Phototherapy
Broadband or narrowband UVB therapy is recommended as second-line therapy in pregnancy. No cases of fetal risk or premature delivery associated with UVB therapy were found in our search.1 Phototherapy can exacerbate melasma47 and decrease folate levels48; as such, some authors recommend folate supplementation in females of childbearing age who are being treated with phototherapy.49 Psoralen, used in psoralen plus UVA therapy, is mutagenic and therefore contraindicated in pregnancy.1
Oral Medications
Both methotrexate, which is a teratogen, abortifacient, and mutagen,1 and systemic retinoids, which are teratogens, are contraindicated in pregnancy.1,47 Acitretin labeling recommends avoiding pregnancy for 3 years posttreatment50 because alcohol intake prolongs the medication’s half-life.22
Apremilast use is not documented in pregnant psoriasis patients51; an ongoing registry of the Organization of Tetralogy Information Specialists has not reported publicly to date.52 Animal studies of apremilast have documented dose-related decreased birthweight and fetal loss.22
Safety data for systemic steroids, used infrequently in psoriasis, are not well established. First-trimester prednisone exposure has been associated with prematurity, low birthweight, and congenital abnormalities.38 A separate evaluation of 1047 children exposed to betamethasone in utero failed to demonstrate significant change in birthweight or head circumference. However, repeat antenatal corticosteroid exposure was associated with attention problems at 2 years of age.39
Data regarding cyclosporine use, derived primarily from organ transplant recipients, suggest elevated risk for prematurity and low birthweight.53,54 A meta-analysis demonstrated that organ transplant recipients taking cyclosporine had a nonsignificantly elevated odds ratio for congenital malformations, prematurity, and low birthweight.42 Cyclosporine use for psoriasis in pregnancy is not well described; in a study, rates of prematurity and low birthweight were both 21%.43 Limited data are available for Janus kinase inhibitors, none of which are approved for psoriasis, though clinical trials in psoriasis and psoriatic arthritis are underway (ClinicalTrials.gov identifiers NCT04246372, NCT03104374, NCT03104400).
Biologics and Small-Molecule Inhibitors
Limited data on biologics in pregnancy exist25 (eTable 3). Placental transport of IgG antibodies, including biologics, increases throughout pregnancy, especially in the third trimester.82 Infants of mothers treated with a biologic with potential for placental transfer are therefore considered by some authors to be immunosuppressed during the first months of life.2
Looking globally across biologics used for psoriasis, limited safety data are encouraging. In a review of PSOLAR (Psoriasis Longitudinal Assessment and Registry), 83 pregnancies with biologic exposure resulted in 59 live births (71%); 18 spontaneous abortions (22%); 6 induced abortions (7%); no congenital abnormalities; and 7 reports of neonatal problems, including respiratory issues, ABO blood group mismatch, hospitalization, and opioid withdrawal.83
Use of tumor necrosis factor (TNF) inhibitors in pregnancy has the most data25 and is considered a reasonable treatment option. Historically, there was concern about the risk for VACTERL syndrome (vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, limb abnormalities) with exposure to a TNF inhibitor,25,84-86 but further reports have alleviated these concerns. Active transplacental transport occurs for adalimumab, infliximab, and golimumab,87 but given structural differences, transport of certolizumab and etanercept is substantially less.88,89 In the CRIB study of placental transfer of certolizumab from mother to infant (N=14), pharmacokinetic data demonstrated no quantifiable certolizumab levels in 13 infants and minimal levels in 1 infant at birth.88 There are fewer data available on the use of other biologics in pregnancy, but for those in which active placental transport is relevant, similar concerns (ie, immunosuppression) might arise (eTable 3).
Concern over biologics largely involves risk for newborn immunosuppression. A case report detailed a Crohn disease patient treated with infliximab who gave birth to an infant who died of disseminated bacille Calmette-Guérin infection at 4.5 months after receiving the vaccine at 3 months.90 This case underscores the importance of delaying live vaccination in infants born to mothers who were treated with a biologic during pregnancy. Authors have provided various data on how long to avoid vaccination; some state as long as 1 year.91
In pregnant females with inflammatory bowel disease treated with a biologic, no correlation was observed among maternal, placental, and infant serum biologic levels and neonatal infection. However, an association between preterm birth and the level of the biologic in maternal and placental (but not infant) serum and preterm birth was observed.92
In another report from the same registry, combination therapy with a TNF inhibitor and another immunomodulator led to an increased risk for infection in infants at 12 months of age, compared to infants exposed to monotherapy89 or exposed to neither agent.93 A strategy to circumvent this potential problem is to avoid treatment with actively transported molecules in the third trimester.
Conclusion
Limited data exist to guide providers who are treating pregnant women with psoriasis. Our understanding of treatment of psoriasis in pregnancy is limited as a consequence of regulations surrounding clinical trials and inadequate detection of pregnancies in registries. Further efforts are necessary to better understand the relationship between psoriasis and pregnancy and how to manage pregnant women with psoriasis.