Daily oral administration of low-dose methotrexate has greater antirheumatic effects in collagen-induced arthritis rats

Objectives: Methotrexate (MTX) is administered once or thrice weekly to patients with rheumatoid arthritis (RA). Even though RA continually progresses, MTX is not administered daily. Therefore, we investigated whether the daily administration of a low dose of MTX inhibits the progression of arthritis in collagen-induced arthritis (CIA) rats. Methods: Methotrexate was orally administered once weekly, thrice weekly and once daily to CIA rats, and arthritis scores were measured. Key findings: When the same dose of MTX was administered, the exacerbation of arthritis was inhibited significantly more in the once-daily group than in the other groups. When the dose in the once-daily group was reduced to one-fourth that of the current standard dosing method, arthritis scores were markedly lower in the once-daily group than in the once and thrice-weekly groups. Conclusions: The daily administration of a low dose of MTX not only maintained normal levels that estimated adverse effects but also suppressed the progression of arthritis significantly more than the current standard dosing method. The results indicate that the reconsideration of dosing schedules based on the characteristics of MTX will lead to more effective RA therapy than that currently used in clinical practice.