Article Text
Abstract
Objective To assess the utility of erythrocyte methotrexate-polyglutamate (MTX-PG) concentrations in determining the safety and efficacy of MTX in patients with rheumatoid arthritis (RA).
Methods 79 MTX-naïve patients with RA were enrolled in this prospective 76-week cohort study. MTX was initiated, and a predefined dose-escalation protocol was followed. Erythrocyte MTX-PG concentrations were measured using liquid chromatography. The associations of MTX-PG concentrations with disease activity and adverse events were analysed.
Results Dose escalation of MTX resulted in increased MTX-PG concentrations and a decrease in the mean Disease Activity Score in 28 joints (DAS28). A significant association was observed between total MTX-PG concentrations and ΔDAS28 at week 12 (β=−0.013, p=0.003) and at week 24 (β=−0.014, p=0.003). The maximum MTX-PG levels were significantly higher in patients presenting with elevated transaminases (≥100 IU/L) than in those without (146 vs 106 nmol/L, p=0.009). Receiver operating characteristic curve analysis revealed that a total MTX-PG concentrations of 83 nmol/L at week 12 was the threshold for a DAS28 improvement of ≥1.2 at week 24, and 105 nmol/L was the threshold for transaminases of ≥50 IU/L and 131 nmol/L for transaminases of ≥100 IU/L. MTX-PG concentrations were strongly influenced by body mass index and a serum albumin level.
Conclusions MTX-PG concentrations are a useful biomarker in MTX therapy, in terms of efficacy and safety.
- Rheumatoid Arthritis
- Methotrexate
- Treatment
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Footnotes
Contributors CT, YK and TT designed the study and analysed and interpreted the data. CT, YK, YO, HT, HO, KI and KY were involved in collecting data and managing the clinical research sites. All authors were involved in the writing of the manuscript and have approved the final version.
Competing interests YK has received lecture fees from Abbvie, Eisai Pharmaceutical, Chugai Pharmaceutical, Bristol Myers Squibb, Astellas Pharmaceutical, Mitsubishi Tanabe Pharma Corporation, Pfizer, Janssen and UCB. HO has received lecture fees from Astellas Pharma, Asahi Kasei, Takeda Pharmaceutical, Bristol Myers Squibb, MSD LLC, Chugai Pharmaceutical, Mitsubishi Tanabe Pharma Corporation and DS Pharma Biomedical Co. KY has received consulting fees and speaking fees from Pfizer, Chugai Pharma, Mitsubishi-Tanabe Pharma, Takeda Industrial Pharma, GlaxoSmithkline, Nippon Shinyaku, Eli Lilly, Janssen Pharma, Eisai Pharma, Astellas Pharma and Acterlion Pharmaceuticals. TT has received research grants and lecture fees from Abbvie, Astra Zeneca, Bristol Myers Squibb, Chugai Pharmaceutical, Eisai Pharmaceutical, Janssen Pharmaceutical, Mitsubishi Tanabe Pharma Corporation, Novartis, Takeda Pharmaceutical, Abbott Japan Co., Astellas Pharma, Daiichi Sankyo, Pfizer, Sanofi–Aventis, Santen Pharmaceutical, Teijin Pharma, Asahikasei Pharma Corp., SymBio Pharmaceuticals, Celtrion, Nipponkayaku Co., Eli Lilly Japan K.K. and Taisho Toyama Pharmaceutical.
Patient consent Obtained.
Ethics approval Keio University School of Medicine, Ethics committee.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement No additional data are available.