What are the treatment options for Monkeypox (Orthopoxvirus)

From the Guidelines

Monkeypox treatment should prioritize the use of Tecovirimat (TPOXX) as the primary antiviral treatment, given its efficacy and safety profile, as supported by recent studies 1. The treatment approach for monkeypox involves a combination of supportive care and antiviral medications. For mild cases, supportive care includes:

• Pain management
• Keeping lesions clean
• Adequate hydration For more severe cases or high-risk patients, antiviral medications such as Tecovirimat (TPOXX) are prescribed, typically given as 600mg twice daily for 14 days for adults. Alternative antivirals like Brincidofovir and cidofovir may be used in certain situations, as noted in studies 1. Vaccinia Immune Globulin Intravenous (VIGIV) might be considered for severe cases. Patients should isolate until all lesions have crusted over, fallen off, and a fresh layer of skin has formed, which typically takes 2-4 weeks. Good hygiene practices are essential, including covering lesions, avoiding sharing personal items, and frequent handwashing. Treatment decisions should be individualized based on disease severity, patient risk factors, and potential complications. The medications work by interfering with viral replication, helping the immune system clear the infection more effectively, as demonstrated in studies on orthopoxviruses 1. It's worth noting that ST-246, an orally bioavailable anti-viral agent, has shown promise in treating orthopoxviruses, including monkeypox, by targeting the F13L gene product required for production of extracellular virus, as reported in a study 1. However, the primary recommendation remains focused on Tecovirimat (TPOXX) due to its established use and recent support in the medical community.

From the FDA Drug Label

The effectiveness of TPOXX for treatment of smallpox disease was established based on results of adequate and well-controlled animal efficacy studies of non-human primates and rabbits infected with non-variola orthopoxviruses. Efficacy studies were conducted in cynomolgus macaques infected with monkeypox virus, and New Zealand white (NZW) rabbits infected with rabbitpox virus. The primary efficacy endpoint for these studies was survival In non-human primate studies, cynomolgus macaques were lethally challenged intravenously with 5 x 107 plaque-forming units of monkeypox virus; tecovirimat was administered orally once daily at a dose level of 10 mg/kg for 14 days, starting at Day 4,5 or 6 post-challenge Treatment with tecovirimat for 14 days resulted in statistically significant improvement in survival relative to placebo, except when given to cynomolgus macaques starting at Day 6 post-challenge

Tecovirimat (TPOXX) is effective in treating monkeypox in animal studies, with statistically significant improvement in survival rates when administered orally once daily at a dose level of 10 mg/kg for 14 days, starting at Day 4 or 5 post-challenge 2.

• The primary efficacy endpoint was survival.
• Treatment initiation at Day 6 post-challenge did not result in statistically significant improvement in survival.
• Key findings include:
  • Statistically significant improvement in survival rates when treatment was initiated at Day 4 or 5 post-challenge.
  • No statistically significant improvement in survival rates when treatment was initiated at Day 6 post-challenge.

From the Research

Treatment Options for Monkeypox

• There are currently no Food and Drug Administration (FDA)-approved treatments for human monkeypox 3.
• Tecovirimat (Tpoxx) is an antiviral drug that has demonstrated efficacy in animal studies and is FDA-approved for treating smallpox, and can be used for treating monkeypox under an Expanded Access Investigational New Drug (EA-IND) mechanism 3, 4, 5.
• Brincidofovir is another medication that has been studied for the treatment of monkeypox, but tecovirimat has shown more promise so far 5.
• Supportive care, such as medication to lower body temperature and pain, can assist in managing symptoms of monkeypox 6, 7.
• Prevention and treatment of secondary bacterial infections, ensuring adequate hydration and nutrition, and protecting vulnerable anatomical locations such as the eyes and genitals are also important aspects of caring for monkeypox patients 7.

Efficacy of Tecovirimat

• A double-blind, randomized, placebo-controlled trial of tecovirimat in patients with monkeypox in the Democratic Republic of Congo found that tecovirimat did not reduce the number of days to lesion resolution in patients with mpox caused by clade I MPXV 4.
• However, another study found that tecovirimat has the strongest evidence to be effective and safe for monkeypox treatment, and if there is a choice between tecovirimat and brincidofovir, tecovirimat has shown more promise so far 5.
• The median interval from initiation of tecovirimat to subjective improvement was 3 days in a study of patients treated with tecovirimat for monkeypox in the United States 3.

Future Perspectives

• Further research is needed to develop effective treatments for monkeypox, including the development of novel antivirals 5.
• The risk of resistance should be considered in patients who failed to respond to tecovirimat, and the target-based design of novel antivirals will enhance the availability and spectrum of effective anti-Orthopoxvirus agents 5.
• Standardized guidelines for the clinical management of monkeypox patients, particularly in low-resource settings, are needed to improve patient outcomes 7.