Anti-TNF Therapy in Pregnant Women With Inflammatory Bowel Disease: Effects of Therapeutic Strategies on Disease Behavior and Birth Outcomes

Abstract

Discontinuation of anti-TNF before gestational week 30 did not increase the risk of relapse in the third trimester. Relapse and continuation of anti-TNF throughout pregnancy were each independently associated with lower birth weight, a marker associated with long-term adverse outcomes.

Biologics for Inflammatory Bowel Disease and Their Safety in Pregnancy: A Systematic Review and Meta-analysis

“…For the metaanalysis, 68 studies comprising 922 women were excluded for the earlier-mentioned reasons, leaving 48 studies with 6963 patients to be included here (Supplementary Table 1). 17,22,23,25,35, Unless specified in Supplementary Table 1, a standard dose of biologics was administered (Supplementary Table 4), although standard dosing is frequently not followed in clinical settings to optimize the clinical response. Because we did not identify any large cohort with more than 600 women with IBD comprising all pregnancy adverse outcomes investigated (disease-specific background population for comparison with our data), 3 published cohorts were selected accordingly.…”

“…Subgroup analyses identified a significantly greater prevalence of preterm birth in patients exposed to VDZ (P ¼ .005), but not for UST (P ¼ .912) as compared with TNF inhibitors, although these data should be interpreted with caution because of limited data available. No relationship was found between concomitant thiopurine use and the prevalence of preterm birth in 21 studies reporting the number of participants receiving thiopurine 17,23,25,38,[41][42][43][45][46][47]50,54,56,58,59,61,[68][69][70][71]74 (slope, 0.067; 95% CI, -0.192 to 0.327). No relationship between the risk of preterm birth and the percentage of participants with disease activity at conception were identified in 20 studies 17,23,25,38,40,41,43,50,[53][54][55][56]58,59,62,64,65,68,69,74 (slope, 0.233; 95% CI, -0.134 to 0.601).…”

“…No relationship was found between concomitant thiopurine use and the prevalence of preterm birth in 21 studies reporting the number of participants receiving thiopurine 17,23,25,38,[41][42][43][45][46][47]50,54,56,58,59,61,[68][69][70][71]74 (slope, 0.067; 95% CI, -0.192 to 0.327). No relationship between the risk of preterm birth and the percentage of participants with disease activity at conception were identified in 20 studies 17,23,25,38,40,41,43,50,[53][54][55][56]58,59,62,64,65,68,69,74 (slope, 0.233; 95% CI, -0.134 to 0.601). The overall pooled prevalence of preterm birth was 9% (95% CI, 7%-11%; I 2 ¼ 89.9%) with biologics use in pregnancy, comparable with a rate of preterm birth of 10% in a cohort of 1960 women with IBD including active disease 81 and 11% in the background population.…”

“…Many clinicians discontinue biologic therapy before the third trimester to lower levels of medication in cord blood. 22,23 Recent studies, however, have shown that a longer duration between the last dose of TNF inhibitors and delivery does not always correlate with lower infant cord blood levels because several factors influence drug metabolism in the fetus. 24,25 The implications of these data are not yet fully understood.…”

Commentary: safety of anti‐TNF use in pregnancy

“…There remains controversy about the timing of giving live vaccines to infants exposed in utero to anti‐TNFs; overall current guidelines suggest waiting 6‐12 months before giving live vaccines. Stopping anti‐TNF earlier in pregnancy in women in remission does not appear to be associated with an increased relapse rate, so may be appropriate in well‐controlled disease.…”