Anti-TNF-alpha agents OK in pregnancy

National report - Preliminary review finds no adverse effects of anti-TNF-alpha agents on pregnancy outcomes. Analyses of limited data collected by the Organization of Teratology Information Services (OTIS) suggest there is no increased risk of major malformations or spontaneous abortions in women who received treatment with an anti-TNF-alpha medication early during pregnancy, reports Christina Chambers, Ph.D., M.P.H., who is current President of OTIS, assistant professor, departments of pediatrics and family and preventive medicine, University of California San Diego, La Jolla, Calif.

"Increasing numbers of women of reproductive age may benefit from treatment with the anti-TNF-alpha medications. Adequate pregnancy safety data are critical to making appropriate treatment decisions for these women, but so far these agents have not been well-studied with regard to use in pregnancy," Dr. Chambers tells Dermatology Times.

OTIS is a not-for-profit organization that was established in 1990 to stimulate and encourage knowledge, education and research in the field of clinical teratology, and to improve the abilities of teratology information services located throughout North America to provide accurate and timely information about prenatal exposures so as to improve public health.

Data on the use of anti-TNF-alpha agents is being collected as part of the OTIS Autoimmune Diseases in Pregnancy Study, which was launched in 2000 and will continue until 2010. Structured as a cohort study, that investigation is designed to evaluate fetal risks associated with rheumatoid arthritis, psoriasis, ankylosing spondylitis and psoriatic arthritis and the medications used in the treatment of these diseases. Of particular interest are the newer biological agents that have recently been expanded in clinical use for the management of a variety of these autoimmune diseases, Dr. Chambers explains.

Potential candidates for inclusion in the study are identified through the North American OTIS network of teratology information services. Women are recruited for participation early in pregnancy, and are tracked until term. Subsequently, their infants are carefully examined by trained physicians for identification of major and minor congenital abnormalities.

The analyses presented by Dr. Chambers includes data from 33 women with rheumatoid arthritis who had first-trimester exposure to etanercept (n=29) or infliximab (n=4) and compares outcomes of their pregnancies against two control groups. One control group consists of 86 women with rheumatoid arthritis who were not treated with an anti-TNF-alpha medication and the second consists of 51 non-diseased controls with neither rheumatoid arthritis nor exposure to an anti-TNF-alpha agent.

Results show little difference

Among the women exposed to etanercept or infliximab, there was a 9.1 percent rate of spontaneous abortion/ stillbirth/blighted ovum, which was not significantly different from the 8.1 percent rate occurring in the rheumatoid arthritis controls or the 3.9 percent rate seen among non-diseased controls. There were also no significant differences between any groups in rates of major structural defects among all enrolled pregnancies, which ranged from 3.0 percent in the anti-TNF-alpha group to 3.5 percent in the rheumatoid arthritis control group and 3.9 percent among women in the non-diseased control group.

The data did reveal that women in both of the rheumatoid arthritis groups had shorter mean pregnancies compared with the non-diseased controls. Also, the diagnosis of rheumatoid arthritis, regardless of treatment group, was also associated with a significantly lower mean infant birth weight.

"Those findings suggest a contributing role of the underlying condition rather than any adverse effect related to use of the anti-TNF-alpha medications," Dr. Chambers says.

Continued recruitment will allow for better characterization of the safety of these new medications when used in pregnancy. In addition, the children will be further studied to identify any potential adverse outcomes. Within six months after birth, children will be carefully examined for structural defects by a pediatric geneticist/dysmorphologist. Data will also be collected from each child's own pediatrician during each child's first year of life to characterize postnatal growth and determine if there is increased risk for various health problems, such as serious infections.