{"title":"采用预定剂量治疗的类风湿关节炎患者体内甲氨蝶呤多谷氨酸浓度与甲氨蝶呤疗效和安全性的关系：MIRACLE 试验的结果。","authors":"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","doi":"10.1136/ard-2024-226350","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>The usefulness of methotrexate-polyglutamates (MTX-PGs) concentration for management of rheumatoid arthritis has been debated. We aimed to clarify the association of MTX-PGs concentration with efficacy and safety in MTX-naïve patients initiating MTX in a prospective interventional clinical trial.</p><p><strong>Methods: </strong>The MIRACLE trial enrolled 300 MTX-naïve patients. Oral MTX was initiated and increased to the maximum tolerated dose by week 12. Patients who did not achieve remission according to the Simplified Disease Activity Index at week 24 were randomised to either the continued dose or reduced dose group and were started on subcutaneous adalimumab. We measured the concentrations of MTX-PGs in erythrocytes using liquid chromatography-tandem mass spectrometry and analysed the association of these concentrations with efficacy and safety.</p><p><strong>Results: </strong>The mean concentration of total MTX-PGs increased with an increasing dose of MTX and continued to elevate for another 12 weeks after the dose was fixed. At week 24, the total MTX-PGs concentration was 110.5 (SD 43.8) nmol/L with MTX dose of 12.6 (3.0) mg/week (0.23 (0.07) mg/kg/week). During MTX monotherapy, the higher MTX-PGs concentration was an independent factor for lower disease activity; however, this association disappeared after adalimumab initiation in patients with continued MTX dose. Hepatotoxicity was related to the higher MTX-PGs concentration regardless of adalimumab use. The total MTX-PGs concentration was significantly elevated by lower estimated glomerular filtration rate, serum albumin and body mass index.</p><p><strong>Conclusions: </strong>The MIRACLE trial demonstrated that higher total MTX-PGs concentration in erythrocytes is related to the higher efficacy and lower safety of MTX.</p><p><strong>Trial registration number: </strong>NCT03505008.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3000,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Association of methotrexate polyglutamates concentration with methotrexate efficacy and safety in patients with rheumatoid arthritis treated with predefined dose: results from the MIRACLE trial.\",\"authors\":\"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\",\"doi\":\"10.1136/ard-2024-226350\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>The usefulness of methotrexate-polyglutamates (MTX-PGs) concentration for management of rheumatoid arthritis has been debated. We aimed to clarify the association of MTX-PGs concentration with efficacy and safety in MTX-naïve patients initiating MTX in a prospective interventional clinical trial.</p><p><strong>Methods: </strong>The MIRACLE trial enrolled 300 MTX-naïve patients. Oral MTX was initiated and increased to the maximum tolerated dose by week 12. Patients who did not achieve remission according to the Simplified Disease Activity Index at week 24 were randomised to either the continued dose or reduced dose group and were started on subcutaneous adalimumab. We measured the concentrations of MTX-PGs in erythrocytes using liquid chromatography-tandem mass spectrometry and analysed the association of these concentrations with efficacy and safety.</p><p><strong>Results: </strong>The mean concentration of total MTX-PGs increased with an increasing dose of MTX and continued to elevate for another 12 weeks after the dose was fixed. At week 24, the total MTX-PGs concentration was 110.5 (SD 43.8) nmol/L with MTX dose of 12.6 (3.0) mg/week (0.23 (0.07) mg/kg/week). During MTX monotherapy, the higher MTX-PGs concentration was an independent factor for lower disease activity; however, this association disappeared after adalimumab initiation in patients with continued MTX dose. Hepatotoxicity was related to the higher MTX-PGs concentration regardless of adalimumab use. The total MTX-PGs concentration was significantly elevated by lower estimated glomerular filtration rate, serum albumin and body mass index.</p><p><strong>Conclusions: </strong>The MIRACLE trial demonstrated that higher total MTX-PGs concentration in erythrocytes is related to the higher efficacy and lower safety of MTX.</p><p><strong>Trial registration number: </strong>NCT03505008.</p>\",\"PeriodicalId\":8087,\"journal\":{\"name\":\"Annals of the Rheumatic Diseases\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":20.3000,\"publicationDate\":\"2024-10-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annals of the Rheumatic Diseases\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1136/ard-2024-226350\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"RHEUMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of the Rheumatic Diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/ard-2024-226350","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
Association of methotrexate polyglutamates concentration with methotrexate efficacy and safety in patients with rheumatoid arthritis treated with predefined dose: results from the MIRACLE trial.
Objectives: The usefulness of methotrexate-polyglutamates (MTX-PGs) concentration for management of rheumatoid arthritis has been debated. We aimed to clarify the association of MTX-PGs concentration with efficacy and safety in MTX-naïve patients initiating MTX in a prospective interventional clinical trial.
Methods: The MIRACLE trial enrolled 300 MTX-naïve patients. Oral MTX was initiated and increased to the maximum tolerated dose by week 12. Patients who did not achieve remission according to the Simplified Disease Activity Index at week 24 were randomised to either the continued dose or reduced dose group and were started on subcutaneous adalimumab. We measured the concentrations of MTX-PGs in erythrocytes using liquid chromatography-tandem mass spectrometry and analysed the association of these concentrations with efficacy and safety.
Results: The mean concentration of total MTX-PGs increased with an increasing dose of MTX and continued to elevate for another 12 weeks after the dose was fixed. At week 24, the total MTX-PGs concentration was 110.5 (SD 43.8) nmol/L with MTX dose of 12.6 (3.0) mg/week (0.23 (0.07) mg/kg/week). During MTX monotherapy, the higher MTX-PGs concentration was an independent factor for lower disease activity; however, this association disappeared after adalimumab initiation in patients with continued MTX dose. Hepatotoxicity was related to the higher MTX-PGs concentration regardless of adalimumab use. The total MTX-PGs concentration was significantly elevated by lower estimated glomerular filtration rate, serum albumin and body mass index.
Conclusions: The MIRACLE trial demonstrated that higher total MTX-PGs concentration in erythrocytes is related to the higher efficacy and lower safety of MTX.
期刊介绍：
Annals of the Rheumatic Diseases (ARD) is an international peer-reviewed journal covering all aspects of rheumatology, which includes the full spectrum of musculoskeletal conditions, arthritic disease, and connective tissue disorders. ARD publishes basic, clinical, and translational scientific research, including the most important recommendations for the management of various conditions.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
