Exposure to systemic corticosteroids is associated with an increased risk of COVID-19 infection and subsequent severe outcomes in patients using the immunosuppressive treatment for noninfectious uveitis (NIU), according to a large cohort study published in Ophthalmology

Between January 20, 2020 and December 31, 2020, researchers conducted a retrospective study of patients with NIU (n=52,286) using the Optum Labs Data Warehouse, a US national de-identified claims database. They estimated unadjusted and adjusted hazard ratios for each variable and COVID-19 outcome utilizing Cox proportional hazards models, with time-updated dichotomous indicators for outpatient immunosuppressive medication exposure. To evaluate the dose-dependent influence of systemic corticosteroid exposure, the mean daily dose (mg) of prednisone spanning the exposed interval was included in the adjusted models as a continuous variable, as well as the dichotomous variable. 

The main study outcome measures were incidence rates of COVID-19 infection, COVID-19-related hospitalization, and COVID-19-related in-hospital death. The average age of the patients in the overall cohort was 62.8 years (60.3% women, 39.6% men, 0.1% unknown).


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Of the 52,286 patients with NIU, 9516 patients (18.2%) were exposed to systemic corticosteroids during the risk period. In total, 22,948 systemic corticosteroid prescriptions were filled by the 9516 users, with a mean duration of 24 days and median duration of 14 days (interquartile range 6-30 days). The most commonly prescribed systemic corticosteroid was prednisone, which comprised 72.4% of SC prescriptions during the risk period. 

According to the adjusted models, exposure to systemic corticosteroids was associated with higher risk of COVID-19 infection (hazard ratio [HR]=2.66; 95% CI: 2.19– 3.24; P <.001), hospitalization (HR=3.26; 95% CI: 2.46–4.33; P <.001), and in-hospital death (HR=1.99; 95% CI: 0.93–4.27; P =.08). The researchers found that incremental increases in the dosage of systemic corticosteroids were associated with a greater risk for these outcomes. Tumor necrosis factor alpha (TNF-α) inhibitors were associated with a greater risk of infection (HR=1.48; 95% CI: 1.08–2.04; P =.02), while other immunosuppressive treatments did not increase the risk of COVID-19 infection, hospitalization or death.

In both unadjusted and adjusted analyses, patients with older age and Black and Hispanic ethnicity had a greater risk of infection, hospitalization and in-hospital death due to COVID-19. In multivariable analyses, comorbidities such as cardiovascular disease, chronic kidney disease, neurologic disease, and diabetes showed associations with each COVID-19 related outcome. 

“Ophthalmologists currently providing care for these patients should think about methods to reduce their patients’ risk of exposure or severe disease by promoting mask-wearing and vaccination,” the researchers explain. “Clinicians can also consider clinical interventions to reduce COVID-19 exposure risk for patients on systemic corticosteroids, such as dedicated time slots for immunosuppressed patients or telehealth follow-up for patients with stable disease.”

Study limitations include a population skewed towards older patients, possibility that all aspects of uveitis disease status were not taken into account, possibility of misclassification of COVID-19 infection, and the exclusion of individuals with basic Medicare plans, Medicaid, or no insurance. Further, the observed exposure period may not fully characterize the true exposed period, potential confounders were only captured at baseline, and some specific drug classes were not analyzed separately due to limited sample size in these subgroups. Lastly, lab tests in Optum Labs Data Warehouse are only available via lab vendors that contract with the insurer, which likely underestimated the correct number of positive COVID-19 tests.

Reference

Sun Y, Miller DC, Akpandak I, Chen EM, Arnold BF, Acharya NR. Association between immunosuppressive drugs and COVID-19 outcomes in patients with non-infectious uveitis in a large US claims database. Ophthalmol. Published online May 16, 2022. doi:10.1016/j.ophtha.2022.05.008