Rishika Chugh, MD: Safety of Vedolizumab and Ustekinumab in Pregnancy

Dr Chugh reviews the results of a recent study of the safety of ustekinumab and vedolizumab among pregnant patients with inflammatory bowel disease.

Rashika Chugh, MD, is an assistant professor of medicine in the Division of Gastroenterology and director of the Intestinal Ultrasound Program in Inflammatory Bowel Disease at the University of California San Francisco.

TRANSCRIPT:

Welcome to this podcast from the Advances in Inflammatory Bowel Disease Network. I'm your moderator, Rebecca Mashaw. And I'm here today with Dr. Rashika Chugh, who's an assistant professor of medicine in the Division of Gastroenterology at the University of California San Francisco, where she is also the Director of the Intestinal Ultrasound Program in Inflammatory Bowel Disease. Dr. Chugh is going to talk with us today about a study from the PIANO registry of IBD among women in pregnancy and outcomes among their infants as well.

This particular program was about maternal and neonatal outcomes among women who had been treated with vedolizumab and ustekinumab during their pregnancies. So thank you for joining us today, Dr. Chugh.

Dr Rashika Chugh: Thank you so much for having me.

Rebecca Mashaw: So what was the objective of this particular study?

Dr Chugh: The objective of the study was really to demonstrate pregnancy-related outcomes in patients who were exposed to vedolizumab and ustekinumab during their pregnancy. So of course we have the original PIANO study that was published in 2020 and that did include some vedolizumab and ustekinumab-exposed pregnancies, but the numbers overall were quite small. And so here we provide updated data, and we included 47 ustekinumab-exposed pregnancies as well as 66 vedoliumab-exposed pregnancies and showed their safety in pregnancy.

Rebecca Mashaw: So safety was the predominant issue that you were examining in the context of your particular study?

Dr Chugh: Absolutely, yes. So the main outcomes that we were really looking for were risk of pregnancy-related outcomes, including spontaneous abortion, small for gestational age size, low birth weight, the need for NICU stay, infections in infants, and then milestones as well.

Rebecca Mashaw: Can you give us an overview? You mentioned 47 patients were on vedolizumab and 66 on ustekinumab, is that correct?

Dr Chugh: 47 on ustekinumab, 66 on vedolizumab, yes.

Rebecca Mashaw: And were these patients across the country because I know that the registry takes information from other centers as well as UCSF?

Dr Chugh: Exactly, yes. So over 30 US centers were included in this study, so yes, from all over the country.

Rebecca Mashaw: And what were your findings?

Dr Chugh: So what we found was that, in fact, in these pregnancies that were vedolizumab-exposed, as well as ustekinumab-exposed, there was actually no increased risk of spontaneous abortion, small for gestational age size, low birth weight, NICU stay, congenital malformations, or growth restriction. And then when we looked at serious infections within the first 12 months of life as well, we found that it was comparable among all cohorts.

So it didn't seem as though patients who were exposed to biologics and specifically these 2 biologics had any increased risk in infections. And then on top of that, we looked at developmental milestones several years out. And once again, we found that infants or children were hitting their developmental milestones, even though they were exposed to these biologic medications in utero. So essentially what we found is that these medications truly are safe and do not result in adverse pregnancy related outcomes.

Rebecca Mashaw: Among those patients, were there some that took these drugs throughout their pregnancy, were they already taking vedolizumab or ustekinumab when they became pregnant and stayed on the drug throughout pregnancy, or did any of them begin the drug during their pregnancies?

Dr Chugh: Yes, absolutely. So there were definitely several patients who began the medication during their pregnancy. Others were on either of these drugs, even prior to conceiving. So it was a mix. In the PIANO registry, we allow patients to enroll within the registry at any time during their pregnancy. So it could be at the time of conception or even into their third trimester.

Rebecca Mashaw: Did you see or did you look for whether there were differences in how patients or their babies fared based on whether they were on the drug for a long time or whether they began the drug after pregnancy.

Dr Chugh: Yeah, so all of the patients would have started either of these medications, either prior to conceiving or during their pregnancy. Now, we did not look specifically at, you know, the timing of medication initiation and how that impacted pregnancy and infant-related outcomes. So for example, we don't have the granular data of, was there a difference with somebody who started a biologic during their first trimester versus their third trimester? But what we did find was just overall in all of these patients who were exposed at any time during their pregnancy to the either of these biologics, there was no impact on pregnancy and infant related outcomes.

