The pre‐ and post‐authorisation data published by the European medicines agency on the use of biologics during pregnancy and lactation

Abstract

Aims The effects of biologics on reproduction/lactation are mostly unknown although many patients that receive biologics are women of reproductive age. The first objective of this study was to investigate the publicly available data on pregnancy/lactation before and after marketing authorization in Europe of biologics for the indications of rheumatologic inflammatory autoimmune diseases and inflammatory bowel disease. Secondary objectives included the assessment of the clinical relevance of the provided data and comparison of initial and post‐authorization data. Methods Initial and post‐authorization data were extracted from the European Public Assessment Reports and the latest versions of Summary of Product Characteristics using publicly available documents on the European Medicines Agency's website. Four sections were categorized regarding pregnancy outcomes: pre‐clinical/animal studies, human female fertility, pregnancy‐related outcomes and congenital malformations in the human fetus. Three sections were categorized regarding lactation outcomes: pre‐clinical/animal studies, excretion in human breast milk and absorption in children through breastfeeding. The clinical applicability of each category was scored by specified criteria, based on scientific literature, and further as defined by the authors. Results For the 16 included biologics, post‐authorization data were delivered only for adalimumab, certolizumab pegol, etanercept and infliximab. For the 12 remaining biologics limited data on pregnancy and lactation during the post‐marketing period of 2–21 years were available. Conclusions In this article several suggestions are provided for improving a multidisciplinary approach to these issues. The initiation of suitable registries by marketing authorization holders and data transparency for clinicians and academics are highly endorsed.

Intrauterine Exposure to Biologics in Inflammatory Autoimmune Diseases: A Systematic Review

“…This systematic review was registered retrospectively at PROSPERO under the code CRD42019135316. The recorded protocol was not provided prospectively in PROSPERO [ 12 ].…”

Practical recommendations for systemic treatment in psoriasis according to age, pregnancy, metabolic syndrome, mental health, psoriasis subtype and treatment history (BETA‐PSO: Belgian Evidence‐based Treatment Advice in Psoriasis; part 1)

“…Based on the available placental transfer and pregnancy outcomes evidence, our recommendation for female patients with psoriasis wishing to conceive or who may be pregnant and where treatment is clinically needed is to use of the Fc‐free biological drug certolizumab pegol as first‐line treatment, followed by either adalimumab or etanercept 9–11 …”

“…-Based on the available placental transfer and pregnancy outcomes evidence, our recommendation for female patients with psoriasis wishing to conceive or who may be pregnant and where treatment is clinically needed is to use of the Fc-free biological drug certolizumab pegol as first-line treatment, followed by either adalimumab or etanercept. [9][10][11] However, the use of Fc-containing biologics (including etanercept, adalimumab) during the third trimester is not recommended. We also advise that infliximab, secukinumab, ixekizumab, brodalumab and ustekinumab may be used in female patients wishing to conceive; however, data are limited with these biological drugs.…”

The Influence of Treatment of Inflammatory Arthritis During Pregnancy on the Long-Term Children’s Outcome

“…A recent meta-analysis on this topic found no association between the use of biologics during pregnancy and the risk of congenital malformation, preterm deliveries or serious infections requiring hospitalization in infants’ first year of life, compared with disease-matched unexposed pregnant women ( Tsao et al, 2020 ). The use of adalimumab (ADA), certolizumab pegol (CTZ), infliximab (IFX), and etanercept (ETA) during pregnancy is now widely accepted if clearly needed, based on the results of the pregnancy registries ( Ghalandari et al, 2020 ). All the TNFα inhibitors showed a good safety profile if used in the first half of pregnancy.…”