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Compassionate Use [treatment results] of Tecovirimat for the Treatment of Monkeypox Infection
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JAMA. Published online August 22, 2022.
Monkeypox is a zoonotic orthopoxvirus in the same genus as variola (the causative agent of smallpox).1A recent global outbreak has led to more than more than 39 000 cases reported as of August 18, 2022.2 Monkeypox is typically self-limited with symptoms generally lasting between 2 and 4 weeks in prior outbreaks. Hospitalization was required in 13% of patients in a recent study, suggesting the need for effective therapy.3
Tecovirimat is an antiviral that inhibits p37, a protein involved in release of enveloped virus, dissemination, and viral virulence.4 In vitro testing has shown activity against both smallpox and monkeypox, and tecovirimat appears to have a favorable clinical safety profile based on the experience of healthy volunteers.4,5 We assessed adverse events and clinical resolution of systemic symptoms and lesions in an uncontrolled cohort study of patients with monkeypox who were treated with tecovirimat on a compassionate use basis.6
Methods
Patients were eligible for tecovirimat treatment following laboratory confirmation of orthopoxvirus infection from skin lesions by polymerase chain reaction. Outpatients referred to UC Davis primarily through the Sacramento County Department of Public Health between June 3, 2022, and August 13, 2022, and who had disseminated disease or lesions in sensitive areas including the face or genital region were offered treatment. Oral treatment with tecovirimat for adult patients was weight-based, administered every 8 or 12 hours, and was taken within 30 minutes of a meal containing moderate to high fat content for improved bioavailability. The duration of therapy was 14 days but could be extended depending on the clinical status of the patient. Clinical data were collected at initial in-person evaluation for treatment and by in-person or telephone interview on day 7 and day 21 following initiation of therapy. All patients provided written informed consent. This protocol was approved by the UC Davis Institutional Review Board.
Results
As of August 13, 2022, 25 patients with confirmed monkeypox infection had completed a course of tecovirimat therapy (Table). All patients were self-reported male and the median age was 40.7 years (range, 26-76). Nine patients had HIV, 1 patient had received the smallpox vaccine more than 25 years prior, and 4 received 1 dose of JYNNEOS vaccination after symptom onset. At the time of treatment, systemic symptoms, lesions, or both were present for a mean of 12 days (range, 6-24). Systemic symptoms included fever in 19 patients (76%), headache in 8 (32%), fatigue in 7 (28%), sore throat in 5 (20%), chills in 5 (20%), backache in 3 (12%), myalgia in 2 (8%), nausea in 1 (4%), and diarrhea in 1 (4%). Almost all patients (23 [92%]) had genital and/or perianal lesions, and 13 (52%) had fewer than 10 lesions over their entire body. All patients had pain associated with lesions.
One patient received 21 days of therapy while the remainder were treated for 14 days. Complete resolution of lesions was reported in 10 patients (40%) on day 7 of therapy, while 23 (92%) had resolution of lesions and pain by day 21. Treatment with tecovirimat was generally well tolerated with no patient discontinuing therapy. The most frequently reported adverse events on day 7 of therapy included the following: fatigue in 7 patients (28%), headache in 5 (20%), nausea in 4 (16%), itching in 2 (8%), and diarrhea in 2 (8%) (Table).
Discussion
In this preliminary study, oral tecovirimat was well tolerated by all patients with monkeypox infection, with minimal adverse effects. However, adverse effects could not always be differentiated from symptoms related to the infection. No control group was included, limiting conclusions of antiviral efficacy pertaining to duration of symptoms or severity. Time from symptom onset to presentation was variable among patients, and conclusions related to antiviral use vs natural evolution of disease should be made with caution.
Limited clinical data exist on the use of tecovirimat for monkeypox infection. In one case report, no new lesions followed 24 hours of therapy and no adverse effects occurred by treatment completion at 14 days.1
Limitations of the study include the small number of patients, lack of a control group, and selection bias. Additional large-scale studies are needed to elucidate antiviral efficacy, dosing, and adverse events.
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