Vedolizumab seems safe during pregnancy

Last Updated: 2019-04-08

By Marilynn Larkin

NEW YORK (Reuters Health) - Pregnant women with inflammatory bowel disease (IBD) who take vedolizumab (VDZ) seem to be at low risk for adverse events, but a higher rate of spontaneous abortions in those taking the drug argue for a larger study with longer follow-up, researchers say.

"Management of IBD during pregnancy is challenging, as it strongly influences the course of pregnancy," Dr. Ariella Bar-Gil Shitrit of the Shaare Zedek Medical Center in Jerusalem told Reuters Health by email. "We present novel and promising results" regarding VDZ's safety.

Dr. Shitrit and colleagues analyzed data from 390 women with IBD (mean age, 30), including 24 treated with VDZ (mean years of disease, 9.1), 82 treated with anti-tumor necrosis factors (mean years of disease, 8.3) and 284 who received conventional therapy with 5-aminosalicylic acid agents and thiopurines (mean years of disease, 7.7).

Disease patterns were similar across groups, except that the VDZ group were not naive to biological treatment. There were no significant differences between the groups regarding gravidity and parity.

All women in the VDZ group were exposed to the treatment for at least three months before conception and continued throughout the third trimester, except for one who decided to stop treatment in week 14 without consultation. All but one were on VDZ monotherapy; that patient, who received salazopyrin combination, had an induced abortion due to a neural tube defect. The second documented induced abortion was voluntary.

As reported online March 29 in The American Journal of Gastroenterology, the rate of preterm births was comparable in all three groups.

Five spontaneous abortions (20.8%) were documented in the VDZ group: three in women with active disease at conception, and two in a 45-year-old woman with active Crohn's disease who had undergone in vitro fertilization.

All pregnancies that continued after the first trimester resulted in live births.

In women with Crohn's disease, perianal disease was a significant predictor for a less favorable pregnancy outcome (odds ratio, 0.19), whereas VDZ treatment seemed associated with a nonsignificant favorable pregnancy outcome (OR, 3.3).

The only predictor independently and significantly associated with lower favorable pregnancy outcome in all groups was active disease during pregnancy (OR, 0.308).

Additional analyses showed the rate of conceptions that occurred during a flare was higher in the VDZ group. Further, the rate of new-flare onset after exclusion of those who conceived during a flare was significantly lower for VDZ compared to the other groups, as was the number of salvage steroid treatments.

The team soon will release "supporting and exciting new data in a much larger retrospective European cohort, in which we strengthen the conclusion regarding the safety of vedolizumab during pregnancy," Dr. Shitrit said. Her team also is launching a prospective registry of pregnant women with IBD "to evaluate in a large cohort the safety of various biological agents during pregnancy and their effect on the offspring."

Dr. Lisa Malter, a gastroenterologist specializing in IBD and associate professor of medicine at NYU School of Medicine in New York City, told Reuters Health that the study "comes at an interesting time," as a call to action to address medication safety in pregnancy was recently published (http://bit.ly/2G7zMIi), as was the American Gastroenterological Association Institute's IBD in Pregnancy Clinical Care Pathway paper (http://bit.ly/2G7RsmT).

"This study is the first prospective evaluation of vedolizumab in pregnancy, which is an important next step in continuing to assess the safety of this medication during this fragile time for female patients," she said by email. "This data is consistent with the previous retrospective data we have that demonstrated reduced flares and steroid use when vedolizumab was used to treat pregnant patients."

"The most important factor that impacts pregnancy outcomes in IBD patients is the disease activity at the time of conception," she said. "We favor controlled disease utilizing most of the therapies on the market for IBD - including vedolizumab - over lack of control and no medication or non-efficacious medication."

"This study confirms all the themes we consider when treating pregnant patients," she said. "We have been using vedolizumab in pregnancy and this data confirms that it is a reasonable choice. "

"The only signal here was a 20% risk of spontaneous abortions," she added. "However, all patients had active disease at conception, which is an independent risk factor for poorer outcomes in pregnancy and 2/5 cases of abortions were in a 45-year old patient undergoing IVF with active disease. This finding is not worrisome, but rather confirms that disease under control is most important to the success of the pregnancy."

Data for the study were derived from a Takeda Pharmaceuticals-supported patient registry. Dr. Shitrit and two coauthors receive fees from the company.

SOURCE: http://bit.ly/2G1fChG

Am J Gastroenterol 2019.