NEW YORK (Reuters Health) – Birth defects are uncommon in offspring of women exposed to leflunomide before conception or in the first trimester of pregnancy, according to a report in the February 3rd online Arthritis & Rheumatism.
“From the available data, we have not yet demonstrated that leflunomide exposure very early in gestation followed by the washout procedure is associated with a measurable increased risk of major birth defects or a pattern of defects,” Dr. Christina Chambers from University of California, San Diego, La Jolla, California told Reuters Health in an email. “So, although pregnancy should continue to be avoided in women taking this drug, in the event of an unplanned but wanted pregnancy, these data can be reassuring.”
Based on earlier animal studies, leflunomide has been assigned a pregnancy category X in the U.S. FDA classification system, and women on therapy are advised to use contraceptive methods and avoid pregnancy or, if exposed inadvertently or planning pregnancy, to undergo a drug elimination procedure.
Dr. Chambers and colleagues describe pregnancy outcomes in 45 women prospectively enrolled in the Organization of Teratology Information Specialists (OTIS) study who had exposure to leflunomide either during pregnancy (16 women) or only prior to conception (29 women).
All but 2 pregnancies (both among women exposed only prior to conception) resulted in live born infants.
Two newborns with major malformations were born to women in the pregnancy-exposed group, and there were no major congenital malformations in the preconception exposure group.
Among 35 infants that received the dysmorphology examination, 50% in the pregnancy-exposed group and 42.9% in the preconception group had 3 or more minor anomalies.
“None of these specific defects were reported in the previously published cohort study nor are they similar to those reported in the animal studies,” the researchers note. “In addition, there is a potential known alternative etiology, unrelated to leflunomide exposure, for at least some of the defects observed.”
“The OTIS Research Group at UCSD is continuing to monitor pregnancies with leflunomide exposure and although the exposure in pregnancy is quite rare, we will continue to evaluate for any evidence of an increased risk for a specific pattern of malformation,” Dr. Chambers said.
Dr. Chambers added, “Even for more common exposures in pregnancy, it is virtually impossible to deem something completely safe. Usually, the best we are able to say is that a specific medication at a specific time in gestation does not appear to increase the risk above a certain level. However, from a practical standpoint, it is important to recognize that all pregnancies carry a risk for adverse outcomes, and the risk for major birth defects is about 3%.”
Source(s):
Pregnancy outcome in women exposed to leflunomide before or during pregnancy
Arthritis & Rheumatism, 3 February 2012
