Anti-TNF Inhibitors for IBD During Pregnancy

An important factor in a healthy pregnancy is achieving remission

Pregnant Woman Holding Stomach on Sofa
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One of the biggest concerns for women with inflammatory bowel disease (IBD) who want to start their family is how to manage medications during pregnancy. The best chance for a healthy pregnancy, birth, and baby is to have the IBD in remission at the time of conception. The "rule of thirds” is often discussed when it comes to pregnancy and IBD: one-third of patients will get better during pregnancy, one-third will stay the same, and one-third will get worse.

For many women with IBD, getting to the point of remission and sustaining it means taking medication along with lifestyle changes or alternative and complementary therapies that are part of their overall treatment plan. For the most part (with methotrexate and thalidomide excluded) commonly used medications used to treat Crohn’s disease and ulcerative colitis are considered safe during pregnancy.

Biologic medications, including anti-tumor necrosis factors (TNF) drugs such as Humira, Remicade, and Cimzia are the latest classification of drugs to be approved for use in treating IBD. Data is still being gathered in how they affect pregnancy.

When Biologics Might Be Stopped

There has been some debate about stopping medications in the third trimester or timing dosing so that the baby will receive the lowest dose of the medication possible. Some women may decide, along with their gastroenterologist and obstetrician, to change their dosage schedule or to discontinue a medication for a certain amount of time.

Others may continue on their medications with little or no change. It’s an individual decision that should be made after having all the information available and considering the risk of the IBD flaring up during the pregnancy or shortly after.

Biologics do not seem to carry an increased risk of birth defects. There have been reports of outcomes such as premature birth, miscarriages, preeclampsia, and low birth weight in pregnancies, but it’s not well-understood how much responsibility for these is from the IBD versus the medications for IBD.

The most important thing is to keep the IBD as quiet as possible, and ideally in remission during pregnancy. In some cases, that means continuing on the medication that is currently working. 

A large national prospective cohort, called the PIANO Registry, followed pregnant women with IBD who received biologics through their pregnancies and until their babies were five years old. The results from this study were reassuring and will help patients and physicians plan for pregnancy where a biologic is needed to keep a patient in remission.

What the Research Says

There has been some research that shows that women who stop receiving Remicade or Humira in the third trimester may be more likely to have their IBD flare-up either in the third trimester or after delivery. One of the chief concerns with stopping a biologic drug during pregnancy is that a flare-up will occur and steroids might be needed to treat it.

There’s no data that shows that corticosteroids are any safer during pregnancy than biologics. The goal is to keep pregnant women in remission throughout pregnancy and delivery because that gives the best chance at a good outcome for both mother and baby. 

Discussion With Your Doctor

Patients and their doctors should discuss the timing of the ant-TNF medication, ideally before conception, but certainly early in pregnancy so that the medication schedule meshes with delivery. For women who have entered deep remission with their IBD, it may open up a discussion of stopping the biologic during the pregnancy or delaying a dose in the third trimester until after delivery.

This is an individualized decision and there are several scenarios to take into account. The first is that remission does need to be more than clinical remission—in other words, this means not only “feeling better” but also an actual lack of disease activity. Some of the tests that doctors might use to understand disease activity include fecal calprotectin level, small bowel ultrasound, or flexible sigmoidoscopy.

Something else to consider is that stopping and starting certain biologics could lead to developing antibodies to that drug.

People with IBD who have developed antibodies to one type of biologic may go on to develop antibodies to another, so it’s important to consider this factor when deciding to stop a drug.

Remicade (Infliximab)

Remicade is given by infusion at regular intervals (typically eight weeks, but this may be shortened to as few as four weeks in some cases, if necessary). Remicade does cross the placenta, so babies whose mothers are receiving infusions of the drug will also have a certain level in their blood. In the first trimester, the transfer across the placenta is considered “minimal." In the third trimester, it increases significantly.

This causes a great deal of concern and worry for many women with IBD who are pregnant or considering pregnancy. However, even though studies show that babies born to mothers who receive Remicade during pregnancy will have the drug in their blood, the data is reassuring that there hasn’t been any link to short-term issues or birth defects.

One small study included 11 pregnant patients with Crohn’s disease who received their last dose of Remicade anywhere between two to 91 days before delivering their baby (the average was 35 days). The level of Remicade that was found in the cord blood or the infant's blood was higher than it was in the mother’s blood.

