Kenneth B Gordon1, Craig L Leonardi2, Mark Lebwohl3, Andrew Blauvelt4, Gregory S Cameron5, Daniel Braun5, Janelle Erickson5, Michael Heffernan5. 1. Northwestern University, Feinberg School of Medicine, Chicago, Illinois. Electronic address: kenneth-gordon@northwestern.edu. 2. Saint Louis University School of Medicine, St Louis, Missouri. 3. Icahn School of Medicine at Mount Sinai, New York, New York. 4. Oregon Medical Research Center, Portland, Oregon. 5. Eli Lilly and Company, Indianapolis, Indiana.
Abstract
BACKGROUND:Patients with moderate to severe plaque psoriasis demonstrated positive responses to ixekizumab, an anti-interleukin-17A monoclonal antibody, in a phase-II, randomized, placebo-controlled trial. OBJECTIVE: We sought to evaluate long-term efficacy and safety of ixekizumab. METHODS: After receiving 10, 25, 75, or 150 mg of ixekizumab or placebo during randomized, placebo-controlled trial, patients with less than 75% improvement from baseline on the Psoriasis Area and Severity Index (PASI) score (PASI75) entered open-label extension (OLE); patients with PASI75 or higher entered a treatment-free period (weeks 20-32), then entered OLE after meeting response criteria. During OLE, patients received 120 mg of subcutaneous ixekizumab every 4 weeks. RESULTS: In all, 120 patients entered OLE; 103 completed 52 weeks or more of treatment. Overall, 77% of patients achieved PASI75 at week 52 (nonresponder imputation). Patients who responded to treatment in the randomized, placebo-controlled trial maintained a high-level response by week 52 of OLE (PASI75 = 95%; 90% improvement from baseline on the PASI score = 94%; 100% improvement from baseline on the PASI score = 82%). Irrespective of dose in the randomized, placebo-controlled trial, each group had similar response rates at week 52 of OLE. The exposure-adjusted incidence rate for adverse events was 0.47 and for serious adverse events was 0.06 per patient-year during OLE. LIMITATIONS: No control group, small sample sizes, and bias toward retention of patients with positive responses limit interpretation. CONCLUSION: A high proportion of patients responded to ixekizumab therapy and maintained clinical responses over 1 year of treatment with no unexpected safety signals.
RCT Entities:
BACKGROUND:Patients with moderate to severe plaque psoriasis demonstrated positive responses to ixekizumab, an anti-interleukin-17A monoclonal antibody, in a phase-II, randomized, placebo-controlled trial. OBJECTIVE: We sought to evaluate long-term efficacy and safety of ixekizumab. METHODS: After receiving 10, 25, 75, or 150 mg of ixekizumab or placebo during randomized, placebo-controlled trial, patients with less than 75% improvement from baseline on the Psoriasis Area and Severity Index (PASI) score (PASI75) entered open-label extension (OLE); patients with PASI75 or higher entered a treatment-free period (weeks 20-32), then entered OLE after meeting response criteria. During OLE, patients received 120 mg of subcutaneous ixekizumab every 4 weeks. RESULTS: In all, 120 patients entered OLE; 103 completed 52 weeks or more of treatment. Overall, 77% of patients achieved PASI75 at week 52 (nonresponder imputation). Patients who responded to treatment in the randomized, placebo-controlled trial maintained a high-level response by week 52 of OLE (PASI75 = 95%; 90% improvement from baseline on the PASI score = 94%; 100% improvement from baseline on the PASI score = 82%). Irrespective of dose in the randomized, placebo-controlled trial, each group had similar response rates at week 52 of OLE. The exposure-adjusted incidence rate for adverse events was 0.47 and for serious adverse events was 0.06 per patient-year during OLE. LIMITATIONS: No control group, small sample sizes, and bias toward retention of patients with positive responses limit interpretation. CONCLUSION: A high proportion of patients responded to ixekizumab therapy and maintained clinical responses over 1 year of treatment with no unexpected safety signals.
Authors: Claus Johansen; Maike Mose; Pernille Ommen; Trine Bertelsen; Hanne Vinter; Stephan Hailfinger; Sebastian Lorscheid; Klaus Schulze-Osthoff; Lars Iversen Journal: Proc Natl Acad Sci U S A Date: 2015-10-12 Impact factor: 11.205
Authors: Yi Fritz; Philip A Klenotic; William R Swindell; Zhi Qiang Yin; Sarah G Groft; Li Zhang; Jaymie Baliwag; Maya I Camhi; Doina Diaconu; Andrew B Young; Alexander M Foster; Andrew Johnston; Johann E Gudjonsson; Thomas S McCormick; Nicole L Ward Journal: J Invest Dermatol Date: 2016-10-27 Impact factor: 8.551