Biologics and Pregnancy
A significant percentage of individuals with psoriasis are women of childbearing age, which can pose a number of treatment challenges. The timely initiation of discussions regarding the potential risks and benefits of biologic use before, during, and after pregnancy is required.
Clinical Professor and Medical Director
“Not only are there robust registry data with TNF blockers during pregnancy in general, but certolizumab in particular does not cross the placenta.”
With respect to treatment options that are compatible with pregnancy, timely discussions and ongoing dialogue are required to optimize patient care and outcomes. The use of certain oral agents such as methotrexate and acitretin is incompatible with pregnancy and is thus best avoided in women of childbearing age.
When considering the use of biologics during pregnancy, the tumor necrosis factor (TNF) blockers have the highest-quality data. We have had registries for years in rheumatoid arthritis and inflammatory bowel disease, and now we also have some data specific to psoriasis, psoriatic arthritis, ankylosing spondylitis, and other chronic inflammatory diseases; however, most of the data are still from rheumatoid arthritis and inflammatory bowel disease. To date, the registry data have generally looked positive for TNF blockers in pregnancy. One French retrospective cohort study suggested that there might be an increased risk of fetal malformations with TNF blockers, but this has not been confirmed.
The TNF blocker certolizumab has the highest-quality data. According to the package insert, certolizumab levels were measured in mothers’ circulating blood vs cord blood, and it was determined that very little drug crossed the placenta (ie, no certolizumab detected [not measurable] in 13 out of 15 infants at birth). This is consistent with the structure of certolizumab, which does not have a fragment crystallizable (Fc) region; it is a truncated immunoglobulin, and the part of the molecule that is needed across the placenta is not there. So, when you measure levels, not surprisingly, there is not much there. Other TNF inhibitors, such as etanercept, infliximab, and adalimumab, bind to the neonatal Fc receptor and cross the placenta. For a pregnant patient who requires systemic treatment with a biologic, certolizumab is a good option. Not only are there robust registry data with TNF blockers during pregnancy in general, but certolizumab in particular does not cross the placenta. To me, that is an appropriate first choice when a biologic is needed. There is also a study showing that certolizumab does not pass into the breast milk. With the other newer agents, we simply do not have enough data yet to make determinations regarding pregnancy.
Clowse ME, Förger F, Hwang C, et al. Minimal to no transfer of certolizumab pegol into breast milk: results from CRADLE, a prospective, postmarketing, multicentre, pharmacokinetic study. Ann Rheum Dis. 2017;76(11):1890-1896. doi:10.1136/annrheumdis-2017-211384
Gottlieb AB, Ryan C, Murase JE. Clinical considerations for the management of psoriasis in women. Int J Womens Dermatol. 2019;5(3):141-150. doi:10.1016/j.ijwd.2019.04.021
Jakobsson GL, Stephansson O, Askling J, Jacobsson LTH. Pregnancy outcomes in patients with ankylosing spondylitis: a nationwide register study. Ann Rheum Dis. 2016;75(10):1838-1842. doi:10.1136/annrheumdis-2015-207992
Johansen CB, Jimenez-Solem E, Haerskjold A, Sand FL, Thomsen SF. The use and safety of TNF inhibitors during pregnancy in women with psoriasis: a review. Int J Mol Sci. 2018;19(5):1349. doi:10.3390/ijms19051349
Kimball AB, Guenther L, Kalia S, et al. Pregnancy outcomes in women with moderate-to-severe psoriasis from the Psoriasis Longitudinal Assessment and Registry (PSOLAR). JAMA Dermatol. 2021;157(3):301-306. doi:10.1001/jamadermatol.2020.5595
Lichtenstein GR, Feagan BG, Mahadevan U, et al. Pregnancy outcomes reported during the 13-year TREAT registry: a descriptive report. Am J Gastroenterol. 2018;113(11):1678-1688. doi:10.1038/s41395-018-0202-9
Luu M, Benzenine E, Doret M, et al. Continuous anti-TNFα use throughout pregnancy: possible complications for the mother but not for the fetus. A retrospective cohort on the French National Health Insurance Database (EVASION). Am J Gastroenterol. 2018;113(11):1669-1677. doi:10.1038/s41395-018-0176-7
Murase JE, Heller MM, Butler DC. Safety of dermatologic medications in pregnancy and lactation: part I. Pregnancy. J Am Acad Dermatol. 2014;70(3):401.e1-401.e14. doi:10.1016/j.jaad.2013.09.010
Owczarek W, Walecka I, Lesiak A, et al. The use of biological drugs in psoriasis patients prior to pregnancy, during pregnancy and lactation: a review of current clinical guidelines. Postepy Dermatol Alergol. 2020;37(6):821-830. doi:10.5114/ada.2020.102089
Porter C, Armstrong-Fisher S, Kopotsha T, et al. Certolizumab pegol does not bind the neonatal Fc receptor (FcRn): consequences for FcRn-mediated in vitro transcytosis and ex vivo human placental transfer. J Reprod Immunol. 2016;116:7-12. doi:10.1016/j.jri.2016.04.284