INTRODUCION: Cladribine tablets are contraindicated during pregnancy.
OBJECTIVES: CLEAR (EUPAS25027) is a cohort study that aims to determine whether exposure to cladribine tablets has an adverse effect on pregnancy and infant outcomes.
AIMS: To describe the study design of CLEAR and provide study status update.
METHODS: Pregnant women with multiple sclerosis (MS) are included in the study if they have been 1a) exposed to cladribine tablets during pregnancy, or within 6 months before last menstrual period (LMP); or 1b) unexposed to any disease-modifying therapy (DMT) within 3 months before LMP. Likewise, pregnancies exposed via a male partner with MS are included if the partner has been 2a) exposed to cladribine tablets within 6 months before LMP; or 2b) unexposed to any DMT within 3 months before LMP. Pregnancies will be followed until the outcome of the pregnancy is known, and live births will be followed for up to one year of age. The study aims to include 447 pregnant women with MS (149 exposed; 298 unexposed) from the participating registries/data sources by the end of data collection period expected in December 2027. Separately in pregnant women with MS and in pregnancies fathered by men with MS, adjusted and unadjusted odds ratio of outcomes such as major congenital anomalies at 1 year (primary outcome) and adverse pregnancy outcomes (e.g., ectopic pregnancy, spontaneous abortion, termination of pregnancy due to fetal anomaly, and stillbirth) comparing participants exposed to cladribine tablets versus unexposed will be estimated within each data source. A meta-analysis pooling aggregated results from each data source will be performed.
RESULTS: Participating data sources are: The German MS Pregnancy Registry, the MEMO Research MS data and Public Health data in Scotland, and the Nordic national health registers linked or not with MS registries (Denmark, Finland, Norway, Sweden). By March 2021, 307 pregnancies (9 exposed, 298 unexposed) had been identified in the study.
CONCLUSIONS: The use of combined population-based data sources and registries will help to identify inadvertent exposure to cladribine tablets during pregnancy and assess pregnancy and infant outcomes with minimal loss to follow-up.
