Abstract
OBJECTIVES: To evaluate disease activity, function, radiographic progression for efficacy and adverse events (AEs) for safety of methotrexate (MTX) at doses of over 8mg/week for rheumatoid arthritis (RA), for which the dose was restricted by the Japanese government until 2011.
METHODS: A retrospective observational study for one year was performed using medical records from 108 RA patients using Disease Activity Score 28-joint assessment using erythrocyte sedimentation rate (DAS28-ESR) to assess disease activity, modified Health Assessment Questionnaire (mHAQ) for functional assessment, modified total Sharp score (mTSS) for image assessment. Safety was evaluated by the relationship between AEs and their prognosis.
RESULTS: DAS28-ESR decreased significantly (P < 0.0001) from 4.3 ± 1.4 to 3.4 ± 1.5 over the one-year observation period. The cases of patients with low disease activity plus remission were significantly increased from 24 (22.2%) at 0 months to 40 cases (47.6%) at 12 months (P < 0.001), with mHAQ changing from 0.69 to 0.55 (P < 0.01), and annual progression of mTSS from 8.2 to 1.02 (P < 0.01). The AEs, such as liver dysfunction, fever, vomiting, pneumonia and shingles were observed by 48 cases (44.4%) and MTX was discontinued in 2 cases. Body weight was one of predictors of AE (P = 0.001). Frequency of severe AEs was significantly related to age （P = 0.02）and combination with DMARDs (P < 0.001).
CONCLUSIONS: Increasing the dose of MTX over 8mg/week showed clinical improvement and effected suppression of joint destruction. However, we need to consider AEs, especially focusing on body weight, age and combination with DMARDs.
