Long-term efficacy and safety of tocilizumab in refractory Takayasu arteritis: final results of the randomized controlled phase 3 TAKT study

Abstract

Objective: To investigate the long-term efficacy and safety of the IL-6 receptor antibody tocilizumab in patients with Takayasu arteritis (TAK).

Methods: Patients completing the randomized, double-blind, placebo-controlled period of the TAKT (Takayasu arteritis Treated with Tocilizumab) trial were followed up during open-label extended treatment with weekly s.c. tocilizumab 162 mg for up to 96 weeks or longer, with oral glucocorticoid tapering performed at the investigators' discretion. Endpoints of the extension analysis included steroid-sparing effects of tocilizumab, imaging data, patient-reported outcomes (36-Item Short Form Health Survey) and safety.

Results: All 36 patients enrolled in the double-blind period entered the open-label extension; 28 patients received tocilizumab for 96 weeks. The median glucocorticoid dose was 0.223 mg/kg/day at the time of relapse before study entry, 0.131 mg/kg/day (interquartile range 0.099, 0.207) after 48 weeks and 0.105 mg/kg/day (interquartile range 0.039, 0.153) after 96 weeks. Overall, 46.4% of patients reduced their dose to <0.1 mg/kg/day, which was less than half the dose administered at relapse before study entry (mean difference -0.120 mg/kg/day; 95% CI -0.154, -0.087). Imaging evaluations indicated that most patients' disease was improved (17.9%) or stable (67.9%) after 96 weeks compared with baseline. Mean 36-Item Short Form Health Survey physical and mental component summary scores and 7 of 8 domain scores were clinically improved from baseline and maintained over 96 weeks of tocilizumab treatment. No unexpected safety issues were reported.

Conclusion: These results in patients with Takayasu arteritis provide evidence of a steroid-sparing effect and improvements in well-being during long-term treatment with once-weekly tocilizumab 162 mg, with no new safety concerns.

Trial registration: JAPIC Clinical Trials Information, http://www.clinicaltrials.jp/user/cteSearch_e.jsp, JapicCTI-142616.

Keywords: Takayasu arteritis; biological therapies; immunosuppressants; quality of life; vasculitis.

Fig. 1

GC dosing in the TAKT study (A) Individual GC dose at each time point. (B) Individual GC dose reductions over time. ^aChange from dose at relapse before study entry. ^bBy 10% per week to a minimum of 0.1 mg/kg/day. Data were collected at 12 weeks (day 85), 24 weeks (day 169), 48 weeks (day 337), 72 weeks (day 506) and 96 weeks (day 673) after TCZ administration. If data were unavailable for the specified time point (definition date) but the patient had other visits within the time window, the most recent data (definition date minus 7 days) were used for dose calculations. The GC doses at each time point were calculated according to each patient’s weight at baseline. GC: glucocorticoid; IQR: interquartile range; Q: quartile; TAKT: Takayasu arteritis Treated with Tocilizumab trial; TCZ: tocilizumab.

Fig. 2

Patient well-being in the TAKT study (A) Patient-reported outcomes measured by the SF-36 component summary scores. (B) Patients with clinically meaningful improvements (MCID >2.5) from baseline. (C) Individual domain scores. Patients with missing baseline data were excluded for these analyses. *Change from baseline MCID of >5.0 for TCZ QW at weeks 48 and 96. ^aFor calculation of age- and gender-matched norms, patients younger than 20 years of age were calculated as 20 years of age. MCS consists of social functioning, mental health, role emotional and vitality domains. PCS consists of physical functioning, role physical, bodily pain and general health domains. SF-36 MCID has not been validated in patients with TAK. BL: baseline; BP: bodily pain; GH: general health; MCID: minimum clinically important difference; MCS: mental component summary; MH: mental health; PCS: physical component summary; PF: physical function; QW: once weekly; RE: role emotional; RP: role physical; SF: social function; SF-36: 36-Item Short Form Health Survey; TAKT: Takayasu arteritis Treated with Tocilizumab trial; TCZ: tocilizumab; VT: vitality.