Biologics During Pregnancy and Breastfeeding Among Women With Rheumatic Diseases: Safety Clinical Evidence on the Road.

Asmaa Beltagy,Laura Trespidi,Pier Luigi Meroni,Azin Aghamajidi,Wally Ossola

doi:10.3389/fphar.2021.621247

Abstract

Females are generally more affected by autoimmune diseases, a fact that underlines the relationship with pregnancy and the safety of anti-rheumatic drugs in pregnancy and lactation. Biologic therapies are increasingly prescribed to treat and maintain remission in a significant number of systemic autoimmune rheumatic diseases. The experience with the use of biologics during gestation is extremely lacking because of the observational nature of the available studies and the difficulty in designing proper clinical trials in pregnancy. Among the studied biologics, more information was published on TNFα inhibitors and, in particular, on their potential passage through the placenta and impact on the fetus. Currently, a fragment of anti-TNFα monoclonal IgG, certolizumab pegol, is considered safe with almost no placental transfer. Subsequent observations are suggesting a comparable safety for the soluble TNFα receptor etanercept. Another biologic, eculizumab, the anti-C5a antibody used to treat complement-mediated microangiopathies, is also considered safe due to the unique engineered IgG2/4κ formulation that limits its passage through the placental barrier. Still, long-term data about children born to women treated with biologics in pregnancy are not attainable. Data on breastfeeding are currently available for several biologics. This article reviews the literature available about which drugs are considered safe during pregnancy and lactation, which are not, and on future prospects.

Highlights

Autoimmune diseases affect around 3%–5% of the population
We review the literature available concerning what is considered safe during pregnancy and lactation, what is not, and the future prospects
Another anti-B cell therapy, belimumab, which is a fully human IgG1 monoclonal antibodies (mAbs) directed against the soluble form of the BAFF was approved by the FDA in 2011 for use in adult autoantibody-positive moderately active systemic lupus erythematosus (SLE) (US Food and Drug Administration, 2019c)

Summary

INTRODUCTION

Autoimmune diseases affect around 3%–5% of the population. The prevalence is high for some diseases like rheumatoid arthritis (RA) representing ≈0.5%–1% and low for other diseases like systemic sclerosis (≈0.04%) (Jacobson et al, 1997; Cooper and Stroehla, 2003; Gabriel and Michaud, 2009; Schirmer et al, 2012). While this database and a case series reported a high percentage of spontaneous abortions (Hoeltzenbein et al, 2016; Weber-Schoendorfer and Schaefer, 2016), data from a smaller Japanese safety study did not find an increase in abortion rates or birth defects (Nakajima et al, 2016) It is recommended, by the EULAR, BSR-BHPR and ACR guidelines, that tocilizumab should be stopped prior to conception and during pregnancy though harm to the fetus is unlikely with unintentional exposure. The BSR-BHPR recommendations specified that rituximab should be stopped 6 months preconception (Flint et al, 2016) Another anti-B cell therapy, belimumab, which is a fully human IgG1 mAb directed against the soluble form of the BAFF was approved by the FDA in 2011 for use in adult autoantibody-positive moderately active SLE (US Food and Drug Administration, 2019c). Refractory LN Stolyar et al (2020) Refractory NPSLE Pamfil et al (2015) Refractory IHA and thrombocytopenia Fanouriakis et al (2019) ANCA associated vasculitis Yates et al (2016) DM Oddis et al (2013) SS Ramos-Casals et al (2020) RA-ILD Dai et al (2020) IgG4-RD Brito-Zerón et al (2016) Add-on therapy in LN Ward and Tektonidou (2020)

Humanized mAb

Findings

DISCUSSION