SAN DIEGO -- The risk of serious or opportunistic infections during infancy is not increased with maternal use of a biologic agent for the treatment of rheumatoid arthritis (RA).
In a prospective observational cohort study, the trimester during which the last dose of biologic was taken did not influence the risk of serious/opportunistic infection, reported Christina Chambers, PhD, MPH, from the University of California, San Diego, at the
The data "provide some reassurance for clinicians" who may be concerned about treatment with a biologic late in pregnancy, she said.
A theoretical concern is that taking an immunosuppressant medication during pregnancy, especially during the third trimester, may have an impact on an infant's immune function postnatally, but this concern was not borne out in the Organization of Tetralogy Information Specialists (OTIS) Autoimmune Diseases in Pregnancy Project.
Little placental transfer is thought to take place with the use of small molecule biologics early in pregnancy, but placental transfer is increased later in pregnancy.
The Autoimmune Diseases in Pregnancy Project enrolled pregnant women with or without rheumatoid arthritis (RA) from the U.S. or Canada. Between 2004 and 2016, 1,184 pregnancies ending in live born infants were selected from the database. The infants were followed to 1 year postpartum. A total of 502 women with RA were treated with biologics during pregnancy with or without non-biologic disease-modifying antirheumatic drugs, 231 women with RA did not use any biologic agents during pregnancy and 423 women had no chronic diseases.
About 80% of the entire cohort was white, 13.2% (non-diseased group) to 17.2% (biologic exposed group) were categorized as obese and 2.2% (non-diseased group) to 43.6% (diseased group not exposed to a biologic) took a corticosteroid at any time.
Exposure was defined as any dose of a biologic for any length of time from the first day of the last menstrual period to the end of pregnancy.
Opportunistic infections were defined a priori as a list of 16 infections that included neonatal sepsis, invasive fungal infection, x-ray proven pneumonia, meningitis, bacteremia, pneumocystis, septic arthritis, osteomyelitis, tuberculosis, herpes, listeria, legionella, mycobacteria, systemic cytomegalovirus, abscess, or an infection that may not have been specified but landed the child in the hospital.
The 1-year follow-up data were collected from medical records abstractions from the delivery hospital, obstetric provider or specialty provider, which were corroborated that with maternal report.
With exposure in pregnancy to a biologic at any time, 20 of the 502 infants had at least one serious or opportunistic infection over their first year, for a rate of 4.0%. Among the subset of 285 who had third trimester exposure to a biologic, 10 infants had at least one serious or opportunistic infection, for a rate of 3.5%. Among the 231 women with RA and no biologic exposure, six infants (2.6%) had at least one serious/opportunistic, and the rate in the group with no chronic diseases was 9 of 423 (2.1%).
When compared with the group with a diagnosis of RA and no biologic exposure, the odds ratio for biologic exposure at any time was 1.56, with a wide confidence interval (95% CI 0.61-3.97), indicating no significant association, and the odds ratio for exposure to a biologic during the third trimester was 1.36 (95% CI 0.47-3.96), again indicating no significant relationship.
When compared with the group of women without chronic disease, the odds ratios were 1.91 (95% CI 0.85-4.28) and 1.67 (95% CI 0.65-4.34), respectively.
The point estimates were higher among women who used corticosteroids in the third trimester but the number of events was limited and the confidence intervals again crossed 1.
The most common infections observed were x-ray proven pneumonia, sepsis, bacteremia, meningitis, and abscess. Between 11 and 19% of infants had more than one infection over the 1-year of follow-up.
"We addressed only the risk for serious or opportunistic infections in that first year of life. We did not address risk for less serious infections so we can't answer the question of whether or not these children have more common colds or more infections," Chambers said. In addition, there was no direct measure of infant immune function at the time these data were collected.
"Our next step is to go back and explore more fully the dose, duration and timing of steroid use throughout pregnancy, and particularly in the third trimester, as it relates to these infection risks," she said.
Disclosures
MotherToBaby Studies receive research funding from AbbVie, Amgen, Bristol Myers Squibb, Celgene, Janssen, Pfizer, Roche, Seqirus, GlaxoSmithKline, UCB and Sanofi-Aventis.
Primary Source
American College of Rheumatology
Chambers CD, et al "Serious or opportunistic infections in infants born to women with rheumatoid arthritis treated with a biologic medication" ACR 2017; Abstract 1785.