Safety and efficacy of T-614 in the treatment of patients with active rheumatoid arthritis: a double blind, randomized, placebo-controlled and multicenter trial.

BACKGROUND A novel anti-rheumatic drug, T-614, has been shown to have an anti-inflammatory effect and to improve abnormal immunological findings in rheumatoid arthritis (RA). To assess the safety and efficacy of T-614 versus placebo in patients with active RA we conducted a 24-week clinical study in 280 Chinese patients. METHODS In a multicenter, randomized, double blind, placebo controlled study, 280 patients were randomly assigned to receive placebo (n = 95) or T-614 at 50 mg (n = 93) or 25 mg (n = 92) daily. Active disease was defined by 4 of the following 5 criteria: >or= 5 tender joints, >or= 3 swollen joints, morning stiffness lasting for >or= 60 minutes, and Westergren erythrocyte sedimentation rate (ESR) >or= 28 mm/h, the assessment of pain at the rest by patient as moderate or severe. Clinical and laboratory parameters were analyzed at baseline, 2, 4, 6, 12, 18 and 24 weeks. The primary efficacy variable at week 24 was the American College of Rheumatology (ACR) response rate using the intent-to-treat population. RESULTS The ACR response rate was significantly higher in the T-614 treatment group compared with the placebo group within 8 weeks after the initiation of treatment. After 24 weeks, the 25 mg/d and 50 mg/d dosage groups and the placebo group showed 39.13%, 61.29% and 24.21% in ACR20 and 23.91%, 31.18% and 7.37% in ACR50, respectively. A time-response in ACR response was observed, with clear superiority for the 25 mg/d and 50 mg/d dosage groups compared to placebo (P < 0.0001), and the 50 mg/d dose compared to the 25 mg/d dose (P < 0.05) when using the ACR response analyses after 24 weeks. ESR and c-reactive protein (CRP) were significantly different in the treatment groups after 24 weeks. The incidence of adverse events (AEs) was not significantly higher with T-614 than with placebo, but upper abdominal discomfort, leucopenia, elevated serum alanine aminotransferase (sALT), skin rash and/or pruritus were more common in the 50 mg and 25 mg dosage groups. CONCLUSION T-614, a new slow-acting drug, is effective in treatment of rheumatoid arthritis and is well tolerated.