OBJECTIVE: In preclinical reproductive studies, leflunomide was found to be 
embryotoxic and teratogenic. Women treated with leflunomide are advised to avoid 
pregnancy; those who become pregnant are advised to reduce fetal exposure 
through a cholestyramine drug elimination procedure. The present study was 
undertaken to investigate pregnancy outcomes in women who received leflunomide 
and were treated with cholestyramine during pregnancy.
METHODS: Sixty-four pregnant women with rheumatoid arthritis (RA) who were 
treated with leflunomide during pregnancy (95.3% of whom received 
cholestyramine), 108 pregnant women with RA not treated with leflunomide, and 78 
healthy pregnant women were enrolled in a prospective cohort study between 1999 
and 2009. Information was collected via interview of the mothers, review of 
medical records, and specialized physical examination of infants.
RESULTS: There were no significant differences in the overall rate of major 
structural defects in the exposed group (3 of 56 live births [5.4%]) relative to 
either comparison group (each 4.2%)(P = 0.13). The rate was similar to the 3-4% 
expected in the general population. There was no specific pattern of major or 
minor anomalies. Infants in both the leflunomide-exposed and 
non-leflunomide-exposed RA groups were born smaller and earlier relative to 
infants of healthy mothers; however, after adjustment for confounding factors, 
there were no significant differences between the leflunomide-exposed and 
non-leflunomide-exposed RA groups.
CONCLUSION: Although the sample size is small, these data do not support the 
notion that there is a substantial increased risk of adverse pregnancy outcomes 
due to leflunomide exposure among women who undergo cholestyramine elimination 
procedure early in pregnancy. These findings can provide some reassurance to 
women who inadvertently become pregnant while taking leflunomide and undergo the 
washout procedure.