FDA indicates Food and Drug Administration; NIH, National Institutes of Health; RECOVERY, Randomised Evaluation of COVID-19 Therapy.
aThe name of the corticosteroid was only available for pharmacy dispensings.
eTable. Data sources and study characteristics
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Bradley MC, Perez-Vilar S, Chillarige Y, et al. Systemic Corticosteroid Use for COVID-19 in US Outpatient Settings From April 2020 to August 2021. JAMA. 2022;327(20):2015–2018. doi:10.1001/jama.2022.4877
In June 2020, preliminary results for the Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial conducted in the UK indicated benefit from dexamethasone in severely ill hospitalized patients with COVID-19 but potential harm in those not requiring oxygen.1,2 In October 2020, the National Institutes of Health (NIH) issued COVID-19 treatment guidelines advising against systemic corticosteroid use in patients with mild to moderate COVID-19.1 Using 2 large US health care claims databases, we examined systemic corticosteroid use among nonhospitalized patients with COVID-19.
Data from Medicare fee-for-service and the US Food and Drug Administration’s (FDA’s) Sentinel System were used. Medicare is a federal health insurance program mostly serving those aged 65 years or older.3 The Sentinel System comprises primarily claims data from commercially insured patients of all ages in a distributed network of data partners.4 The Sentinel Rapid COVID-19 data source used in this analysis included 2 national insurance claims data partners and 2 integrated delivery care systems.
Nonhospitalized, noninstitutionalized patients with incident COVID-19 between April 2020 and August 2021 (July 2021 for Sentinel) were included. Incident outpatient COVID-19 was defined as a diagnosis code for COVID-19 or positive SARS-CoV-2 laboratory test (Sentinel only) recorded on an outpatient claim, including emergency department claims without subsequent hospitalization. Those with COVID-19 within the prior 183 days and those with use of systemic corticosteroids within the prior 90 days were excluded. Patients were followed up from COVID-19 diagnosis date until the earliest occurrence of a claim for a new oral or injectable corticosteroid in an outpatient setting, hospitalization, death, disenrollment, or 14 days. Demographics, clinical characteristics, and among corticosteroid initiators, corticosteroid type, timing, setting of initiation, prescriber specialty, and concomitant therapies were examined (eTable in the Supplement).
Analyses were descriptive and performed using SAS version 9.4 (SAS Institute Inc). This study was classified as public health surveillance by the FDA and exempted from review by the institutional review board in accordance with the updated Common Rule.
There were 576 885 eligible patients with COVID-19 in Medicare and 766 105 in Sentinel, the mean age was 74.6 years (SD, 7.2 years) and 48.5 years (SD, 19.9 years), respectively, and the proportion of males was 43.2% and 46.7% (Table). Of these, 16.4% in Medicare and 9.4% in Sentinel received systemic corticosteroids in an outpatient setting within 14 days of COVID-19 diagnosis (Figure). The proportion of patients initiating corticosteroids in the South was higher than in any other region. Use increased with age until approximately 79 years. Corticosteroid use increased over time from 2.2% initiating in April 2020 to 21.1% in August 2021 in Medicare, and from 2.2% in April 2020 to 13.8% in July 2021 in Sentinel.
Among pharmacy dispensings, the most commonly used corticosteroids were dexamethasone in Medicare (43.8%) and prednisone in Sentinel (34.1%). The most common prescriber specialties in Medicare were internal medicine or family/general practice (39.9%) and emergency medicine (18.6%). Treatment often started on the day of COVID-19 diagnosis (58.8% for Medicare vs 51.3% for Sentinel), largely through pharmacy dispensings (70.8%-80.3%) rather than during medical encounters. On the day corticosteroid use was initiated, 24.7% in Medicare had visited the emergency department vs 22.9% in Sentinel. Azithromycin was the most common concomitant therapy (44.8% for Medicare vs 48.8% for Sentinel)—often initiated on the same date as the corticosteroid—followed by monoclonal antibodies (Medicare: 7.1%; Sentinel: 2.0%), inhaled corticosteroids (Medicare: 2.4%; Sentinel: 6.7%), ivermectin (Medicare: 3.9%; Sentinel: 3.5%), and nonoral anticoagulants (Medicare: 3.6%; Sentinel: 3.1%).
Despite NIH recommendations, increasing numbers of nonhospitalized patients with COVID-19 were prescribed systemic corticosteroids, often on the day of diagnosis. Use appeared to be more prominent in the South and was not restricted to older patients. Limitations of the study included inability to capture date of symptom onset and indication for use, and potential for misclassifying mild to moderate COVID-19 disease due to overburdened resources and limited ability to accurately capture elements to define disease severity, including oxygen use. Given the increasing use of corticosteroids through August 2021, the potential safety signal,2,5,6 and the lack of efficacy data in patients with mild to moderate COVID-19,1 it is critical that prescribers consider the NIH guidelines in the therapeutic management of nonhospitalized patients with COVID-19.
Accepted for Publication: March 15, 2022.
Published Online: April 8, 2022. doi:10.1001/jama.2022.4877
Corresponding Author: Marie C. Bradley, PhD, MPharm, MScPH, Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, US Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, MD 20903 (email@example.com).
Author Contributions: Mr Chillarige and Dr Martinez had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Bradley, Perez-Vilar, Chillarige, Martinez, Weckstein, Dal Pan.
Acquisition, analysis, or interpretation of data: Bradley, Perez-Vilar, Chillarige, Dong, Martinez, Weckstein.
Drafting of the manuscript: Bradley, Perez-Vilar.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Chillarige, Dong, Martinez, Weckstein.
Obtained funding: Dal Pan.
Administrative, technical, or material support: Bradley, Martinez, Weckstein, Dal Pan.
Supervision: Bradley, Perez-Vilar, Chillarige, Dal Pan.
Conflict of Interest Disclosures: Mr Chillarige reported receiving personal fees from Acumen LLC. Mr Weckstein reported being employed by and having an ownership interest (stock options or existing equity) in Aetion, a technology company that provides analytic software and services to the health care industry. No other disclosures were reported.
Funding/Support: This study was funded through interagency agreement 21-182 between the US Food and Drug Administration (FDA) and the Centers for Medicare & Medicaid Services (CMS) (task order 75FCMC21F0067) for which Acumen LLC is the contractor, with additional funding from the FDA and the Centers for Drug Evaluation and Research (contract 75F40119D10037). The Sentinel System Initiative is funded by the FDA through contract 75F40119F19001 from the US Department of Health and Human Services (DHHS).
Role of the Funder/Sponsor: The authors who were employees or contractors of the FDA, the CMS, or the Veterans Health Administration (VHA) played a role in the design; however, other officials at the FDA, the CMS, and the VHA had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The manuscript was subjected to administrative review before submission, but this review did not alter its content.
Disclaimer: The views expressed in this article are those of the authors and do not necessarily reflect those of the FDA, the CMS, the VHA, or the DHHS.
Additional Contributions: We thank David J. Graham, MD, MPH, Efe Eworuke, PhD, and Hana Lee, PhD (FDA); Jeffrey A. Kelman, MD, MSSc (CMS); Sandia Akhtar, BS, Hai Lyu, MS, and Kushal B. Naik, MBBS, MPH (Acumen LLC); and Austin Cosgrove, BS, Noelle Cocoros, DSc, MPH, and Judith Maro, PhD, MS (Department of Population Medicine, Harvard Medical School). We also thank the institutional partners that provided the data used in the Sentinel analysis: CVS Health Clinical Trial Services (an affiliate of Aetna), HealthPartners Institute, Humana Inc, and Kaiser Permanente Northwest Center. No compensation was received for this work.