Serious Adverse Effects Associated With Short-Term Use of Oral Corticosteroids

Corticosteroids, also known as glucocorticoids, are natural hormones made by the adrenal glands. Synthetic forms of these hormones are widely used, including oral forms such as cortisone (generic only), hydrocortisone (ALKINDI SPRINKLE, CORTEF), prednisone (RAYOS), prednisolone (ORAPRED, PEDIAPRED, PRELONE), dexamethasone (HEMADY) and methylprednisolone (MEDROL).[1] Dexamethasone given by injection in the hospital has recently received much attention because it is the only drug that has demonstrated effectiveness in reducing deaths related to serious COVID-19 infection.[2]

Systemic (oral and injectable) corticosteroids influence the body’s metabolism (of carbohydrates, proteins and fats), the cardiovascular and skeletal muscular systems, and the brain systems that control sleep and mood.[3] Corticosteroids additionally act by suppressing the body’s sometimes self-injurious inflammatory responses. Accordingly, corticosteroids may be used to treat inflammation related to illnesses such as asthma (typically via inhalation) and arthritis. These drugs are further used to treat inflammatory illness tied to skin irritation, allergies, certain cancers, bronchitis and hormonal disorders.[4]

Public Citizen’s Health Research Group previously has written that even as systemic corticosteroids can be highly effective therapies, they should be used in the lowest dose and for the shortest duration possible because they are often overprescribed and can cause severe adverse effects such as immune suppression (increasing risk of infection), osteoporosis (bone-density reduction), high blood pressure, gastrointestinal ulcers, psychiatric disturbance (ranging from confusion and depression to psychosis) and weight gain.[5]

A recently published study shows that even short-term (14 or fewer days) use of oral corticosteroids is associated with an increased risk of serious adverse effects.

New study[6]

A study published in the Sep. 1, 2020, issue of Annals of Internal Medicine used nationwide medical claims data from Taiwan to examine the association between corticosteroid “bursts” (short-term use, ≤14 days) and three severe adverse events: gastrointestinal bleeding, heart failure and sepsis (life-threatening reaction to infection). These adverse events were selected because they are among some of the most consequential harms previously observed with long-term use of corticosteroids. Short-duration use was the focus in this research because few prior studies have scrutinized such therapy.

The National Health Insurance Research database of Taiwan was used as the main data source for this research. Records were reviewed for the four-year period spanning 2012 through 2015. Only those with enrollment in Taiwan’s national health care system for all four of those years were included, and only adults age 20 to 64 in the year of 2013. New corticosteroid users were defined as those without corticosteroid burst or other corticosteroid prescriptions in 2012, but with one burst prescription sometime between January 2013 and September 2015.

Nearly 16 million adult person-records were included in the database. Of those, 25% (about 4 million people) were defined as new corticosteroid burst users, and about 2.6 million met all study criteria including the absence of corticosteroid use or the diagnosis of any of the three severe adverse events of interest in 2012.

The top 10 (comprising 59% of all) reasons for using corticosteroid bursts were skin and respiratory tract disorders including dermatitis and eczema, bronchitis, acute sinusitis or tonsillitis, pruritus (severely itchy skin) and common colds. Eighty-seven percent of prescriptions were written by five specialties: dermatology (31%), otolaryngology (21%), family practice (18%), internal medicine (11%) and pediatrics (6%). According to the researchers, approximately 8% of Taiwanese adults use short-term corticosteroids annually, a rate that is similar to that observed by one large study in the U.S.[7]

Compared with the three-month period before the corticosteroid burst, patients prescribed such treatment had an approximately twofold, statistically significant increase in the rates of gastrointestinal bleeding, sepsis and heart failure events during the 30-day period after initiation of the corticosteroid burst. The rates of these three adverse events subsequently decreased in the 31-to-90-day period after initiation of the burst but were still statistically significantly higher than the baseline rates observed during the three-month period before the burst.

The Taiwan-based researchers concluded that physicians everywhere who consider prescribing corticosteroid bursts need to weigh the potential benefits against the risks for rare but potentially serious adverse events. Importantly, the use of corticosteroid bursts likely was inappropriate for many of the patients included in the Taiwan study. For example, such treatment generally is not appropriate for the common cold.

What You Can Do

If you need to consider oral corticosteroid therapy, discuss the potential risks and benefits of such medication use with your doctor, including the strong possibility that even short-term use (≤ 14 days) can elevate your risk of rare but severe adverse effects such as gastrointestinal bleeding, sepsis and heart failure. Talk to your doctor about alternative treatments and steps that can be taken to mitigate those risks if corticosteroids are your best treatment option.
 

References

[1] Worst Pills, Best Pills Monographs. Drug Profile: oral glucocorticoids. November 30, 2020. https://www.worstpills.org/monographs/view/114. Accessed March 23, 2021.

[2] RECOVERY Collaborative Group, Horby P, et al. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021;384(8):693-704.

[3] Ibid.

[4] Worst Pills, Best Pills Monographs. Drug Profile: oral glucocorticoids. November 30, 2020. https://www.worstpills.org/monographs/view/114. Accessed April 7, 2021.

[5] Ibid.

[6] Yao TC, Huang YW, Chang SM, et al. Association between oral corticosteroid bursts and severe adverse events: a nationwide population-based cohort study. Ann Intern Med. 2020;173(5):325-330.

[7] 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.