The Remicade level in the babies was tested and found to lower to undetectable levels somewhere between two and seven months after delivery. None of the babies required treatment in the neonatal intensive care unit (NICU) or had any birth defects.

A record database called the Crohn’s Therapy, Resource, Evaluation and Assessment Tool (TREAT) database was used to track pregnancies where the mother received Remicade. The authors of one study based on the TREAT registry state that babies born to who women who received Remicade had similar "clinical condition” to those born to women with Crohn’s who didn’t have treatment with Remicade.

This means that there wasn’t any noticeable increase in complications between the two groups. There was one concern, however, which was that there were fewer live births in the Remicade group. The researchers report that these patients had more severe disease and/or were receiving other medications, and it’s not possible to know how much those factors affected the pregnancies.

Remicade is pregnancy category B, and as more data on its use in pregnancy is becoming available, scientists who specialize in IBD and pregnancy lean towards considering it to be a low-risk medication.

The timing of doses of Remicade during the third trimester should be carefully discussed.

Patients, along with their gastroenterologist and obstetrician, should make decisions based on the risks and benefits for the mother and the baby.

Humira (Adalimumab)

Humira is given by injection at home, usually in intervals of every week or every other week. Babies whose mothers are receiving injections of Humira in the third trimester will also have a certain level in their blood after birth because this drug does cross the placenta. Transfer through the placenta during the first trimester is described as “minimal” and it increases in the third trimester.

Even though Humira will be in the babies’ blood for mothers who receive it during the third trimester, studies have shown no link to short-term issues or birth defects.

Mothers with Crohn’s disease who received their last dose of Humira anywhere between .14 to 8 weeks before delivering their baby (the average was 5.5 weeks) were included in one small study of 11 patients. After delivery, the cord blood or the infant’s blood was tested for Humira levels, and in all cases, the levels were higher than what they were in the mother’s blood.

About 11 weeks after delivery, the level of Humira became undetectable in the babies’ blood. There were no babies that needed treatment in the NICU and there were no birth defects or infections reported.

Humira is a pregnancy category B drug. Three case reports and the OTIS (Organization for Teratology Information Specialists) registry lead researchers who specialize in IBD to consider it to be a low-risk medication in pregnancy.

Pregnant women with IBD will want to talk with their physicians about timing doses of Humira during the third trimester or close to delivery based on the risks and benefits for the mother and the baby.

Cimzia (Certolizumab Pegol)

Cimzia is given by injection at home, usually in intervals of about four weeks. The loading dose is normally given in two injections of 200 milligrams each on day 0 (day 0), week two (day 14), and week four (day 28). Thereafter, two injections of 200 mg are given every four weeks (28 days). Cimzia is different than Remicade and Humira (which are actively transported across the placenta) because this drug is passively transported across the placenta.

This means that less of the drug is passed to the baby from the mother. This makes Cimzia seem more attractive to mothers who are considering a change in treatment either prior to or during pregnancy. However, it’s important to consider all aspects of a medication before making a change, including the potential for maintaining remission (which is the most important factor in planning a pregnancy with IBD).

A small study included 10 pregnant women who received Cimzia between five and 42 days (the average was 19 days) before delivering their baby or babies (there were two sets of twins). All of the mothers had pegol in their blood after delivery, but none of the babies had detectable levels in their blood or in cord blood.

The level of Cimzia in the blood from the infants or the cord blood after birth was low enough that researchers didn’t test further. No infants in the study had infections, birth defects, or required a stay in the NICU.

Cimzia is a pregnancy category B drug. It is considered to be low-risk during pregnancy and the amount of the drug that’s passed to an infant during the third trimester is low.

Cimzia may be treated differently than other biologics that pass through the placenta in that the dosing schedule is usually not altered in the third trimester.

A Word From Verywell

Most women considering pregnancy want to be able to stop all medications but with IBD and other autoimmune conditions, that may not be the best course of action. Stopping IBD medications without first discussing with healthcare professionals how that decision may affect the disease (and, indeed, the pregnancy) isn’t recommended.

Anti-TNF medications have not been shown to carry an increased risk of birth defects and most IBD experts consider them safe to use during pregnancy. Be sure to speak with your doctor and healthcare professionals to determine your best course of action.

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