Studies of the efficacy and safety of XXXX at dosages over 8 mg/week using the IORRA cohort database.

@entity1 @entity1501 @entity8 @entity134 @entity358 @entity1500 @entity1499 @entity309
The maximum dosage of @entity1499 ( @entity1500 ) for treatment of @entity309 ( @entity309 ) formally approved in Japan is 8 mg/week. We intended to examine the efficacy and safety of @entity1500 at dosages over 8 mg/week in Japanese @entity309 @entity1 using the large Institute of Rheumatology, @entity309 (IORRA) cohort database. Among 9,122 @entity1 registered in the IORRA database from the October 2000 survey to the October 2007 survey, 5,201 @entity1 who had been treated with @entity1500 were selected. We attempted to overcome the drawbacks innate to nonrandomized studies by using longitudinal analyses and multifactorial logistic regression analyses. Cross-sectional analysis of data obtained from the October 2007 survey indicated that dosages of @entity1500 higher than 8 mg/week were used in 27.5% of @entity1 treated with @entity1500 . Longitudinal analyses based on data from three consecutive phases showed that final Disease Activity Score-28 (DAS28) values were significantly lower [n = 260, mean difference 0.563, 95% confidence interval (CI) 0.438-0.688, P < 2.2   10(-22), two-sided paired t test] than initial values when @entity1500 was increased from 8 mg/week or lower to over 8 mg/week. In addition, longitudinal analyses based on data from two consecutive phases indicated decreases in DAS28 values of 0.26    1.04 (n = 690, P = 6.78   10(-11), two-sided paired t test) when @entity1500 dosages were increased from 8 mg/week or lower to over 8 mg/week, compared with decreases of 0.07    0.89 (n = 2,125, P = 0.000307) when the dosage was maintained at 8 mg/week. The decreases in DAS28 values were significantly larger in the former than the latter (P = 2.27   10(-6), two-sided unpaired t test). Concerning safety of @entity1500 at dosages over 8 mg/week, we performed logistic regression analysis in which the objective variable was the existence or nonexistence of self-reported side-effects and the explanatory variable was the @entity1500 dosage in the former phase, with adjustments made for age, sex, body mass index (BMI), @entity134 administration, @entity1501 administration, concomitant @entity358 , and @entity8 . The results indicated that @entity1500 dosages over 8 mg/week did not have any association with either severe or severe + moderate side-effects. These data regarding both efficacy and safety of @entity1500 at dosages over 8 mg/week in Japanese @entity309 @entity1 would provide the basis for use of the drug at dosages currently not formally approved by the Japanese government.
