Safety and effectiveness of high-dose methotrexate (over 8 mg/week) in 2838 Japanese patients with rheumatoid arthritis: a postmarketing surveillance report

Post-marketing surveillance of high-dose methotrexate (>8 mg/week) in Japanese patients with rheumatoid arthritis: A post hoc sub-analysis of patients according to duration of prior methotrexate use

“…As such, the favorable results observed with high-dose MTX in the overall PMS study population may have been influenced by the fact that some patients had previously received long-term low-dose MTX, potentially leading to greater overall tolerability and effectiveness. This hypothesis was further supported by risk factor analyses, which found that an MTX usage of !1 year decreased the risk of hepatic disorders in the overall PMS study population [6].…”

“…The study design has been described previously [6]. In brief, between 2011 and 2012, the study enrolled Japanese patients with RA starting with high-dose MTX (Rheumatrex V R 2 mg capsule (Pfizer Japan Inc, Tokyo, Japan) at a dose of >8 mg/week) at the discretion of their prescribing physician.…”

“…Primary analyses of the PMS study data indicated that high-dose MTX was well tolerated and improved disease control over both 24-and 52-week follow-up periods [6]. It has previously been suggested that tolerance to MTX increases with duration of treatment [7].…”

“…In Japan, MTX was approved initially for the treatment of RA at a maximum dose of 8 mg/week, with the Ministry of Health, Labour and Welfare (MHLW) later approving doses of up to 16 mg/week, based on study data that suggested that higher doses could confer improved antirheumatic effects in Japanese populations [4,5]. In line with regulatory requirements mandated upon the approval of higher MTX doses, a post-marketing surveillance (PMS) study was implemented to evaluate the safety and effectiveness of high-dose MTX (>8 mg/week) in Japanese patients with RA in a real-world clinical setting [6].…”

Weekly split‐dose regimen for oral methotrexate reduced polyglutamation in red blood cells in patients with rheumatoid arthritis compared with single‐dose regimen: Results from a multicentered randomized control trial

“…Methotrexate (MTX) is a globally recognized disease‐modifying anti‐rheumatic drug considered as the anchor drug for the treatment of rheumatoid arthritis (RA); however, the major dose regimens vary among countries and region 1‐3 . For example, the weekly dose is taken as a single dose in the US, but is generally divided into 2‐4 parts taken at 12‐hour intervals in Japan when it exceeds 8 mg.…”