Abstract
Objective: Methotrexate (MTX) is considered as an anchor drug in the treatment of rheumatoid arthritis (RA) and the importance of dose incrementation has also become more apparent in Japan since 2011. This study assesses the effects and safety of MTX at a dose of > 8 mg/week in patients with RA.
Methods: Among 199 patients with RA treated with MTX, we examined 35 of them who were prescribed a dose > 8 mg/week, between January 2011 and June 2012 inclusive. Blood values, DAS28 CRP, adverse events and concomitant drug use were analyzed before and at the time of the last observation, an average of 11 months after increasing the dose of MTX.
Results: Seventeen patients were concurrently taking biologic agents in addition to MTX. The maximum average dose used in this patient population was 11.0 mg/week (range: 10 mg to 14 mg/week). The reason for increasing the MTX dose included: poor control of RA, a need to decrease corticosteroid use, and discontinuing biologic agents due to economic or other reasons. The average DAS28 values significantly improved from 2.88 to 2.18, respectively, from prior to the dose increase, and at the time of the last observation. Over half of the patients responded according to the European League Against Rheumatism (EULAR) response criteria. Adverse events included three cases. One case was with interstitial pneumonia, another one was mycoplasma pneumonia and the other was stomatitis. Liver damage that occurred in five patients improved in one case by decreasing the dose of MTX and by adding or increasing the dose of folic acid in four cases, respectively. Cytopenias were not apparent in this study population.
Conclusion: Increasing the dose of MTX decreased the disease activity of RA in our study population. Although some patients developed side effects related to increased MTX doses, these were clinically tolerable.
