Biologics in Pregnancy: Are They Safe? Save

Exposure to biologic therapies among women with autoimmune diseases was not associated with increased risks of preterm delivery or having small for gestational age babies, a population-based Canadian study found.

Among 109 women who had 120 pregnancies and who received a biologic medication during or 3 months prior to pregnancy, the odds ratio for preterm delivery after high-dimensional propensity score matching was 1.13 (95% CI 0.67-1.90), which was not significantly different from the risk seen among women not receiving biologics, according to Mary A. De Vera, PhD, of the University of British Columbia in Vancouver, and colleagues.

And also after propensity score matching, the risk of small for gestational age birth compared with nonuse of biologics was 0.91 (95% CI 0.46-1.78) among users, they reported online in Annals of the Rheumatic Diseases.

A critical component of autoimmune disease is the dysregulation of regulatory cytokines and chemokines, with tumor necrosis factor (TNF) being key.

"In pregnancy, TNF-alpha controls cyclo-oxygenases that affect blastocyst implantation, endometrial permeability and decidualization, and contributes to the process of labor. Abnormally high levels of TNF-alpha and other cytokines have been implicated in pregnancy complications including preterm delivery, fetal growth retardation, early and unexplained spontaneous abortions, and miscarriages," De Vera's group explained.

This suggests that these undesirable outcomes correlate with levels of disease activity, which is held in check by effective treatments such as TNF inhibitors.

To see if these two adverse outcomes associated with infant morbidity and mortality were influenced by biologic use shortly before or during pregnancy, the researchers analyzed data from Population Data British Columbia, which contains longitudinal data on health services for all residents of British Columbia.

Additional information was obtained from the Medical Services Plan database, the Discharge Abstract Database, Population Data BC, PharmaNet, and the BC Perinatal Database Registry.

The study cohort included women with recorded diagnoses of rheumatoid arthritis (RA), inflammatory bowel disease (IBD), psoriasis/psoriatic arthritis, juvenile idiopathic arthritis, systemic lupus erythematosus, and other connective tissue diseases.

Preterm delivery was birth before 37 weeks' gestation, and small for gestational age was weight below the 10th percentile of age- and sex-specific neonatal weight.

High-dimensional propensity score matching was used to limit the likelihood of confounding by indication. This was based on an algorithm that took into account the use of multiple medications, concurrent disorders and symptoms, and previous adverse obstetric outcomes.

The analysis included 6,218 women with autoimmune disease and their 8,607 pregnancies.

Mean maternal age at delivery was 31, and the majority of women had either RA or IBD. The most commonly used biologics were infliximab (Remicade) in 37%, etanercept (Enbrel) in 31%, and adalimumab (Humira) in 26%.

A total of 21 of the 120 babies with biologic exposure (18%) were born preterm, as were 95 of 600 (16%) not exposed, for an unadjusted odds ratio of 1.64 (95% CI 1.02-2.63). Small for gestational age births were seen in 11 of 120 (9%) of babies who were biologics exposed, and in 60 of 600 (10%) of those who were unexposed, for an unadjusted OR of 1.34 (95% CI 0.72-2.51). After propensity score matching, however, neither outcome was statistically significant.

Among the small for gestational age neonates, mean Apgar scores for those who were biologics exposed were 8.1 and 9 at 1 and 5 minutes, respectively, while for the nonexposed, the corresponding scores were 7.7 and 8.7.

An important feature of this study was the use of high-dimensional propensity scoring, so that differences in baseline characteristics were taken into account. Earlier studies found odds ratios for preterm delivery of 2 to 2.71. However, those studies did not attempt to adjust for the effects of disease severity or other confounders and therefore had limited generalizability.

"Indeed, addressing confounding by indication is of utmost importance in the population of women with autoimmune disease, given the association between disease activity and adverse pregnancy outcomes," De Vera's group stated.

Despite being limited by relatively small numbers, the 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 concluded.

The study was funded by The Arthritis Society.