Désirée van der Heijde1,2,3, Dafna D Gladman4,5,6, Mitsumasa Kishimoto4,5,6, Masato Okada4,5,6, Suchitrita S Rathmann4,5,6, Susan R Moriarty4,5,6, Catherine L Shuler4,5,6, Hilde Carlier4,5,6, Olivier Benichou4,5,6, Philip J Mease4,5,6. 1. From the Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands; Division of Rheumatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Immuno-Rheumatology Center, St. Luke's International Hospital, St. Luke's International University, Tokyo, Japan; Eli Lilly and Company, Indianapolis, Indiana, USA; Laboratoires Lilly France, Neuilly, France; Department of Rheumatology, Swedish Medical Center; University of Washington, Seattle, Washington, USA. mail@dvanderheijde.nl. 2. D. van der Heijde has received consulting fees from AbbVie and Eli Lilly and Company. D.D. Gladman has received grants or consulting fees from AbbVie and Eli Lilly and Company. M. Kishimoto received honoraria and advisory fees from AbbVie and Eli Lilly and Company. S. Rathmann, S. Moriarty, C. Shuler, and H. Carlier are employees and stockholders of Eli Lilly and Company. O. Benichou is an employee and stockholder of Laboratoires Lilly France. P.J. Mease has received research grants and has been a consultant and/or speaker for AbbVie and Eli Lilly and Company. mail@dvanderheijde.nl. 3. D. van der Heijde, MD, PhD, Department of Rheumatology, Leiden University Medical Center; D.D. Gladman, MD, FRCPC, Division of Rheumatology, Department of Medicine, University of Toronto; M. Kishimoto, MD, PhD, Immuno-Rheumatology Center, St. Luke's International Hospital, St. Luke's International University; M. Okada, MD, Immuno-Rheumatology Center, St. Luke's International Hospital, St. Luke's International University; S.S. Rathmann, PhD, Eli Lilly and Company; S.R. Moriarty, MD, Eli Lilly and Company; C.L. Shuler, MS, Eli Lilly and Company; H. Carlier, PhD, Eli Lilly and Company; O. Benichou, MD, PhD, MBA, Laboratoires Lilly France; P.J. Mease, MD, Department of Rheumatology, Swedish Medical Center, and University of Washington. mail@dvanderheijde.nl. 4. From the Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands; Division of Rheumatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Immuno-Rheumatology Center, St. Luke's International Hospital, St. Luke's International University, Tokyo, Japan; Eli Lilly and Company, Indianapolis, Indiana, USA; Laboratoires Lilly France, Neuilly, France; Department of Rheumatology, Swedish Medical Center; University of Washington, Seattle, Washington, USA. 5. D. van der Heijde has received consulting fees from AbbVie and Eli Lilly and Company. D.D. Gladman has received grants or consulting fees from AbbVie and Eli Lilly and Company. M. Kishimoto received honoraria and advisory fees from AbbVie and Eli Lilly and Company. S. Rathmann, S. Moriarty, C. Shuler, and H. Carlier are employees and stockholders of Eli Lilly and Company. O. Benichou is an employee and stockholder of Laboratoires Lilly France. P.J. Mease has received research grants and has been a consultant and/or speaker for AbbVie and Eli Lilly and Company. 6. D. van der Heijde, MD, PhD, Department of Rheumatology, Leiden University Medical Center; D.D. Gladman, MD, FRCPC, Division of Rheumatology, Department of Medicine, University of Toronto; M. Kishimoto, MD, PhD, Immuno-Rheumatology Center, St. Luke's International Hospital, St. Luke's International University; M. Okada, MD, Immuno-Rheumatology Center, St. Luke's International Hospital, St. Luke's International University; S.S. Rathmann, PhD, Eli Lilly and Company; S.R. Moriarty, MD, Eli Lilly and Company; C.L. Shuler, MS, Eli Lilly and Company; H. Carlier, PhD, Eli Lilly and Company; O. Benichou, MD, PhD, MBA, Laboratoires Lilly France; P.J. Mease, MD, Department of Rheumatology, Swedish Medical Center, and University of Washington.
