TY - JOUR
T1 - Efficacy and Safety of Ixekizumab in the Treatment of Radiographic Axial Spondyloarthritis
T2 - Sixteen-Week Results From a Phase III Randomized, Double-Blind, Placebo-Controlled Trial in Patients With Prior Inadequate Response to or Intolerance of Tumor Necrosis Factor Inhibitors
AU - The COAST-W Study Group
AU - Deodhar, Atul
AU - Poddubnyy, Denis
AU - Pacheco-Tena, Cesar
AU - Salvarani, Carlo
AU - Lespessailles, Eric
AU - Rahman, Proton
AU - Järvinen, Pentti
AU - Sanchez-Burson, Juan
AU - Gaffney, Karl
AU - Lee, Eun Bong
AU - Krishnan, Eswar
AU - Santisteban, Silvia
AU - Li, Xiaoqi
AU - Zhao, Fangyi
AU - Carlier, Hilde
AU - Reveille, John D.
AU - Antolini, Christopher
AU - Azevedo, Valderilio
AU - Barkham, Magnus
AU - Rodriguez, Aaron Alejandro Barrera
AU - Berman, Alberto
AU - Blicharski, Tomasz
AU - Brzezicki, Jan
AU - Burmester, Gerd
AU - Carrio, Judith
AU - Collantes, Eduardo
AU - Combe, Bernard
AU - Cons-Molina, Fidencio
AU - Cortes-Maisonet, Gregorio
AU - Dudek, Anna
AU - Barragan, Sergio Duran
AU - Elkayam, Ori
AU - Flint, Kathleen
AU - Galeazzi, Mauro
AU - Gaylis, Norman
AU - Goddard, David
AU - Fernandez, Carlos Gonzalez
AU - Goupille, Philippe
AU - Masmitja, Jordi Gratacos
AU - Greenwald, Maria
AU - Gremese, Elisa
AU - Hong, Seung Jae
AU - Howell, Mary
AU - Hrycaj, Pawel
AU - Ince, Akgun
AU - Ju, Ji Hyeon
AU - Kaine, Jeffrey
AU - Kang, Seong Wook
AU - Keiserman, Mauro
AU - Reitblat, Tatiana
N1 - Funding Information:
ClinicalTrials.gov identifier: NCT02696798. Supported by Eli Lilly and Company.
Publisher Copyright:
© 2018 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.
PY - 2019/4/1
Y1 - 2019/4/1
N2 - Objective: To investigate the efficacy and safety of ixekizumab in patients with active radiographic axial spondyloarthritis (SpA) and prior inadequate response to or intolerance of 1 or 2 tumor necrosis factor inhibitors (TNFi). Methods: In this phase III randomized, double-blind, placebo-controlled trial, adult patients with an inadequate response to or intolerance of 1 or 2 TNFi and an established diagnosis of axial SpA (according to the Assessment of SpondyloArthritis international Society [ASAS] criteria for radiographic axial SpA, with radiographic sacroiliitis defined according to the modified New York criteria and ≥1 feature of SpA) were recruited and randomized 1:1:1 to receive placebo or 80-mg subcutaneous ixekizumab every 2 weeks (IXEQ2W) or 4 weeks (IXEQ4W), with an 80-mg or 160-mg starting dose. The primary end point was 40% improvement in disease activity according to the ASAS criteria (ASAS40) at week 16. Secondary outcomes and safety were also assessed. Results: A total of 316 patients were randomized to receive placebo (n = 104), IXEQ2W (n = 98), or IXEQ4W (n = 114). At week 16, significantly higher proportions of IXEQ2W patients (n = 30 [30.6%]; P = 0.003) or IXEQ4W patients (n = 29 [25.4%]; P = 0.017) had achieved an ASAS40 response versus the placebo group (n = 13 [12.5%]), with statistically significant differences reported as early as week 1 with ixekizumab treatment. Statistically significant improvements in disease activity, function, quality of life, and spinal magnetic resonance imaging–evident inflammation were observed after 16 weeks of ixekizumab treatment versus placebo. Treatment-emergent adverse events (AEs) with ixekizumab treatment were more frequent than with placebo. Serious AEs were similar across treatment arms. One death was reported (IXEQ2W group). Conclusion: Ixekizumab treatment for 16 weeks in patients with active radiographic axial SpA and previous inadequate response to or intolerance of 1 or 2 TNFi yields rapid and significant improvements in the signs and symptoms of radiographic axial SpA versus placebo.
AB - Objective: To investigate the efficacy and safety of ixekizumab in patients with active radiographic axial spondyloarthritis (SpA) and prior inadequate response to or intolerance of 1 or 2 tumor necrosis factor inhibitors (TNFi). Methods: In this phase III randomized, double-blind, placebo-controlled trial, adult patients with an inadequate response to or intolerance of 1 or 2 TNFi and an established diagnosis of axial SpA (according to the Assessment of SpondyloArthritis international Society [ASAS] criteria for radiographic axial SpA, with radiographic sacroiliitis defined according to the modified New York criteria and ≥1 feature of SpA) were recruited and randomized 1:1:1 to receive placebo or 80-mg subcutaneous ixekizumab every 2 weeks (IXEQ2W) or 4 weeks (IXEQ4W), with an 80-mg or 160-mg starting dose. The primary end point was 40% improvement in disease activity according to the ASAS criteria (ASAS40) at week 16. Secondary outcomes and safety were also assessed. Results: A total of 316 patients were randomized to receive placebo (n = 104), IXEQ2W (n = 98), or IXEQ4W (n = 114). At week 16, significantly higher proportions of IXEQ2W patients (n = 30 [30.6%]; P = 0.003) or IXEQ4W patients (n = 29 [25.4%]; P = 0.017) had achieved an ASAS40 response versus the placebo group (n = 13 [12.5%]), with statistically significant differences reported as early as week 1 with ixekizumab treatment. Statistically significant improvements in disease activity, function, quality of life, and spinal magnetic resonance imaging–evident inflammation were observed after 16 weeks of ixekizumab treatment versus placebo. Treatment-emergent adverse events (AEs) with ixekizumab treatment were more frequent than with placebo. Serious AEs were similar across treatment arms. One death was reported (IXEQ2W group). Conclusion: Ixekizumab treatment for 16 weeks in patients with active radiographic axial SpA and previous inadequate response to or intolerance of 1 or 2 TNFi yields rapid and significant improvements in the signs and symptoms of radiographic axial SpA versus placebo.
UR - http://www.scopus.com/inward/record.url?scp=85060108324&partnerID=8YFLogxK
U2 - 10.1002/art.40753
DO - 10.1002/art.40753
M3 - Article
C2 - 30343531
AN - SCOPUS:85060108324
SN - 2326-5191
VL - 71
SP - 599
EP - 611
JO - Arthritis and Rheumatology
JF - Arthritis and Rheumatology
IS - 4
ER -