Letter: J

Janus kinase inhibitors (JAK-Is), including abrocitinib, baricitinib, deucravacitinib, filgotinib, ritlecitinib, delgocitinib, ruxolitinib, tofacitinib and upadacitinib, selectively inhibit various Janus-associated kinases (JAKs) to modulate the immune and inflammatory response. JAK-Is are used in the treatment of numerous chronic inflammatory and immune-mediated disorders.

Uncontrolled inflammatory conditions in pregnancy are associated with increased risks of adverse pregnancy outcomes, including miscarriage, preterm delivery and low birth weight. The benefits of continuing treatment with existing medications or offering alternative treatment options for which there may be more pregnancy exposure safety data should be considered on a case-by-case basis.

Although animal models have demonstrated adverse fetal and offspring developmental outcomes following in utero exposure to JAK-Is, the doses administered were generally far greater than those used therapeutically in humans or resulted in maternal toxicity. As such, these data do not reliably predict a direct causal association with embryo or fetal toxicity following JAK-I use in human pregnancy.

Data regarding the safety of JAK-Is in human pregnancy are limited, consisting of uncontrolled case series and case reports which together describe the outcomes of approximately 370, mainly first trimester only, JAK-I-exposed pregnancies (including exposure to baricitinib, delgocitinib, filgotinib, ruxolitinib, tofacitinib and upadacitinib). No data have been located for abrocitinib, deucravacitinib or ritlecitinib. Given these data are provided from uncontrolled sources, which describe a high frequency of maternal discontinuation in early pregnancy often with concomitant medication use, limited conclusions can be provided regarding the risks associated with JAK-I use in pregnancy.

Human pregnancy exposure data generally describe healthy live-born infants following early pregnancy JAK-I exposure, but cases of miscarriage, malformation, low birth weight, small for gestational age and preterm delivery have been reported. However, these data do not provide reliable evidence of a causal relationship between JAK-I exposure and adverse pregnancy outcomes. Data regarding longer-term outcomes, such as child health and neurodevelopment, are highly limited.

Given the data limitations, the use of JAK-Is in pregnancy should be reserved for situations where alternative treatments, with better quality pregnancy safety data, are either not appropriate or do not provide adequate control of the maternal condition. Inadvertent exposure to JAK-Is at any stage in pregnancy would not usually be regarded as medical grounds for termination of pregnancy or any additional fetal monitoring. However, other risk factors which could independently increase the risk of adverse pregnancy outcome may be present in individual cases. Such factors are important to consider when performing case-specific risk assessments.