TNF Inhibitors and Pregnancy

Megan E.B. Clowse, MD: The structure of certolizumab makes it somewhat different in pregnancy compared with the other TNF inhibitors. The other TNF inhibitors are based on an antibody. They basically have the full human antibody structure. They have a specific part of that antibody called the Fc [fragment crystallizable] portion, and that Fc portion is actually what is grabbed at the placenta and makes the drug drag across the placenta into the baby. So it’s that Fc portion that is really key to transferring the drug from the mother to the infant during pregnancy.

For certolizumab, the structure is different. It does not have an Fc portion. Instead, it has this big kind of globular molecule, and so it can’t be grabbed and pulled across the placenta. Therefore, when we look at babies whose mothers have been treated with TNF inhibitors during pregnancy, when we look at adalimumab-exposed or infliximab-exposed infants, we see that there is actually a pretty high level of drug in the baby compared with the mother. In fact, the baby generally has a higher concentration of the drug on the day of delivery compared with the mom.

Certolizumab, on the other hand, doesn’t move across the placenta because it’s a different molecule. If you check the baby’s level on the day of delivery, the level is either 0 or is very close to 0 and is much lower than what it is in the mother. Because of that, we use the medication in the second half of pregnancy a bit differently. I’m comfortable with patients taking certolizumab through delivery. I often actually have them skip taking it during the week of delivery because of infection risk, but it won’t harm their baby if they take the drug throughout delivery and keep taking it through lactation and breast-feeding.

However, I generally stop treating patients with the other TNF inhibitors about 2 months or so before delivery. The reason for that is because it takes time for the drug to get out of the mother’s system. By doing this, it also allows time for the drug to get out of the baby’s system. When the baby is born, he or she might have a smidgen of the drug in their system, but the level would be low enough that we wouldn’t really worry about the risk for infection.

There is not really a clear guideline as to exactly when to stop each of those medications. I personally pick somewhere between 30 and 34 weeks for most of them. I also negotiate that a little with the woman based on how her arthritis is doing. If she’s really having a lot of trouble with her arthritis, I might continue it a little longer. If she’s doing fantastic, I might stop it a bit sooner. But then in those patients for whom I’ve stopped the drug, it’s key to restart it right after delivery. For women who are on TNF inhibitors before and during pregnancy, if they don’t start back up with a TNF inhibitor after delivery, they will most likely flare, and so I start people back on the drug 1 or 2 weeks after delivery. They can take it during breast-feeding without difficulty. That really avoids the postpartum flare quite effectively.