Pregnancy Outcomes in Women Exposed to Adalimumab

Abstract

Purpose: The fully human, anti-tumor necrosis factor monoclonal antibody adalimumab is approved for the treatment of rheumatoid arthritis (RA), psoriatic arthritis, ankylosing spondylitis, Crohn's disease, and psoriasis in the United States, Europe, and elsewhere, as well as for juvenile idiopathic arthritis in the United States. Methods: This report describes preliminary outcomes from an ongoing study of the safety of adalimumab in RA patients during pregnancy conducted by the Organization of Teratology Information Specialists (OTIS). Through a prospective cohort design, women with RA treated with adalimumab during the first trimester of pregnancy were followed for 1-year postpartum. Pregnancy outcomes were compared with those from a disease-matched group of pregnant women with RA who had not been treated with adalimumab during their pregnancies, and a non-diseased group of women who neither had RA nor had been treated with adalimumab. In addition to conducting the cohort study, the OTIS investigators also collected information on adalimumab-exposed pregnancies that did not meet the cohort criteria, but were followed as a case series. The case-series pregnancies are presented separately as they have no comparison group. They include patients treated for diseases other than RA, as well as retrospectively reported outcomes. Results: As of May 15, 2008 (4 years of the study), pregnancy outcomes were available for 126 women in the cohort (Table). Two major structural defects (6.6%) had been reported for 30 women with adalimumab exposure during their first trimesters for whom pregnancy outcomes were known: 1 with undescended testicle and 1 with microcephaly. For 51 pregnancies in the disease-matched comparison group for which pregnancy outcomes were known, 1 fetus (2.0%) was diagnosed with chromosomal abnormalities. Two major structural defects (5.1%) have been reported via 39 pregnancies with known outcomes in the healthy comparison group. In the case-series group (data not included in the Table), of the 66 known outcomes, 7 (10.6%) resulted in major congenital defects — 3 chromosomal anomalies, 1 spina bifida with hydrocephalus, 1 ventricular septal defect, 1 congenital hip dysplasia with inguinal hernia, and 1 congenital hypothyroidism. Of these 66 known outcomes in the case series, 23 had a diagnosis of Crohn's disease.Table: Pregnancy Outcomes in the OTIS Cohort StudyConclusion: Based on these preliminary data, no concerns have been raised regarding increased risks for adverse pregnancy outcomes associated with early pregnancy exposure to adalimumab in the treatment of RA. Firm conclusions await accumulation of sufficient sample size in this prospective cohort study. In Fall 2008, the OTIS cohort study will expand enrollment to include patients with Crohn's disease.