Mark C Genovese1, Daniel K Braun2, Janelle S Erickson2, Pierre-Yves Berclaz2, Subhashis Banerjee2, Michael P Heffernan2, Hilde Carlier2. 1. From the Division of Immunology and Rheumatology, Stanford University Medical Center, Palo Alto, California; Eli Lilly and Company, Indianapolis, Indiana; Bristol-Myers Squibb, Princeton, New Jersey, USA.M.C. Genovese, MD, James W. Raitt Professor of Medicine, Co-Chief of Division of Immunology and Rheumatology, Stanford University School of Medicine; D.K. Braun, MD, Medical Fellow; Eli Lilly and Company; J.S. Erickson, PhD, Statistician, Eli Lilly and Company; P.Y. Berclaz, MD, Senior Medical Director, Eli Lilly and Company; M.P. Heffernan, MD, Senior Medical Director, Eli Lilly and Company; H. Carlier, MD, Senior Medical Advisor, Eli Lilly and Company, Indianapolis; S. Banerjee, MD, Bristol-Myers Squibb. genovese@stanford.edu. 2. From the Division of Immunology and Rheumatology, Stanford University Medical Center, Palo Alto, California; Eli Lilly and Company, Indianapolis, Indiana; Bristol-Myers Squibb, Princeton, New Jersey, USA.M.C. Genovese, MD, James W. Raitt Professor of Medicine, Co-Chief of Division of Immunology and Rheumatology, Stanford University School of Medicine; D.K. Braun, MD, Medical Fellow; Eli Lilly and Company; J.S. Erickson, PhD, Statistician, Eli Lilly and Company; P.Y. Berclaz, MD, Senior Medical Director, Eli Lilly and Company; M.P. Heffernan, MD, Senior Medical Director, Eli Lilly and Company; H. Carlier, MD, Senior Medical Advisor, Eli Lilly and Company, Indianapolis; S. Banerjee, MD, Bristol-Myers Squibb.
Abstract
OBJECTIVE: To evaluate ixekizumab, an anti-interleukin 17A monoclonal antibody, for safety and effectiveness through 64 weeks in biologic-naive and tumor necrosis factor-inadequate responder (TNF-IR) patients with rheumatoid arthritis. METHODS: Patients completing the 16-week double-blind period of a phase II study were eligible to enter the open-label extension (OLE) for an additional 48 weeks of ixekizumab treatment. After a treatment hiatus between weeks 10 to 16, 232 biologic-naive and 158 TNF-IR patients entered the OLE with all patients receiving 160 mg ixekizumab at weeks 16, 18, and 20, and then every 4 weeks through Week 64. RESULTS:A total of 201 (87%) biologic-naive and 99 (62%) TNF-IR patients completed the OLE. Treatment-emergent adverse events (AE) occurred in 168 (72%) biologic-naive and 115 (73%) TNF-IR patients during the OLE. Most AE were mild to moderate in severity and did not lead to study discontinuation. Serious AE (SAE) occurred in 17 (7%) biologic-naive patients, including 5 (2%) serious infections and 2 (1%) deaths. SAE occurred in 18 (11%) TNF-IR patients, including 4 (3%) serious infections and 1 (1%) death. No mycobacterial or invasive fungal infections were reported. Clinical responses [American College of Rheumatology (ACR) 20, ACR50, ACR70, and 28-joint Disease Activity Score with C-reactive protein] observed at Week 16 were maintained or improved through Week 64. CONCLUSION:Ixekizumab was well tolerated, and safety findings in the OLE were consistent overall with those in the double-blind period of this study. Clinical improvements observed with ixekizumab through Week 16 were maintained or improved in patients participating in the OLE through Week 64. TRIAL REGISTRATION NUMBER: NCT00966875.
RCT Entities:
OBJECTIVE: To evaluate ixekizumab, an anti-interleukin 17A monoclonal antibody, for safety and effectiveness through 64 weeks in biologic-naive and tumor necrosis factor-inadequate responder (TNF-IR) patients with rheumatoid arthritis. METHODS:Patients completing the 16-week double-blind period of a phase II study were eligible to enter the open-label extension (OLE) for an additional 48 weeks of ixekizumab treatment. After a treatment hiatus between weeks 10 to 16, 232 biologic-naive and 158 TNF-IR patients entered the OLE with all patients receiving 160 mg ixekizumab at weeks 16, 18, and 20, and then every 4 weeks through Week 64. RESULTS: A total of 201 (87%) biologic-naive and 99 (62%) TNF-IR patients completed the OLE. Treatment-emergent adverse events (AE) occurred in 168 (72%) biologic-naive and 115 (73%) TNF-IR patients during the OLE. Most AE were mild to moderate in severity and did not lead to study discontinuation. Serious AE (SAE) occurred in 17 (7%) biologic-naive patients, including 5 (2%) serious infections and 2 (1%) deaths. SAE occurred in 18 (11%) TNF-IR patients, including 4 (3%) serious infections and 1 (1%) death. No mycobacterial or invasive fungal infections were reported. Clinical responses [American College of Rheumatology (ACR) 20, ACR50, ACR70, and 28-joint Disease Activity Score with C-reactive protein] observed at Week 16 were maintained or improved through Week 64. CONCLUSION:Ixekizumab was well tolerated, and safety findings in the OLE were consistent overall with those in the double-blind period of this study. Clinical improvements observed with ixekizumab through Week 16 were maintained or improved in patients participating in the OLE through Week 64. TRIAL REGISTRATION NUMBER: NCT00966875.