Rheumatoid arthritis and pregnancy: evolution of disease activity and pathophysiological considerations for drug use

Abstract

It has long been known that pregnancy and childbirth have a profound effect on the disease activity of rheumatic diseases. For clinicians, the management of patients with RA wishing to become pregnant involves the challenge of keeping disease activity under control and adequately adapting drug therapy during pregnancy and post-partum. This article aims to summarize the current evidence on the evolution of RA disease activity during and after pregnancy and the use of anti-rheumatic drugs around this period. Of recent interest is the potential use of anti-TNF compounds in the preconception period and during pregnancy. Accumulating experience with anti-TNF therapy in other immune-mediated inflammatory diseases, such as Crohn's disease, provides useful insights for the use of TNF blockade in pregnant women with RA, or RA patients wishing to become pregnant.

Fig. 1

Mechanisms of feto-maternal tolerance. Pregnancy is a situation of induced immunological tolerance in the mother against the semi-allogeneic fetus. The immunological mechanisms responsible for this state of tolerance consist of local components, triggered by trophoblast-induced changes in uterine cytokine profile, decreased T- and NK-cell function and complement activation. In addition, systemic changes in immune function during pregnancy include progesterone-induced thymus involution, decreased NK-cell activity and a shift towards a more Th2-dominated immune-response pattern. KIR: killer cell immunoglobulin-like receptor; uNK: uterine natural killer cell.

Fig. 2

Evolution of maternal and serum IgG levels during pregnancy [94, 95]. IgG levels of maternal origin in the fetal circulation increase over the course of pregnancy. At the end of gestation, fetal IgG levels exceed those in the maternal circulation, which indicates that the placenta develops an active transport mechanism for IgG molecules. Adapted from Malek A, Sager R, Kuhn P, Nicolaides KH, Schneider H. Evolution of maternofetal transport of immunoglobulins during human pregnancy. Am J Reprod Immunol 1996;36:248–55, with permission from John Wiley & Sons Ltd.

Fig. 3

Active transplacental transport mechanism for IgG. Fc receptors on syncytiotrophoblast cells at the feto-maternal interface bind IgG from the maternal circulation in a pH-dependent way, transport it over the syncytiotrophoblast cells via transcytosis, and release the bound IgG in the fetal circulation.