Rheumatoid arthritis is a chronic inflammatory multisystem disease of unknown cause. The disease occurs in approximately 0.8% of the population, with women of childbearing age being more than four times more frequently affected than men. Low-dose oral glucocorticoids inhibit the inflammatory response and may also delay the development and progression of possible bone joint destruction.⁽¹⁾

As the research team reports, due to ethical and practical limitations, there is limited data on the pharmacokinetics and safety of commonly used corticosteroids such as prednisone. Common preclinical models, including animal studies, do not provide sufficient information about the drug exposure of the mother and the unborn child. Amonsgst others, this project investigated whether certain drugs can cross the blood-placenta barrier in pregnant women.⁽²⁾

To do this, the research team developed a microphysiological system (MPS) using human intestinal, liver and placental tissue models, and additionally used a digital twin model to predict pharmacokinetics and fetal drug exposure. The multiorgan-on-a-chip model was applied to simulate oral administration of the drug, measure its metabolism and transplacental transfer. The company ESQ Labs integrated experimental data from the multi-organ platform into mathematical models. The computer models allowed the simulation of acute and long-term drug effects.⁽³⁾

The researchers were able to use their models to accurately mimic drug dynamics in the human body, with predictions closely matching clinical data from pregnant women.  

They concluded that the approach could provide a potential animal-free alternative to help clarify the behavior of drugs and the safety of vulnerable populations such as pregnant women.

Original paper:
Graf K, Murrieta-Coxca JM, Vogt T, Besser S, Geilen D, Kaden T, Bothe A-K, Morales-Prieto DM, Amiri B, Schaller S, Kaufmann L, Raasch M, Ammar RM & Maass C (2025). Digital twin-enhanced three-organ microphysiological system for studying drug pharmacokinetics in pregnant women. Front. Pharmacol. 16:1528748. doi: 10.3389/fphar.2025.1528748

Further information:
⁽¹⁾ Charité Berlin, www.embryotox.de: Rheumatoide Arthritis. https://www.embryotox.de/erkrankungen/details/ansicht/erkrankung/rheumatoide-arthritis
⁽²⁾ Dynamic42 (2025). Dynamic42 and research partners present three-organ system to reduce animal testing. Pilot project “Multi Organ Model” successfully completed. Press release 19.02.25. https://dynamic42.com/press-release-dynamic42-and-research-partners-present-three-organ-system-to-reduce-animal-testing/
⁽³⁾ Laborpraxis (2025).  „Organ-on-Chip“-Plattform statt Tierversuch - Drei-Organ-System testet Wirkstoffe für Schwangere. 24.02.25. online: https://www.laborpraxis.vogel.de/neue-organ-on-chip-plattform-reduziert-tierversuche-in-medikamentenforschung-a-907f2ca09e0a907e33d2e9849ee563fe/