Abstract
This study uses 2 large US health care claims databases (Medicare fee-for-service and the US Food and Drug Administration’s Sentinel System) to examine systemic corticosteroid use among nonhospitalized patients with COVID-19.
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.
Methods
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.
Results
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.
Table. Characteristics and Comorbidities of Patients With COVID-19 and Those Initiating Systemic Corticosteroids Within 14 Days of Diagnosis.
| Medicare (April 1, 2020-August 31, 2021) | US FDA’s Sentinel System (April 1, 2020-July 31, 2021) | |||||
|---|---|---|---|---|---|---|
| COVID-19 diagnosis | Corticosteroid usea | Rate, %b | COVID-19 diagnosis | Corticosteroid usec | Rate, %b | |
| Demographic and clinical characteristics | ||||||
| Total No. of patients | 576 885 | 94 781 | 16.4 | 766 105 | 72 124 | 9.4 |
| Age, mean (SD), y | 74.6 (7.2) | 74.4 (6.9) | 48.5 (19.9) | 57.7 (16.7) | ||
| Age group, No. (%), y | ||||||
| <44 | 339 385 (44.3) | 18 008 (25.0) | 5.3 | |||
| 45-64 | 204 350 (26.7) | 23 552 (32.7) | 11.5 | |||
| 65-79 | 443 664 (76.9) | 74 300 (78.4) | 16.7 | 176 533 (23.0) | 24 811 (34.4) | 14.1 |
| ≥80 | 133 211 (23.1) | 20 481 (21.6) | 15.4 | 45 837 (6.0) | 5753 (8.0) | 12.6 |
| Sex, No. (%) | ||||||
| Male | 249 044 (43.2) | 42 516 (44.9) | 17.1 | 357 697 (46.7) | 32 988 (45.7) | 9.6 |
| Female | 327 841 (56.8) | 52 265 (55.1) | 15.9 | 408 408 (53.3) | 39 136 (54.3) | 9.2 |
| Race and ethnicity, No. (%)d | ||||||
| Asian | 9391 (1.6) | 1080 (1.1) | 11.5 | 19 210 (2.5) | 1146 (1.6) | 6.0 |
| Black or African American | 26 425 (4.6) | 3048 (3.2) | 11.5 | 50 417 (6.6) | 4530 (6.3) | 9.0 |
| Hispanic | 14 423 (2.5) | 1944 (2.1) | 13.5 | 53 420 (7.0) | 4453 (6.2) | 8.3 |
| Native American | 3226 (0.6) | 409 (0.4) | 12.7 | 2965 (0.4) | 280 (0.4) | 9.4 |
| Native Hawaiian/other Pacific Islander | 3738 (0.5) | 329 (0.5) | 8.8 | |||
| White | 500 563 (86.8) | 85 302 (90.0) | 17.0 | 298 976 (39.0) | 30 797 (42.7) | 10.3 |
| Othere | 6971 (1.2) | 862 (0.9) | 12.4 | |||
| Unknown | 15 886 (2.8) | 2136 (2.3) | 13.4 | 390 799 (51.0) | 35 042 (48.6) | 9.0 |
| US region, No. (%)f | ||||||
| Northeast | 104 929 (18.2) | 8864 (9.4) | 8.4 | 139 333 (18.2) | 7284 (10.1) | 5.2 |
| Midwest | 135 261 (23.5) | 20 394 (21.5) | 15.1 | 152 091 (19.9) | 11 792 (16.3) | 7.8 |
| South | 241 340 (41.8) | 53 437 (56.4) | 22.1 | 302 766 (39.5) | 43 523 (60.3) | 14.4 |
| West | 94 553 (16.4) | 12 056 (12.7) | 12.8 | 161 097 (21.0) | 9167 (12.7) | 5.7 |
| Comorbidities, No. (%) | ||||||
| Hematologic cancer | 10 798 (1.9) | 1784 (1.9) | 16.5 | 4159 (0.5) | 581 (0.8) | 14.0 |
| Congestive heart failure | 40 961 (7.1) | 7022 (7.4) | 17.1 | 22 893 (3.0) | 3285 (4.6) | 14.3 |
| Hospitalized acute myocardial infarction | 2173 (0.4) | 319 (0.3) | 14.7 | 1147 (0.1) | 85 (0.1) | 10.9 |
| Hypertension | 351 427 (60.9) | 59 589 (62.9) | 17.0 | 217 346 (28.4) | 30 880 (42.8) | 14.2 |
| Stroke or transient ischemic attack | 1890 (0.3) | 261 (0.3) | 13.8 | 1098 (0.1) | 85 (0.1) | 7.7 |
| Chronic kidney disease | 65 747 (11.4) | 10 770 (11.4) | 16.4 | 40 355 (5.3) | 5559 (7.7) | 13.8 |
| Diabetes | 148 235 (25.7) | 24 070 (25.4) | 16.2 | 110 730 (14.5) | 14 733 (20.4) | 13.3 |
| Taking immunosuppressant therapies | 33 600 (5.8) | 5625 (5.9) | 16.7 | 15 702 (2.0) | 2122 (2.9) | 13.5 |
| Obesity | 90 793 (15.7) | 17 250 (18.2) | 19.0 | 104 244 (13.6) | 15 416 (21.4) | 14.8 |
| Chronic obstructive pulmonary disease | 41 908 (7.3) | 9892 (10.4) | 23.6 | 26 625 (3.5) | 5581 (7.7) | 21.0 |
| Asthma | 30 596 (5.3) | 6706 (7.1) | 21.9 | 32 055 (4.2) | 5123 (7.1) | 16.0 |
| Rheumatologic and inflammatory conditions | 37 238 (6.5) | 6669 (7.0) | 17.9 | 28 411 (3.7) | 4042 (5.6) | 14.2 |
| Smoking | 69 016 (12.0) | 12 191 (12.9) | 17.7 | 51 602 (6.7) | 7215 (10.0) | 14.0 |
| Combined Charlson and Elixhauser comorbidity indicesg | ||||||
| Mean (SD) | 0.8 (1.8) | 0.8 (1.8) | 0.5 (1.4) | 0.7 (1.7) | ||
| Median (IQR) | 0 (0-1.0) | 0 (0.1-1.0) | ||||
A total of 13 007 eligible patients (2.25%) were censored because they died, were disenrolled, or were hospitalized within 14 days after COVID-19 diagnosis.
Calculated as corticosteroid use/outpatient COVID-19 diagnosis.
A total of 336 eligible patients (<1%) were censored because they died or were disenrolled and 29 960 (3.9%) because they were hospitalized within 14 days after COVID-19 diagnosis.
In Sentinel, race and ethnicity were separate variables, so a patient could have both a race and Hispanic ethnicity; therefore, the percentages do not equal 100%.
Patients reported “other” and did not select another category.
A small percentage of patients were not categorized into a region; therefore, the percentages do not equal 100%.
The assessment period was 183 days prior to COVID-19 diagnosis. Additional details appear in the Supplement.
Figure. Proportion of Patients With COVID-19 Initiating Systemic Corticosteroids Within 14 Days of Diagnosis.
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.
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%).
Discussion
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.
Section Editors: Jody W. Zylke, MD, Deputy Editor; Kristin Walter, MD, Associate Editor.
eTable. Data sources and study characteristics
References
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
eTable. Data sources and study characteristics