Psoriasis, therapy and pregnancy

Psoriasis is a systemic disease. It not only leads to a reduced quality of life, but also to systemic inflammation, which can affect the entire pregnancy. Several cohort studies have identified different risks of premature mortality or low birth weight in children depending on the severity of psoriasis (Bobotsis R et al. 2016) Overall, however, there is no clear evidence of an increase in adverse outcomes in pregnant women with psoriasis. 30-40% of pregnancies are unplanned and predominantly occur between the ages of 20 and 44, an age at which psoriasis often occurs for the first time. In this respect, possible pregnancies must be taken into account when making treatment decisions.

For mild forms of psoriasis, mild to moderate topicals are usually sufficient. In refractory cases, UVB therapy may be considered. Problems arise in severe exacerbations of psoriasis or in systemically treated patients who become pregnant.

In the last ten years, numerous systemic drugs have been approved for the treatment of psoriasis vulgaris and psoriatic arthritis (PsA). However, it is not easy to decide on treatment for women who wish to have children or who are pregnant or breastfeeding, as there is little data available for these cases.

Topical medications

• Corticosteroids: The best evidence for treatment of psoriasis during pregnancy is for topical corticosteroids.
• Topical calcipotriol as well as topical dithranol and topical tacrolimus also appear to be safe options for controlling localized psoriasis in pregnancy (Tauscher AE et al. 2002).
• UVB: Medically supervised application of UVB is the safest treatment for extensive psoriasis during pregnancy, especially when topical application of other agents is not practical.

Systemic medications

Contraindicated in pregnancy (Balakirski G et al. 2022; Sheet N et al. 2009):

• Fumaric acid esters (FAE): the data situation is unclear with regard to pregnancy in psoriasis. It is recommended to discontinue medication at the onset of pregnancy. Elective termination of pregnancy is not necessary solely due to previous therapy with FAE (Embryotox-FAE).
• Methotrexate (proven teratogenic in animal studies)
• Retinoids (proven teratogenic potential - fetal retinoid syndrome due to retinoid applications in the 1st trimester of pregnancy). The use of retinoids during breastfeeding is not justified. The current S3 guideline on PV therapy considers breastfeeding to be an absolute contraindication to acitretin administration (Balakirski G et al. 2022).
• Leflunomide (as a pyrimidine synthesis inhibitor, a teratogenic potential is assumed for this preparation.

Systemic therapeutics during pregnancy:

Ciclosporin: Among the classic systemic therapeutics, the greatest clinical experience is available for ciclosporin, which can also be continued during pregnancy if medically necessary. Ciclosporin is probably the safest option for treating severe psoriasis in pregnancy that has not responded to topical or UVB treatment.

TNF-alpha inhibitors: The best evidence for systemic therapy during pregnancy and lactation is available for the group of TNF-alpha inhibitors, which is also reflected in the respective medical product information. This is particularly important for psoriatic arthritis. Adalimumab, etanercept and infliximab as representatives of this group do not have to be discontinued if the disease is well controlled and the patient wishes to have children. Continuation of therapy is also possible throughout pregnancy. Studies on the transfer of these substances into breast milk are rare for the entire group of TNF-alpha inhibitors. It is assumed that secretion is low (due to the size of the molecule).

• Certolizumab-pegol: A representative of this group - certolizumab-pegol - can be used during pregnancy and breastfeeding if clinically necessary. Only very small amounts of the active substance pass through the placenta into the fetal circulation. It is only detected in small quantities in breast milk.
• Adalimumab: There is experience of its use during pregnancy in patients with chronic inflammatory bowel disease. More than 1000 pregnancies under ongoing therapy have been documented in the literature. There are no indications of teratogenicity (Balakirski G et al. 2022).
• Etanercept and infliximab: There are several hundred reports on the use of both preparations during pregnancy in the fields of gastroenterology and rheumatology (Balakirski G et al. 2022). There were no indications of increased malformation risks or teratogenicity during therapy.

