1: Association of methotrexate polyglutamates concentration with methotrexate efficacy and safety in patients with rheumatoid arthritis treated with predefined dose: results from the MIRACLE trial.
Science of the Month - November 2024
Ann Rheum Dis.
Hiroya Tamai, Kei Ikeda, Toshiaki Miyamoto, Hiroaki Taguchi, Chang-Fu Kuo, Kichul Shin, Shintaro Hirata, Yutaka Okano, Shinji Sato, Hidekata Yasuoka, Masataka Kuwana, Tomonori Ishii, Hideto Kameda, Toshihisa Kojima, Yurie Nishi, Masahiko Mori, Hideaki Miyagishi, Genta Toshima, Yasunori Sato, Wen-Chan Tsai, Tsutomu Takeuchi, Yuko Kaneko; MIRACLE Study Group
Methotrexate (MTX) remains the anchor drug in the treatment of rheumatoid arthritis, even today when various targeted therapies are available. MTX taken into the bloodstream rapidly moves into cells, where it is polyglutamylated (PGs), allowing it to remain within the cells and exert its effects. This study is a report on the concentration of MTX-PGs in red blood cells from the MIRACLE trial, a randomized controlled trial for patients with rheumatoid arthritis in Japan, South Korea, and Taiwan, conducted jointly with Eisai Co., Ltd., and led by our university. In this trial, the MTX dose was increased to the maximum tolerated dose by week 12 and then continued at the same dose. However, the concentration of MTX-PGs in red blood cells continued to rise from week 12 to week 24. We showed that high MTX-PGs concentrations are associated with the efficacy of MTX and with liver damage, a typical adverse event. Furthermore, MTX-PGs concentrations were significantly elevated in patients with low renal function, low albumin (Alb), and low BMI. In recent years, the population of patients with rheumatoid arthritis has been aging, and it is hoped that treatment can be optimized by utilizing the concentration of MTX-PGs in red blood cells.
I would like to express my sincere gratitude to the faculty members both inside and outside the university who supported this trial, as well as to Professor Yasunori Sato and Dr. Genta Toshima of the Department of Biostatistics for their guidance in the analysis. I will continue to devote myself to further research.
(Hiroya Tamai, Department of Rheumatology and Collagen Disease, 91st Graduating Class)