The use of TNF inhibitors during pregnancy is not associated with worse fetal or obstetric outcomes

According to new research at ACR Convergence 2023, the annual meeting of the American College of Rheumatology (ACR), use of tumor necrosis factor inhibitors during pregnancy is not associated with worse fetal or obstetric outcomes and may reduce the risk of serious maternal infections during pregnancy ( Abstract #0477).

Tumor necrosis factor (TNF) inhibitors such as adalimumab and infliximab are often prescribed for inflammatory forms of arthritis that have not improved with other treatments. Although research shows the drugs are safe during pregnancy, many women stop taking them for fear of harming the fetus. Unlike other medications used for inflammatory arthritis, such as methotrexate, which can cause serious fetal complications, TNF inhibitors are not known teratogens (an agent that causes abnormalities after fetal exposure during pregnancy).

To further test the safety of persistent TNF inhibitors during pregnancy, Anna Molto, MD, PhD, HDR, a rheumatologist and researcher at Cochin Hospital in Paris, France, and her colleagues used data from a nationwide French health insurance database to create a ​​to emulate a randomized database. clinical trial (RCT). This type of research relies on observational data to conduct a study when a gold standard RCT may not be ethical or feasible.

The researchers identified more than 2,000 women treated with TNF inhibitors for rheumatoid arthritis (579 patients) or spondyloarthritis (1,503 patients) between 2008 and 2017. Each had a singleton pregnancy, with 1,497 (72%) stopping treatment when they learned they were pregnant. The average age of the women at the start of pregnancy was 31 years±5 years and the average duration of illness was 4 ±5 years.

The results showed no statistically significant difference in poor obstetric, fetal or infant outcomes, including spontaneous abortion (a loss of pregnancy naturally before twenty weeks of gestation), medical termination of pregnancy, preeclampsia or eclampsia, gestational diabetes, premature birth, small birth weight or serious birth defects.

Interestingly, women who continued to use TNF inhibitors were less likely to be hospitalized for serious infections during pregnancy during six weeks postpartum compared to those who stopped treatment (0.2 versus 1.3 percent, respectively). Molto says this finding was the most surprising.

“Although we had assumed that pregnancy outcomes would be at least comparable in both groups, we did not expect that there would be a lower risk of maternal infections in patients who continued TNFi, as the risk of infection is known to be higher with these treatments” , she says. She speculates that the finding may be due to lower concomitant use of corticosteroids, but does not yet have results to confirm her theory.

Regarding the overall study results, Molto says: “These data add to the increasingly reassuring data on the use of TNFi during pregnancy. And most importantly, if a rheumatologist is considering stopping a TNFi during pregnancy because of the risk of infection, this study suggests that this may not be justified.”

Molto acknowledges the limitations of relying on claims data, noting that disease activity cannot be measured, but also points out that the use of a national database ensures that “all French participants are included, [thereby avoiding] selection bias.”

The next step, Molto says, is to test the hypothesis in a randomized controlled trial.

This study was carried out thanks to the funding program of the French Ministry of Health.