Cokkie van der Ent

Effects of Discontinuing Anti–Tumor Necrosis Factor Therapy During Pregnancy on the Course of Inflammatory Bowel Disease and Neonatal Exposure

BACKGROUND & AIMS We assessed the course of inflammatory bowel disease (IBD) among pregnant women who stopped taking anti-tumor necrosis factor (TNF) agents. We also analyzed levels of anti-TNF agents in cord blood samples. METHODS We followed 31 pregnancies in 28 women with IBD between April 2006 and April 2011 who were treated with anti-TNF agents (18 received infliximab, and 13 received adalimumab) during pregnancy. We used enzyme-linked immunosorbent assays to measure levels of anti-TNF agents in cord blood collected from 18 newborns (12 whose mothers took infliximab, and 6 whose mothers took adalimumab). RESULTS Among the patients taking infliximab, 12 (71%) discontinued treatment before gestational week 30; all patients remained in remission. All the patients taking adalimumab discontinued treatment before gestational week 30; two patients had relapses of IBD. There were 28 live births, 1 miscarriage among patients taking infliximab (at gestational week 6), and 2 miscarriages among patients taking adalimumab (at weeks 6 and 8); there were no congenital malformations. The mean cord blood level of infliximab was 6.4 ± 1.6 μg/mL; it was significantly lower among women who received the drug 10 weeks or less before delivery (2.8 ± 1.1 μg/mL) than those who received infliximab closer to delivery (10 ± 2.3 μg/mL; P = .02). Adalimumab was detected in 5 samples of cord blood (mean concentration, 1.7 ± 0.4 μg/mL); 1 cord blood sample from a woman who discontinued the treatment at gestational week 22 had an undetectable level of the drug. CONCLUSIONS Discontinuation of anti-TNF therapy appears to be safe for pregnant women with quiescent IBD. However, these drugs are still detected in cord blood samples.

Sa2034 Early Discontinuation of Infliximab During Pregnancy Reduces Neonatal Exposure to Infliximab and is Safe for the Inflammatory Bowel Disease Patients

tomy. The estimated clearance of infliximab with induction IFX infusions was 2.8 days (range: 1.3-6.2). At 30 wks, 8/13 patients were treatment failures with steroid-dependent clinical and endoscopic activity, 3 of whom had colectomy; 5 patients achieved steroid-free remission. Low titre ATI with drug was detected in 5 patients during induction, 4 of whom had detectable serum IFX and steroid-free remission at 30 wks. Conversely, undetectable induction serum IFX with or without low titre ATI was associated with the development of high titre ATI and treatment failure with or without colectomy. Conclusions: Severe UC patients show accelerated clearance of infliximab that was associated with undetectable serum IFX and failure in over half of patients. Accelerated clearance of drug was not associated with concurrent immune complex formation but, as reported previously, may relate to low serum albumin. Although the mechanism for accelerated clearance requires further study, these findings suggest that three-dose induction of 5 mg/kg infliximab at 0, 2 and 6 weeks may not be the optimal dose/interval strategy for avoiding colectomy in all acute UC patients.