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Women with rheumatoid arthritis (RA) being treated with methotrexate had no increase in the rate of induced abortions despite the drug's known teratogenicity, a case-control study showed.

In fact, women exposed to methotrexate in early pregnancy had fewer abortions than those with RA not given the drug, with an adjusted rate ratio of 0.47 (95% CI 0.25 to 0.89), according to Évelyne Vinet, MD, of McGill University in Montreal, and colleagues.

There are several possible explanations for this, including the use of effective contraception among women exposed to methotrexate and the possibility that more severe disease in women requiring disease-modifying treatment interferes with sexual activity.

"Furthermore, spontaneous abortions may be increased in women on [methotrexate], consequently resulting in lower induced abortion rates," the researchers observed online in Arthritis Care & Research.

Women with RA who become pregnant inadvertently while being treated with methotrexate may decide to abort the fetus because of the possibility of the severe birth defects that may result, including skeletal abnormalities, hydrocephalus, and microcephaly.

But little is known about the actual rates of induced abortion among these women, so Vinet's group examined rates in administrative databases in Quebec between 1996 and 2008.

The time frame of concern was the 16 weeks before the index date of abortion, because current recommendations advise withdrawal of the drug at least 12 weeks before attempting pregnancy.

They also conducted a multivariate analysis looking at other potential factors that might influence decisions about abortion, such as the use of anti-tumor necrosis factor (TNF) agents and extra-articular manifestations of disease.

Among 5,967 women of childbearing age with RA, there were 112 abortions. These cases were matched with 5,855 controls who had RA but no methotrexate exposure.

The rate of abortions in the overall study population was 6.78 cases per 1,000 person-years.

A total of 10.7% of cases were exposed to methotrexate, as were 21.7% of controls.

The primary analysis excluded women using intrauterine devices and those with sterilization or infertility, and a sensitivity analysis that included these women had similar results, with an adjusted rate ratio of 0.36 (95% CI 0.18 to 0.74), the researchers reported.

In the multivariate analysis, there was a trend for higher rates of abortion with the use of anti-TNF therapy (RR 2.07, 95% CI 0.81 to 5.27).

No specific recommendations have been formulated for contraception in women on TNF inhibitors, and safety guidelines issued by the British Society for Rheumatology simply state that treatment withdrawal should be considered if a patient on this type of treatment becomes pregnant unless the risk of stopping treatment is high.

"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," the researchers explained.

None of the other factors in the analysis, including use of prednisone, the presence of extra-articular disease such as rheumatoid lung, and number of physician visits or hospitalizations showed significant associations.

Previous research has shown that the rate of abortions in women with RA is only about half that in the wider population, but abortions were fairly common in this study, "suggesting an inappropriately high rate of unplanned pregnancies in women exposed to [methotrexate]," the researchers observed.

"This stresses the need to improve contraception counseling in women on [methotrexate], not only at initiation of therapy, but also while it is ongoing," they advised.

The researchers acknowledged that their analysis had certain limitations, including reliance on administrative data and the exclusion of nonsteroidal anti-inflammatory drugs (NSAIDs) as potential predictors of induced abortion.

"NSAID exposure is particularly difficult to ascertain accurately, as these drugs can be obtained over-the-counter (in which case exposure is not captured in the database) and are frequently prescribed as needed, which increases the difficulty in assessing the timing of exposure relative to a specific event," the researchers explained.

"These results raise concerns on the rate of unplanned pregnancies in women with [rheumatoid arthritis], particularly those on anti-TNF agents, and should prompt future research on counseling, contraception use, and unplanned pregnancies," they concluded.

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