Takayasu Arteritis: Efficacy and Safety of Tocilizumab vs Placebo

Tocilizumab improves time to relapse in Takayasu arteritis with a favorable safety and tolerability profile, according to findings from a randomized, double-blind trial published in the Annals of Rheumatic Diseases.

Patients with Takayasu arteritis who had relapsed within 12 weeks prior to the start of the study were administered oral glucocorticoid therapy to induce remission. Patients in the intent-to-treat and safety populations were randomly assigned to receive weekly 162 mg tocilizumab (n=18) or subcutaneously administered placebo (n=18). In the per-protocol analysis, a total of 16 and 17 patients were treated with tocilizumab and placebo, respectively.

The investigators tapered oral glucocorticoids 10% per week from week 4 of the study to a minimum of 0.1 mg/kg/day until 19 patients relapsed. Investigators assessed the time to Takayasu arteritis relapse as the primary end point, which was defined as the presence of ≥2 of: elevated inflammation markers, ischemic symptoms, objective systemic symptoms, subjective systemic symptoms, and vascular signs and symptoms.

Although the primary end point was not met, fewer patients in the tocilizumab-treated group experienced relapse compared with patients randomly assigned to placebo in the intent-to-treat population (8 vs 11, respectively; hazard ratio [HR], 0.41; 95.41% CI, 0.15-1.10; P =.0596). In the per-protocol set, significantly more patients treated with placebo experienced relapse vs patients receiving treatment (11 vs 7, respectively; HR 0.34, 95.41% CI, 0.11-1.00; P =.0345). A total of 2 patients treated with placebo experienced serious adverse events compared with 1 patient who received tocilizumab. No differences were observed between the 2 groups with regard to time to relapse based on clinical symptoms only (HR, 0.70; 95.41% CI, 0.29-1.70; P =.4224).

The primary limitation of this study was the small number of patients included in the analysis. In addition, the study may have provided more clinically relevant findings if the investigators assessed the impact of tocilizumab in patients who were also taking disease-modifying antirheumatic drugs or immunosuppressants.

To improve chances of remission, the investigators suggest that “higher serum tocilizumab concentrations may be required to completely inhibit interleukin (IL)-6 binding to IL-6R in patients with active [Takayasu arteritis].”

Reference

Nakaoka Y, Isobe M, Takei S, et al. Efficacy and safety of tocilizumab in patients with refractory Takayasu arteritis: results from a randomised, double-blind, placebo-controlled, phase 3 trial in Japan (the TAKT study). Ann Rheum Dis. 2018;77(3):348-354.