(S) Use of Methotrexate in Girls and Women of Childbearing Age and Occurrence of Methotrexate-Exposed Pregnancies in Germany

Publication Number: 643

Background: Methotrexate (MTX), indicated for rheumatic diseases and malignancies, should be withdrawn well before pregnancy due to its teratogenic potential.

Objectives: To assess trends in the use of MTX in girls and women of childbearing age, characterize prescribers and estimate the number of pregnancies occurring under treatment with MTX in Germany.

Methods: Based on the German Pharmacoepidemiological Research Database (GePaRD) covering ~20% of the German population, we conducted cross-sectional analyses among girls and women aged 13-49 years to determine age-standardized prevalence of use of MTX for each year between 2004 and 2018 (nominator: women with ≥1 dispensation in the respective year; denominator: mid-year population). For each year, we described the speciality of physicians prescribing MTX. Furthermore, we conducted a cohort analysis to determine the number of pregnancies occurring during MTX therapy. For that purpose, we assigned an exposure window to each dispensation (date of dispensation + number of dispensed defined daily doses) and assessed whether it overlapped with the onset of pregnancy. The study was financed by the German Federal Institute for Drugs and Medical Devices (BfArM).

Results: The age-standardized prevalence among girls and women with at least one MTX dispensation increased by 45% between 2004 and 2018 (1.6/1,000 vs. 2.33/1,000). In 2018, 44% of MTX prescriptions were issued by a rheumatologist as compared to 15% in 2008. In the same time interval, the proportion of prescriptions issued by general practitioners and specialists for internal medicine decreased (from 27% to 14% and from 37% to 16%). Overall, we identified 142 pregnancies exposed to MTX at the onset of pregnancy. The number was four times higher when the six months before pregnancy were also considered as relevant exposure period.

Conclusions: In Germany, the use of MTX in girls and women of childbearing age has substantially increased since 2004. Regarding prescribing specialties, we observed a shift from general practitioners and internists to rheumatologists. Despite the known teratogenic effect and the delayed clearance of MTX, there were a considerable number of pregnancies exposed to MTX at the onset or in the six months before.