332. LONG-TERM EFFICACY AND SAFETY OF TOCILIZUMAB IN PATIENTS WITH REFRACTORY TAKAYASU ARTERITIS: FINAL RESULTS FROM THE TAKT STUDY

Abstract

Background: Takayasu arteritis (TAK) is a rare inflammatory vasculitis affecting the aorta and its major branches. In the TAKT study (the first randomized, double-blind, placebo-controlled, multicenter, phase 3 trial of tocilizumab TCZ] in patients with refractory TAK), we demonstrated a favorable effect for TCZ over placebo for time-to-relapse (hazard ratio, 0.41 95.41% CI, 0.15-1.10]; p = 0.0596) while the background glucocorticoid (GC) was mandatorily tapered by 10%/week. However, only short-term TCZ treatment (median 19.00 weeks) was assessed during the double-blind period, and no prospective study assessing the Sk long-term o e ntent cy and safety of TCZ in TAK patients has been reported. This study aimed to use the final results of the TAKT study to evaluate the long-term efficacy and safety of TCZ in patients with TAK in the real-world clinical setting, where GC dose can be adjusted at the physician's discretion. Method(s): All 36 enrolled patients, who had received a weekly dose of either 162 mg TCZ (n = 18) or placebo (n = 18) along with scheduled GC tapering after achieving remission with GC therapy in the double-blind period of the TAKT study, moved on to the open-label extension period and received subcutaneous TCZ. Key endpoints of the long-term extension analysis included the steroid-sparing effect, imaging data, quality of life (QOL) assessed by the 36-Item Short Form Health Survey (SF-36), and safety. Result(s): TCZ demonstrated a steroid-sparing effect in patients with TAK after 96 weeks of treatment; the median GC dose was reduced to 0.105 mg/kg/day, which was less than half the dose (0.223 mg/kg/day) administered at the time of relapse before study entry. By Week 24, 62.5% of patients were able to reduce their GC dose to < 0.2 mg/kg/day. By Week 96, 85.7% of patients had reduced their GC dose to < 0.2 mg/kg/day, and 46.4% had reduced their GC dose to < 0.1 mg/kg/day. Imaging (per physician judgment) showed that the status of 85.7% of patients had improved (17.9%) or stabilized (67.9%) after 96 weeks of TCZ compared with their baseline status. Patients also experienced improvement in QOL, as demonstrated by improvement from baseline in SF-36 scores that reached clinically meaningful thresholds. Long-term safety results of treatment with TCZ at 162 mg/week for more than 96 weeks were consistent with the known safety profile of TCZ. Conclusion(s): In this prospective clinical trial, long-term weekly treatment with 162 mg TCZ demonstrated a clear steroid- sparing effect and clinically meaningful improvements in patient QOL, with no new safety concerns.