Antirheumatic Drugs and Pregnancy: A Primer

From Medscape Rheumatology > Ask the ExpertsAntirheumatic Drugs and Pregnancy: A Primer Robert I. Fox, MD, PhD Posted: 12/13/2011 Question In a patient taking methotrexate (MTX) for psoriatic arthritis or rheumatoid arthritis, how long of a washout period should be considered before she can safely attempt to conceive? Is there any published information on the long-term use of MTX being related to birth defects or abnormal deliveries once MTX is stopped? Response from Robert I. Fox, MD, PhD Chief, Rheumatology Clinic, Scripps Memorial Hospital, La Jolla, California Women taking methotrexate for arthritis should discontinue this drug and use contraception for at least 3 months before conception based on the recommendations of the American College of Rheumatology. There have been several published studies in the older literature that suggest that for structural anomalies, the critical time interval off methotrexate is from 8 to 10 weeks after the first day of the last menstrual period and the critical dose associated with fetal defects is ≥ 10 mg/week. MTX is a potent abortifacient, and its use during pregnancy is associated with multiple skeletal abnormalities. Methotrexate-induced developmental toxicity is strongly related to when the drug is given and also the dose. There is no evidence that the duration of treatment or the "net total dose" is a predictor of miscarriage or fetal malformation. What About Other Antirheumatic Therapies? Several other examples of antirheumatic therapy and pregnancy are reviewed below: Hydroxychloroquine crosses the placenta. However, there does not appear to be fetal toxicity with hydroxychloroquine doses used for the treatment of connective tissue disorders. Leflunomide (LEF) was teratogenic in animal models, and effective contraception is essential for women of childbearing potential for whom LEF is prescribed. LEF is considered by the US Food and Drug Administration as a "Category X" drug in terms of the risks associated with its use in pregnancy. LEF-treated patients should "wash out" drug using cholestyramine and then wait at least 90 days before attempting pregnancy. Infliximab: According to the manufacturer's prescribing information, infliximab should be given to a pregnant woman only if clearly needed. This information is available at http://www.remicade.com/remicade/assets/HCP_PPI.pdf. However, no maternal toxicity, embryotoxicity, or teratogenicity to infliximab was observed in a murine toxicity model conducted by the manufacturer. Rates of live births, miscarriages, and therapeutic terminations do not appear to be significantly different in women exposed to infliximab during pregnancy according to a registry maintained to track birth defects in women receiving tumor necrosis factor inhibitors during pregnancy. Adalimumab: Studies in monkeys have not revealed harm to the fetus when adalimumab was given during pregnancy. There are no well-controlled studies in humans. Certolizumab pegol: There are no well-controlled studies of certolizumab pegol in pregnant or lactating women. Studies in rats showed that pegylated Fab fragments did not cross the placenta and did not reveal evidence of harm to the fetus. However, exposure to certolizumab pegol during pregnancy is too limited to draw any conclusions.