Pregnant RA Patients Often Stop Biologic Tx: Study

Treatment interruptions in pregnancy less common for IBD patients

Judy George,October 15, 2017 from MedPage Today

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More than half of pregnant women who used biologic therapy to treat inflammatory autoimmune diseases from 2002 to 2012 stopped treatment in their first two trimesters, according to a study in British Columbia.

Within the first trimester of pregnancy, 31% (34/110) of women with inflammatory autoimmune diseases discontinued biologics and 38% (30/79) stopped in the second trimester. Women with rheumatoid arthritis (RA) had three times higher odds (OR 3.40, 95% CI 1.33-8.71) of discontinuing biologic therapy during pregnancy than women with inflammatory bowel disease (IBD), reported Mary A. De Vera, PhD, of the University of British Columbia in Vancouver, and colleagues, online in Arthritis Care and Research.

"Our study was the first to explore the relationships between maternal demographics, having RA versus IBD, and a number of indicators for disease severity, with the odds of discontinuing biologics before and during pregnancy," they wrote. "Despite the preponderance of autoimmune diseases during childbearing years, evidence is limited on their management, given the exclusion of pregnant women from clinical drug trials."

Up to 50% of women with autoimmune diseases require treatment throughout pregnancy to control disease activity and prevent adverse outcomes. Some disease-modifying agents interfere with fetal development, the authors noted, making biologic therapy a viable alternative.

For this study, the researchers studied patients in a registry that holds longitudinal data about all health services of the 4.6 million residents of British Columbia, including all prescriptions dispensed in community pharmacies and medications administered in infusion clinics. These data were linked to another registry that allowed precise dates of conception to be calculated.

Women who had pregnancies ending in live or still birth from 2002 through 2012 were included in the sample. These women had one or more autoimmune diseases that could be treated with a biologic, including RA, IBD, psoriasis, psoriatic arthritis, juvenile idiopathic arthritis, systemic autoimmune rheumatic diseases, multiple sclerosis, or vasculitic diseases, and at least one prescription for a biologic at any point from 1 year before conception until delivery.

From a pool of 8,431 pregnancies in 6,218 women with autoimmune disease, the researchers identified 144 pregnancies (1.7%) of 131 women who filled a prescription for a biologic either in the 1-year preconception period or during pregnancy. The most common autoimmune diseases were psoriasis, RA, and IBD. The most commonly used biologics were infliximab (Remicade), etanercept (Enbrel), and adalimumab (Humira).

Biologics use in this study increased from 0% in 2002 to 5.7% by 2012. This was considerably less than use among a similar cohort of U.S. women, who used biologic agents nearly three times more frequently by 2012. Differences in access might account for this, the researchers observed: in Canada, patients must fulfill certain criteria, including failure or intolerance to first-line or combination therapy, to receive biologics.

During the preconception period, about 1.3% of all women with autoimmune diseases used biologics. Within the first trimester of pregnancy, 31% (34/110) of women discontinued their biologic. Another 38% (30/79) stopped biologic treatment during the second trimester. All but one of the 51 women who remained on biologics during their second trimester continued with treatment in their third trimester.

The researchers analyzed this data by disease type, studying women with RA or IBD (n=127) since they used biologics most frequently. During the preconception period, they found no statistically significant associations between the time period women used biologics, maternal age at delivery, disease severity, or disease type and the odds of stopping biologic treatment.

During pregnancy, however, disease type was independently associated with discontinuation. After adjusting for disease severity and maternal age, women with RA had 3 times higher odds of stopping biologic therapy than women with IBD.

Dafna Gladman, MD, of the University of Toronto, who was not involved in the study, suggested the way pregnancy affects each disease might be a factor.

"Patients with RA usually get better during pregnancy, and both patients and physicians prefer that they do not use immunosuppressive therapies during pregnancy," she told MedPage Today. "Patients with IBD do not have a lot of other effective medications so they tend to stay on the biologics more than the RA patients."

The DeVera team wrote that other research shows only 16% to 27% of women with RA achieve complete remission during pregnancy, and sometimes that does not occur until the third trimester. This may mean that women with RA could be discontinuing biologics early in pregnancy regardless of disease severity, they observed.

The authors noted that the main strengths of this study are its population-based design and its ability to determine a precise pregnancy start date through the perinatal database registry. Findings should be viewed with caution, however, as the 95% confidence intervals of many estimates in the study are very wide. Additionally, the investigators did not examine disease outcomes, such as symptom flares, in women who stopped biologic therapy during pregnancy.

This study was funded by grants from The Arthritis Society and the Canadian Institutes of Health Research.

One member of the research team received honoraria from Boehringer Ingelheim and Pfizer Canada for consulting services unrelated to this study. The other researchers had no relevant relationships with industry.

Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner