Maternal Biologics for Inflammatory Disease Not Tied to Congenital Abnormalities

By Lisa Rapaport

April 06, 2020

(Reuters Health) - Women with inflammatory systemic diseases who take biologics during pregnancy are not at increased risk for preterm delivery or congenital abnormalities after accounting for underlying disease, a systematic review and meta-analysis suggests.

"When we combined findings from studies that have accounted for underlying disease, we found no association between biologic use during pregnancy and outcomes of congenital anomalies, preterm deliveries and infant infections," said senior study author Mary De Vera, an assistant professor at the University of British Columbia Faculty of Pharmaceutical Sciences in Vancouver.

"We could not arrive at conclusions for other perinatal outcomes," De Vera said by email. "Nonetheless, this study does add further evidence to inform decisions on weighing the benefits and harms of biologics during pregnancy, which women should discuss with their physicians."

Overall, 24 studies were included in the meta-analysis. Nineteen studies examined TNF inhibitors only, and five included non-TNF inhibitor biologics.

Meta-analyses of crude risk estimates resulted in pooled odds ratios (OR) for the association of biologic use during pregnancy and the following respective outcomes: congenital anomalies (1.30, 95% CI: 1.02, 1.67), preterm birth (OR 1.61, 95% CI: 1.37, 1.89), and low birth weight (OR 1.68, 95% CI: 1.21, 2.31).

However, in pooled analyses of adjusted risk estimates, the association between biologics use during pregnancy in disease-matched exposed and unexposed pregnant women was no longer statistically significant for congenital anomalies (adjusted OR 1.18, 95% CI: 0.88, 1.57).

Researchers looked at several other outcomes and found no association between biologics use during pregnancy and stillbirth or infant infections. They lacked sufficient data to determine pooled risk for infants born small for gestational age or for maternal infections.

Uncontrolled disease activity prior to conception and disease flares during pregnancy represent the greatest risks to maternal and infant outcomes, the study team writes in Rheumatology. Biologics, particularly those targeting TNF, are increasingly used among pregnant patients to minimize disease flareups.

The current analysis is the largest systematic review and meta-analysis to date to examine the potential maternal and neonatal risks associated with anti-TNFs, the study team notes.

Still, the results highlight a need for subsequent studies to better control for potential confounding, especially as it relates to disease activity, as well as increased consistency and transparency in reporting of confounder selection and methodological approaches, the study authors conclude.

"The studies available in literature and analyzed in this meta-analysis did not use the same criteria to design the study and to evaluate the outcomes," said Dr. Laura Andreoli, an associate professor of rheumatology at the University of Brescia, in Italy, who was not involved in the study.

This made it difficult to summarize the data and obtain robust results, Dr. Andreoli said by email. It also wasn't possible to differentiate between the impact of drugs and the impact of disease activity because this information wasn't present in the studies.

Other biologics might have different pregnancy outcomes, Dr. Andreoli added.

"The present study speaks about biological exposure but it should be kept in mind that most of the studies were on the TNF inhibitors, which is only one class of biologics used in systemic inflammatory diseases," Dr. Andreoli said. "Further studies should add more information on other classes of biological drugs."

SOURCE: Rheumatology, online March 2, 2020.