:

• patients with no asthma,
• patients with moderate asthma,
• patients with severe asthma.

Average healthcare costs per person per year ranged from €560 - €1324 for the non-asthma control cohort to £2603 - £4533 for the severe asthma cohort [Barry].

The additional GC-associated adverse event-related costs vary. These additional costs are particularly high for osteoporosis (4.3 times higher for the severe asthma cohort compared to the non-asthma control), osteopenia (4 times higher), and dyspeptic disorders (2 times higher).

GC-associated adverse events in rheumatoid arthritis

A similar picture is seen in rheumatoid arthritis. GC-associated adverse events cause approximately 100% higher costs in steroid-using patients compared with non-steroid users!

Pisu et al. evaluated the cost of steroid toxicity in rheumatoid arthritis and found that for every dollar spent on glucocorticoids, an additional $0.46 had to be spent on treating the drugs’ side effects.

In general, the higher the glucocorticoid dose, the greater the cost to treat glucocorticoid-related adverse events treatment and the higher the mortality rate [Pisu].

What can healthcare systems and pharma companies do to minimize adverse events?

Many of the side effects of corticosteroids can be minimized through careful patient monitoring using instruments such as the Steritas GTI, and the implementation of preventive measures such as using the lowest effective steroid dose required for management of the underlying condition. It is also essential to inform patients about the AEs associated with systemic corticosteroid exposure.

Liu et al. suggest that patients should be encouraged to seek medical attention if they experience signs of steroid-related AEs and should be advised to carry a “steroid treatment card” so that medical personnel involved in their care and treatment can get a correct picture of their medical history. There are also differences in the monitoring and care of adults and children to consider, particularly regarding GC-associated complications related to growth, and osteoporosis [Liu].

Conclusion

Despite the high costs of steroid toxicity both to patients and healthcare systems, more than 60% of patients taking glucocorticoids are not monitored for steroid-toxicity [Fardet] With the annual incremental cost of steroid toxicity for patients being prescribed high doses of steroids reaching $29,000 the need for new approaches to this public health challenge is clear.

Fortunately, there are an increasing number of steroid-sparing alternatives becoming available and with the availability of the Glucocorticoid Toxicity Index, the benefits of these new therapeutic options can now be clearly measured and patient outcomes monitored.

References

Liu D, Ahmet A, Ward L, Krishnamoorthy P, Mandelcorn ED, Leigh R, Brown JP, Cohen A, Kim H. A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. Allergy Asthma Clin Immunol. 2013 Aug 15;9(1):30. doi: 10.1186/1710-1492-9-30. PMID: 23947590; PMCID: PMC3765115.

Rice JB, White AG, Scarpati LM, Wan G, Nelson WW. Long-term Systemic Corticosteroid Exposure: A Systematic Literature Review. Clin Ther. 2017 Nov;39(11):2216-2229. doi: 10.1016/j.clinthera.2017.09.011. Epub 2017 Oct 19. PMID: 29055500.

Pisu M, James N, Sampsel S, Saag KG. The cost of glucocorticoid-associated adverse events in rheumatoid arthritis. Rheumatology (Oxford). 2005 Jun;44(6):781-8. doi: 10.1093/rheumatology/keh594. Epub 2005 Mar 15. PMID: 15769791.

Canonica GW, Colombo GL, Bruno GM, Di Matteo S, Martinotti C, Blasi F, Bucca C, Crimi N, Paggiaro P, Pelaia G, Passalaqua G, Senna G, Heffler E; SANI Network. 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 Jan 26;12(1):100007. doi: 10.1016/j.waojou.2018.12.001. PMID: 30937132; PMCID: PMC6439414.

Fardet L, Petersen I, Nazareth I. Prevalence of long-term oral glucocorticoid prescriptions in the UK over the past 20 years. Rheumatology (Oxford). 2011 Nov;50(11):1982-90. doi: 10.1093/rheumatology/ker017. Epub 2011 Mar 10. PMID: 21393338.

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 Jun 26;18(1):129. doi: 10.1186/s12931-017-0614-x. PMID: 28651591; PMCID: PMC5485660.

Laurence Fardet, MD, PhD, Irene Petersen, PhD, and Irwin Nazareth, MD, PhD Monitoring of Patients on Long-Term Glucocorticoid Therapy- A Population-Based Cohort Study. Medicine. Volume 94, Number 15, April 2015