A brief report indicates that for women who undergo the recommended cholestyramine washout, exposure to leflunomide during early pregnancy does not result in significantly increased risk of malformations.

Leflunomide is embryotoxic and teratogenic in animal studies, and is therefore contra-indicated in women who are or who may become pregnant. Because it has a long half-life, women who take it are advised to avoid pregnancy for up to 2 years after stopping treatment with it, or a shorter period if they undergo washout treatment with cholestyramine until blood levels fall below 0.2mg/l. The same washout is used should a woman accidentally become pregnant during treatment, however there is limited information on outcomes after this procedure.

The authors report pregnancy outcomes from women reporting to a North American network of teratology centres pregnancy counselling service. They carried out a prospective cohort study using data obtained by the service over a ten-year period (1999-2009). The cohort included 64 pregnant women with rheumatoid arthritis (RA) who took leflunomide, 108 pregnant women with RA not treated with leflunomide, and 78 healthy pregnant women. Mean time for the last dose of leflunomide was 3.2 weeks after conception, and virtually all (n=61, 95.3%) the women in the leflunomide group had at least one course of cholestyramine washout.

The number of major malformations in the leflunomide group was not significantly greater than that in either of the control groups (3/56 live births or 5.4% vs. 4.2% and 4.2%, p = 0.13). It was similar to that expected in the general population (3 to 4%).  Infants in both RA groups were born earlier and smaller than healthy controls, however after adjustment for confounding factors there was no significant difference between those exposed and controls. 

The authors conclude that in women who are taking leflunomide during early pregnancy, their data do not indicate a substantial increase in risk of adverse pregnancy outcomes for those who undergo the recommended cholestyramine washout procedure. They note that the number exposed is relatively small, but comment that they did not find any consistent pattern of abnormalities in exposed infants.