Corticosteroids even short term increase adverse events

Corticosteroids, prescribed for as many as one in five Americans in commercial insurance plans, can significantly increase the risk for adverse effects even when given short term, as found in a study recently published in BMJ (British Medical Journal). The authors note that though the severe adverse effects of longer term use or oral corticosteroids is well known, little has been understood about short term risks.

“…long term use of corticosteroids is generally avoided, given the risks of serious acute complications such as infection, venous thromboembolism, avascular necrosis, and fracture, as well as chronic diseases such as diabetes mellitus, hypertension, osteoporosis, and other features of iatrogenic Cushing’s syndrome…Indeed, corticosteroids are one of the most common reasons for admission to hospital for drug related adverse events…In contrast with long term use, however, the risk of complications from short term use is much less understood, and evidence is generally insufficient to guide clinicians.”

Corticosteroids often used where evidence is lacking

Until now little is know about the potential harms of short term use for the range of outpatient conditions for which they are often prescribed.

“…anecdotally corticosteroids are also used often in the short term to treat many other prevalent conditions where evidence is lacking, such as non-specific musculoskeletal pain and rashes. Despite such pervasive indications for use of oral corticosteroids, little is known about the prescribing patterns of short term use of these drugs in the general adult population, or their potential harm.”

Thus they set out to correlate short term use in an outpatient population and the risk of acute adverse events by analyzing data for 1,548,945 subjects who were prescribed oral corticosteroids for less than 30 days (non-oral forms were excluded from this study).

“We chose three acute events listed as adverse events on the Food and Drug Administration mandated drug label for oral corticosteroids (sepsis, venous thromboembolism, fracture). Given the inherent challenges related to confounding, we employed a self controlled case series (SCCS) design. This design has been used to examine drug and vaccine safety.”

The most common prescription was a six day methylprednisolone “dosepak”, most commonly given for upper respiratory tract infections, spinal conditions, and intervertebral disc disorders, allergies, bronchitis, and (non-bronchitic) lower respiratory tract disorders by family medicine and general internal medicine practitioners, but also by specialists in emergency medicine, otolaryngology, and orthopedics.

Significantly higher rates of sepsis, venous thromboembolism, and fracture

The authors identified a serious risk:

“Within 30 days of drug initiation, there was an increase in rates of sepsis (incidence rate ratio 5.30, 95% confidence interval 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<0.001).”

It defies common sense to use an agent that suppresses the immune system during an infection in all but the rare cases of severe immune excess, especially when there are numerous, more benign alternatives.

Quoted in Medscape Family Medicine, lead author Akbar K. Waljee, MD, an assistant professor of gastroenterology at the University of Michigan in Ann Arbor, states:

“On the basis of these findings, Dr Waljee recommended prescribing the smallest possible amount of corticosteroids for treating the condition in question. “If there are alternatives to steroids, we should be use those when possible,” he said in the release. “Steroids may work faster, but they aren’t as risk-free as you might think.”

From the study:

  • This study of 1.5 million privately insured adults (18-64 years) in the US found that one in five patients in an outpatient setting used short term oral corticosteroid over a three year period (2012-14)

  • 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

  • Greater attention to initiating prescriptions of these drugs and monitoring for adverse events may potentially improve patient safety

The authors conclude:

“Oral corticosteroids are frequently prescribed for short term use in the US for a variety of common conditions and by numerous provider specialties. Over a three year period, approximately one in five American adults in a commercially insured plan used oral corticosteroids for less than 30 days. The short term use of these drugs was associated with increased rates of sepsis, venous thromboembolism, and fracture; even at relatively low doses.”

Patients on steroids must have Vit D levels checked

A study just published in The Journal of Clinical Endocrinology & Metabolism alerts clinicians to the need for vigilance in attending to vitamin D levels for patients on chronic steroid medication. The authors state:

“In many disorders requiring steroid therapy, there is substantial decrease in bone mineral density. The association between steroid use and 25-hydroxyvitamin D [25(OH)D] deficiency has not been confirmed in large population-based studies, and currently there are no specific vitamin D recommendations for steroid users…The aim of the study was to evaluate the association of serum 25(OH)D deficiency [defined as 25(OH)D <10 ng/ml] with oral steroid use.”

They performed a cross-sectional analysis on a nationally representative sample of 22,650 U.S. children and adults from the NHANES study. (This is considered representative of 286 million U.S. residents.) It’s not clear why they set the bar so high, but their main outcome measure was serum 25(OH)D levels below 10 ng/ml which is a severe deficiency. What did the data show?

“A total of 181 individuals (0.9% of the population) used steroids within the past 30 d. Overall, 5% of the population had 25(OH)D levels below 10 ng/ml. Among steroid users, 11% had 25(OH)D levels below 10 ng/ml, compared to 5% among steroid nonusers. The odds of having 25(OH)D deficiency were 2-fold higher in those who reported steroid use compared to those without steroid use. This association remained after multivariable adjustment and in a multivariable model using NHANES III data.”

It’s a bit of a jolt to know that as many as 5% of the US population has 25(OH)D levels below 10 ng/ml. The risk is doubled for those on chronic steroids. The authors conclude:

Steroid use is independently associated with 25(OH)D deficiency in this nationally representative cohort limited by cross-sectional data. It suggests the need for screening and repletion in patients on chronic steroids.”

Adverse events are common with steroids

This meta-analysis of data retrieved from 28 studies comprising 2382 patients was just published in the journal Annals of the Rheumatic Diseases. The important thing to note is that “High rates of adverse events were reported in high-quality studies with short follow-up” for low to medium doses. (All patients received prednisilone.) Rates of adverse events were especially high with inflammatory bowel disease, but significant also for the rheumatic diseases included in the study. This highlights one of the advantages of the functional medicine approach that minimizes dependence on steroids by addressing the underlying immune system dysfunction.