TNF inhibition beyond 24 weeks: How safe in pregnant mums?

Continued treatment with tumor necrosis factor (TNF) inhibitors after 24 weeks of pregnancy appears safe and is associated with lower chances of maternal inflammatory bowel disease (IBD) relapse, without increasing adverse neonatal outcomes, new research suggests.

French women with IBD who received TNF inhibitors from weeks 24–32 of pregnancy experienced adverse birth outcomes at lower – or the same –  rates as those who stopped anti-TNF treatment before week 24, said lead author Dr Antoine Meyer from the Hôpital Bicêtre & Université Paris-Saclay, Le Kremlin Bicêtre in Paris, France.

Moreover, there were fewer premature deliveries with continued TNF inhibitors beyond 24 weeks. The rates of Cesarean sections, stillbirths, serious infections, and small or large weight for gestational age were comparable between the two groups.

“We found no increased risk from TNF inhibitors,” reported Meyer. “Our results support the recommendation for anti-TNF therapy throughout pregnancy in women with IBD.”

Differences of opinion

TNF inhibitors, such as infliximab and adalimumab, are common second-line therapies for IBD, including Crohn’s disease and ulcerative colitis. However, guidelines differ in terms of TNF inhibitor recommendations during pregnancy.

While the North American guidelines advise the continuation of anti-TNF therapy throughout pregnancy, the European guidelines call for the cessation of anti-TNF therapy at about 24 weeks of gestation in women who are in stable remission.

Meyer and team examined the records of women with IBD  from France’s national health data system, with pregnancies exposed to TNF inhibitors. [Ann Intern Med 2022;175:1374-1382]

A total of 5,293 pregnancies were included in the study. There were 2,890 women who stopped anti-TNF treatment before 24 weeks of pregnancy and 2,403 women who continued beyond 24 weeks. Their pregnancy outcomes were compared.

There were no major differences between the two groups at baseline. About 80 percent had Crohn’s disease, with a median duration of IBD of 6 years. Among those who took an anti-TNF therapy during pregnancy, 50 percent took infliximab, 47.2 percent adalimumab, 2.5 percent golimumab, and 1.3 percent certolizumab.

Less IBD flare

Women who continued TNF inhibitors beyond 24 weeks were significantly less likely to experience an IBD flare during the remainder of their pregnancy and the 6-month postpartum period (adjusted risk ratio [adjRR], 0.93) and had fewer premature deliveries (adjRR, 0.82).

About 88.3 percent of women who continued anti-TNF therapy after 24 weeks of pregnancy were still on the regimen 6 months after delivery; 71.1 percent of those who had stopped TNF inhibition restarted therapy.

There were 1,013 serious infections during the first 5 years of life, with rates similar between groups (54.2 vs 50.2 per 1,000 person-years for those who continued vs those who stopped anti-TNF therapy).

Children exposed to anti-TNF therapy beyond 24 weeks had a higher rate of ear, nose, and throat infections. Rates of infections at other sites were similar between groups as were bacterial, viral, and opportunistic infections.

Pregnancy outcomes were similar for women with Crohn’s disease relative to ulcerative colitis, as well as those exposed to intravenous vs subcutaneous anti-TNF therapy.

“It is reassuring to know that continuation of anti-TNF therapy during pregnancy is not harmful to the mother or infant, whereas stopping it is associated with adverse events for both,” commented Dr Uma Mahadevan, director of the Colitis and Crohn’s Disease Center at the University of California, San Francisco, US, who is not involved in the study. “This confirmation on a large scale of existing data is important for the clinical management of this vulnerable population.”