Tsutomu Takeuchi1, Yoshiya Tanaka2, Hisashi Yamanaka3, Kanzo Amano4, Ryuji Nagamine5, Won Park6, Kazuko Shiozawa7, Michishi Tsukano8, James Cheng-Chung Wei9,10,11, Jing Shao12, Osamu Togo12, Hideki Mashimo12. 1. a Division of Rheumatology, Department of Internal Medicine , School of Medicine, Keio University , Tokyo, Japan . 2. b The First Department of Internal Medicine , School of Medicine, University of Occupational and Environmental Health , Kitakyushu City , Fukuoka Prefecture , Japan . 3. c Institute of Rheumatology, Tokyo Women's Medical University , Japan . 4. d Hiroshima Clinic , Hiroshima, Japan . 5. e Center of Joint Arthroplasty and Rheumatism, Fukuoka Tokushukai Hospital , Kasuga , Fukuoka Prefecture , Japan . 6. f Inha University Hospital , Incheon , Korea . 7. g Kohnan Kakogawa Hospital , Hyogo , Japan . 8. h Kumamoto Orthopaedic Hospital , Kumamoto, Japan . 9. i Division of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital , Taichung , Taiwan . 10. j Institute of Medicine, Chung Shan Medical University , Taichung , Taiwan . 11. k nstitute of Integrative Medicine, China Medical University , Taichung , Taiwan , and. 12. l UCB Pharma , Tokyo , Japan.
Abstract
OBJECTIVES: This phase II, dose-ranging, double-blind, placebo-controlled, randomized study (NCT01463059) evaluated efficacy and safety of olokizumab (OKZ), a humanized anti-interleukin 6 monoclonal antibody, in Asian patients with moderately-to-severely active rheumatoid arthritis (RA) who had previously failed anti-TNF therapy. METHODS: Patients were randomized to one of six treatment arms: placebo or OKZ (60 mg/120 mg/240 mg every four weeks [Q4W]; or 60 mg/120 mg every two weeks [Q2W]); stratified by country and number of prior anti-TNFs. Primary efficacy variable was Week 12 change from baseline (CFB) in DAS28 CRP for 4-week cumulative dose groups of OKZ and placebo; secondary efficacy variables were Week 12 ACR20/ACR50/ACR70 response rates. Patients continued MTX treatment from baseline, without additional csDMARDs. RESULTS: Of 119 randomized patients, 88.2% completed the study. Greater improvements in DAS28(CRP) mean CFB at Week 12 were observed in all OKZ 4-week cumulative dose groups (60 mg/120 mg/240 mg) versus placebo (p < 0.0001). Week 12 ACR20/ACR50 response rates were higher in all OKZ cumulative dose groups versus PBO (p < 0.05). Incidences of adverse events were similar across OKZ 4-week cumulative dose groups (76.9-84.4%) and placebo (82.8%) with no deaths. CONCLUSIONS:OKZ demonstrated improvements in efficacy variables versus placebo in Asian patients with moderately-to-severely active RA who had previously failed anti-TNF therapy. The safety profile was as expected for this class of drug.
RCT Entities:
OBJECTIVES: This phase II, dose-ranging, double-blind, placebo-controlled, randomized study (NCT01463059) evaluated efficacy and safety of olokizumab (OKZ), a humanized anti-interleukin 6 monoclonal antibody, in Asian patients with moderately-to-severely active rheumatoid arthritis (RA) who had previously failed anti-TNF therapy. METHODS:Patients were randomized to one of six treatment arms: placebo or OKZ (60 mg/120 mg/240 mg every four weeks [Q4W]; or 60 mg/120 mg every two weeks [Q2W]); stratified by country and number of prior anti-TNFs. Primary efficacy variable was Week 12 change from baseline (CFB) in DAS28 CRP for 4-week cumulative dose groups of OKZ and placebo; secondary efficacy variables were Week 12 ACR20/ACR50/ACR70 response rates. Patients continued MTX treatment from baseline, without additional csDMARDs. RESULTS: Of 119 randomized patients, 88.2% completed the study. Greater improvements in DAS28(CRP) mean CFB at Week 12 were observed in all OKZ 4-week cumulative dose groups (60 mg/120 mg/240 mg) versus placebo (p < 0.0001). Week 12 ACR20/ACR50 response rates were higher in all OKZ cumulative dose groups versus PBO (p < 0.05). Incidences of adverse events were similar across OKZ 4-week cumulative dose groups (76.9-84.4%) and placebo (82.8%) with no deaths. CONCLUSIONS:OKZ demonstrated improvements in efficacy variables versus placebo in Asian patients with moderately-to-severely active RA who had previously failed anti-TNF therapy. The safety profile was as expected for this class of drug.
Authors: Andreas Kerschbaumer; Alexandre Sepriano; Josef S Smolen; Désirée van der Heijde; Maxime Dougados; Ronald van Vollenhoven; Iain B McInnes; Johannes W J Bijlsma; Gerd R Burmester; Maarten de Wit; Louise Falzon; Robert Landewé Journal: Ann Rheum Dis Date: 2020-02-07 Impact factor: 19.103
Authors: Tsutomu Takeuchi; Carter Thorne; George Karpouzas; Shihong Sheng; Weichun Xu; Ravi Rao; Kaiyin Fei; Benjamin Hsu; Paul P Tak Journal: Ann Rheum Dis Date: 2017-08-30 Impact factor: 19.103
Authors: Maria Gabriella Raimondo; Martina Biggioggero; Chiara Crotti; Andrea Becciolini; Ennio Giulio Favalli Journal: Drug Des Devel Ther Date: 2017-05-24 Impact factor: 4.162