Conference Coverage

Study offers reassuring data on certolizumab use in pregnancy

Key clinical point: Consider off-label certolizumab in women with psoriasis who need a biologic and are pregnant or planning to become so.

Major finding: The rate of major congenital malformations in a large prospective series of pregnancies in women on certolizumab was reassuringly low at 4.2%, with no pattern of malformations being seen.

Data source: This was a report on maternal and fetal outcomes of 256 prospectively followed pregnancies in women on certolizumab.

Disclosures: The presenter reported receiving research funds from and serving as a consultant to UCB, which markets certolizumab and maintains the pregnancy registry.


 

AT THE EADV CONGRESS

– Data from a large prospective registry of pregnancy outcomes in women on certolizumab are reassuring to date, Alexa B. Kimball, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

“This unique dataset of pregnancies exposed to a single agent suggests that exposure is really not a problem, although we’ll continue to collect prospective data and anticipate doing so in women with psoriasis going forward,” said Dr. Kimball, professor of dermatology at Harvard Medical School, Boston.

Dr. Alexa B. Kimball

Dr. Alexa B. Kimball

She presented an update on 256 pregnancies prospectively followed in women on certolizumab (Cimzia) in a registry maintained by UCB, which markets the monoclonal antibody. Most of the women were on the biologic for treatment of Crohn’s disease or rheumatoid arthritis. The data showed no increased risk of maternal pregnancy-associated complications, and the 4.2% major congenital malformation rate was within the range that the Centers for Disease Control and Prevention estimates to be the background U.S. rate. Moreover, there was no pattern to the congenital malformations, as would have been expected if they were causally related to a drug exposure.

Certolizumab is a tumor necrosis factor–alpha inhibitor currently approved in the United States for the treatment of Crohn’s disease, rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. It is now in clinical trials for psoriasis, and Dr. Kimball said she expects that it will eventually receive an indication for that disease as well. In the interim, she switches her psoriasis patients who are pregnant or plan to become so to either off-label certolizumab or etanercept (Enbrel). She does the same for her psoriatic arthritis patients, although in that situation certolizumab is on-label therapy.

The reason she turns to etanercept or certolizumab in pregnancy or anticipated pregnancy is that these two biologics, unlike others, don’t cross the placenta in the third trimester.

“I’m concerned about the selective uptake of other monoclonal antibodies in the third trimester. We do see in babies born to moms exposed to these other drugs – like ustekinumab, infliximab, and adalimumab – that the baby’s drug blood levels at birth are higher than the mom’s, so you have potentially put them at some risk for infections unnecessarily and maybe have affected how their immune system develops. So if a woman comes to me who is pregnant and on a biologic agent I would either stop treatment in the second trimester or switch to etanercept or certolizumab,” the dermatologist said.

Of the 256 pregnancies prospectively followed in the UCB certolizumab registry, 80.9% resulted in live births, and 10.2% ended in spontaneous abortion or miscarriage. In addition, the induced abortion rate was 8.6%, and there was a single stillbirth.

Of note, the mean age at pregnancy was 31 years, and 29% of the women became pregnant at age 35 or older. In contrast, the mean age at first pregnancy in the general population is 26, and only about 10% are 35 or older. These data are consistent with Dr. Kimball’s own clinical experience, which is that women with moderate to severe psoriasis or psoriatic arthritis often have trouble conceiving, and if they eventually succeed it’s often at a more advanced age.

The rate of maternal complications in this series was unremarkable: preeclampsia in 3.5%, infection in 3.9%, disease flare in 5.1%, and gestational diabetes in 3.1%. The median gestational age at birth was 39 weeks. The rate of early preterm birth before 32 weeks was 3.5%, with 12.6% of babies arriving at 32-36 weeks. Considering these are older moms being treated for serious underlying systemic inflammatory diseases, these numbers look good, according to Dr. Kimball.

Most women were exposed to certolizumab during the first trimester at least, and many were on the drug throughout pregnancy.

She said about one-third of psoriasis patients experience improvement in their skin diseases during pregnancy.

“If they’re doing really well, I see no reason to keep them on systemic therapy during pregnancy. But I will say that I see a lot of very bad postpartum flares, and I’m quite cautious about that. For the women with psoriatic arthritis there may not be a choice; you may need to continue to treat them all the way through their pregnancy to keep from getting permanent joint destruction,” the dermatologist said.

Dr. Kimball reported receiving research grants from and serving as a consultant to UCB and numerous other pharmaceutical companies.

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