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IBD drugs may have no role in birth defects

NEW YORK (Reuters Health) – For pregnant patients with inflammatory bowel disease (IBD), the highest source of risk to the fetus may be the disease itself, and not the drugs taken for it, new data suggest.

In a study designed to assess the safety of immunomodulators and biologic drugs during pregnancy, the medications appeared to have few adverse effects.

“The biggest risk to pregnancy in IBD remains disease activity,” Dr. Uma Mahadevan, a gastroenterologist who led the study at the University of California in San Francisco, told Reuters Health by email.

Dr. Mahadevan presented her results May 21 at the Digestive Disease Week conference in San Diego, Calif.

As advice to practicing physicians, Dr. Mahadevan says, “Women with IBD, even in remission, should be followed as high-risk obstetric patients. Ideally, women should be in remission going into pregnancy.”

She and her colleagues have enrolled 1,115 pregnant women with IBD at 30 U.S. medical centers to study the effects of azathioprine, 6-mercaptopurine, or anti-tumor-necrosis-factor drugs on the women and their children.

The women fall into four categories: 306 unexposed patients who did not take the drugs under study (but who did take mesalamine, steroids, and antibiotics); 204 patients who took 6-MP and azathioprine; 291 patients who took the anti-TNF drugs infliximab, adalimumab, and certolizumab; and 75 who took both the immunomodulators and biologic therapy.

To date, 896 of the women have completed their pregnancies. After adjusting for the effects of IBD itself, there were no increases in rates of spontaneous abortion, congenital anomalies, or stays in the neonatal intensive care unit. Also, there were no significant differences in the babies’ height, weight and development at four, nine, and 12 months of age after adjusting for disease activity.

There was a significantly higher rate of spontaneous abortion and Cesarean section in the anti-TNF group, however, and of preterm birth in women exposed to those drugs plus the biological response modifiers.

Looking at the specific diseases, Crohn’s Disease patients did not suffer increased adverse drug effects, but babies of patients with ulcerative colitis exposed to both of the drug classes under study had higher rates of any complication, including preterm birth, low birth weight, and neonatal intensive care.

There was no overall increase in infant infections from drug exposure, but when the researchers removed certolizumab from the anti-TNF and the anti-TNF plus biologics group, infections increased at 1 year of age in the combined drug group (relative risk 1.38).

Several new IBD medications have been introduced in the last decade and their safety during pregnancy is not yet well understood, said Dr. Jerrold Turner of the University of Chicago, who moderated a press conference at the meeting. “Understanding the toxicity profiles of the medications not just over a week or a month or a year but over a lifetime will be critical.”

Dr. Mahadevan said she advises doctors that they can continue azathioprine and biologic therapy with low-risk pregnancies and lactation.

“Given the suggestion of an increased risk of infections on combination therapy, if the azathioprine used in combination with a biologic is purely for immunogenicity, I stop the azathioprine and continue the biologic to minimize infectious risk,” she added.

“For infliximab, I give the last dose at week 32 of gestation and then after delivery. For adalimumab, this is more difficult as it is dosed every two weeks. I generally give the last dose around week 36-37. As certolizumab has minimal placental transfer, I dose on schedule through pregnancy,” Dr. Mahadevan says.