Abstract
OBJECTIVE: To evaluate the efficacy and safety of ixekizumab (IXE), an interleukin 17A antagonist, in patients with psoriatic arthritis (PsA) after 52 weeks in a phase III study. METHODS: Patients were initially randomly assigned to IXE 80 mg every 2 weeks (IXEQ2W) or every 4 weeks (IXEQ4W) after a 160-mg starting dose, placebo (PBO), or adalimumab (ADA) 40 mg Q2W. At Week 24 (Week 16 for inadequate responders), ADA (8-week washout before starting IXE) and PBO patients were rerandomized to IXEQ2W or IXEQ4W. Six treatment groups were evaluated in the extension period (weeks 24-52): IXEQ2W/IXEQ2W, IXEQ4W/IXEQ4W, ADA/IXEQ2W, ADA/IXEQ4W, PBO/IXEQ2W, and PBO/IXEQ4W. The extension period population (EPP) included patients who received ≥ 1 dose of study medication during the extension period. RESULTS: There were 381/417 (91.4%) patients who entered the extension period. In the IXEQ4W/IXEQ4W and IXEQ2W/IXEQ2W groups (EPP), respectively, American College of Rheumatology (ACR)20 (69.1% and 68.8%), ACR50 (54.6% and 53.1%), and ACR70 (39.2% and 39.6%) response rates were sustained at Week 52. Patients rerandomized to IXE also demonstrated efficacy measured by ACR response rates at Week 52. A similar pattern was observed for Psoriasis Area and Severity Index outcomes. Radiographic progression in all 6 groups was minimal. The most frequently reported treatment-emergent adverse events (≥ 4%) were nasopharyngitis, injection site reaction, injection site erythema, upper respiratory tract infection, and back pain. No deaths were reported, and serious adverse event frequency was 0-4% with IXE. CONCLUSION: During the extension period, IXEQ4W or IXEQ2W treatment demonstrated sustained efficacy in key PsA domains with a safety profile consistent with other studies investigating IXE. Clinical trial number: NCT01695239; EudraCT 2011-002326-49.
RCT Entities:
OBJECTIVE: To evaluate the efficacy and safety of ixekizumab (IXE), an interleukin 17A antagonist, in patients with psoriatic arthritis (PsA) after 52 weeks in a phase III study. METHODS:Patients were initially randomly assigned to IXE 80 mg every 2 weeks (IXEQ2W) or every 4 weeks (IXEQ4W) after a 160-mg starting dose, placebo (PBO), or adalimumab (ADA) 40 mg Q2W. At Week 24 (Week 16 for inadequate responders), ADA (8-week washout before starting IXE) and PBO patients were rerandomized to IXEQ2W or IXEQ4W. Six treatment groups were evaluated in the extension period (weeks 24-52): IXEQ2W/IXEQ2W, IXEQ4W/IXEQ4W, ADA/IXEQ2W, ADA/IXEQ4W, PBO/IXEQ2W, and PBO/IXEQ4W. The extension period population (EPP) included patients who received ≥ 1 dose of study medication during the extension period. RESULTS: There were 381/417 (91.4%) patients who entered the extension period. In the IXEQ4W/IXEQ4W and IXEQ2W/IXEQ2W groups (EPP), respectively, American College of Rheumatology (ACR)20 (69.1% and 68.8%), ACR50 (54.6% and 53.1%), and ACR70 (39.2% and 39.6%) response rates were sustained at Week 52. Patients rerandomized to IXE also demonstrated efficacy measured by ACR response rates at Week 52. A similar pattern was observed for Psoriasis Area and Severity Index outcomes. Radiographic progression in all 6 groups was minimal. The most frequently reported treatment-emergent adverse events (≥ 4%) were nasopharyngitis, injection site reaction, injection site erythema, upper respiratory tract infection, and back pain. No deaths were reported, and serious adverse event frequency was 0-4% with IXE. CONCLUSION: During the extension period, IXEQ4W or IXEQ2W treatment demonstrated sustained efficacy in key PsA domains with a safety profile consistent with other studies investigating IXE. Clinical trial number: NCT01695239; EudraCT 2011-002326-49.
Authors: Julia Manasson; David S Wallach; Giuliana Guggino; Matthew Stapylton; Michelle H Badri; Gary Solomon; Soumya M Reddy; Roxana Coras; Alexander A Aksenov; Drew R Jones; Parvathy V Girija; Andrea L Neimann; Adriana Heguy; Leopoldo N Segal; Pieter C Dorrestein; Richard Bonneau; Monica Guma; Francesco Ciccia; Carles Ubeda; Jose C Clemente; Jose U Scher Journal: Arthritis Rheumatol Date: 2020-03-12 Impact factor: 10.995