Study suggests limiting oral corticosteroid use to 90 days reduces adverse effects in atopic dermatitis patients

By Vijay Kumar MalesuReviewed by Danielle Ellis, B.Sc.Jul 24 2024

In a recent study published in the JAMA Network Open, a group of researchers evaluated the association between long-term oral corticosteroid use and adverse events (AEs) in adult patients with atopic dermatitis  (AD) (Chronic skin inflammation).

Background 

AD is a chronic inflammatory disease causing significant morbidity and is prevalent in adults (2.1%-4.9% across countries). Up to 10% of adults with moderate to severe AD require medication. Despite guidelines advising limited short-term use, many patients use oral corticosteroids long-term, potentially leading to complications. Few studies have examined the long-term effects of oral corticosteroids on AD patients. This highlights the need for more research to understand the safety and possible complications of prolonged use in this population.

About the study 

The present study used the South Korean Health Insurance Review and Assessment Service (HIRA) database from January 1, 2012, to October 31, 2021, covering comprehensive healthcare data for residents. The institutional review board of Sungkyunkwan University approved the study, waiving informed consent due to anonymized data. The cohort included patients prescribed oral corticosteroids with an AD diagnosis from January 1, 2013, to October 31, 2020. Exclusions were applied to those with immune-mediated inflammatory diseases, any of 11 specified outcomes, or those younger than 18.

Exposure was assessed yearly, defining long-term use as over 30 or 90 days per year with a daily dose exceeding 5 mg of prednisolone equivalent. Covariates included comorbidities, health status proxies, demographics, comedications, and AD severity. Cases were AD patients diagnosed with any outcome of interest post-cohort entry, matched with controls by various factors.

Multivariable conditional logistic regression estimated adjusted odds ratios for composite and individual outcomes, considering cumulative or consecutive years of corticosteroid use. Subgroup analyses examined adverse effects by sex, age, and AD severity, with sensitivity analyses modifying exposure definitions and follow-up periods. Statistical analyses were conducted using SAS Enterprise Guide, version 7.1, following Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.

Study results 

The study involved 1,025,270 patients with AD who had at least one prescription of oral corticosteroids between 2013 and 2020. Among these, 164,809 cases (mean age 39.4 years; 56.9% women) were matched with 328,303 controls (mean age 39.3 years; 56.9% women) in a 1:2 ratio using risk-set sampling. The matching criteria included entry date, sex, age, cohort follow-up duration, and AD severity, achieving balance for most covariates with an absolute standardized difference of less than 0.1.

The most common comorbidity was allergic rhinitis (Nasal inflammation due to allergies) (42.2% in cases and 38.7% in controls), and the most frequently prescribed concurrent medication was antibiotics (71.3% in cases and 66.8% in controls). The multivariable logistic regression adjusted for imbalanced variables such as concurrent medication use and the number of outpatient visits.

In this cohort, 5533 cases (3.4%) and 10,561 controls (3.2%) were exposed to oral corticosteroids for over 30 days, while 684 cases (0.4%) and 1153 controls (0.4%) were exposed for over 90 days. The analysis revealed no increased risk of AEs with corticosteroid use exceeding 30 days (AOR, 1.00; 95% CI, 0.97-1.04). However, corticosteroid use exceeding 90 days was associated with an 11% increased risk of composite AEs (AOR, 1.11; 95% CI, 1.01-1.23). Each cumulative or consecutive year of long-term exposure (>90 days a year) was linked to a slightly increased risk of AEs (AOR, 1.06; 95% CI, 1.00-1.13).

Individual outcome analysis showed an increased risk of hypertension (High blood pressure) (AOR, 1.09; 95% CI, 1.03-1.15), avascular necrosis (AVN) (AOR, 2.56; 95% CI, 1.82-3.62), and cataract (Clouding of the eye lens) (AOR, 3.22; 95% CI, 1.05-9.85) with corticosteroid use over 30 days. For use over 90 days, there was an increased risk of fracture (AOR, 1.22; 95% CI, 1.05 - 1.42) and hyperlipidemia (high levels of fats in the blood) (AOR, 1.16; 95% CI, 1.03 - 1.30). Additionally, the risk of myocardial infarction (heart attack) (AOR, 2.22; 95% CI, 1.17- 4.22) and AVN (AOR, 6.88; 95% CI, 3.53 -13.42) was also elevated.

Subgroup analyses indicated that the risk of composite AEs associated with long-term corticosteroid usage was consistent with the main findings, with no significant differences observed by sex, age group, or AD severity. Sensitivity analyses demonstrated a high degree of consistency in the results of composite outcomes across various point estimates, confirming the robustness of the study's conclusions.

Conclusions 

To summarize, the study identified 164,809 cases and 328,303 controls of patients with AD. Long-term use of oral corticosteroids exceeding 30 days was not significantly associated with composite adverse outcomes, but usage over 90 days showed a slight risk increase.

Both cumulative and consecutive years of long-term use were linked to a higher risk of AEs. Specific risks were noted for fracture, myocardial infarction, hyperlipidemia, AVN, hypertension, and cataracts. Consistent findings were observed across sensitivity analyses. These results align with previous studies on asthma patients, highlighting the association of corticosteroid use with bone, metabolic, cardiovascular, and ocular AEs.