Immunomodulators.(Drugs, Pregnancy, and Lactation)

Several immunologic agents--adalimumab, anakinra, etanercept, three classes of interferons, and thalidomide--are classified in the general category of immunomodulators. They are used for various approved and offlabel indications: multiple sclerosis, rheumatoid arthritis, autoimmune disorders, and complications of leprosy, and for antitumor, antiviral, and antibacterial uses.

With the exception of thalidomide, these compounds are large molecules and may not reach the fetus. But their complex pharmacologic mechanisms may directly affect a number of maternal biologic processes, such as immune functions, response to infections and inflammation, cell proliferation, leukocyte migration, and prevention of cartilage degradation. Except for thalidomide, the human pregnancy experience with these agents is limited or completely lacking, making the decision about whether to use them during gestation problematic.

The tumor necrosis factor blockers adalimumab (Humira) and etanercept (Enbrel) and the interleukin-1 receptor antagonist anakinra (Kineret), which are administered subcutaneously, are approved for treating rheumatoid arthritis. All three are rated pregnancy risk category B: Animal studies have not revealed any evidence of harm to the embryo or fetus at serum levels or doses that are much higher than those used in humans.

Although this information is reassuring, the lack of pregnancy data in humans does not allow assessment of the fetal risks posed by these drugs. To help provide such information for one of these agents, the Organization of Teratology Information Services has started a Humira pregnancy registry. (Enroll patients by calling 877-311-8972.) Until pregnancy data are available, it would be prudent for women to undergo a pregnancy test before starting these drugs, but inadvertent exposure in pregnancy probably represents a low risk.

No information is available concerning the use of these agents during lactation, but since they are amino acid derivatives, they would likely be digested in the infant's gut if excreted into breast milk. Still, the safest course for a woman taking one of these agents is to avoid breast-feeding because of the potential for toxicity in the infant.

The three classes of interferons--alfa, beta, and gamma--are each rated C and administered parenterally. The interferon alfa agents include interferon alfa-2a (Roferon-A), peginterferon alfa-2a (Pegasys), interferon alfa-2b (Intron A), ...