Contraception Advice Urged for Women Taking MTX for RA

Induced abortion rates were lower in women with rheumatoid arthritis (RA) treated with methotrexate (MTX) than in unexposed women but were still high enough to be concerning, Evelyne Vinet, MD, from the Division of Clinical Epidemiology and the Division of Rheumatology, McGill University Health Centre, Montreal, Canada, and colleagues report in an article published online April 16 in Arthritis Care & Research.

"Our hypothesis was that we might find more [induced abortions] among women taking MTX, so the findings were in a sense the opposite of what we expected, but still very interesting," senior author Sasha Bernatsky, MD, PhD, told Medscape Medical News. "It may be that in fact we are pretty good about warning women with MTX use about [the] need for good pregnancy planning, and/or we may be following them more closely, and/or their disease may be so severe/active that they avoid pregnancy." Dr. Bernatsky is also from the Division of Clinical Epidemiology and the Division of Rheumatology at the McGill University Health Centre.

To expand evidence of induced abortion rates in women with RA exposed to MTX, the researchers performed a nested case-control study using Quebec's physician billing and hospitalization databases from 1996 to 2008. Women with RA who were between the ages of 15 and 45 years were identified, with cases classified as women who had an induced abortion. MTX exposure was defined as filling a prescription for the drug less than 16 weeks before the date of abortion.

The team identified 112 women with RA who had an induced abortion (cases) and 5855 RA control patients. Exposure to MTX was found in 10.7% of case patients and 21.7% of control patients. Compared with the unexposed RA control patients, women with RA who were exposed to MTX had a 53% lower rate of induced abortions (rate ratio [RR] 0.47; 95% confidence interval [CI], 0.25 - 0.89). The team also found a potential increase in the rate of induced abortions among women exposed to TNF inhibitors, but it did not reach statistical significance.

According to the authors, although the rate of induced abortions in women with RA receiving MTX was half the rate of similar patients who had not taken MTX, the data still suggest "an inappropriately high rate of unplanned pregnancies in women exposed to MTX" and a need for better contraception counseling of women on MTX at initiation of and throughout therapy.

MTX is a known teratogen and is associated with the fetal aminopterin syndrome, which includes skeletal anomalies, microcephaly, and hydrocephalus.

"We demonstrated that women with RA exposed to MTX have a lower rate of induced abortions compared to unexposed women. There are many potential reasons for this, one possibly being the use of effective contraception. Alternatively, women with RA on MTX may have less sexual activity than unexposed women, potentially due to increased disease activity.

"Furthermore, spontaneous abortions may be increased in women on MTX, consequently resulting in lower induced abortion rate," the authors note.

"Moreover, we observed that women exposed to anti-TNF agents may be at increased risk of induced abortions, presumably for unplanned pregnancies. Because there is no specific recommendation for contraception in women on anti-TNF agents, health care professionals may omit contraception counseling in these women.... Women on anti-TNF agents may be misinformed about the fetal risk following exposure during the conception period or early pregnancy, and inadvertently terminate a pregnancy thinking that the risk is unduly increased.... Thus, comprehensive contraception counseling should be offered not only to women exposed to teratogenic drugs, such as MTX, but also to women with severe disease and/or on anti-TNF agents," the authors conclude.

Dr. Bernatsky added, "I think we are all aware of the need for pregnancy counselling, but sometimes we are so busy that this issue may not be discussed adequately. It might improve the situation if our patients were also followed by family doctors, who could then counsel the patients as well. At our institution, it would also be nice to include more nurses and nurse practitioners to ensure these issues are covered."

"Mother Nature has a hand in helping many women with RA once they become pregnant," Nathan Wei, MD, told Medscape Medical News. "Roughly, 80% of women who have RA go into spontaneous remission once they become pregnant. Why that happens is still not known. Unfortunately, once delivery occurs, the RA flares again. As clinicians, we counsel patients to go off their [MTX] for at least 3 months before trying to conceive because of the teratogenicity associated with the drug." Dr. Wei, who is president and chief executive officer of the Arthritis Treatment Center, Frederick, Maryland, was not involved in the study.

"As far as [tumor necrosis factor (TNF)] inhibitors, 2 observational studies (one from [the University of California], San Francisco, and the other from Erasmus Medical Center, Rotterdam) showed that stopping Remicade [Janssen Biotech] and Humira [AbbVie] at the end of the second trimester reduces the amount of antibody transferred to the infant and shortens the time for the infant to clear the antibody. Cimzia [UCB] doesn't need to be stopped since it doesn't cross the placenta. The danger here, of course, is the immunosuppressive effect of the TNF inhibitors transferred to the infant. The Vinet paper stated that abortions were higher in the TNF-treated patients. They didn't segregate out the type of TNF inhibitor patients were on. Still, the [result] with TNF inhibitors is disturbing, since it obviously has implications as far as counseling," Dr. Wei concluded.

The authors and Dr. Wei have disclosed no relevant financial relationships.

Arthritis Care Res. Published online April 16, 2013. Abstract