Pregnancy outcomes in women exposed to biologic treatment and affected by chronic arthritis

Background: information on new drugs does not include their possible effects on pregnancy, because pregnant women are excluded from clinical trials. Although not classified as teratogenic in animals, limited data are available on new biological agents used to treat chronic arthritis and their safety in human pregnancy. Objectives: to provide information on biological treatment in pregnant patients with chronic arthritis. Methods: Pregnancy outcome and maternal disease variations were retrospectively recorded by 6 Italian Rheumatology Centres. Patients exposed at time of conception or during pregnancy to biological agents (anti-TNF-alfa agents, anakinra, rituximab, abatacept) entered the study. Pregnancy and disease outcomes were derived from medical records review. The primary (congenital malformations) and secondary outcome measures (premature birth, low-birth weight, small for gestational age infants, caesarean sections, maternal disease activity during pregnancy) were assessed. Results: between 1999 and 2009 38 exposed pregnancies were reported, 25 occurred after maternal (mean maternal age at the conception: 32.5 yrs) and 13 after paternal exposure. Rheumatoid arthritis (23), spondyloarthropathies (5), psoriatic arthritis (5) and juvenile rheumatoid arthritis (5) were treated with etanercept (30), adalimumab (5), infliximab (2), anakinra (1). Anti-TNF had been administered during the first trimester of pregnancy to 24 mothers while only one was exposed during second and third trimester. At time of conception 14 female patients were under low dose of prednisone (medium dosage 3.6 mg/day), 2 male and 4 female patients were taking methotrexate or were in the washout period, 2 female leflunomide, 6 hydroxychloroquine, 1 cyclosporine A, 1 sulfasalazine. The median length of exposition to biologic agents during pregnancy was 36±21 days. Data about fetal/neonatal outcomes are showed in table 1. In 9/14 mothers a caesarean section was performed. A death due to foetal respiratory distress occurred still after birth in one baby, whose father was exposed to etanercept at time of conception. Polyclonal activated T lymphocytes and positive anti-beta2-GPI IgM without any clinical features were found at birth in a baby whose mother was treated with etanercept during second and third trimester. At the baseline mean DAS28 (based on C reactive protein) was 3,1±1,6. Longitudinal comparison of DAS28 scores at baseline, 1st, 2nd, 3rd trimester and during postpartum period didn't reveal any statistical difference. Conclusion: Anti-TNF treatment might appear safe during conception, representing a possible therapeutic choice also in young ladies affected by aggressive form of chronic arthritis and hoping for a pregnancy. On the other hand, reports of exposure during second/third trimester are too limited to allow any conclusion about the safety of these drugs when used during whole pregnancy