Fingolimod, teriflunomide and cladribine for the treatment of multiple sclerosis in women of childbearing age: description of drug utilization and exposed pregnancies in Germany.

ABSTRACT

BACKGROUND: Authorizations of fingolimod, teriflunomide and cladribine were accompanied by risk minimization measures concerning their teratogenic potential. Real-world data on their use are scarce. We aimed to assess trends in the use of fingolimod, teriflunomide and cladribine among women of childbearing age, estimate the number of pregnancies occurring under treatment and explore the occurrence of malformations in newborns exposed during early pregnancy in Germany. METHODS: Using the German Pharmacoepidemiological Research Database (GePaRD, claims data from ∼20% of the German population), we determined annual age-standardized prevalences of fingolimod, teriflunomide and cladribine use from their authorization until 2019 among women aged 13-49 years (cross-sectional analyses). In longitudinal analyses, we estimated the number of exposed pregnancies by assessing whether there was an overlap between the exposure windows assigned to dispensations and the onset of pregnancy or a dispensation in the first eight weeks of pregnancy. For live births, a mother-baby linkage was performed. All available data of children with in-utero exposure and malformation codes in the first year of life were reviewed to verify the occurrence of congenital malformations. RESULTS: For fingolimod, the age-standardized prevalence of use per 1,000 females increased from 0.14 in 2011 to 0.46 in 2019; for teriflunomide, from 0.06 in 2013 to 0.28 in 2019; for cladribine, from 0.01 in 2017 to 0.07 in 2019. The proportion of users aged ≤40 years was 60% for fingolimod, 45% for teriflunomide and 65% for cladribine. We identified 136 pregnancies exposed to fingolimod, 50 to teriflunomide and one to cladribine. For fingolimod and teriflunomide, respectively, 72% and 62% of exposed pregnancies ended in a live birth. Mother-newborn linkage was successful in 64 (fingolimod) and 20 (teriflunomide) live-born children. Among these, there were six with relevant malformations (mainly heart defects) for fingolimod and two for teriflunomide. CONCLUSION: Use of fingolimod, teriflunomide and cladribine among women of childbearing age has substantially increased in Germany. A high proportion of users was in age groups in which pregnancies typically occur. Despite risk minimization measures, early pregnancy exposure to these drugs was observed.