Therapeutics for treating mpox in humans

Abstract

Background Mpox was declared a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO) on 23 July 2022, following the identification of thousands of cases in several non‐endemic countries in previous months. There are currently no licenced therapeutics for treating mpox; however, some medications may be authorized for use in an outbreak. The efficacy and safety of possible therapeutic options has not been studied in humans with mpox. There is a need to investigate the evidence on safety and effectiveness of treatments for mpox in humans; should any therapeutic option be efficacious and safe, it may be approved for use around the world. Objectives There are two parts to this Cochrane Review: a review of evidence from randomized controlled trials (RCTs), and a narrative review of safety data from non‐randomized studies. Randomized controlled trials review To systematically review the existing evidence on the effectiveness of therapeutics for mpox infection in humans compared to: a) another different therapeutic for mpox, or b) placebo, or c) supportive care, defined as the treatment of physical and psychological symptoms arising from the disease. Non‐randomized studies review To assess the safety of therapeutics for mpox infection from non‐randomized studies (NRS). Search methods Randomized controlled trials review We searched the following databases up to 25 January 2023: MEDLINE (OVID), Embase (OVID), Biosis previews (Web of Science), CAB Abstracts (Web of science), and Cochrane CENTRAL (Issue 1 2023). We conducted a search of trial registries (Clinicaltrials.gov and International Clinical Trials Registry Platform (ICTRP)) on 25 January 2023. There were no date or language limits placed on the search. We undertook a call to experts in the field for relevant studies or ongoing trials to be considered for inclusion in the review. Non‐randomized studies review We searched the following databases on 22 September 2022: Cochrane Central Register of Controlled Trials (CENTRAL; Issue 9 of 12, 2022), published in the Cochrane Library; MEDLINE (Ovid); Embase (Ovid); and Scopus (Elsevier). We also searched the WHO International Clinical Trials Registry Platform and ClinicalTrials.gov for trials in progress. Selection criteria For the RCT review and the narrative review, any therapeutic for the treatment of mpox in humans was eligible for inclusion, including tecovirimat, brincidofovir, cidofovir, NIOCH‐14, immunomodulators, and vaccine immune globulin. Randomized controlled trials review Studies were eligible for the main review if they were of randomized controlled design and investigated the effectiveness or safety of therapeutics in human mpox infection. Non‐randomized st...

Longitudinal Analysis of Mpox Virus DNA Detectability From Multiple Specimen Types During Acute Illness: A Cohort Study

“…However, in both studies, tecovirimat use was based on clinician judgment and drug availability rather than randomization, treatment was initiated over 1 week after illness onset, and sample sizes were small. Randomized trials comparing tecovirimat and placebo for mpox are ongoing [ 34 , 35 ], and enrollment in these studies should be prioritized where possible. In a case series of 3 individuals with severe mpox treated with tecovirimat, viremia was high compared with a larger cohort of patients with less severe disease and declined by a median of 2.21 log over 1 week, but viral DNA load was more variable in other compartments [ 36 ].…”

Necrotic ulcers in a HIV-positive man

“…The antiviral medications tecovirimat, brincidofovir, and cidofovir as well as intravenous vaccinia immune globulin have been used. 2 Tecovirimat inhibits proteins involved in formation of the enveloped virion needed for viral dissemination. Tecovirimat has been shown to be highly effective against mpox 2 and is the preferred therapy in eligible patients with or at risk of developing severe disease.…”

“… 2 Tecovirimat inhibits proteins involved in formation of the enveloped virion needed for viral dissemination. Tecovirimat has been shown to be highly effective against mpox 2 and is the preferred therapy in eligible patients with or at risk of developing severe disease. 3 Remdesivir – Incorrect.…”

Emerging and re-emerging pediatric viral diseases: a continuing global challenge

“… 150 The anti-viral TPOXX (tecovirimat; SIGA Technologies), an FDA-approved treatment for smallpox, 151 was used for treatment of severe mpox under the FDA-regulated Expanded Access Investigational New Drug program, with encouraging but limited efficacy and safety data. 152 – 154 Other drugs investigated, given pre-clinical effectiveness against mpox, include brincidofovir and cidofovir, but use of either drug is limited secondary to their side-effect profiles. 154 , 155 Of note, a disproportionate fraction of mpox cases were experienced by people living with HIV, 144 – 146 , 156 emphasizing the importance of education, communication, and prevention efforts in high-risk communities.…”