Birth outcomes in women who have taken leflunomide during pregnancy

Abstract

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.

Leflunomide use during pregnancy and the risk of adverse pregnancy outcomes

“…A study from OTIS included 64 leflunomide-exposed pregnant women with rheumatoid arthritis in comparison with 108 disease-matched and 78 healthy pregnant women 13. The overall rates of MCM were similar among groups 13. In this study, however, leflunomide was taken within the first 3 weeks after conception, discontinued upon recognition of pregnancy, and 95.3% underwent at least one cholestyramine washout procedure.…”

“…Case reports and small case series have not shown an increased risk of malformations with leflunomide use during pregnancy 5 7 10 11. A study from OTIS included 64 leflunomide-exposed pregnant women with rheumatoid arthritis in comparison with 108 disease-matched and 78 healthy pregnant women 13. The overall rates of MCM were similar among groups 13.…”

Efecto de las resinas secuestradoras de ácidos biliares en los desenlaces cardiovasculares y en los niveles séricos de lípidos

“…En vista de que no pasan a la circulación sistémica, los principales efectos adversos de las RSAB son gastrointestinales, entre los cuales sobresale el estreñimiento 20 . Su perfil de seguridad se ha comprobado en pacientes embarazadas 21 , en quienes no solo se usan como hipolipemiantes, sino como depuradoras de medicamentos fetotóxicos como metotrexate y leflunomida 22 .…”

Novel Therapeutic Approaches to Autoimmune Demyelinating Disorders

“…The main concerns are related to its teratogenic effects in view of the long elimination half-life. A recent study on women with rheumatoid arthritis exposed to leflunomide in pregnancy and treated with cholestyramine confirmed the efficacy of this wash out procedure in preventing birth defects [45].…”