Rebecca Mashaw: Your article mentioned that the infant concentrations at birth among those who were born to women on ustekinumab were increased, whereas the opposite was true among the babies born to women who took vedolizumab. Did that seem to make any difference or did you even examine for that?

Dr Chugh: Yeah, so interestingly, even though concentrations of ustekinumab were higher in the infants compared to vedolizumab concentration, so when we were collecting from the cord blood, we didn't notice any real difference in infant-related outcomes. So even rates of serious infections at birth, 4 months, and within the first 12 months of life were comparable among all cohorts.

And then same with developmental milestones and need for NICU stay, really comparable among all cohorts. So that higher concentration of ustekinumab in the core blood or in the infant compared to vedolizumab did not negatively impact infant -related outcomes.

You know, it's interesting because all of these biologics are really actively transported across the placenta during pregnancy. And primarily that happens with the development of the FC receptor. And so the FC receptor continues to actively transport monoclonal antibodies. So do all of these biologics, with the exception of certolizumab, throughout pregnancy. But it does it at an increasing rate within the third trimester. So what's wonderful is that organogenesis ends by week 8 and the drug is really primarily being transported across the placenta or to the infant primarily in the third trimester. And the thought is that maybe the FC receptor affinity for vedolizumab is slightly less than the other biologics. So ustekinumab really seems to be transferred across the placenta in a similar fashion to the anti-TNF medications.

Rebecca Mashaw: So what significance would this have for clinicians who are working with patients who are pregnant or want to become pregnant, who have IBD?

Dr Chugh: I hope that this data just provides some reassurance that these medications can be continued throughout pregnancy at the time of conception, you know, and that they that there is no negative impact on pregnancy and infant-related outcomes. What we have seen separately, not in this particular study, but in prior studies that the disease activity is really the main thing that will negatively impact outcomes. And so staying on one of these medications throughout pregnancy, now we're able to show that it gets the disease under control.

So it reduces those adverse risks associated with active disease and that it doesn't seem to negatively impact pregnancy or infant-related outcomes in any way. So I hope it just provides some reassurance and allows providers and patients to feel comfortable continuing these medications throughout pregnancy and then also throughout breastfeeding, which has been covered separately in other studies.

Rebecca Mashaw: Is it true that there are still OBGYNs who will recommend to their patients with IBD that they stop their IBD medications and they're concerned about them continuing with that treatment and how do you address that?

Dr Chugh: Yeah, I think that the discovery that biologic medications such as these are safe to continue during pregnancy is relatively new. And so the first major PIANO study was published in 2020, you know, which included over a thousand pregnancies and was, you know, a very large and major study that showed the safety of these biologic medications. So I think the news is still spreading that these monoclonal antibodies, that these drugs are safe to take during pregnancy.

And the best that we can really do is continue to educate people, continue to spread the word, continue to do things like we're doing today where we just increase awareness about the safety of these medications. And certainly, if there are any one-on-one encounters with OBGYNs or other providers who want to discontinue these drugs prior to conception or during pregnancy, we just share the data with them.

And that's really all we can do, is just let them know that in our clinical experience and with this very robust data that we have now from over 30 centers, over 1600 pregnancies, we see that it's safe.

Rebecca Mashaw: And are the moms pretty comfortable with this now as well?

Dr Chugh: Absolutely, I think we've done a really good job kind of trying to spread the word, educate people on this. And also just demonstrating that active disease does lead to adverse outcomes. And so I think overall it seems like patients have become more comfortable with this. And we at UCSF, and I know at other institutions as well, start this conversation very early. So even prior to a woman considering pregnancy, if she is of child-bearing age, will generally start that discussion and let them know, okay, at any point when you are planning pregnancy, know that these medications are safe. This is the data that's out there so that they're already thinking about it and prepared when it comes time to conceive.

Rebecca Mashaw: So the old adage remains: true, healthy mom, healthy baby? 

Dr Chugh: Yes, absolutely. Yes, healthy mom, healthy baby.

Rebecca Mashaw: Well, thank you very much and we look forward to talking with you again as the research continues.

Dr Chugh: That sounds good, thank you so much for having me, Rebecca.