Biologics in Pregnancy Safe, Pose No Preterm or SGA Risk

Tara Haelle

March 13, 2018

Using biologics to treat autoimmune disease during pregnancy does not appear to increase the risk for preterm birth or infants born small-for-gestational-age (SGA), according to a new study published online March 7 in the Annals of the Rheumatic Diseases.

"While we examined all biologics used in the cohort, [tumor necrosis factor]-alpha inhibitor biologics (94%) were the most common, and as such, our results mostly apply to these biologics and less so to those that are not TNF-alpha inhibitors," write Nicole W. Tsao, a PhD candidate at the University of British Columbia Faculty of Pharmaceutical Sciences in Vancouver, Canada, and colleagues.

"Indeed the population-based setting of this study lends more generalisability to the results," and the statistical methods used allow for better control of confounding compared with traditional modeling methods, "thus contributing to better understanding of the use of biologics in the pregnant population," the authors write.

"Our study represents an important contribution to the accumulation of evidence on the safety of the use of biologics in pregnant women, which may lead to increased prescriber comfort and patient acceptance, decreased uncertainty and improved maternal and neonatal outcomes in this population," they add.

Those Taking Biologics Matched to Women Who Weren't

Given the pathophysiology of autoimmune disease, with cytokine and chemokine dysfunction, and the role of the immune system during pregnancy, pregnant women with autoimmune disease activity have a higher risk for adverse maternal and neonatal outcomes, research shows.

Abnormally increased TNF-alpha in particular, along with other cytokines, has been linked to "pregnancy complications including preterm delivery, fetal growth retardation, early and unexplained spontaneous abortions and miscarriages," Tsao and colleagues explain.

The researchers used population-based administrative data from more than 4 million British Columbian residents, including 305,351 women with pregnancies during the study period. They compared the outcomes of 8607 pregnancies in 6218 women with autoimmune diseases, from January 2002 through December 2012.

The following conditions were included: rheumatoid arthritis, irritable bowel disease (including Crohn's and ulcerative colitis), psoriasis and psoriatic arthritis, juvenile idiopathic arthritis, and systemic autoimmune rheumatic diseases, including systemic lupus erythematosus and other connective tissue diseases.

One hundred nine women, with 120 pregnancies, who took at least one biologic medication during or up to 3 months' gestation were identified and each matched to approximately five women with autoimmune disease who did not take biologics during pregnancy (584 women and 600 infants). Matching was performed with high-dimensional propensity scores, a statistical method of using combined similarities among participants to act as proxies for potential confounders.

The most common diagnoses were rheumatoid arthritis and irritable bowel disease (49% and 46%, respectively). The most common prescriptions were infliximab (39%), etanercept (30%), and adalimumab (25%).

Odds of Preterm Birth, SGA, With Biologics Not Significant After Adjustment

Preterm births occurred among 18% of the women taking biologics and 16% of the matched women who did not take biologics. Nine percent of women taking biologics had SGA infants compared with 10% of unexposed matched women.

There was a higher likelihood of preterm birth or SGA among infants exposed to biologics in the overall population before adjustment, although it wasn't significant. Unadjusted odds ratios were 1.64 for preterm delivery and 1.34 for SGA among women taking biologics. 

After the 1:5 matching, odds ratios fell to 1.13 for preterm delivery and 0.91 for SGA.

"Furthermore, examination of the Apgar scores of SGA newborns showed inappreciable differences," the authors report. "[T]hose exposed to biologics had mean Apgar scores of 8.1 ([standard deviation (SD)] 1.5) at 1 minute, and 9.0 (SD 1.0) at 5 minutes, and those unexposed had Apgar scores of 7.7 (SD 2.2) at 1 minute and 8.7 (SD 1.7) at 5 minutes."

Several past studies have found risks for preterm delivery with use of biologics during pregnancy, but they involved small sample sizes (<80 participants) and did not "adjust for the effects of the underlying disease severity or effects from measured and unmeasured confounders," the authors note. Only two other studies have accounted for confounding and found nonsignificant hazard ratios.

Of the only two studies investigating risk for SGA with biologics use, neither adjusted their findings for participants' different characteristics.

The study's use of population databases reduced likelihood of recall or selection bias or misclassification because the researchers could "accurately determine the timing of all medication dispensations with respect to milestone pregnancy dates for each pregnancy in the cohort," the authors explain. They also used the perinatal registry to ensure accurate data on gestational ages and birthweight.

"Our findings suggest that biologics may be a safe treatment option for women with certain autoimmune diseases who, as previous research suggest, are at higher risk of adverse pregnancy outcomes due to their disease," the authors say.

The research was funded by The Arthritis Society. One coauthor has consulted for Pfizer Canada and Boehringer Ingelheim. The other authors have disclosed no relevant financial relationships.

Ann Rheum Dis. Published online March 7, 2018. Abstract

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