Interleukin -23 inhibitors:

• Ustekinumab: No evidence of fetal toxicity or teratogenicity was found in animal studies (Martin PL et al. 2010). As the data available in humans is limited, the information for healthcare professionals recommends avoiding therapy during pregnancy.
• Guselkumab/Risankizumab/Tildrakizumab: There are no reports on these specific IL-23p19 inhibitors regarding pregnancy and breastfeeding. As a precautionary measure, their use should be avoided during pregnancy.

Interleukin-17 inhibitors:

• Secukinumab: in a larger observational study with psoriasis, psoriatic arthritis or ankylosing spondylitis (n=238), no fetal or maternal risks were demonstrated (Warren RB et al. 2018). The rates of fetal miscarriages or fetal malformations were comparable to those of the normal population. A total of 177 pregnant psoriatic patients have been described on secukinumab to date. The information for healthcare professionals advises against the use of this preparation during pregnancy for precautionary reasons (Balakirski G et al. 2022).

IL-17RA blockers/IL-17A inhibitors:

• Brodalumab (IL-17RA inhibitor):
• Ixekizumab (IL-17A inhibitor):
• The data on psoriasis and pregnancy is sparse. For precautionary reasons, the use of these preparations during pregnancy is not recommended. Breastfeeding is also not recommended (Balakirski G et al. 2022).

IL-17A/F inhibitors

• Bimekizumab: The data on psoriasis and pregnancy is sparse. For precautionary reasons, the use of this preparation during pregnancy is not recommended. Breastfeeding is also not recommended (Balakirski G et al. 2022).

Recombinant fusion preparations (CTLA-4/Fc portion of human IgG1)

• Abatacept: The preparation is approved for the treatment of active psoriatic arthritis. No embryotoxic effects in offspring were observed in animal experiments. Limited changes in immune function have been demonstrated at greatly increased doses - increase in the T-cell-dependent antibody response. Abatacept must not be used during pregnancy. During treatment and up to 14 weeks afterwards, women of childbearing age should use reliable contraception. The use of Abatacept is also not recommended during breastfeeding.

Newer therapies (small molecules)

• Apremilast (PDE4 inhibitor): The preparation has been approved for the treatment of psoriasis vulgaris and psoriatic arthritis since 2015. To date, there is no literature on apremilast and pregnancies. In animal experiments, the substance can be detected in the milk of lactating mice. The use of the preparation is not recommended during pregnancy and in breastfeeding women.

Janus kinase (JAK) inhibitors

• Tofacitinib: The JAK inhibitor is approved for the treatment of psoriatic arthritis, but only in combination with MTX. It can be assumed that the substance can pass the blood-placenta barrier due to its small size. Teratogenicity has been demonstrated in animal experiments. As the approval is only valid for the MTX combination, it is contraindicated during pregnancy. The preparation should also not be administered during breastfeeding.
• Upadacitinib: As with tofacitinib, this preparation is also contraindicated in pregnancy. The preparation should also not be used during breastfeeding.

1. Balakirski G et al. (2022) Therapy of psoriasis during pregnancy and breast-feeding. J Dtsch Dermatol Ges 20:653-683.
2. Bobotsis R et al. (2016) Psoriasis and adverse pregnancy outcomes: a systematic review of observational studies. Br J Dermatol 175:464-472.
3. Embryotox fumaric acid esters. Available from: https://www. Embryotox. De/arzneimittel/details/Fumaric acid esters (12.2024)
4. Martin PL et al. (2010) Development in the cymomologus macaque following andministration of ustekinumab, a human anti-IO-12(23p40 monoclonal antibody, during pregnancy and lactation. Birth defects research. Part B, Developmental and Reprod Toxicol 89: 351-363 .
5. Sheet N et al. (2009) Generalized pustular psoriasis of pregnancy treated with infliximab. Clin Exp Dermatol 34: 521-522
6. Tauscher AE et al (2002) Psoriasis and pregnancy. J Cutan Med Surg 6:561-570.
7. Warren RB et al. (2018) Secukinimab in pregnancy: outcomes in psoriasis, psoriatic arthritis and ankylosing spondylitis from global safety database. Br J Dermatol 179:1205-1207