Ivermectin, hydroxychloroquine prescriptions during the COVID-19 pandemic soared far above pre-pandemic levels
U.S. outpatient prescriptions for hydroxychloroquine and ivermectin increased 2- to 10-fold above pre-pandemic rates, respectively, to treat COVID-19, despite strong evidence disproving their effectiveness, new UCLA-led research shows.
Nearly three million COVID-related prescriptions were issued in the three and a half years between January 30, 2020 and June 30, 2023, totaling $272 million in estimated spending. Usage was three times higher among adults aged 65 and older compared with those aged 18 to 64. Ivermectin use in particular was higher among people living in the most socially vulnerable neighborhoods and markedly higher in the Southern United States.
These findings, published in the peer-reviewed journal Health Affairs, may inform future policies aimed at reducing the harms caused by reliance on non-evidence-based treatments, especially among vulnerable communities.
“Our findings underscore the urgent need for policy reforms to combat misinformation and mistrust in scientific institutions. Eliminating undue industry influence in government, enhancing transparency around scientific uncertainty, and earmarking public funding for clinical trials of new drugs are good places to start,” said Dr. John Mafi, associate professor-in-residence in the UCLA Division of General Internal Medicine and Health Services Research and the study’s senior author.
The researchers used insurance claims listed in the Milliman MedInsight Emerging Experience Research Database for 8.1 million patients from across all 50 states to assess utilization and spending for the two medications from January 30, 2020 to June 30, 2023.
Among the findings were:
- Nearly three million COVID-related prescriptions in outpatient settings during the study period, totaling $272 million.
- Hydroxychloroquine use peaked in March 2020 to 133% of pre-pandemic rates
- Ivermectin use surged in 2020 and throughout 2021, and by August 2021 peaked at more than 10 times higher than pre-pandemic rates
- After FDA-authorized COVID-19 medications (e.g., Paxlovid) became available, ivermectin and hydroxychloroquine use dropped by 93% in outpatient settings from March 1, 2022 to June 30, 2023.
- Of the estimated $272 million spent for COVID-19-related hydroxychloroquine and ivermectin, approximately $18 million was spent after March 2022 when FDA-authorized COVID medications became available.
- Limited availability of COVID-19 medications does not appear to explain the wide geographic variation in ivermectin prescribing, particularly in the South.
There are some limitations to the study. The cohort included what is called a “convenience sample,” meaning that the researchers used data from a group that was easy, or convenient, to sample rather than randomly chosen. While the findings may thus not be generalizable, prior work confirms that the demographics in the dataset the researchers used reflect the U.S. population as a whole. In addition, medications that patients obtained without insurance or a prescription were not included in the analysis; variations in the price of ivermectin and hydroxychloroquine around the country may not have been captured in the researcher’s spending estimates for the drugs. Additionally, the researchers attributed the increase in the drugs’ usage rate to their utilization for COVID treatment although not all the claims in the data noted that.
“To our knowledge, this is the first study to report on trends in ivermectin and hydroxychloroquine utilization and spending in U.S. outpatient settings throughout the entire COVID-19 pandemic. This utilization represents wasteful spending and potentially avoidable harm. Our findings highlight the complex drivers of non-evidence based care, particularly in a time of uncertainty and distress. Multilevel efforts to enhance equitable, high-value care while minimizing non-evidence-based care are needed,” said Dr. Michelle Rockwell, the study’s lead author and assistant professor of family & community medicine at Virginia Tech Carilion School of Medicine.
Study co-authors included Sitaram Vangala and Dr. Katherine Kahn of UCLA; Jonathan Cantor and Cheryl Damberg of RAND Corporation; Michael Hadfield, Dale Skinner and Melody Craff of Milliman MedInsight, and Dr. A. Mark Fendrick of the University of Michigan.
This study was funded by the Commonwealth Fund, the National Center for Advancing Translational Sciences, National Institutes of Health (KL2TR003016 and UL1TR003015), and the National Institute on Aging/National Institutes of Health (K76AG064392).
Journal
Health Affairs
Method of Research
Data/statistical analysis
Subject of Research
People
Article Title
Demographic Variation In US Outpatient Hydroxychloroquine And Ivermectin Use During The COVID-19 Pandemic
Article Publication Date
19-Feb-2025
Paxlovid’s impact on hospitalization and death in COVID-vaccinated older adults far weaker than previously thought
University of California - Los Angeles Health Sciences
Paxlovid does not significantly reduce COVID-19 hospitalization and mortality among vaccinated older adults, according to new UCLA-led research.
