Safety and efficacy of immunomodulators and biologics during pregnancy and lactation for the treatment of inflammatory bowel disease

Abstract

Introduction The inflammatory bowel diseases (IBD) are chronic, idiopathic, inflammatory conditions of the gastrointestinal tract that peak in incidence during the reproductive years. Therefore, the safety of IBD medications during pregnancy and lactation is of significant interest to many patients. Unfortunately, the current pregnancy labeling used by the United States Food and Drug Association (FDA) is often misinterpreted and may mislead healthcare providers and their patients to believe that risk increases from category A to B to C to D to X which, in fact, is not the case. In addition, the FDA categories do not always distinguish between risks based on human versus animal data or between differences in frequency, severity, and type of fetal developmental toxicities. Thus, providers should not rely solely on the FDA category labels when making medication choices in pregnant and lactating women and should instead be familiar with the primary safety data for the medications they prescribe. Areas Covered This article will discuss general safety data and safety classifications for medication use in pregnancy. It will also provide an in-depth review of the available safety data during pregnancy and lactation for the more potent immunosuppressants used to treat IBD: the immunomodulators and biologics. Lastly, it will include the authors’ expert opinions on the use of these medications during these critical periods. Expert Opinion The benefit-to-risk ratio for most immunomodulators and biologics used in the treatment of IBD favors medication continuation during pregnancy. Certain immunomodulators, however, can cause extreme fetal harm and should be used with caution in all individuals of reproductive potential. While human safety data regarding teratogenesis and some data on pregnancy outcomes exist for most IBD medications, long-term follow-up studies of children and young adults exposed to these drugs in utero are lacking. These studies are needed to determine if these drugs are of sufficiently low risk to be considered safe.

Inflammation in Complicated Pregnancy and Its Outcome

“…Because the peak incidence of the disease occurs between 20 and 40 years of age, this is of great concern for women in their reproductive years, especially the effect of IBD medications on the developing fetus. 119 It is thought that as long as IBD is under control prior to conception, the disease will remain in a state of quiescence throughout pregnancy. 120 Disease activity at conception has been associated with preterm births, LBW, and fetal loss.…”

“…Prospective studies have shown that GDM treatment can reduce PreE by 30% and a recent case report has shown that dietary management in addition to insulin therapy can resolve angiogenic imbalance and improve pregnancy outcomes. 119 To optimally select patients for clinical trials, it would be useful to have rapid, reliable tests for detecting intra-amniotic inflammation and/or microbial invasion of the amniotic cavity. Combs et al suggest several different tests, including 16 rDNA polymerase chain reaction (PCR), rapid bedside tests for IL-6, MMP-8, and other inflammatory mediators, and proteomic profiling of amniotic fluid or cervicovaginal secretions.…”

Mode of Childbirth and Long-Term Outcomes in Women with Inflammatory Bowel Diseases

“…Reassuringly, apart from a weak increase in incidence of preterm births and low birth weight babies, neither CD nor UC are associated with other adverse pregnancy or health outcomes 6-15 . Furthermore, most of the current medications for treatment of IBD may be safely continued during pregnancy and in the post-partum period 10, 16-18 .…”