Outpatient treatment of COVID-19 practice points issued by ACP
Presenter: Rebecca Andrews, MD, University of Connecticut, Farmington.
Outpatient treatment of confirmed COVID-19: living, rapid practice points from the American College of Physicians (version 1). Presented April 27, 2023.
The American College of Physicians (ACP) has developed a series of rapid practice points on the outpatient treatment of confirmed COVID-19. Version 1 of the practice points, developed by ACP’s Population Health and Medical Science Committee, assesses the evidence from 26 randomized controlled trials (RCTs) of various interventions with a total of 21,212 COVID-19-positive participants.
All included studies were conducted before Omicron was dominant, so recommendations were “based on the best evidence at that time,” said Rebecca Andrews, MD, from the University of Connecticut in Farmington. Included studies did not allow for conclusions about how treatment effects may vary with patient characteristics. The ACP is currently working on version 2 of the practice points, to be published later in 2023.
Practice points are meant as guidance, but determining the best approach to treatment of COVID‐19 in the outpatient setting should be a personalized decision based on clinical judgment and discussion and shared decision-making with the patient about potential treatment benefits, harms, patient characteristics (such as risk factors, comorbid conditions, and disease severity), and patient preferences. In general, outpatient treatment should be considered only in patients with confirmed mild to moderate COVID-19.
Treatments supported by evidence are molnupiravir, nirmatrelvir–ritonavir combination therapy, and remdesivir.
- Molnupiravir can be considered to treat patients with confirmed mild to moderate COVID‐19 in the outpatient setting who are within 5 to 7 days of the onset of symptoms and at high risk for progressing to severe disease (2 RCTs; low certainty of evidence that molnupiravir reduces the risk of all-cause mortality and COVID-19 mortality).
- Nirmatrelvir–ritonavir may be considered to treat patients with confirmed mild to moderate COVID‐19 in the outpatient setting who are within 5 days of the onset of symptoms and at high risk for progressing to severe disease (1 RCT; moderate certainty of evidence that the combination reduces the risk of all-cause mortality and hospital admission due to COVID-19).
- Remdesivir can be considered to treat patients with confirmed mild to moderate COVID‐19 in the outpatient setting who are within 7 days of the onset of symptoms and at high risk for progressing to severe disease (1 RCT; low certainty that remdesivir improves time to recovery and reduces the risk of hospital admission due to COVID-19).
Risk stratification is an important step in the initial evaluation to decide the best approach to COVID-19 treatment in the outpatient setting. Before initiating outpatient treatments, patients should meet all treatment approval criteria, including careful consideration of potential drug interactions. The use of remdesivir requires administration by intravenous infusion in a specialized setting (ie, an infusion center).
The aforementioned suggested treatments should not be used in asymptomatic patients with confirmed COVID-19. Evidence on outpatient treatment of mild to moderate COVID-19 is rapidly changing as SARS-CoV-2 variants continue to emerge, reminded Dr. Andrews.
Despite the efficacy demonstrated by nirmatrelvir–ritonavir among high-risk individuals when started within 3 days of symptom onset, this agent has been underused. US physicians have prescribed it to only 13% of people with new COVID-19 cases, perhaps owing to rebound, she said. Rebound of COVID-19 has been reported to occur with the use of nirmatrelvir–ritonavir combination therapy between 2 and 8 days after initial recovery and is characterized by a recurrence of COVID-19 symptoms or a new positive result on a viral test after having tested negative.
Three treatments are not supported by evidence in patients with confirmed mild to moderate COVID‐19 in the outpatient setting unless considered effective against a SARS‐CoV‐2 variant or subvariant locally in circulation: casirivimab–imdevimab combination therapy, regdanvimab, and sotrovimab.
The use of several treatments for patients with confirmed mild to moderate COVID‐19 in the outpatient setting is not supported by evidence, according to the ACP guideline. These include azithromycin, chloroquine or hydroxychloroquine, ivermectin, nitazoxanide, and lopinavir–ritonavir combination therapy. Others are convalescent plasma, ciclesonide, and fluvoxamine.
Version 2 will expand the inclusion criteria to include not only RCTs but “also some cohort studies to keep up with the latest evidence” and will only include studies with enrollment on or after November 26, 2021 to capture the Omicron variant, said Dr. Andrews.
References
Qaseem A, Yost J, Miller MC, et al. Outpatient treatment of confirmed COVID-19: living, rapid practice points from the American College of Physicians (version 1). Ann Intern Med 2023; 176(1):115-124. doi: 10.7326/M22-2249. https://doi.org/10.7326/M22-2249
Kozlov M. COVID drug Paxlovid was hailed as a game-changer. What happened? Nature 2023; 613(7943):224-225. doi: 10.1038/d41586-022-04576-6 https://www.nature.com/articles/d41586-022-04576-6
Disclosures
Rebecca Andrews, MD, has disclosed relationships with entities whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients. All relevant relationships have been mitigated. Other: expert witness; various law firms.