Long-Term Follow-Up of Dupilumab Treatment During Conception, Pregnancy and Lactation

Sir, Disclosure: Honorarium, grant or other forms of payment were not given to any of the authors to produce the manuscript. All authors made substantive intellectual contributions to the published study, and each author listed in the manuscript has seen and approved the submission of the manuscript. Dupilumab is a fully human monoclonal antibody, which targets the shared receptor component for interleukin (IL)-4 and IL-13. Currently, it is approved to treat moderate-to-severe atopic dermatitis (AD), asthma and chronic rhinosinusitis with nasal polyps. Blocking IL-4 and IL-13 signalling may be crucial to achieve sustained control of AD signs and symptoms with an acceptable safety profile, particularly in patients with high burden of disease and when topical treatments are ineffective. Due to a favourable benefit–risk profile, a continuous treatment is currently regarded as appropriate.[1] Real-world data show that dupilumab has a good safety profile. Conjunctivitis is the most common adverse event reported.[2] As the AD incidence is high in all age-groups,[3] a significant number of affected female patients may be in childbearing age. However, as regards treatment during pregnancy, no data are available from clinical trials.[4] A 35-year-old woman presented with severe AD from birth to age 14 followed by remission up to age 31. Her past medical history was significant for allergic rhinoconjunctivitis. Previous treatments included high-potency topical and systemic corticosteroids. On examination, she had diffused AD affecting 75% of her total body surface area with an Eczema Area and Severity Index (EASI) score of 36.1, an Investigator Global Assessment (IGA) score of 4 and a Dermatology Life Quality Index (DLQI) of 20 [Figure 1a]. The patient was commenced on cyclosporine 3.5 mg/kg/day. Due to hypertrichosis, cyclosporine dose was stopped and the patient was administered dupilumab subcutaneous injections with a loading dose of 600 mg, followed by 300 mg every other week. At week 16, she had, respectively, an EASI score of 4.0 and DLQI score of 6 with further improvement at week 24. The patient became pregnant 24 months later. We warned the patient about the possible risk–benefit assessment, suggesting a temporary drug discontinuation. After 2 weeks of cessation, the patient experienced a mild relapse of skin inflammatory lesions, especially on the face. Because then, she decided to restart and continue dupilumab during pregnancy until gestation, unless abnormal foetal development was detected. EASI score fell to 0 and remained so throughout the pregnancy [Figure 1b]. No antenatal complications happened. At 37 weeks and 5 days of gestation, the patient discharged a healthy female infant (weight 3,120 g, length 48.4 cm) via an uncomplicated spontaneous vaginal delivery. The patient chose to breastfeed while receiving dupilumab as well. No complications were observed 48 months after the start of therapy with dupilumab and 18 months after delivery.Figure 1: (a) Severe atopic dermatitis involving face and neck before dupilumab treatment. (b) Complete clinical remission after dupilumab treatment during pregnancyDue to its high prevalence, AD may be considered the most common skin disease in pregnancy. The management of AD in this context may be challenging: the need to limit presumed hazardous therapies for the foetus must be balanced with that of avoiding dermatitis flares, distress and significant impact on patient global health and quality of life. Dupilumab is an immunoglobin G4 (IgG4) antibody that is able to cross the placenta with upconcentration expected in the foetus.[5] Bosma et al. reported four cases of patients (two men and two women) who conceived during dupilumab treatment without complications.[6] Additional observations reported clinical experiences during pregnancy with a favourable maternal and newborn outcome [Table 1]. More limited are the experiences during pregnancy and lactation together. As far as we know, it is not clear whether dupilumab is excreted in human milk or engrossed systemically after oral intake. The secretion of biologic agents in breast milk seems to be minimal, except during the first 3 days after drug administration.Table 1: Clinical experiences with dupilumab during pregnancyOur case is one of the few reporting dupilumab treatments in the conception, pregnancy and breastfeeding phases. Significant data will be available from the observational retrospective cohort study conducted on women with AD (NCT03936335), which has an estimated study completion data in 2027. In the meantime, for each pregnant patient with AD, an accurate assessment of the risk and benefits, intended above all in the protection of the physical and psychological well-being, is necessary. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.