An analysis of over 7,100 mpox patients in the US who were prescribed tecovirimat (Tpoxx) between 2022 and 2023 indicates that serious adverse events (SAEs) and deaths were primarily observed in individuals with compromised immune systems. The Centers for Disease Control and Prevention (CDC) study, published in NEJM Evidence, raises questions about the drug's efficacy and safety, particularly in vulnerable populations.
The antiviral drug was mainly prescribed to treat rash and pain, especially in sensitive areas. The study parsed data from 49 states, Puerto Rico, and Washington, DC, under an expanded-access Investigational New Drug (EA-IND) program, as tecovirimat was stockpiled for potential smallpox reintroduction.
Patient Demographics and Treatment
The majority of patients receiving tecovirimat were men (median age 35) who have sex with men, reflecting the demographics of the clade 2 mpox outbreak. However, the cohort also included 220 women, 12 pregnant women, and 17 children under 12. Most patients received a 14-day course of tecovirimat, with a median of 7 days elapsing between symptom onset and prescription.
Clinicians reported that 77.1% of patients had a rash at illness onset, with the skin (76.3%) and anogenital region (73.1%) being the most commonly affected areas. Lesions in the mouth (17.3%) and eyes (4.2%) were also reported.
Adverse Events and Outcomes
Of the 7,181 patients with returned intake forms, 22.6% also returned outcome forms. The analysis revealed that 3.1% (223 patients) experienced SAEs, and 0.6% (40 patients) died. Hospitalization was required for 3.9% of the patients. The most common SAEs included headache, nausea, vomiting, elevated liver enzymes, hives, fatigue, acute kidney injury, abdominal pain, dizziness, and tremor. Children, pregnant women, and those with conditions compromising skin integrity did not have severe outcomes.
Impact of Immunocompromise
A significant finding was the correlation between weakened immune systems and poor outcomes. Approximately 52% of patients with returned intake forms had HIV, and 8.5% had other underlying illnesses. Among HIV patients with low CD4 counts, some received multiple tecovirimat courses, including intravenous administration, and often experienced adverse outcomes. One severely immunocompromised patient reported hallucinations after receiving twice the recommended dose.
Study Limitations and Future Directions
The study authors emphasized that the EA-IND data are not definitive and that controlled clinical trials are essential to determine the appropriate use of tecovirimat. They cautioned that the current data cannot establish the drug's safety and effectiveness. "The EA-IND data are not definitive; controlled clinical trial data are essential to elucidating if and how tecovirimat should be used," the authors stated.
This analysis underscores the need for further research to understand the role of tecovirimat in managing mpox, particularly in immunocompromised individuals. Further studies are needed to determine optimal dosing and administration strategies, as well as to identify potential risk factors for adverse events.
