Application of chronotherapy of antirheumatic drug to perform proper therapy

We have performed the randomized double blind controlled trial of chronotherapy against rheumatoid arthritis (RA) patients treated methotrexate (MTX). We divided into two groups of the standard MTX schedule and chronotherapy schedule, in which the dose and number of doses per week were not changed from the standard MTX schedule of each patient but MTX was administered once a day at bedtime. In interim report, the chronotherapy schedule group improved therapeutic effects compared with the standard MTX schedule group. In basic study, we investigated what cytokines and/or transcriptional factors are involved in the formation of 24-hour variations in TNF-alpha levels after the onset of RA using MRL/lpr mice. SAA and TNF-alpha concentrations clearly exhibited 24-hour rhythms with higher levels at the light phase and lower levels at the dark phase after RA crisis. One of the causes of the 24-hour rhythm of TNF-alpha expression in RA may have been clarified by this study.