Comparison of two different XXXX doses with @entity1499 - a randomized controlled trial (FOLVARI Study).

@entity1501 @entity1 @entity137 @entity627 @entity6822 @entity1503 @entity854 @entity1499 @entity309
INTRODUCTION: There is reasonable evidence that @entity1501 5-10 mg per week leads to reduction in @entity1499 ( @entity6822 ) @entity137 in @entity309 ( @entity309 ). However, this is based on studies conducted with lower @entity6822 dosage than used currently. It is unclear whether higher doses of @entity1501 may be better in reducing @entity137 . METHODS: This was a double-blind randomized controlled trial of 24 weeks duration. To be eligible, @entity1 should have @entity309 (1987 American College of Rheumatology criteria), be 18-75 years of age, not be on @entity6822 and have active disease as defined by 'Modified Disease Activity Score using three variables' (DAS28(3)) > 3.2. @entity6822 was started at 10 mg/week and escalated to 25 mg/week by 12 weeks. @entity1501 was given at a dose of 10 mg (FA10) or 30 mg per week (FA30). Co-primary endpoints were incidence of @entity137 (undesirable symptoms and @entity854 ) and change in disease activity by 24 weeks. Intention-to-treat and per-protocol analyses were performed. RESULTS: Among 100 @entity1 enrolled, 51 and 49 were randomized to FA10 and FA30 respectively. By 24 weeks, there were 6 @entity1 withdrawals in either group and mean(  SD) dose of @entity6822 was 22.8    4.4 and 21.4    4.6 mg per week (p = 0.1). Frequency of @entity1 with undesirable symptoms was non-significantly lower by 7.4 % (95 % confidence interval -27.4 to 12.7 %) in FA10 compared to FA30. There was also no difference in frequency of transaminitis (>Upper limit of normal (ULN)) (42.6, 45.7 %, p = 0.7) or transminitis as per primary endpoint (>2xULN) (10.6, 8.7 %, p = 1.0) or @entity1503 (4.3, 4.3 %, p = 0.9). There was no difference in the primary end-point of occurrence of any adverse effect (symptom or laboratory) in FA10 and FA30 (46.8, 54.3 %, p = 0.5). At 24 weeks, DAS28(3) declined in both groups by a similar extent (-1.1    1.0, -1.3    1.0, p = 0.2) and 'European League Against @entity627 ' good or moderate response occurred in 56.9 and 67.4 % (p = 0.3). CONCLUSIONS: Even with the high doses of @entity6822 used in current practice, there was no additional benefit (or harm) of a higher dose of @entity1501 (30 mg/week) over a usual dose (10 mg/week). TRIAL REGISTRATION: Clinicaltrials.gov NCT01583959 Registered 15 March 2012.
