Efficacy and safety of olokizumab in Asian patients with moderate-to-severe rheumatoid arthritis, previously exposed to anti-TNF therapy: Results from a randomized phase II trial

• Published in: Modern rheumatology Vol. 26; no. 1; pp. 15 - 23
• Main Authors: Takeuchi, Tsutomu, Tanaka, Yoshiya, Yamanaka, Hisashi, Amano, Kanzo, Nagamine, Ryuji, Park, Won, Shiozawa, Kazuko, Tsukano, Michishi, Wei, James Cheng-Chung, Shao, Jing, Togo, Osamu, Mashimo, Hideki
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.01.2016; Informa Healthcare
• Subjects: Adult; Aged; Anti-IL6; Anti-TNF therapy failures; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - therapeutic use; Antirheumatic Agents - adverse effects; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - drug therapy; DMARDs (biologic); Double-Blind Method; Female; Humans; Male; Medical treatment; Middle Aged; Monoclonal antibodies; Olokizumab; Rheumatoid arthritis; Rheumatology; Treatment Outcome; Tumor Necrosis Factor-alpha; Anti-IL6; DMARDs (biologic); Olokizumab; Anti-TNF therapy failures; Rheumatoid arthritis
• ISSN: 1439-7595; 1439-7609
• DOI: 10.3109/14397595.2015.1074648

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.