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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)

OBJECTIVE: To investigate the efficacy and safety of the interleukin-6 receptor antibody tocilizumab in patients with Takayasu arteritis (TAK). METHODS: Patients with TAK who had relapsed within the previous 12 weeks were induced into remission with oral glucocorticoid therapy. In this double-blind,...

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Autores principales: Nakaoka, Yoshikazu, Isobe, Mitsuaki, Takei, Syuji, Tanaka, Yoshiya, Ishii, Tomonori, Yokota, Shumpei, Nomura, Akira, Yoshida, Seitaro, Nishimoto, Norihiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5867398/
https://www.ncbi.nlm.nih.gov/pubmed/29191819
http://dx.doi.org/10.1136/annrheumdis-2017-211878
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author Nakaoka, Yoshikazu
Isobe, Mitsuaki
Takei, Syuji
Tanaka, Yoshiya
Ishii, Tomonori
Yokota, Shumpei
Nomura, Akira
Yoshida, Seitaro
Nishimoto, Norihiro
author_facet Nakaoka, Yoshikazu
Isobe, Mitsuaki
Takei, Syuji
Tanaka, Yoshiya
Ishii, Tomonori
Yokota, Shumpei
Nomura, Akira
Yoshida, Seitaro
Nishimoto, Norihiro
author_sort Nakaoka, Yoshikazu
collection PubMed
description OBJECTIVE: To investigate the efficacy and safety of the interleukin-6 receptor antibody tocilizumab in patients with Takayasu arteritis (TAK). METHODS: Patients with TAK who had relapsed within the previous 12 weeks were induced into remission with oral glucocorticoid therapy. In this double-blind, placebo-controlled trial, patients were randomly assigned 1:1 to receive weekly tocilizumab 162 mg or placebo subcutaneously, and oral glucocorticoids were tapered 10 %/week from week 4 to a minimum of 0.1 mg/kg/day until 19 patients relapsed. The primary endpoint was time to relapse of TAK, defined as ≥2 of the following: objective systemic symptoms, subjective systemic symptoms, elevated inflammation markers, vascular signs and symptoms or ischaemic symptoms. RESULTS: The intent-to-treat and safety populations included 18 tocilizumab-treated and 18 placebo-treated patients. The per-protocol set (PPS) included 16 tocilizumab-treated and 17 placebo-treated patients. HRs for time to relapse of TAK were 0.41 (95.41% CI 0.15 to 1.10; p=0.0596) in the intent-to-treat population (primary endpoint) based on relapse in eight tocilizumab-treated and 11 placebo-treated patients and 0.34 (95.41% CI 0.11 to 1.00; p=0.0345) in the PPS. The secondary endpoints, time to relapse assessed by Kerr’s definition and clinical symptoms only, were consistent with the primary endpoint. Serious adverse events were reported in one tocilizumab-treated and two placebo-treated patients. There were no serious infections and no deaths. CONCLUSION: Although the primary endpoint was not met, the results suggest favour for tocilizumab over placebo for time to relapse of TAK without new safety concerns. Further investigation is warranted to confirm the efficacy of tocilizumab in patients with refractory TAK. TRIAL REGISTRATION NUMBER: JapicCTI-142616.
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spelling pubmed-58673982018-03-27 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) Nakaoka, Yoshikazu Isobe, Mitsuaki Takei, Syuji Tanaka, Yoshiya Ishii, Tomonori Yokota, Shumpei Nomura, Akira Yoshida, Seitaro Nishimoto, Norihiro Ann Rheum Dis Clinical and Epidemiological Research OBJECTIVE: To investigate the efficacy and safety of the interleukin-6 receptor antibody tocilizumab in patients with Takayasu arteritis (TAK). METHODS: Patients with TAK who had relapsed within the previous 12 weeks were induced into remission with oral glucocorticoid therapy. In this double-blind, placebo-controlled trial, patients were randomly assigned 1:1 to receive weekly tocilizumab 162 mg or placebo subcutaneously, and oral glucocorticoids were tapered 10 %/week from week 4 to a minimum of 0.1 mg/kg/day until 19 patients relapsed. The primary endpoint was time to relapse of TAK, defined as ≥2 of the following: objective systemic symptoms, subjective systemic symptoms, elevated inflammation markers, vascular signs and symptoms or ischaemic symptoms. RESULTS: The intent-to-treat and safety populations included 18 tocilizumab-treated and 18 placebo-treated patients. The per-protocol set (PPS) included 16 tocilizumab-treated and 17 placebo-treated patients. HRs for time to relapse of TAK were 0.41 (95.41% CI 0.15 to 1.10; p=0.0596) in the intent-to-treat population (primary endpoint) based on relapse in eight tocilizumab-treated and 11 placebo-treated patients and 0.34 (95.41% CI 0.11 to 1.00; p=0.0345) in the PPS. The secondary endpoints, time to relapse assessed by Kerr’s definition and clinical symptoms only, were consistent with the primary endpoint. Serious adverse events were reported in one tocilizumab-treated and two placebo-treated patients. There were no serious infections and no deaths. CONCLUSION: Although the primary endpoint was not met, the results suggest favour for tocilizumab over placebo for time to relapse of TAK without new safety concerns. Further investigation is warranted to confirm the efficacy of tocilizumab in patients with refractory TAK. TRIAL REGISTRATION NUMBER: JapicCTI-142616. BMJ Publishing Group 2018-03 2017-11-30 /pmc/articles/PMC5867398/ /pubmed/29191819 http://dx.doi.org/10.1136/annrheumdis-2017-211878 Text en © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
spellingShingle Clinical and Epidemiological Research
Nakaoka, Yoshikazu
Isobe, Mitsuaki
Takei, Syuji
Tanaka, Yoshiya
Ishii, Tomonori
Yokota, Shumpei
Nomura, Akira
Yoshida, Seitaro
Nishimoto, Norihiro
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)
title 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)
title_full 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)
title_fullStr 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)
title_full_unstemmed 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)
title_short 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)
title_sort 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)
topic Clinical and Epidemiological Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5867398/
https://www.ncbi.nlm.nih.gov/pubmed/29191819
http://dx.doi.org/10.1136/annrheumdis-2017-211878
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