ACR 2017 | Daily Highlights
Serious or Opportunistic Infections in Infants Born to Pregnant Women with Rheumatoid Arthritis and Treated with a Biologic Medication
Authors: Christina D Chambers1, Diana L Johnson2, Yunjun Luo3, Ronghui Xu4 and Kenneth L Jones3, 1Pediatrics and Family Medicine and Public Health, University of California San Diego, La Jolla, CA, 2Department of Pediatrics, University of California, San Diego, La Jolla, CA, 3Pediatrics, University of California San Diego, La Jolla, CA, 4Department of Family Medicine and Public Health, University of California, San Diego, La Jolla, CA
Use of biologic therapies for rheumatoid arthritis (RA) in pregnancy is common. There is theoretical concern that these medications could interfere with postnatal immune function in the infant.
The Organization of Teratology Information Specialists (OTIS) Autoimmune Diseases in Pregnancy Project enrolled pregnant women from U.S. or Canada with or without RA in a prospective observational cohort study. Women were followed with 3-4 telephone interviews; medical records were abstracted from the delivery hospital, obstetric and specialty providers; follow-up data were obtained from the pediatrician through 1 year of age. Maternal use of biologic medications including start/stop dates was captured, and questions were asked about serious/opportunistic infections in the infant. These were defined as an infection requiring hospitalization or any of the following: neonatal sepsis, invasive fungal infection, x-ray proven pneumonia, meningitis, bacteremia, pneumocystis, septic arthritis, osteomyelitis, tuberculosis, herpes, listeria, legionella, mycobacteria, systemic cytomegalovirus, or abscess. We estimated relative risks (RR) and 95% confidence intervals (CI) using generalized estimating equations. We further stratified comparisons by gestational timing of last dose of the biologic after 24 and 32 weeks gestation, respectively.
Between 2004-2016, 1,184 pregnancies ending in live born infants, including 73 infants of twin pregnancies, were followed to 1 year postpartum (252 with RA treated with a biologic in pregnancy, 463 with RA but no treatment with a biologic in pregnancy, and 469 with no chronic diseases). Of those in the RA biologic group, 97 (38.4%) took their last dose in the 1st or 2nd trimester and 155 (61.5%) received their last dose in the 3rd trimester (Figure). Serious or opportunistic infections were reported in 7/252 (2.8%) of infants born to women with RA treated with a biologic, 18/463 (3.9%) of infants born to women with RA not treated with a biologic (RR 0.71, 95% CI 0.30, 1.71), and 12/469 (2.6%) of those infants whose mothers had no chronic diseases (RR 1.09, 95% CI 0.43, 2.72). Restricting the group treated with a biologic to women whose last dose was sometime after 24 weeks gestation, 6/155 (3.9%) reported infant infections in the biologics group compared to 18/463 (3.9%) in the RA comparison group (RR 1.00, 95% CI 0.40, 2.48). Further stratification at 32 weeks gestation resulted in infections reported in 5/143 (3.5%) in the RA biologics group compared to the 3.9% in the RA untreated group (RR 0.90, 95% CI 0.34, 2.39).
We found no evidence of increased risk of serious/opportunistic infections in infants in this sample. These data are reassuring for pregnant women who require treatment with a biologic medication. However, it is possible that less serious infections occur more frequently, and further research is needed.
C. D. Chambers, AbbVie, 2,Amgen, 2,Bristol Myers Squibb, 2,Celgene, 2,Janssen Pharmaceutica Product, L.P., 2,Pfizer Inc, 2,Roche Pharmaceuticals, 2,Seqirus, 2,GSK, 2,UCB, 2,Sanofi-Aventis Pharmaceutical, 2; D. L. Johnson, None; Y. Luo, None; R. Xu, Amgen, 2,AbbVie, 2,Celgene, 2,Janssen Pharmaceutica Product, L.P., 2,Bristol Myers Squibb, 2,GSK, 2,Seqirus, 2,Pfizer Inc, 2,Sanofi-Aventis Pharmaceutical, 2,Roche Pharmaceuticals, 2,UCB, 2; K. L. Jones, AbbVie, 2,Amgen, 2,Bristol Myers Squibb, 2,Roche Pharmaceuticals, 2,Janssen Pharmaceutica Product, L.P., 2,Celgene, 2,Pfizer Inc, 2,UCB, 2,Sanofi-Aventis Pharmaceutical, 2,GSK, 2,Seqirus, 2.
In recent years, biologics have increasingly been continued during the first months of pregnancy, and the Swiss treatment recommendations (www.rheuma-net.ch) suggest that this is safe with most anti-TNF agents, at least up to the 20th week of gestation.
This large cohort of live born infants of mothers with RA explored the fear that biologic therapies could interfere with postnatal immune function in their infant. The authors found no evidence of increased risk of serious opportunistic infections in infants in mothers taking biologic medications. They further explored the possibility that later administration in the third trimester could increase this risk, but found no evidence for this hypothesis. While this study is reassuring, the authors only analyzed serious infections, and does not exclude the possibility of an increased risk of mild infections in these infants. However, there is currently no signal that would suggest this is the case.
Prof. Dr. Axel Finckh
Geneva University Hospital