Supplemental Table.
Current and novel therapies for monkeypox and their safety in pregnancy
| CDC and WHO options | Licensed indication | Effectiveness data against monkeypox in humans | Reproductive safety data in animals | Reproductive safety data in humans | Notes |
|---|---|---|---|---|---|
| Small molecules | |||||
| Tecovirimat | 1. Authorization by the EMA for the treatment of orthopoxvirus infections (cowpox, monkeypox, and smallpox) and to treat complications because of replication of vaccinia virus after vaccination against smallpox in adults and children with a body weight of at least 13 kg 2. Authorization by the FDA is limited to human smallpox disease in adults and pediatric patients weighing at least 13 kg. Therefore, the CDC provides a nonresearch EA-IND protocol that allows its use for treatment of nonvariola orthopoxvirus infections, including monkeypox, in adults and children of all ages |
None2; effectiveness relies on animal studies | Reproductive risk assessment based on available animal reproductive toxicity studies are inconclusive as the chosen dosage margins were questionable3 | None | May be safe in pregnancy Effectiveness data are required for a risk-benefit assessment |
| Cidofovir | 1. Authorization by the EMA and the FDA for the treatment of CMV retinitis in adult patients with AIDS without renal impairment, when other therapies are considered inappropriate Medical countermeasure in case of smallpox or monkeypox bioterrorism attack by the US government |
None2; effectiveness relies on animal studies | Studies have shown that cidofovir is clastogenic in vitro and is embryotoxic in rats and rabbits at doses below the one used in human therapeutics4 | None | Best avoided in pregnancy unless critically ill (teratogenic potential) Renal toxicity resulting in kidney damage is the major dose-limiting side effect of cidofovir |
| Brincidofovir | 1. In 2016, orphan designation (EU/3/16/1697) was granted by the European Commission for the treatment of adenovirus infection in immunocompromised patients 2. Authorization in 2021 by the FDA for the treatment of smallpox in adult and pediatric patients, including neonates |
None2; effectiveness relies on animal studies | Studies have shown that brincidofovir is clastogenic in vitro and is embryotoxic in rats and rabbits at doses below the one used in human therapeutics5 | None | Best avoided in pregnancy unless critically ill (teratogenic potential) Brincidofovir is a prodrug of cidofovir with a lipid conjugate that improves drug delivery to the target cells and greatly reduces nephrotoxicity |
| Intravenous immunoglobulin | |||||
| VIGIV | Authorization by the FDA for the treatment of complications from vaccinia virus vaccination | None | Carcinogenicity, genotoxicity, and fertility studies have not been conducted with VIGIV6 | None specific to VIGIV; evidence of relative safety of other intravenous immunoglobulin treatments therapies used in pregnancy (eg, anti-D immunoglobulin and varicella zoster immunoglobulin) | Very likely safe in pregnancy |
| Vaccines | |||||
| ACAM2000: second-generation smallpox vaccine | FDA approved live vaccinia virus vaccine to prevent smallpox May be used under nonresearch EA-IND protocol for the treatment of monkeypox |
Smallpox effectiveness based on 2 pivotal clinical trials that demonstrated noninferiority to Dryvax (a first-generation vaccine used to eradicate smallpox) As MPXV is closely related to the smallpox virus, the smallpox vaccine is considered cross-protective against monkeypox with an 85% effectiveness rate7 |
None found | As a live vaccinia virus, it can cause fetal vaccinia, a rare (ranges from 1/10,000 to 1/100,000) but serious complication of exposure during pregnancy that often results in fetal or neonatal death8,9 Data from a meta-analysis of 12,201 pregnant women showed that live smallpox vaccination was not associated with an increased risk of congenital defects (pooled RR, 1.25; 95% CI, 0.99–1.56) or fetal vaccinia in any trimester of pregnancy10 |
Best avoided in pregnancy Administered percutaneously using the multiple puncture technique and creating a lesion in case of successful inoculation (ie, called a “take”). Unvaccinated persons who have close contact with the inoculation site can be infected with the vaccinia virus More highly stockpiled by countries than the newer MVA-BN and LC16 vaccines11 |
| MVA-BN (also called Imvanex, Jynneos, or Imvamune): third-generation smallpox vaccine | The FDA (2019) and the EMA (2013) approved a replication-deficient vaccine (Ankara vaccine) for the prevention of smallpox The FDA approved (2019) for the prevention of monkeypox as well |
Effectiveness relies on comparative immunogenicity and protection studies in animal studies, but effectiveness rate is considered similar to ACAM2000 | Studies assessing fertility and embryofetal and postnatal toxicity did not reveal any particular risk to humans | 300 exposed pregnancies with follow-up without safety signal12 Replication-deficient virus technology carries a low risk of fetal vaccinia |
Likely safe in pregnancy Administered subcutaneously as 2 doses separated by 4 wk (1 dose at week 0 and a second dose at week 4) for primary vaccinees and 1 dose for individuals previously vaccinated against smallpox |
| LC16: third-generation smallpox vaccine | Japan (1975) approved live attenuated (minimally replicating) smallpox vaccine for the prevention of smallpox The FDA (2014) provided a nonresearch EA-IND protocol for smallpox13 |
Effectiveness relies on comparative immunogenicity and protection studies in animal studies14 | None found | None found | Theoretically less risk of developing fetal vaccinia than ACAM2000 Administered similar to ACAM2000 |
| Novel agents for repurposing or in the development stage | |||||
| Imatinib15 | The FDA and the EMA approved for the treatment of cancer | None; antiviral activity against orthopoxvirus in in vitro infection models | Studies have shown that imatinib is clastogenic in vitro and is teratogenic in rats and rabbits at the maximal doses used in human therapeutics | Case reports showing normal and abnormal outcomes16 | Best avoided in pregnancy (teratogenic) |
| Olomoucine15 | Preclinical research stage | None; antiviral activity against orthopoxvirus in in vitro infection models | None found | None | NA |
| Terameprocol15 | Clinical research phase 1 | None; antiviral activity against orthopoxvirus in in vitro infection models | None found | None | NA |
| Mitoxantrone15 | The FDA and the EMA approved for the treatment of cancer | None; antiviral activity against orthopoxvirus in in vitro infection models | Studies have shown that mitoxandrone is clastogenic and mutagenic in vitro and is fetotoxic in rats and rabbits at doses below the one used in human therapeutics17 | Considered a potential human teratogen because of its mechanism of action | Best avoided in pregnancy (teratogenic) |
| Bisbenzimide derivatives15 | Preclinical research stage | None; antiviral activity against orthopoxvirus in in vitro infection models | None found | None | NA |
| Resveratrol18 | Preclinical research stage | None; antiviral activity against orthopoxvirus in in vitro infection models | None found | None | NA |
CDC, Centers for Disease Control and Prevention; CI, confidence interval; CMV cytomegalovirus; EA-IND, Expanded Access for an Investigational New Drug; EMA European Medicines Agency; FDA, Food and Drug Administration; MPXV, monkeypox virus; NA, not available; RR, risk ratio; VIGIV, vaccinia immune globulin intravenous; WHO, World Health Organization.
Dashraath. Monkeypox and pregnancy. Am J Obstet Gynecol 2022.