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The published experience with biologics in childbearing age with autoimmune and inflammatory diseases mainly deals with the use of TNFα inhibitors (TNFα-i). Limited data are available for biologics targeting other cytokines or immunocompetent cells, especially for the inflammasome targeted therapy including IL-1 inhibitors and colchicine. We conducted a nested case-control study by using the US Food and Drug Administration Adverse Event Reporting System database aimed at quantifying the association between the use of IL-1 inhibitors/colchicine in pregnant women and the occurrence of maternal/fetal adverse effects. The reporting odds ratio was used as a measure of disproportional reporting. From the total cohort (40,033 pregnant women), we retrieved 7,620 reports related to neonatal AEs, 2,889 to fetal disorders, 8,364 to abortion, 8,787 to congenital disorders, and 7,937 to labor/delivery complications. Inflammasome-targeted drugs did not present any disproportionate reporting for all these clusters of AEs. TNFα-i confirmed their safety during pregnancy with aROR < 1 for all clusters of AEs except for labor complications. Finally, we performed a systematic review of the current literature. Data from the eligible studies (12 observational studies and 6 case reports; yielding a total of 2,075 patients) were reassuring. We found no major safety issues on malformations risk of inflammasome targeted therapies in pregnancy. However, due to limited data, the routine use of these agents should be considered in pregnancy only if risk benefit assessment justifies the potential risk to the fetus.

Obtaining data without the intervention of a health care provider represents an opportunity to expand understanding of the safety of medications used in difficult-to-study situations, like the first trimester of pregnancy when women may not present for medical care. While it is widely agreed that personal data, and in particular medical data, needs to be protected from unauthorized use, data protection requirements for population-based studies vary substantially by country. For public-private partnerships, the complexities are enhanced. The objective of this viewpoint paper is to illustrate the challenges related to data protection based on our experiences when performing relatively straightforward direct-to-patient noninterventional research via the Internet or telephone in four European countries. Pregnant women were invited to participate via the Internet or using an automated telephone response system in Denmark, the Netherlands, Poland, and the United Kingdom. Information was sought on medications, other factors that may cause birth defects, and pregnancy outcome. Issues relating to legal controllership of data were most problematic; assuring compliance with data protection requirements took about two years. There were also inconsistencies in the willingness to accept nonwritten informed consent. Nonetheless, enrollment and data collection have been completed, and analysis is in progress. Using direct reporting from consumers to study the safety of medicinal products allows researchers to address a myriad of research questions relating to everyday clinical practice, including treatment heterogeneity in population subgroups not traditionally included in clinical trials, like pregnant women, children, and the elderly. Nonetheless, there are a variety of administrative barriers relating to data protection and informed consent, particularly within the structure of a public-private partnership.