(262) Exposure to potentially harmful drugs during pregnancy in women with rheumatoid arthritis – a German claims data analysis

Background: Women with rheumatoid arthritis (RA) may need treatment during pregnancy as an active disease may cause complications. However, some drugs are contraindicated during the entire pregnancy like leflunomide (LEF) and methotrexate (MTX), others should not be used late in pregnancy, e.g., non-steroidal anti-inflammatory drugs (NSAIDs) after the second trimester, due to an increased risk for the fetus.

Objectives: To describe treatment with potentially harmful drugs before and during pregnancy in women with RA.

Methods: We used data from the German Pharmacoepidemiological Research Database (GePaRD; claims data covering ~20% of the German population). First, we identified women with incident RA between 2005 and 2020. Among those, we identified pregnancies beginning between 2005 and 2020 using established algorithms. We only included pregnancies in mothers aged 13-49 years at pregnancy beginning. We described the outcome of pregnancies and assessed drug treatment in pre-defined time windows before (from one year before to pregnancy onset in 90-day-intervals) and during pregnancy (per trimester). We calculated the proportion of pregnancies with at least one dispensing of MTX, LEF or NSAID in these time windows. The study was funded by the German Federal Ministry of Education and Research.

Results: Overall, we included 3,283 pregnancies in 2,362 women. 79% of pregnancies ended in a live birth, of these 9.5% were preterm births. From the first to the last 90-day time interval before pregnancy, the proportion of pregnancies with at least one dispensing of MTX decreased from 7.6% to 1.7%. For LEF it remained at 0.4%. During pregnancy, MTX was used in 0.5% of pregnancies in the first, in 0.2% in the second, and in 0.2% in the third trimester. For LEF, these proportions were 0.2%, 0.1%, and 0%, respectively. The proportion of pregnancies with an NSAID dispensing remained constant in the 90-day time intervals before pregnancy (~16%-18%). In the first, second and third trimester, this proportion was 8.0%, 2.1% and 0.8%, respectively.

Conclusions: In pregnant women with RA, the dispensation of MTX, LEF, and NSAIDs before and during pregnancy we observed in our study largely reflected the guidelines, but in a few cases, there was potentially harmful in-utero exposure.