Low levels of TNFi’s were found in the cord blood samples. Adalimumab was detectable in 48% of cord blood samples, with a median concentration of 0.5 µg/mL and a median concentration ratio of 0.062. Etanercept was not detected in any cord blood samples. Infliximab was detectable in 57% of cord blood samples, with a median concentration of 0.4 µg/mL and a median concentration ratio of 0.012. Certolizumab pegol was detectable in 5.9% of cord blood samples, with a median concentration of 0.3 µg/mL and a median cord/maternal concentration ratio of 0.010.
Following the EULAR guidance led to no or low concentrations of these agents in cord blood. These findings indicate that newborns whose mothers continued to take a TNFi during pregnancy are most likely not immunologically compromised and are unlikely to have ill effects from these agents.
Study Strengths & Limitations
All patients in the analysis by Ghalandari et al. were treated at the same healthcare facility by the same healthcare practitioners. Therefore, the differences between healthcare practitioners were minimal. Patient data were retrieved directly from the study patients.
A limitation of the current study is that peak and trough values of maternal TNFi concentrations were not measured. Also, the concentration ratios calculated are less accurate than those that would have been calculated in a pharmacokinetic study. Another limitation: The majority of patients using etanercept switched or stopped the agent earlier than the EULAR recommended stop time of 32 weeks, which may have affected the results.
Detected TNFi concentrations in cord blood were much lower than maternal concentrations during active use. The potential harmful effects of low TNFi concentrations in cord blood are unknown and require further study. If the TNFi concentrations in cord blood are determined to be clinically important, then stopping infliximab and adalimumab at an earlier gestational age than what EULAR currently recommends may be appropriate.
Michele B. Kaufman, PharmD, BCGP, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.
References
- Ghalandari N, Kemper E, Crijns I, et al. Analysing cord blood levels of TNF inhibitors to validate the EULAR points to consider for TNF inhibitor use during pregnancy. Ann Rheum Dis. 2021 Sep 7;annrheumdis-2021-221036. Online ahead of print.
- Skorpen CG, Hoeltzenbein M, Tincani A, et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis. 2016 May;75(5):795–810.
- Hazes JMW. Preconceptional counselling in active rheumatoid arthritis (PreCARA). ClinicalTrials.gov. 2016 Apr 28.
- Smeele HT, Rhöder E, Wintjes HM, et al. Modern treatment approach results in low disease activity in 90% of pregnant rheumatoid arthritis patients: The PreCARA study. Ann Rheum Dis. 2021 Jul;80(7):859–864.
