Ixekizumab, an interleukin-17A antagonist in the treatment of ankylosing spondylitis or radiographic axial spondyloarthritis in patients previously untreated with biological disease-modifying anti-rheumatic drugs (COAST-V): 16 week results of a phase 3 randomised, double-blind, active-controlled and placebo-controlled trial

COAST-V study group

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35 Citations (Scopus)

Abstract

Background: Biological disease-modifying anti-rheumatic drugs (bDMARDs) are recommended for radiographic axial spondyloarthritis, otherwise known as ankylosing spondylitis, when conventional therapies are not effective. We report efficacy and safety data on ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A (IL-17A), in patients with radiographic axial spondyloarthritis who have not previously been treated with bDMARDs. Methods: In this phase 3, randomised, double-blind, placebo-controlled superiority study of ixekizumab, adult patients with inadequate response or intolerance to non-steroidal anti-inflammatory drugs, an established diagnosis of radiographic axial spondyloarthritis, radiographic sacroiliitis centrally defined by modified New York criteria, and at least one spondyloarthritis feature according to the Assessment of SpondyloArthritis international Society (ASAS) criteria, were recruited from 84 sites (12 countries) in Europe, Asia, and North America. By use of a computer-generated random sequence, patients were randomly assigned (1:1:1:1) to 80 mg subcutaneous ixekizumab every two (Q2W) or four (Q4W) weeks, 40 mg adalimumab Q2W (active reference group), or placebo. The primary objective was to compare the proportion of patients achieving an ASAS40 response, a composite measure of clinical improvement in axial spondyloarthritis, at week 16 for both ixekizumab treatment groups versus the placebo group. The adalimumab reference group was included as an in-study active reference for comparison with placebo to provide additional context to interpretation of the ixekizumab study results. Findings: Between June 20, 2016, and Aug 22, 2017, 341 patients were randomly assigned to either the placebo group (n=87), adalimumab group (n=90), ixekizumab Q2W (n=83), or ixekizumab Q4W (n=81). At week 16, compared with placebo (16 [18%] of 87), more patients achieved ASAS40 with ixekizumab Q2W (43 [52%] of 83; p<0·0001), ixekizumab Q4W (39 [48%] of 81; p<0·0001), and adalimumab (32 [36%] of 90; p=0·0053). One serious infection occurred in each of the ixekizumab Q2W (1%), ixekizumab Q4W (1%), and adalimumab (1%) groups; none were reported with placebo. One (1%) Candida infection occurred in the adalimumab group and one (1%) patient receiving ixekizumab Q2W was adjudicated as having probable Crohn's disease. No treatment-emergent opportunistic infections, malignancies, or deaths occurred. Interpretation: Each dosing regimen of ixekizumab was superior to placebo for improving radiographic axial spondyloarthritis signs and symptoms in patients not previously treated with bDMARDs; the safety profile was consistent with previous indications of ixekizumab. Funding: Eli Lilly and Company

Original languageEnglish (US)
JournalThe Lancet
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

LY2439821
Antirheumatic Agents
Interleukin-17
Ankylosing Spondylitis
Placebos
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

