After two plus years we know a lot about Covid 19. We certainly don’t know it all, but we know a lot more about what works and what doesn’t than we did a few years ago. In spite of many published articles, it is disappointing to hear and read about the continued prescribing of these medications. It is important for patients to be aware of this.
First here is the latest on the ineffectiveness of Ivermectin from a recent article in The New England Journal of Medicine, followed by how much Medicare is spending on it. The next is on azithromycin, a commonly used antibiotic, followed by methyprednisolone, a steroid.
Effect of Early Treatment with Ivermectin among Patients with Covid-19
List of authors.
- Gilmar Reis, M.D., Ph.D.,
- Eduardo A.S.M. Silva, M.D., Ph.D.,
- Daniela C.M. Silva, M.D., Ph.D.,
- Lehana Thabane, Ph.D.,
- Aline C. Milagres, R.N.,
- Thiago S. Ferreira, M.D.,
- Castilho V.Q. dos Santos,
- Vitoria H.S. Campos,
- Ana M.R. Nogueira, M.D.,
- Ana P.F.G. de Almeida, M.D.,
- Eduardo D. Callegari, M.D.,
- Adhemar D.F. Neto, M.D., Ph.D.,
Abstract
BACKGROUND
The efficacy of ivermectin in preventing hospitalization or extended observation in an emergency setting among outpatients with acutely symptomatic coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is unclear.
METHODS
We conducted a double-blind, randomized, placebo-controlled, adaptive platform trial involving symptomatic SARS-CoV-2–positive adults recruited from 12 public health clinics in Brazil. Patients who had had symptoms of Covid-19 for up to 7 days and had at least one risk factor for disease progression were randomly assigned to receive ivermectin (400 μg per kilogram of body weight) once daily for 3 days or placebo. (The trial also involved other interventions that are not reported here.) The primary composite outcome was hospitalization due to Covid-19 within 28 days after randomization or an emergency department visit due to clinical worsening of Covid-19 (defined as the participant remaining under observation for >6 hours) within 28 days after randomization.
RESULTS
A total of 3515 patients were randomly assigned to receive ivermectin (679 patients), placebo (679), or another intervention (2157). Overall, 100 patients (14.7%) in the ivermectin group had a primary-outcome event, as compared with 111 (16.3%) in the placebo group (relative risk, 0.90; 95% Bayesian credible interval, 0.70 to 1.16). Of the 211 primary-outcome events, 171 (81.0%) were hospital admissions. Findings were similar to the primary analysis in a modified intention-to-treat analysis that included only patients who received at least one dose of ivermectin or placebo (relative risk, 0.89; 95% Bayesian credible interval, 0.69 to 1.15) and in a per-protocol analysis that included only patients who reported 100% adherence to the assigned regimen (relative risk, 0.94; 95% Bayesian credible interval, 0.67 to 1.35). There were no significant effects of ivermectin use on secondary outcomes or adverse events.
CONCLUSIONS
Treatment with ivermectin did not result in a lower incidence of medical admission to a hospital due to progression of Covid-19 or of prolonged emergency department observation among outpatients with an early diagnosis of Covid-19. (Funded by FastGrants and the Rainwater Charitable Foundation; TOGETHER ClinicalTrials.gov number, NCT04727424. opens in new tab.)
Next is a research letter from the Journal of the American Medical Association which estimates that the government is spending close to $130 million for this ineffective treatment.
US Insurer Spending on Ivermectin Prescriptions for COVID-19
We conducted a cross-sectional analysis of the IQVIA PharMetrics Plus for Academics database. During the study period, the database included a convenience sample of 5 million patients with private insurance and 1.2 million with Medicare Advantage across the US. Compared with all US patients with private and Medicare Advantage insurance, the database contains a higher proportion of patients residing in the Midwest and a lower proportion of patients residing in the South. Because data were deidentified, the institutional review board of the University of Michigan Medical School exempted analyses from review.
We identified oral ivermectin prescriptions dispensed during the study period, excluding those for patients who lacked continuous enrollment or had a diagnosis code for a parasitic infection (B65.XXX-B89.XXX) during the 7 days before dispensing. We assumed the remaining prescriptions were for COVID-19. This approach maximized sensitivity because it captured prescriptions written during visits in which COVID-19 was not coded and during visits not billed to insurance.
For each payer type, we calculated mean insurer reimbursement, out-of-pocket spending (deductibles plus coinsurance and co-payments), and total spending (insurer reimbursement plus out-of-pocket spending) per prescription. To assess the degree to which insurers covered prescription costs, we divided aggregate insurer reimbursement across prescriptions by aggregate total spending.
To assess the potential magnitude of US insurer spending on ivermectin prescriptions for COVID-19, we estimated private and Medicare plan spending on these prescriptions during the week of August 13, 2021, the most recent week for which dispensing data were available.2 We assumed that all 88 000 ivermectin prescriptions dispensed that week were for COVID-19 except 3600, the average US weekly dispensing total in the 12 months before the pandemic2; that 52% (43 888) and 28% (23 632) of the remaining 84 400 prescriptions were paid by private and Medicare plans, mirroring the overall distribution of payer type for US prescriptions3; and that our estimates of insurer reimbursement per prescription generalized to all private and Medicare plans. We multiplied by 52 to estimate annual spending. Analyses used SAS version 9.4.
Of 5939 ivermectin prescriptions, 348 (5.9%) were excluded. Of the remaining 5591 prescriptions, 4700 (84.1%) were for privately insured patients. Mean patient age was 51.8 years (SD, 15.7 years) (Table 1).
