OCS Overuse

How steroids are used in asthma

Oral corticosteroids (OCS) are used to manage acute asthma exacerbations and severe symptoms.^1,2 A recent meta-analysis conducted a search to identify randomized controlled trials comparing the effectiveness of intramuscular (IM) or oral (PO) short-course or long-course corticosteroids to prevent relapse in adults with acute asthma.¹ Thirteen studies of moderate quality were included. Four studies compared systemic corticosteroids (SCS) to placebo, in which SCS significantly reduced relapse (RR = 0.43; 95% CI, 0.25 to 0.74). In the network meta-analysis, a significant reduction in relapse within 10 days of discharge was found in adults receiving IM (OR = 0.21; 95% CrI, 0.05 to 0.73) and PO long-course (OR = 0.31; 95% CrI, 0.09 to 0.95) corticosteroids. The network analysis identified IM corticosteroids and PO long-course corticosteroids as the most effective strategies to prevent relapse among adults with acute asthma, compared to PO short-course corticosteroids.¹

Systemic corticosteroids and adverse events (AEs)

In a long-term observational study, investigators matched medical records in patients (≥18 years) with active asthma to investigate the onset of adverse outcomes.³ Investigators matched 24,117 pairs of patients with median record availability before SCS initiation of 9.9 and 8.7 years and median follow-up 7.4 and 6.4 years in SCS and non-SCS arms, respectively. Compared with patients in the non-SCS arm, patients prescribed SCS had significantly increased risk of osteoporosis/osteoporotic fracture (adjusted hazard ratio 3.11; 95% CI, 1.87-5.19), pneumonia (2.68; 2.30-3.11), cardio-/cerebrovascular diseases (1.53; 1.36-1.72), cataract (1.50; 1.31-1.73), sleep apnea (1.40; 1.04-1.86), renal impairment (1.36; 1.26-1.47), depression/anxiety (1.31; 1.21-1.41), type 2 diabetes (1.26; 1.15-1.37), and weight gain (1.14; 1.10-1.18). A dose-response relationship for cumulative SCS exposure with most adverse outcomes began at cumulative exposures of 1.0- <2.5 g and for some outcomes at cumulative exposures of only 0.5- <1.0 g, equivalent to four lifetime SCS courses.³

In another retrospective study of asthma patients through insurance claims data, the number of OCS prescriptions was examined for any association with AEs.⁴ There were 72,063 and 156,373 subjects in the OCS and non OCS cohorts, respectively. Subjects taking 4 or more OCS prescriptions within one year had 1.29 times higher odds of experiencing a new AE within the year; similarly, those taking 1-3 OCS prescriptions within the same time frame had 1.04 times higher odds of experiencing a new AE compared to the non OCS group. Each year of exposure to 4 or more OCS prescriptions (current and past) resulted in 1.20 times greater odds of having an AE in the current year. Exposure to 4 or more prescriptions was associated with significantly greater odds of AEs for osteoporosis, hypertension, obesity, type 2 diabetes, gastrointestinal ulcers/bleeds, fractures, and cataracts (odds, 1.21-1.44 depending on the AE). The authors noted that the number of prescriptions dispensed within a year is strongly associated with AEs, irrespective of dose and duration.⁴

Is there AE risk with short-term OCS?

Complications of chronic OCS use are well documented; however, the potential risks associated with the use of short-term oral corticosteroids and their overall use in a general population has not been fully characterized. Complications with corticosteroids include a wide variety of adverse effects.⁵ In a study of 1.5 million privately insured adults (18-64 years) in the US, researchers reported that one in five patients in an outpatient setting used short term oral corticosteroids over a three-year period (2012-2014).⁶ Short-term use of oral corticosteroids was defined as less than 30 days duration. The most common indications for use were upper respiratory tract infections, spinal conditions, and allergies. Within 30 days of drug initiation, there was an increase in rates of sepsis (incidence rate ratio 5.30, 95% CI, 3.80 to 7.41), venous thromboembolism (3.33, 2.78 to 3.99), and fracture (1.87, 1.69 to 2.07), which diminished over the subsequent 31-90 days. The increased risk persisted at prednisone equivalent doses of less than 20 mg/day (incidence rate ratio 4.02 for sepsis, 3.61 for venous thromboembolism, and 1.83 for fracture; all P < .001).⁶ Within 30 days of corticosteroid initiation, the incidence of acute adverse events that result in major morbidity and mortality (sepsis, venous thromboembolism, fracture) increased by twofold, to fivefold above background rates.⁶

Although OCS for the treatment of asthma has been prescribed for more than 60 years and have shown benefit, these agents are associated with costly AEs and complications.⁷ Referral to specialist care has been demonstrated to reduce the risk of OCS use and its accompanying adverse events. Alarmingly, a high proportion of patients with severe asthma do not receive specialist care, due to under-recognition of severity, a lack of guideline awareness, and delays in referral.⁵ GINA guidelines recommend expert referral in a number of situations, such as persistent or severely uncontrolled asthma, suspected occupational asthma, and risk for asthma-related death.⁸

Clinical trials findings for a number of biologic compounds, benralizumab (ZONDA), dupilumab (VENTURE), and mepolizumab (SIRIUS) demonstrate that maintenance oral glucocorticoid therapy can be reduced or eliminated while maintaining asthma control.^9-11 Specialist care can optimize the steroid-sparing effects of biological agents while maintaining control of the patients’ asthma.⁸

References

Rowe B, Kirkland S, Vandermeer B, et al. Prioritizing systemic corticosteroid treatments to mitigate relapse in adults with acute asthma: A systematic review and network meta-analysis. Acad Emerg Med. 2017;24:371-381.
Normansell R, Kew K, Mansour G. Different oral corticosteroid regimens for acute asthma. Cochrane Database Syst Rev. 2016;(5):CD011801.
Price D, Trudo F, Voorham J, et al. Adverse outcomes from initiation of systemic corticosteroids for asthma: long-term observational study. J Asthma Allergy. 2018;11:193-204.
Sullivan P, Ghushchyan V, Globe G, Schatz M. Oral corticosteroid exposure and adverse effects in asthmatic patients. J Allergy Clin Immunol. 2018;141:110-116.
Murphy K, Meltzer E, Blaiss M, et al. Asthma management and control in the United States: results of the 2009 asthma insight and management survey. Allergy Asthma Proc. 2012;33:54-64.
Waljee AK, Rogers MA, Lin P, et al. Short term use of oral corticosteroids and related harms among adults in the United States: population based cohort study. BMJ. 2017;357:j1415.
Chung L, Upham J, Bardin J, et al. Rational oral corticosteroid use in adult severe asthma: A narrative review. 2020; 25:161-172.
Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention (2023 update). Updated July, 2023. https://ginasthma.org/wp-content/uploads/2023/07/GINA-2023-Full-report-23_07_06-WMS.pdf Accessed 1/30/24.
Nair P, Wenzel S, Rabe K, et al. Oral glucocorticoid–sparing effect of benralizumab in severe asthma. N Engl J Med. 2017;376:2448-2458.
Rabe K, Nair P, Brusselle G, et al. Efficacy and safety of dupilumab in glucocorticoid-dependent severe asthma. N Engl J Med. 2018; 378:2475-2485.
Bel E, Wenzel S, Thompson P, et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med. 2014;371:1189-1197.