Efficacy and Safety of Ixekizumab in the Treatment of Radiographic Axial Spondyloarthritis

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

the COAST-W Study Group

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10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)599-611
Number of pages13
JournalArthritis and Rheumatology
Volume71
Issue number4
DOIs
Publication statusPublished - Apr 1 2019

Fingerprint

LY2439821
Tumor Necrosis Factor-alpha
Placebos
Safety
Therapeutics
Sacroiliitis
Signs and Symptoms
Magnetic Resonance Spectroscopy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology

Cite this

@article{2e08e9dde5b444f99d078cc3a7485e76,
title = "Efficacy and Safety of Ixekizumab in the Treatment of Radiographic Axial Spondyloarthritis: 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",
abstract = "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.",
author = "{the COAST-W Study Group} and Atul Deodhar and Denis Poddubnyy and Cesar Pacheco-Tena and Carlo Salvarani and Eric Lespessailles and Proton Rahman and Pentti J{\"a}rvinen and Juan Sanchez-Burson and Karl Gaffney and Lee, {Eun Bong} and Eswar Krishnan and Silvia Santisteban and Xiaoqi Li and Fangyi Zhao and Hilde Carlier and Reveille, {John D.} and Christopher Antolini and Valderilio Azevedo and Magnus Barkham and Rodriguez, {Aaron Alejandro Barrera} and Alberto Berman and Tomasz Blicharski and Jan Brzezicki and Gerd Burmester and Judith Carrio and Eduardo Collantes and Bernard Combe and Fidencio Cons-Molina and Gregorio Cortes-Maisonet and Anna Dudek and Barragan, {Sergio Duran} and Ori Elkayam and Kathleen Flint and Mauro Galeazzi and Norman Gaylis and David Goddard and Fernandez, {Carlos Gonzalez} and Philippe Goupille and Masmitja, {Jordi Gratacos} and Maria Greenwald and Elisa Gremese and Hong, {Seung Jae} and Mary Howell and Pawel Hrycaj and Akgun Ince and Ju, {Ji Hyeon} and Jeffrey Kaine and Kang, {Seong Wook} and Mauro Keiserman and Kim, {Tae Hwan}",
year = "2019",
month = "4",
day = "1",
doi = "10.1002/art.40753",
language = "English",
volume = "71",
pages = "599--611",
journal = "Arthritis and Rheumatology",
issn = "2326-5191",
publisher = "John Wiley and Sons Ltd",
number = "4",

}

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 - Kim, Tae Hwan

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.

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U2 - 10.1002/art.40753

DO - 10.1002/art.40753

M3 - Article

VL - 71

SP - 599

EP - 611

JO - Arthritis and Rheumatology

JF - Arthritis and Rheumatology

SN - 2326-5191

IS - 4

ER -