Managing Atopic Dermatitis During Pregnancy and Breastfeeding

Key highlights

Treating AD during pregnancy involves navigating the ethical challenges of clinical trials in pregnant women, as current guidelines deem it unethical to perform such trials. Consequently, there is a lack of high-level evidence on the efficacy and safety of systemic treatments in this population. The consensus emphasizes the importance of patient education and individualized advice, ideally in collaboration with an obstetrician¹.

Article of interest:

Deleuran M. et al, Systemic anti-inflammatory treatment of atopic dermatitis during conception, pregnancy, and breastfeeding: Interdisciplinary expert consensus in Northern Europe. J Eur Acad Dermatol Venereol. 2024 Jan;38(1):31-41

Pre-pregnancy and AD Management

Guidance for Women: Effective planning and treatment are crucial during the pre-pregnancy phase to manage AD and minimize risks. Cyclosporine A is recommended as the first-choice treatment due to its favorable risk-benefit profile, although it requires close monitoring for renal impairment and arterial hypertension¹. Short courses of prednisolone are also considered relatively safe for acute flares¹. Regarding second line systemics, there is no specific recommendation for biologics during pre-conception in the product SmPC. However, the experts thought that women should avoid JAK inhibitors, methotrexate, and mycophenolate mofetil pre-conception, with appropriate washout periods¹. Specific recommendations for contraception during and after treatment with these drugs are provided in their summary of product characteristics^5-7. Women of child-bearing potential should be advised to use effective contraception during treatment and for 4 weeks following the final dose of any JAKi treatment⁸.

Guidance for Men: For men planning to conceive, cyclosporine A, azathioprine, and corticosteroids are suggested as appropriate options, with no significant effect on male fertility¹. Dupilumab may also be used despite limited information on its effects on male fertility¹. Animal studies showed no impairment of fertility and fertility studies conducted in male and female mice using a surrogate antibody against IL-4Ra showed no impairment of fertility². Methotrexate and mycophenolate mofetil are discouraged due to potential adverse effects on sperm, and the data on JAK inhibitors are scarce, and the experts reached no consensus on their use in men wishing to conceive¹.

Pregnancy and AD Management

Effective management of AD during pregnancy is necessary to maintain maternal quality of life and prevent severe symptoms. This consensus supports the use of systemic therapies when the benefits outweigh potential risks for the fetus. Furthermore, physicians should consider systemics if AD is severe and topical therapies or UVB are inadequate. A collaborative approach involving dermatologists and obstetricians is crucial for optimizing outcomes¹.

Cyclosporine A is the preferred long-term systemic treatment during pregnancy and short courses of prednisolone are recommended for flare management and with acceptable safety for short-term use. However, those therapies should not be used during pregnancy unless the potential benefit to the mother justifies the potential risk to the fetus.^1,9,10

The experts reached no consensus on biologics as there is a limited amount of data from the use of dupilumab, tralokinumab and lebrikizumab in pregnant women¹.

• Dupilumab product SmPC mentions that the animal studies did not indicate direct or indirect harmful effects with respect to reproductive toxicity, and that dupilumab should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus².
• Tralokinumab and lebrikizumab product SmPC mention that as a precautionary measure, it is preferable to avoid the use of tralokinumab and lebrikizumab during pregnancy^3,4.

JAK inhibitors, methotrexate, and mycophenolate mofetil are contraindicated during pregnancy due to their teratogenic effects. The consensus strongly advises against their use to prevent fetal harm¹.

Breastfeeding and AD Management

The World Health Organization advocates for breastfeeding due to its numerous benefits for both mother and child. The consensus supports accommodating mothers who wish to breastfeed while managing AD. This decision should always be made in collaboration with the patient. Similar as for previous stages, the safety of both the mother and the infant is paramount when selecting systemic AD treatments, and in certain cases, prioritizing the control of AD over breastfeeding might be necessary¹.

Cyclosporine A is highlighted as the first-choice treatment during breastfeeding due to its established safety and efficacy, with prednisolone recommended for flares¹.

The safety of newer biologics during breastfeeding is not well-established, and a decision must be made whether to discontinue breastfeeding or the biologic therapy based on the benefits and risks¹. It is unknown whether newer biologics are excreted in human milk or absorbed systemically after ingestion². The excretion in breast milk should be small due to dupilumab high molecular weight; however, more studies need to be conducted to determine its effects during lactation⁸.

Similar to pregnancy, JAK inhibitors, methotrexate, azathioprine, and mycophenolate mofetil should be avoided during breastfeeding due to potential risks to the infant¹.

Conclusion