Among ivermectin prescriptions, mean (SD) out-of-pocket spending was $22.48 ($24.78) for privately insured patients and $13.78 ($26.24) for Medicare Advantage patients; mean insurer reimbursement was $35.75 ($50.63) and $39.13 ($40.18), respectively; and mean total spending was $58.23 ($51.47) and $52.91 ($42.47), respectively. Aggregate total spending was $273 681.00 for privately insured patients and $47 142.81 for Medicare Advantage patients, of which insurer reimbursement represented 61.4% and 74.0%, respectively (Table 2).
In the week of August 13, 2021, private and Medicare plans paid an estimated $1 568 996.00 (43 888 × $35.75) and $924 720.16 (23 632 × $39.13) for ivermectin prescriptions for COVID-19. The weekly total of $2 493 716.16 extrapolated to $129 673 240.30 annually.
Here is a research letter, also from JAMA, which details the amount of Medicare spending for Azithromycin. Have you ever asked your doctor for a Z pak?
Antibiotic Prescriptions Associated With COVID-19 Outpatient Visits Among Medicare Beneficiaries, April 2020 to April 2021
Antibiotics are ineffective treatment for viral syndromes, including COVID-19. We characterized antibiotic prescribing in older adults with outpatient COVID-19 visits to identify opportunities to improve prescribing practices.
We used 100% Medicare carrier claims and Part D event files to identify beneficiaries with a COVID-19 outpatient visit and associated antibiotic prescriptions. We included beneficiaries aged 65 years and older who had fee-for-service plus Part D coverage and a visit during April 2020 to April 2021. We identified telehealth visits with Current Procedural Terminology codes1 and in-person visits (office, urgent care, and emergency department [ED]) with place-of-service codes. To identify visits with a primary diagnosis of COVID-19, we first limited them to those with International Classification of Diseases and Related Health Problems, 10th Revision diagnosis code U07.1. We then excluded visits with additional diagnosis codes for conditions for which antibiotics are always or sometimes appropriate based on clinical guidelines using a previously described tiered system.2 Visits were then linked to an antibiotic if prescribed within 7 days before or after the visit. We reported visits by setting and month, including antibiotic classes.
We performed 2-sided χ2 tests to compare the distribution of characteristics between beneficiaries with COVID-19 who were and were not prescribed an antibiotic by age, sex, race, and prescribers’ location. This study was deemed nonhuman subjects research by the Centers for Disease Control and Prevention and did not require institutional review board review. Analyses were performed in SAS version 9.4. P < .05 defined statistical significance.
During April 2020 to April 2021, 346 204 (29.6%) of 1 169 120 COVID-19 outpatient visits were associated with an antibiotic prescription, which varied by month, with higher rates of antibiotic prescribing occurring during a wave of COVID-19 cases during the winter of 2020-2021 (range, 17.5% in May 2020 to 33.3% in October 2020) (Figure). Prescribing was highest in the ED (33.9%), followed by telehealth (28.4%), urgent care (25.8%), and office (23.9%) (Figure) visits. Azithromycin was the most frequently prescribed antibiotic (50.7%), followed by doxycycline (13.0%), amoxicillin (9.4%), and levofloxacin (6.7%). Urgent care had the highest percentage of azithromycin prescriptions (60.1%), followed by telehealth (55.7%), office (51.5%), and ED (47.4%). Differences were observed by age, sex, and location (Table). Non-Hispanic White beneficiaries received antibiotics for COVID-19 more frequently (30.6%) than other racial and ethnic groups: American Indian/Alaska Native (24.1%), Asian/Pacific Islander (26.5%), Black or African American (23.2%), and Hispanic (28.8%) (Table).
During the first year of the COVID-19 pandemic, 30% of outpatient visits for COVID-19 among Medicare beneficiaries were linked to an antibiotic prescription, 50.7% of which were for azithromycin. Randomized clinical trials demonstrated no benefit of azithromycin in treating COVID-19,3,4 and its use for the disease has been linked to antimicrobial resistance.5 The largest number of visits and highest rates of antibiotic prescribing were observed in the ED, perhaps reflecting acuity of care, and urgent care centers had the highest rate of azithromycin prescribing. Telehealth visits had the second highest antibiotic prescribing rate and were close in volume to office visits, emphasizing the importance of optimizing antibiotic prescribing practices in this setting. Antibiotic prescribing occurred at a higher rate for non-Hispanic White beneficiaries than for those from other racial and ethnic groups. Although described in pediatrics, this racial difference has not been well characterized in older adults and warrants further evaluation because it may indicate more services are being provided to White beneficiaries, even if not indicated.6
Study limitations include that, although only visits for which COVID-19 was the primary diagnosis were included and visits with a diagnosis code that putatively justified an antibiotic were excluded, misclassification was possible. Underlying chronic medical conditions or severity of illness and subsequent hospital admission were not controlled for. These data may not be representative of the entire US population nor adults aged 65 years and older without Medicare prescription drug coverage. Data since April 2021 were not available, and strong evidence against azithromycin use was not published until the end of the observation period.
These observations reinforce the importance of improving appropriate antibiotic prescribing in outpatient settings and avoiding unnecessary antibiotic use for viral infections such as COVID-19 in older adult populations.
Systemic Corticosteroid Use for COVID-19 in US Outpatient Settings From April 2020 to August 2021
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.
