Long-Term Use of Oral Corticosteroids and Safety Outcomes for Patients With Atopic Dermatitis

Abstract

Importance: The use of oral corticosteroids for prolonged periods may be associated with adverse events (AEs). Nevertheless, the risk of AEs with oral corticosteroids, especially among patients with atopic dermatitis (AD), has not been comprehensively investigated and lacks evidence on duration of treatment.

Objective: To assess the association between long-term exposure to oral corticosteroids and AEs among adult patients with AD.

Design, setting, and participants: This nested case-control study used data from the Health Insurance Review and Assessment Service database of South Korea between January 1, 2012, and October 31, 2021, which included 1 year prior to the cohort entry date of January 1, 2013, for assessing exclusion criteria and baseline characteristics, and 1 year after the study end date of October 31, 2020, to ensure a minimum duration for assessing exposure. Among the population of adults with AD, patients diagnosed with any of 11 AEs were matched with patients who had never received a diagnosis of any of the 11 AEs.

Exposure: Long-term use of oral corticosteroids was defined as cumulative supply of more than 30 days or more than 90 days of oral corticosteroid prescription per year.

Main outcomes and measures: We used multivariable conditional logistic regression analyses to measure the risk of 11 individual outcomes (osteoporosis, fracture, type 2 diabetes, hyperlipidemia, hypertension, myocardial infarction, stroke, heart failure, avascular necrosis, cataract, or glaucoma) as the composite outcome, controlling for potential confounders. We further classified the composite outcome to individual outcomes to evaluate the AE-specific risk.

Results: Among 1 025 270 patients with AD between 2013 and 2020, 164 809 cases (mean [SD] age, 39.4 [14.8]; 56.9% women) were matched with 328 303 controls (mean [SD] age, 39.3 [14.7]; 56.9% women) for sex, age, cohort entry date, follow-up duration, and severity of AD, where the balance of most baseline characteristics was achieved. A total of 5533 cases (3.4%) and 10 561 controls (3.2%) were exposed to oral corticosteroids for more than 30 days, while 684 cases (0.4%) and 1153 controls (0.4%) were exposed to oral corticosteroids for more than 90 days. Overall, there was no increased risk of AEs with use of oral corticosteroids for more than 30 days (adjusted odds ratio [AOR], 1.00; 95% CI, 0.97-1.04), whereas the risk was slightly higher with use of oral corticosteroids for more than 90 days (AOR, 1.11; 95% CI, 1.01-1.23). The small elevation in experiencing an AE was observed with each cumulative or consecutive year of ever long-term use.

Conclusions and relevance: This case-control study found a slightly increased risk of AEs associated with use of oral corticosteroids for more than 90 days per year, which warrants future research to fully elucidate the observed findings.

Figure 1.. Study Flowchart for the Composite Adverse Outcome

AD indicates atopic dermatitis; OCS, oral corticosteroid. ^aRheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, psoriasis, Crohn disease, ulcerative colitis, Sjögren syndrome, systemic sclerosis, dermatomyositis, polymyositis, thromboangiitis obliterans, Behçet disease, sarcoidosis, pemphigus, and vitiligo. ^bPatients who received a diagnosis of the outcomes of interest (osteoporosis, fracture, type 2 diabetes, hyperlipidemia, hypertension, myocardial infarction, stroke, heart failure, avascular necrosis, cataract, or glaucoma) during 1 year before or 1 year after the cohort entry date were excluded.

Figure 2.. Sensitivity Analyses for Evaluating the Risk of the Composite Adverse Outcome Associated With Long-Term Use of Oral Corticosteroids Among Adults With Atopic Dermatitis

OR indicates odds ratio. ^aModified definition of the exposure from cumulative duration of more than 30 days per year and more than 90 days per year to a cumulative duration of more than 60 days per year. ^bThe long-term use of oral corticosteroids was defined as a cumulative supply of more than 30 days or more than 90 days with a greater than 5-mg daily prednisolone-equivalent dose of oral corticosteroids, which places patients at risk of systemic adverse effects, and we assessed the long-term use of oral corticosteroids annually. To exclude potential use of oral corticosteroids for conditions other than atopic dermatitis, we restricted exposure to prescriptions for patients with a diagnosis of atopic dermatitis. ^cRestricted to patients who could be followed up for at least 3 years from the cohort entry date. ^dRestricted to patients who could be followed up for at least 5 years from the cohort entry date.