Abstract 667: A Safety Assessment of TNF Antagonists during Pregnancy: A Review of the FDA Database
Authors:
J. D. Carter, A. Ladhani, L. Ricca, J. Valeriano, F. B. Vasey
Methods
The US Food and Drug Administration Database was searched for using the keyword “congenital anomaly” for the TNF inhibitors etanercept, infliximab, and adalimumab from the time that each agent became commercially available until December of 2005. Duplicate reports were identified and all available information from the report (including concomitant medications) was recorded.
Results
A total of 41 children with congenital anomalies born to mothers exposed to TNF inhibitors were reported. Among these, 22 were exposed to etanercept, 19 to infliximab, and none to adalimumab. In 24 of the cases (59%) the TNF inhibitor was listed as the only medication. Timing of exposure was not specified in most of the reports. Of the 41 reports, 12 were for congenital heart defects, including atrial and ventricular septal defects, Tetralogy of Fallot, great vessel malformations, and ventricular hypokinesia. Other anomalies included cystic kidney, hypospadius, tracheal sternosis, teratoma, trisomy 21, and hydrocele. Seven (17%) of the congenital anomalies were not specified. Only 1 case met criteria for VATCTERL, a syndrome characterized by multiple diffuse congenital abnormalities (the index case from this site that prompted further investigation in which the mother was treated with etanercept throughout her pregnancy.)
Conclusions
TNF inhibitor exposure during pregnancy may increase the risk of congenital anomaly.
Editorial Comment
Although provocative, this type of survey tends to be uninformative, and may even be misinformative for a number of reasons. First, reporting is voluntary and may not represent the true number of congenital anomalies in the population. Second, there is no denominator of persons exposed without the outcome in order to gauge the magnitude in the population at risk. Third, there is little information about competing risk factors, making the connection between exposure and outcome difficult to support. Finally, the congenital anomalies described tend to be the most common in the population. Only one case of VACTERL was encountered (the index case from the author’s center), and single components of VACTERL (i.e. “cardiac abnormalities”) are too frequently seen in isolation to tie all of them into the same pathogenic mechanism. Alternate epidemiologic methods are required to determine if a causal link between TNF inhibitor exposure and adverse pregnancy outcomes truly exists.
