The use of biologic therapies
In a 2017 review of biologic safety for patients with psoriasis during pregnancy, Alexa B. Kimball, MD, MPH, professor of dermatology at Harvard Medical School, Boston; Martina L. Porter, MD, currently with the department of dermatology at Beth Israel Deaconess Medical Center, Boston; and Stephen J. Lockwood, MD, MPH, of the department of dermatology at Harvard Medical School, concluded that an increasing body of literature suggests that biologic agents can be used during pregnancy and breastfeeding. Anti-TNF agents “should be considered over IL-12/23 and IL-17 inhibitors due to the increased availability of long-term data,” they wrote.
“In general,” said Dr. Murase, “there’s more and more data coming out from gastroenterology and rheumatology to reassure patients and prescribing physicians that the TNF-blocker class is likely safe to use in pregnancy,” particularly during the first trimester and early second trimester, when the transport of maternal antibodies across the placenta is “essentially nonexistent.” In the third trimester, the active transport of IgG antibodies increases rapidly.
If possible, said Dr. Sammaritano, who served as lead author of the ACR’s reproductive health guideline, TNF inhibitors “will be stopped prior to the third trimester to avoid [the possibility of] high drug levels in the infant at birth, which raises concern for immunosuppression in the newborn. If disease is very active, however, they can be continued throughout the pregnancy.”
The TNF inhibitor certolizumab pegol (Cimzia) has the advantage of being transported only minimally across the placenta, if at all, she and Dr. Murase both explained. “To be actively carried across, antibodies need what’s called an Fc region for the placenta to grab onto,” Dr. Murase said. Certolizumab – a pegylated anti–binding fragment antibody – lacks this Fc region.
Two recent studies – CRIB and a UCB Pharma safety database analysis – showed “essentially no medication crossing – there were barely detectable levels,” Dr. Murase said. Certolizumab’s label contains this information and other clinical trial data as well as findings from safety database analyses/surveillance registries.
“Before we had much data for the biologics, I’d advise transitioning patients to light therapy from their biologics and a lot of times their psoriasis would improve, but it was more of a dance,” she said. “Now we tend to look at [certolizumab] when they’re of childbearing age and keep them on the treatment. I know that the baby is not being immunosuppressed.”
Consideration of the use of certolizumab when treatment with biologic agents is required throughout the pregnancy is a recommendation included in Dr. Kimball’s 2017 review.
As newer anti-interleukin agents – the IL-12/23 and IL-17 inhibitors – play a growing role in the treatment of psoriasis and PsA, questions loom about their safety profile. Dr. Murase and Dr. Sammaritano are waiting for more data. “In general,” Dr. Sammaritano said, “we recommend stopping them at the time pregnancy is detected, based on a lack of data at this time.”
Small-molecule drugs are also less well studied, she noted. “Because of their low molecular weight, we anticipate they will easily cross the placenta, so we recommend avoiding use during pregnancy until more information is available.”
Postpartum care
The good news, both experts say, is that the vast majority of medications, including biologics, are safe to use during breastfeeding. Methotrexate should be avoided, Dr. Sammaritano pointed out, and the impact of novel small-molecule therapies on breast milk has not been studied.
In her 2019 review of psoriasis in women, Dr. Murase and coauthors wrote that too many dermatologists believe that breastfeeding women should either not be on biologics or are uncertain about biologic use during breastfeeding. However, “biologics are considered compatible for use while breastfeeding due to their large molecular size and the proteolytic environment in the neonatal gastrointestinal tract,” they added.
Counseling and support for breastfeeding is especially important for women with psoriasis, Dr. Murase emphasized. “Breastfeeding is very traumatizing to the skin, and psoriasis can form in skin that’s injured. I have my patients set up an office visit very soon after the pregnancy to make sure they’re doing alright with their breastfeeding and that they’re coating their nipple area with some type of moisturizer and keeping the health of their nipples in good shape.”
Timely reviews of therapy and adjustments are also a priority, she said. “We need to prepare for 6 weeks post partum” when psoriasis will often flare without treatment.
Dr. Murase disclosed that she is a consultant for Dermira, UCB Pharma, Sanofi, Ferndale, and Regeneron. She is also coeditor in chief of the International Journal of Women’s Dermatology. Dr. Sammaritano reported that she has no disclosures relating to the treatment of PsA.