OBJECTIVE: To investigate pregnancy-related disease activity in a contemporary multiple sclerosis (MS) cohort. METHODS: Using data from the MSBase Registry, we included pregnancies conceived after 31 Dec 2010 from women with relapsing-remitting MS or clinically isolated syndrome. Predictors of intrapartum relapse, and postpartum relapse and disability progression were determined by clustered logistic regression or Cox regression analyses. RESULTS: We included 1998 pregnancies from 1619 women with MS. Preconception annualized relapse rate (ARR) was 0.29 (95% CI 0.27-0.32), fell to 0.19 (0.14-0.24) in third trimester, and increased to 0.59 (0.51-0.67) in early postpartum. Among women who used fingolimod or natalizumab, ARR before pregnancy was 0.37 (0.28-0.49) and 0.29 (0.22-0.37), respectively, and increased during pregnancy. Intrapartum ARR decreased with preconception dimethyl fumarate use. ARR spiked after delivery across all DMT groups. Natalizumab continuation into pregnancy reduced the odds of relapse during pregnancy (OR 0.76 per month [0.60-0.95], p=0.017). DMT re-initiation with natalizumab protected against postpartum relapse (HR 0.11 [0.04-0.32], p<0.0001). Breastfeeding women were less likely to relapse (HR 0.61 [0.41-0.91], p=0.016). 5.6% of pregnancies were followed by confirmed disability progression, predicted by higher relapse activity in pregnancy and postpartum. CONCLUSION: Intrapartum and postpartum relapse probabilities increased among women with MS after natalizumab or fingolimod cessation. In women considered to be at high relapse risk, use of natalizumab before pregnancy and continued up to 34 weeks gestation, with early re-initiation after delivery is an effective option to minimize relapse risks. Strategies of DMT use have to be balanced against potential fetal/neonatal complications.

• Publication type
• Journal Article MeSH

INTRODUCTION: Multiple sclerosis (MS) is more common in women and can occur during childbearing years; thus, information on outcomes following exposure to MS therapy during pregnancy is important. No formal studies of daclizumab have been conducted in pregnant women. Here, we report available nonclinical and clinical data on pregnancy outcomes from the daclizumab clinical study program. METHODS: Reproductive and developmental toxicity studies were conducted in cynomolgus monkeys. Reports of pregnancies that occurred during the daclizumab clinical study program through March 9, 2015 were collated and summarized. In the event of pregnancy, daclizumab was discontinued and safety monitoring continued. RESULTS: Studies in cynomolgus monkeys showed no daclizumab-related effects on maternal well-being, embryo-fetal development, indirect fertility end points, and pre- and postnatal development and growth. Across the clinical study program, 38 pregnancies were reported in 36 daclizumab-exposed women (on treatment ≤6 months from last dose); 20 resulted in live births and four (11%) in spontaneous abortions or miscarriages. One congenital heart defect (complex transposition of great vessels) occurred in one live birth (considered unrelated to daclizumab); daclizumab had been discontinued and intramuscular interferon beta-1a and lisinopril were used at conception. Eight women had an elective termination, two had an ectopic pregnancy, and two were lost to follow-up; two pregnancy outcomes are pending. Six additional pregnancies occurred in five women >6 months after their last daclizumab dose; in one additional pregnancy, exposure was unknown. CONCLUSION: Spontaneous abortion rate in daclizumab-exposed women was consistent with early pregnancy loss in the general population (12%-26%). Data on pregnancies exposed to daclizumab do not suggest an increased risk of adverse fetal or maternal outcomes, although the numbers are too small for definitive conclusions. CLINICALTRIALS. GOV IDENTIFIERS: NCT00390221, NCT01064401, NCT01462318, NCT00870740, NCT01051349, and NCT01797965. FUNDING: Biogen and AbbVie Biotherapeutics Inc.

• Keywords
• Clinical trials, Daclizumab, Multiple sclerosis, Pregnancy, Teratogenicity,
• Publication type
• Journal Article MeSH