Therapeutic infliximab drug level in a child born to a woman with ulcerative colitis treated until gestation week 31

Abstract

A 26 year old woman with ulcerative colitis was treated with regular infliximab (IFX) infusions until gestation week 31, and gave birth to a healthy child at gestation week 37. Maternal IFX trough level was relatively high during the course of pregnancy. In the infant, therapeutic level of IFX was detectable at week 16 after birth, but not at reassessment at week 28. Anti-IFX antibodies were consistently below the detection limit in the patient and in the child. This case illustrates that IFX is transferred through the placenta to the embryo, and may result in therapeutic drug levels in the newborn child despite IFX discontinuation in third trimester 6 weeks prior to delivery. The half life of IFX appeared markedly longer in infants as compared to adults. The safety of IFX beyond the first trimester is unknown, and this case highlights the need for further investigations of maternal transfer of IFX as well as the risks associated with IFX administrations in the second and third trimester.

Safety of TNF-α inhibitors during IBD pregnancy: a systematic review

“…In the early days of biologic treatment for IBD, IFX was reported to be associated with adverse pregnancy outcomes in some case reports [20,21], but not in others [22-27], and in case series where IFX was administered throughout pregnancy to maintain remission in IBD, no harm to the fetus/child was reported [16,19,28-34]. Furthermore, larger and subsequent studies did not report any increased risk for adverse events compared with unexposed IBD pregnancies [12,17,35-49].…”

“…In this systematic review, identifying 17 case reports related to IFX [14,16,20,22,23,29,30,33],[34,40,41,45,47,63-66], 13 case series [12,17,19,28,32,37-39,42,43],[46,67,68], 2 uncontrolled cohort studies [19,36, and 2 controlled cohort studies [48,69] (Table 2), we found the prevalence of pregnancy complications, including preterm delivery, stillbirth, low birth weight, miscarriages, or congenital malformations in children exposed to IFX throughout pregnancy is limited, even after exposure to biologics throughout the third trimester. However, the use of IFX up to week 30 of gestation results in fetal intra-uterine exposure to high IFX levels (up to three-fold higher than in the maternal peripheral blood), which may raise concerns about the long-term effects of IFX on these children, including effects on their immune system [50].…”

The Toronto Consensus Statements for the Management of Inflammatory Bowel Disease in Pregnancy

“…89 Correspondingly, cord blood levels of certolizumab are very low. 90 In contrast, use of infliximab and adalimumab during pregnancy has been shown to result in fetal and cord blood levels that may be up to 4-fold higher than in the maternal peripheral blood, [90][91][92][93][94] and levels were detectable in infants for up to 6 months. 90 However, some studies fail to show measurable levels of anti-TNF agents in children born to mothers treated with these agents.…”

Vaccination Guidelines for Patients With Immune-Mediated Disorders on Immunosuppressive Therapies

“…85,88 Furthermore, routine childhood vaccinations were well tolerated, resulting in no safety concerns or severe AEs. [85][86][87][88][89][90][91] More recently, data from the Pregnancy in Inflammatory Bowel Disease and Neonatal Outcomes (PIANO) registry comparing vaccine responses in infants born of mothers who were exposed to biologic therapies (IFX, adalimumab, vedolizumab, certolizumab pegol, golimumab, natalizumab, or ustekinumab) vs those unexposed during gestation revealed no significant differences in seroprotection rates to the Hib ( 92 Three case reports examined the efficacy of routine childhood immunizations such as tetanus, diphtheria, and HBV among infants exposed to RTX up to the third trimester (last RTX dose at 30-34 weeks' gestation). [93][94][95] Despite all infants exhibiting low 94 or undetectable 93,95 B-cell counts at birth, protective antibody levels were generally achieved following vaccination without serious AEs.…”