PT  - JOURNAL ARTICLE
AU  - KYUNG JIN CHOI
AU  - YU-YON KIM
AU  - SUN YOUNG JANG
AU  - YOUNG GIL AHN
AU  - KWEE HYUN SUH
AU  - YOUNG HOON KIM
AU  - HYUNG SIK KIM
TI  - Synergistic Effects of BTK Inhibitor HM71224 and Methotrexate in a Collagen-induced Arthritis Rat Model
AID  - 10.21873/invivo.12619
DP  - 2021 Nov 01
TA  - In Vivo
PG  - 3245--3251
VI  - 35
IP  - 6
4099  - http://iv.iiarjournals.org/content/35/6/3245.short
4100  - http://iv.iiarjournals.org/content/35/6/3245.full
SO  - In Vivo2021 Nov 01; 35
AB  - 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. ED50 and ED90 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.