OBJECTIVE:Pregnant women with inflammatory arthritis may be at increased risk for preterm delivery (PTD), yet it is unclear what drives this risk. This aim of this prospective cohort study of pregnant women with rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), or healthier comparison women was to analyze the independent effects of maternal disease activity, medication use, and comorbid pregnancy conditions on PTD risk. METHODS:Women were enrolled before 19 weeks completed gestation as part of the Organization of Teratology Information Specialists (OTIS) Autoimmune Disease in Pregnancy Project. Data on pregnancy events, medications, disease activity, and outcomes were obtained by maternal report and validated by medical records. Poisson regression with robust standard errors estimated risk ratios (RR), multivariable adjusted risk ratios (ARRs), and 95% confidence intervals (95% CIs). RESULTS:A total of 657 women with RA, 170 with JIA, and 564 comparison women without autoimmune disease who delivered live born infants, from 2004 to 2017 were included for analysis. Both the RA and JIA groups had an increased risk of PTD versus the comparison group (RR 2.09 [95% CI 1.50-2.91] and RR 1.81 [95% CI 1.14-2.89], respectively). Active RA at enrollment (ARR 1.58 [95% CI 1.10-2.27]) and any time during pregnancy (ARR 1.52 [95% CI 1.06-2.18]) was associated with PTD. Corticosteroid use in every trimester was associated with an approximate 2- to 5-fold increased risk for PTD for both arthritis groups, independent of disease activity. CONCLUSION:Women with RA and women with JIA are at increased risk for PTD. Maternal disease activity and corticosteroid use may contribute to some of this excess risk.

Objective

Anti-tumor necrosis factor (anti-TNF) medications are effective in controlling chronic inflammatory diseases, but information about their use and safety in pregnancy is limited. Consequently, anti-TNF agents are often discontinued early in gestation. Certolizumab pegol (CZP), a PEGylated, Fc-free anti-TNF agent approved for the treatment of rheumatic diseases and/or Crohn's disease, has minimal to no active placental transfer. This analysis was undertaken to evaluate pregnancy outcomes in women receiving CZP, especially those exposed during early pregnancy.

Methods

Prospective and retrospective data on maternal CZP exposure were extracted from the UCB Pharma safety database through March 6, 2017. Analysis was limited to prospective reports to avoid potential bias associated with retrospective submissions. The numbers of live births, miscarriages, elective abortions, stillbirths, and major congenital malformations were ascertained.

Results

Of 1,137 prospectively reported pregnancies with maternal exposure to CZP, 528 (including 10 twin pregnancies) had 538 known outcomes: 459 live births (85.3%), 47 miscarriages (8.7%), 27 elective abortions (5.0%), and 5 stillbirths (0.9%). There were 8 major congenital malformations (1.7%) among the 459 infants. First trimester exposure occurred in 367 (81.2%) of 452 pregnancies resulting in 459 live births. Exposure during all 3 trimesters occurred in 201 (44.5%) of 452 pregnancies.

Conclusion

This analysis represents the largest cohort of pregnant women exposed to an anti-TNF agent for management of chronic inflammatory diseases. Analysis of pregnancy outcomes does not indicate a teratogenic effect of CZP, compared to the general population, nor an increased risk of fetal death. The data are reassuring for women of childbearing age considering treatment with CZP.