Synergistic Effects of BTK Inhibitor HM71224 and Methotrexate in a Collagen-induced Arthritis Rat Model

Autor: Yu-Yon Kim, Kyung Jin Choi, Young Gil Ahn, Sun Young Jang, Young Hoon Kim, Kwee Hyun Suh, Hyung Sik Kim
Rok vydání: 2021
Předmět:
Zdroj: In Vivo
ISSN: 1791-7549
0258-851X
DOI: 10.21873/invivo.12619
Popis: Background/Aim: Using a rat model of collagen-induced arthritis (CIA), we evaluated the therapeutic effects of HM71224 (BTKi), as well as the drug-drug interactions in combined therapy with methotrexate (MTX) based on both drugs’ pharmacological role in immune regulation and antiinflammation. Materials and Methods: Arthritis in rats was induced using type II collagen and incomplete Freund’s adjuvant. The therapeutic effects of HM71224 (alone or in combination with MTX) were evaluated by arthritis score, paw volume, body weight, and histopathological examination (H&E and Safranin-O staining). The drug-drug interactions between HM71224 and MTX were investigated by measuring plasma, liver enzyme and creatinine levels and blood cell counts. Results: HM71224 reduced the clinical signs of arthritis, paw volume, and body weight loss in CIA rats. ED(50) and ED(90 )were 1.0 and 2.5 mg/kg, respectively. HM71224 combined with MTX decreased the arthritis score, bone erosion, synovitis, and cartilage degradation without apparent interaction. Conclusion: The combination of HM71224 and MTX improved the therapeutic effect with no drug-drug interactions in RA.
Databáze: OpenAIRE