1. In order to determine the optimal oral dose of methotrexate for the treatment of Japanese patients suffered from chronic rheumatoid arthritis (RA), a multi-insti-tutional double-blind study was performed using three different doses (2, 6 and 9 mg/week), each of which was divided into three rations and administered far twelve weeks.
2. The overall improvement ratios at the end of study for each dosing groups were as follows; 26.9% (14/52) in 2 mg/week dosing group, 60.4% (32/53) in 6 mg/week dosing group and 64.4% (29/45) in 9 mg/week dosing group. There was no significant statistical difference between the ratios of 6 and 9 mg/week dosing groups. Although, the latter dosing group seemed to have gained better results than the former dosing group.
3. The respective general safety ratios for 2, 6 and 9 mg/week dosing groups were 72.7% (46/66), 64.7% (44/68) and 64.6% (42/65) . These results indicated no significant statistical difference among these groups ; The general safety ratio of 6 and 9 mg/week dosing groups leveled each other, whereas that of 2 nag/week dosing group appeared to be most favorable.
4. The incidence ratios of the adverse side effects were 10.6% (7/66; 16 cases) in 2 mg/week dosing group, 17.6% (12/68; 24 cases) in 6 mg/week dosing group, and 12.3% (8/65: 12 cases) in 9 mg/week dosing group, indicating that no significant statistical difference exists among these groups. As a severe adverse symptoms, one case of loss of consciousness was observed in 2 mg/week dosing group, one case of vomiting accompanied with diarrhea which required hospitalization was observed in 6 mg/week dosing group, and one case of interstitial pneumonia was observed in 9 mg/week dosing group.
5. The incidence ratios of abnormalities in the clinical chemistry were 23.4% (15/64 ; 7 cases) in 2 mg/week dosing group, 23.8; (15/63 ; 33 cases) in 6 nag/week dosing group and 36.7% (22/60 54 cases) in 9 nag/week dosing group, indicating that no significant statistical difference exists between these groups despite of the highest ratio observed at 9 mg/week dosing group. Decrease in leukocyte and platelet counts were detected in 9 mg/week dosing group only.
6. The usefulness (benefits for patients) ratios at the end of study for each dosing groups were as follows: 19.6% (11/56) in 2 nag/week dosing group, 45.2% (28/62) in 6mg/week dosing group and 38.9% (21/54) in 9 mg/week dosing group. Thus, the statistically significant difference in the usefulness ratios was observed between the 2 and 6 mg/week dosing group only.
7. On the basis of the above described efficacy and safety assessment of methotrexate, the optimal dose for Japanese patients with RA is assumed to be 6 mg/week. In reference to previous reports on Japanese patients, possible oral doses for clinical practice in RA were regarded to be ranged from 4 to rug/week. However, the maximal dose of 9 mg/week should be adopted under meticulous care of the adverse reactions, and only when neither the lower doses elicited sufficient effects nor adverse side effects is observed.
