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

Background: Inflammatory autoimmune diseases are chronic diseases that often affect women of childbearing age. Therefore, detailed knowledge of the safety profile of medications used for management of inflammatory autoimmune diseases during pregnancy is important. However, in many cases the potential harmful effects of medications (especially biologics) during pregnancy (and lactation) on mother and child have not been fully identified. Objective: Our aim was to update the data on the occurrence of miscarriages and (major) congenital malformations when using biologics during pregnancy based on newly published articles. Additionally, we selected several different secondary outcomes that may be of interest for clinicians, especially information on adverse events in the use of a specific biologic during pregnancy. Material and Methods: A search was conducted from 1 January 2015 until 4 July 2019 in Embase.com, Medline Ovid, Web of Science, Cochrane CENTRAL, and Google Scholar with specific search terms for each database. Selection of publications was based on title/abstract and followed by full text (double blinded, two researchers). An overview was made based on outcomes of interest. References of the included publications were reviewed to include and minimize the missing publications. Results: A total of 143 publications were included. The total number of cases ranged from nine for canakinumab to 4276 for infliximab. The rates of miscarriages and major congenital malformations did not show relevant differences from those rates in the general population. Conclusion: Despite limitations to our study, no major safety issues were reported and no trend could be identified in the reported malformations

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

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

Male Sexual Health and Reproduction in Cutaneous Immune-Mediated Diseases: A Systematic Review

Introduction: Information about the possible effects of cutaneous immune-mediated diseases (cIMDs) on male sexual function and reproduction is scarce. Factors known to impair sexual health and reproduction, such as inflammation, medication use, and hypogonadism, can be present in a significant proportion of male patients with cIMD. Objectives: To systematically review the literature for the influence of paternal cIMD on many aspects of male sexual and reproductive health, such as sexual function, reproductive hormones, fertility, and pregnancy and offspring outcomes. Methods: A systematic literature search was performed. The searches combined keywords regarding male sexual function and fertility, pregnancy outcomes, and offspring's health with a list of cIMDs. Results: The majority of the identified studies included patients with psoriasis (22 of 27), and sexual function was the most common outcome of interest (20 of 27). For patients diagnosed with psoriasis, the prevalence of male sexual dysfunction reported in these studies ranged from 34 to 81%. Hypogonadism in patients with psoriasis was reported in 2 of 3 studies. Sperm analysis abnormalities in patients with psoriasis were reported in 3 of 4 studies. No information about the effect of paternal disease on pregnancy and offspring outcomes was identified. Conclusions: Disease activity in psoriasis might play an important role in the development of sexua