Background: The ECCO pregnancy guideline provides recommendations regarding anti-TNF treatment during pregnancy that apply to all anti-TNF types. However, in our prospective cohort we found that women using adalimumab (ADA) had lower anti-TNF drug levels in cord blood than women using infliximab (IFX). We aimed to develop a stopping model for women using anti-TNF during pregnancy that can be used in clinical practice.
Methods: Women with IBD were prospectively enrolled at our preconception outpatient clinic from Dec '08 until Jul '16 and were counseled according to the ECCO pregnancy guideline. During bimonthly visits, information on disease activity, medication use, weight gain and complications were recorded. If patients were in remission 6 months before conception until gestational week 20; anti-TNF treatment was stopped at week 22–24. At birth, anti-TNF was measured in cord blood and considered of low risk for the newborn when below 3 μg/mL. A multiple linear regression was performed to determine independent predictors of the anti-TNF level in cord blood. In addition, a linear model was developed to predict anti-TNF cord blood drug level at birth.
Results: In total, 320 live births were documented of which 131 were exposed in utero to anti-TNF (73 IFX/58 ADA) born to 103 women (84 (82%) CD, 18 (17%) UC, 1 (1%) IBDU). Concomitant treatment with thiopurines was more often used with IFX (n=29;40%) than with ADA (n=5;9%) (p=0.0001). Median anti-TNF stop week was the same for IFX and ADA: respectively 23.0 (IQR 21.0–31.5) and 23.0 (IQR 22.0–37.0) (p=0.56). There was a trend towards more relapses during pregnancy in the ADA group compared to the IFX group, however, this difference was not statistically significant. There were 94 cord blood samples obtained (52IFX, 42ADA). At birth, median anti-TNF cord blood was significantly higher in IFX users (4.9 μg/mL (IQR 1.9–14.7)) than ADA users (1.1 μg/mL (IQR0.4–37.0)) (p=0.0001) and the median maternal anti-TNF was higher in IFX users (1.7 μg/mL (IQR0.4–6.9)) than ADA users (0.6 μg/mL (IQR0.3–3.6) (p=0.05). The multiple linear regression model demonstrated that 2 variables had a significant influence on anti-TNF cord blood level, namely: type of anti-TNF and gestational anti-TNF stop week. In the final model, the optimal time to stop anti-TNF, defined as gestational anti-TNF stop week leading to a cord blood level of 3 μg/mL, was 24,6 weeks for IFX and 36,8 weeks for ADA (Fig. 1).
Conclusions: These results suggest that the continuation of ADA up till the first half of the 3th trimester does not lead to high anti-TNF cord blood levels.