The Use and Safety of TNF Inhibitors during Pregnancy in Women with Psoriasis: A Review

Abstract

Psoriasis is a chronic immune-mediated inflammatory disease affecting women of childbearing potential. Biologic agents, notably Tumor Necrosis Factor inhibitors (TNFi), are the only current non-contraindicated systemic treatment option during pregnancy. TNFi comprised of complete immunoglobulin G (IgG) antibodies antibodies (adalimumab, golimumab, and infliximab) actively cross the placenta from the second trimester and are detectable in the child up to one year postpartum. Data on safety of TNFi are conflicting; however a trend towards drug-specific harm has been reported, with increased risk of congenital malformations and preterm birth. TNFi exposure may alter the immune system of the infant towards hypersensitivity and reduced response to intracellular infections. Confounding by indication should be considered, as chronic inflammatory disease itself may pose a risk of adverse pregnancy outcomes. The quality of the current evidence is very low and no studies specifically address TNFi safety in women with psoriasis. Nonetheless, risks associated with TNFi treatment must be balanced against the as-yet uncertain risk of adverse outcomes in infants born to women with severe psoriasis. We searched PubMed using Medical Subject Headings (MeSH) terms and identified relevant studies and guidelines. Herein, we present the current knowledge of the use and safety of TNFi during pregnancy in women with psoriasis.

Interaction of psoriasis and pregnancy: Maternal and fetal outcomes

“…However, the authors stated that the diverse fi ndings across disease groups in this study may indicate an association related to the underlying disease activity rather than to agent-specifi c effects [71]. As a general approach, it is recommended that women using anti-TNF- avoid pregnancy and be monitored if they have already become pregnant, but there is no conclusive evidence that adalimumab, infl iximab, etanercept and certolizumab pegol treatments are embryotoxic or teratogenic [59][60][61]. Therefore, it has been reported that the continuation of the treatment according to the risk-benefi t balance should be decided individually in each patient.…”

“…In these periods, the most appropriate treatment after topical agents is broadband or especially narrow band that these anomalies may be biased because they actually refl ect negative outcomes collected by the FDA [66,67]. Data on the safety of anti-TNF- treatments during pregnancy are increasing gradually [59][60][61]. Since these treatments are mostly used in infl ammatory bowel diseases and rheumatoid arthritis, most of the data have been obtained from the literature of gastroenterology and rheumatology [68,69].…”

Psoriasis and pregnancy in the biologic era, a feared scenario. What do we do now?

“…Unlike others previously mentioned, this biologic lacks the receptor to bind to the Fc placental portion, therefore disabling the possibility of active transport toward fetal circulation. Diverse studies have detected minimal concentrations in neonates whose mothers were treated with this biologic, but it has been inferred that these concentrations might be due to passive transplacental transfer (Johansen et al, ). Likewise, a series of cases regarding 14 pregnant women diagnosed with diverse chronic inflammatory diseases, uninterruptedly treated with certolizumab during pregnancy, demonstrated that neonate concentrations were undetectable or, except one case, minimal (infant/mother plasma ratio of 0.0009) (Mariette et al, ).…”

“…In fact, it has been observed that when Th17 activity increases above Treg, complications arise, such as preterm labor, preeclampsia, and spontaneous abortions in patients diagnosed with inflammatory diseases such as systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis (Figueiredo & Schumacher, 2016). By extrapolation one can infer that psoriasis in itself is a condition that overshadows pregnancy, as its severity is directly related to complications, according to Yang et al, Johansen et al, Odorici et al, and Bröms et al, it can cause spontaneous abortions, preterm labor, and restricted intrauterine growth (Bröms, Haerskjold, Granath, et al, 2018;Figueiredo & Schumacher, 2016;Johansen, Jimenez-Solem, Haerskjold, Sand, & Thomsen, 2018;Odorici et al, 2019;Yang, Chen, Chen, & Lin, 2011).…”

“…On the other hand, the European Crohn's and Colitis Organization guidelines considers timely treatment with anti-TNF, followed by discontinuation at 24-26 weeks of pregnancy (Van der Woude, Ardizzone, Bengtson, et al, 2015). that active transport begins at 22 weeks of pregnancy, and that organogenesis is carried out throughout weeks 3 to 8, therefore none of the anti-TNF agents would adversely affect organogenesis (Johansen et al, 2018;Malek, Sager, & Schneider, 1994;Saji, Samejima, Kamiura, & Koyama, 1999;Story, 1994). Several publications regarding pregnant women with IBS treated with biologics, studied the duration of these molecules in neonates blood samples, finding that adalimumab persists 4 months, while infliximab 7.3 months (Julsgaard et al, 2016).…”