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

Author:

Nakaoka Yoshikazu12,Isobe Mitsuaki3,Tanaka Yoshiya4,Ishii Tomonori5,Ooka Seido6,Niiro Hiroaki7,Tamura Naoto8,Banno Shogo9,Yoshifuji Hajime10,Sakata Yasushi2,Kawakami Atsushi11,Atsumi Tatsuya12,Furuta Shunsuke13,Kohsaka Hitoshi14,Suzuki Katsuya15,Hara Ryoki16,Maejima Yasuhiro17,Tsukamoto Hiroshi18,Takasaki Yoshinari19,Yamashita Katsuhisa20,Okada Norihiro20,Yamakido Shinji20,Takei Syuji21,Yokota Shumpei22,Nishimoto Norihiro23

Affiliation:

1. Department of Vascular Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita Japan

2. Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka Japan

3. Sakakibara Heart Institute, Tokyo Japan

4. The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu Japan

5. Clinical Research, Innovation and Education Center, Tohoku University Hospital, Sendai Japan

6. Division of Rheumatology and Allergology, Department of Internal Medicine, St Marianna University School of Medicine, Kawasaki Japan

7. Department of Medical Education, Faculty of Medical Sciences, Kyushu University, Fukuoka Japan

8. Department of Internal Medicine and Rheumatology, Juntendo University Faculty of Medicine, Tokyo Japan

9. Division of Nephrology and Rheumatology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute Japan

10. Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto Kyoto, Japan

11. Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki Japan

12. Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo Japan

13. Department of Allergy and Clinical Immunology, Chiba University Hospital, Chiba Japan

14. Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo Japan

15. Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo Japan

16. Department of Pediatrics, Graduate School of Medicine, Yokohama City University, Yokohama Japan

17. Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo Japan

18. Department of Rheumatology, Shin-Kokura Hospital, Kitakyushu Japan

19. Juntendo University Koshigaya Hospital, Juntendo University Faculty of Medicine, Saitama Japan

20. Chugai Pharmaceutical Co., Ltd, Tokyo Japan

21. Pediatrics and Developmental Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima Japan

22. Pediatric Rheumatology, Fuji Toranomon Orthopedics Hospital, Shizuoka, Japan

23. Department of Molecular Regulation for Intractable Diseases, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan

Abstract

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.

Funder

Chugai Pharmaceutical Co. Ltd.

Publisher

Oxford University Press (OUP)

Subject

Pharmacology (medical),Rheumatology

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