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

<b>Objectives:</b> To confirm the safety and effectiveness of high-dose (&gt;8 mg/week) methotrexate (MTX) for the treatment of rheumatoid arthritis in Japan. <b>Methods:</b> A postmarketing surveillance program enrolled Japanese patients with rheumatoid arthritis starting on high-dose MTX followed up for either 24- or 52-weeks. Analyses for safety, risk factors affecting safety, and effectiveness were conducted. <b>Results:</b> The safety/effectiveness analysis sets included 2838/2779 and 335/326 patients in the 24-weeks and 52-weeks follow-up groups, respectively. Incidence rates of adverse drug reactions (ADRs) and serious ADRs were 21.42% and 1.66% in the 24-weeks, and 35.52% and 2.69% in the 52-weeks groups, respectively. The Disease Activity Score in 28 Joints (DAS28) was significantly decreased as early as four weeks from the start of high-dose MTX; after 24-weeks (4.09–3.21) and 52-weeks of treatment (3.91–2.80; both <i>p</i> <b>Conclusions:</b> High-dose MTX was well tolerated in Japanese patients, resulted in improved disease control, and can be considered a step forward in achieving treat-to-target goals.