The study questions the assumption that Paxlovid’s effectiveness in reducing COVID-19 hospitalizations and deaths in unvaccinated adults also applies to vaccinated adults. Pfizer’s 2022 clinical trial found reduced COVID-19 hospitalization in unvaccinated middle-aged adults; while a subsequent 2024 clinical trial found no significant reduction in vaccinated middle-aged adults. Since most older Americans have already received two or more COVID-19 vaccines, Paxlovid’s effectiveness on vaccinated older adults has remained an important unanswered question.
“Since the strongest predictor of severe COVID-19 is advanced age, it has been crucial to obtain evidence on whether the results of the Pfizer trials generalized to older and vaccinated populations,” said Dr. John Mafi, an associate professor-in-residence of medicine in the division of general internal medicine and health services research at the David Geffen School of Medicine at UCLA and the study’s lead author.
“Our study effectively rules out the notion that Paxlovid causes large reductions in COVID-19 hospitalization in vaccinated older adults,” Mafi said. “While we cannot rule out a small reduction in COVID-19 hospitalization, our results indicate that at best, Paxlovid’s potential effect on COVID-19 hospitalization among vaccinated older adults is four times weaker than the effect originally reported in Pfizer’s 2022 clinical trial.”
The findings, to be published in the peer-reviewed JAMA, “are important because Pfizer’s 2022 clinical trial continues to serve as the foundation of evidence supporting Paxlovid’s perceived effectiveness, list price of about $1,650 per treatment course, and widespread global use,” Mafi said.
“Since the study found no significant effect on COVID-19 hospitalizations and deaths among vaccinated older adults, our findings underscore the urgent need for further randomized-clinical trials investigating Paxlovid’s effects in higher-risk populations, such as older subgroups who are frail or immunosuppressed,” said Dr. Katherine Kahn, distinguished professor of medicine in the general internal medicine division and the study’s senior author.
To determine the association between Paxlovid and COVID-19-related hospitalizations, all-cause hospitalizations and all-cause mortality outcomes, the researchers exploited a natural experiment in Ontario, Canada. Between April 1 and November 30, 2022, Ontario implemented an age-restrictive policy on access to Paxlovid—reserving it for symptomatic, COVID-19-positive adults aged 70 years and older, unless they were immunocompromised or had other risk factors. The researchers used data from several Ontario health databases linked by ICES, the major steward of Ontario health data.
They compared outcomes of patients who were just below vs just above 70-years-old who were plausibly similar except for their exposure to Paxlovid. The researchers found that among 1.6 million highly vaccinated older Ontarians, the policy to restrict Paxlovid to those aged 70, increased the rate of Paxlovid prescriptions by 118% at age 70. This doubling in the prescription rate did not, however, translate into improved COVID-19-related hospitalization, all-cause hospitalization, or all-cause mortality outcomes.
By restricting Paxlovid access by age, the policy created a rare natural experiment that the study analyzed to evaluate Paxlovid’s impact on key health outcomes, effectively avoiding the common observational research pitfall known as unobserved confounding. “Unobserved confounding is a problem because the decision to use Paxlovid is not random, and the factors that influence its use are able to influence the risk of hospitalization or mortality,” said study co-author Sitaram Vangala, biostatistician in the Department of Medicine Statistics Core.
“Because access to Paxlovid in this study was in effect randomized for those close to the age 70 cutoff, our results are unlikely to reflect unobserved confounding,” Vangala said. “This may explain why our results align with the recent negative 2024 clinical trial among vaccinated middle-aged adults, but not with observational studies showing that Paxlovid is associated with large reductions in hospitalization and mortality in vaccinated older adults.”
The study is limited by a lack of individual patient-level data regarding symptoms, timing of previous COVID-19 vaccinations, receipt of Paxlovid, and medication adherence.
Additional co-authors Manying Cui and Artem Romanov of UCLA, and Dr. Moira Kapral and Dr. Peter Wu of the University of Toronto. Dr. Wu is affiliated with ICES.
The study was funded by the Commonwealth Fund and a National Institute on Aging Beeson Emerging Leaders in Aging Research Career Development Award (K76AG064392-01A1). This study was also supported by ICES, which is supported by an annual grant from the Ontario Ministry of Health (MOH) and the Ministry of Long-Term Care (MLTC).
Journal
JAMA
Method of Research
Data/statistical analysis
Subject of Research
People
Article Title
Hospitalizations and Mortality Among Older Adults With and Without Restricted Access to Nirmatrelvir-Ritonavir
Article Publication Date
20-Feb-2025
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