Sobering Data on Risks of Short-Term Oral Corticosteroids

Corticosteroid bursts as short as 2 weeks or less were still linked to severe adverse events among relatively healthy users, according to a large study from Taiwan.

For people taking oral steroids over a median 3 days, the risk of such events was elevated in the 5-30 days after steroid therapy initiation compared with the reference period (5-90 days before initiation):

• GI bleeding: 27.1 per 1,000 person-years (incidence rate ratio 1.80, 95% CI 1.75-1.84)
• Sepsis: 1.5 per 1,000 person-years (IRR 1.99, 95% CI 1.70-2.32)
• Heart failure: 1.3 per 1,000 person-years (IRR 2.37, 95% CI 2.13-2.63)

Patients with and without comorbid conditions experienced similar increases in adverse events following their steroid bursts. While risk attenuated somewhat during days 31-90, it remained elevated, reported Tsung-Chieh Yao, MD, PhD, of Chang Gung Memorial Hospital in Taoyuan, and colleagues in the Annals of Internal Medicine.

"Our findings are important for physicians and guideline developers because short-term use of oral corticosteroids is common and the real-world safety of this approach remains unclear," according to the investigators.

Notably, one corticosteroid that fits the bill is dexamethasone, now commonly used as a COVID-19 treatment. The NIH currently recommends dexamethasone 6 mg/day for up to 10 days in COVID-19 patients under mechanical ventilation (dexamethasone is not recommended for people not requiring supplemental oxygen).

"We are now learning that bursts as short as 3 days may increase risk for serious AEs [adverse events], even in young and healthy people. As providers, we must reflect on how and why we prescribe corticosteroids to develop strategies that prevent avoidable harms," according to Beth Wallace, MD, and Akbar Waljee, MD, both of the VA Ann Arbor Healthcare System and Michigan Medicine.

"Although many providers already avoid corticosteroids in elderly patients and those with comorbid conditions, prescribing short bursts to 'low-risk' patients has generally been viewed as innocuous, even in cases where the benefit is unclear. However, Yao and colleagues provide evidence that this practice may risk serious harm, making it difficult to justify in cases where corticosteroid use lacks evidence of meaningful benefit," they wrote in an accompanying editorial.

The self-controlled case series was based on national medical claims records. Included were adults, ages 20-64, covered by Taiwan's National Health Insurance in 2013-2015.

Out of a population of more than 15.8 million, study authors identified 2,623,327 people who received a steroid burst during the study period. These individuals were age 38 on average, and 55.3% women. About 85% had no baseline comorbid conditions.

The most common indications for the steroid burst were skin disorders and respiratory tract infections.

Study authors acknowledged that they could not adjust for disease severity and major lifestyle factors such as alcohol use, smoking, and BMI. Their reliance on prescription data also meant they couldn't tell if patients actually complied with oral corticosteroid therapy.

Furthermore, the exclusion of the elderly and younger populations also left room for underestimation of the risks of steroid bursts, they said.

"Medication-related risks for AEs can, of course, be outweighed by major treatment benefit. However, this study and prior work show that corticosteroid bursts are frequently prescribed for self-limited conditions, where evidence of benefit is lacking," Wallace and Waljee noted.

"As we reflect on how to respond to these findings, it is useful to note the many parallels between use of corticosteroid bursts and that of other short-term medications, such as antibiotics and opiates. All of these treatments have well-defined indications but can cause net harm when used -- as they frequently are -- when evidence of benefit is low," the editorialists emphasized.

Comment