@article{34840d2767f54824a12fa38815370f6c,
title = "Ixekizumab, an interleukin-17A antagonist in the treatment of ankylosing spondylitis or radiographic axial spondyloarthritis in patients previously untreated with biological disease-modifying anti-rheumatic drugs (COAST-V): 16 week results of a phase 3 randomised, double-blind, active-controlled and placebo-controlled trial",
abstract = "Background: Biological disease-modifying anti-rheumatic drugs (bDMARDs) are recommended for radiographic axial spondyloarthritis, otherwise known as ankylosing spondylitis, when conventional therapies are not effective. We report efficacy and safety data on ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A (IL-17A), in patients with radiographic axial spondyloarthritis who have not previously been treated with bDMARDs. Methods: In this phase 3, randomised, double-blind, placebo-controlled superiority study of ixekizumab, adult patients with inadequate response or intolerance to non-steroidal anti-inflammatory drugs, an established diagnosis of radiographic axial spondyloarthritis, radiographic sacroiliitis centrally defined by modified New York criteria, and at least one spondyloarthritis feature according to the Assessment of SpondyloArthritis international Society (ASAS) criteria, were recruited from 84 sites (12 countries) in Europe, Asia, and North America. By use of a computer-generated random sequence, patients were randomly assigned (1:1:1:1) to 80 mg subcutaneous ixekizumab every two (Q2W) or four (Q4W) weeks, 40 mg adalimumab Q2W (active reference group), or placebo. The primary objective was to compare the proportion of patients achieving an ASAS40 response, a composite measure of clinical improvement in axial spondyloarthritis, at week 16 for both ixekizumab treatment groups versus the placebo group. The adalimumab reference group was included as an in-study active reference for comparison with placebo to provide additional context to interpretation of the ixekizumab study results. Findings: Between June 20, 2016, and Aug 22, 2017, 341 patients were randomly assigned to either the placebo group (n=87), adalimumab group (n=90), ixekizumab Q2W (n=83), or ixekizumab Q4W (n=81). At week 16, compared with placebo (16 [18{\%}] of 87), more patients achieved ASAS40 with ixekizumab Q2W (43 [52{\%}] of 83; p<0·0001), ixekizumab Q4W (39 [48{\%}] of 81; p<0·0001), and adalimumab (32 [36{\%}] of 90; p=0·0053). One serious infection occurred in each of the ixekizumab Q2W (1{\%}), ixekizumab Q4W (1{\%}), and adalimumab (1{\%}) groups; none were reported with placebo. One (1{\%}) Candida infection occurred in the adalimumab group and one (1{\%}) patient receiving ixekizumab Q2W was adjudicated as having probable Crohn's disease. No treatment-emergent opportunistic infections, malignancies, or deaths occurred. Interpretation: Each dosing regimen of ixekizumab was superior to placebo for improving radiographic axial spondyloarthritis signs and symptoms in patients not previously treated with bDMARDs; the safety profile was consistent with previous indications of ixekizumab. Funding: Eli Lilly and Company",
author = "{COAST-V study group} and {van der Heijde}, D{\'e}sir{\'e}e and {Cheng-Chung Wei}, James and Maxime Dougados and Philip Mease and Deodhar, {Atulya (Atul)} and Maksymowych, {Walter P.} and {Van den Bosch}, Filip and Joachim Sieper and Tetsuya Tomita and Robert Landew{\'e} and Fangyi Zhao and Eswar Krishnan and Adams, {David H.} and Beth Pangallo and Hilde Carlier and Melvin Churchill and Kathleen Flint and Geoffrey Gladstein and Maria Greenwald and Mary Howell and Akgun Ince and Jeffrey Kaine and Daksha Mehta and Eric Peters and Roel Querubin and John Reveille and Richard Roseff and Roger Diegel and Christine Thai and Louis Bessette and Frederic Morin and Proton Rahman and {Barrera Rodriguez}, {Aaron Alejandro} and Fidencio Cons-Molina and {Duran Barragan}, Sergio and Cassandra Skinner and {Pacheco Tena}, Cesar and {Ramos Remus}, Cesar and {Rizo Rodriguez}, {Juan Cruz} and Hong, {Seung Jae} and Lee, {Yeon Ah} and Ju, {Ji Hyeon} and Kang, {Seong Wook} and Kim, {Tae Hwan} and Lee, {Chang Keun} and Lee, {Eun Bong} and Lee, {Sang Heon} and Park, {Min Chan} and Kichul Shin and Lee, {Sang Hoon}",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/S0140-6736(18)31946-9",
language = "English (US)",
journal = "The Lancet",
issn = "0140-6736",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Ixekizumab, an interleukin-17A antagonist in the treatment of ankylosing spondylitis or radiographic axial spondyloarthritis in patients previously untreated with biological disease-modifying anti-rheumatic drugs (COAST-V)

T2 - 16 week results of a phase 3 randomised, double-blind, active-controlled and placebo-controlled trial

AU - COAST-V study group

AU - van der Heijde, Désirée

AU - Cheng-Chung Wei, James

AU - Dougados, Maxime

AU - Mease, Philip

AU - Deodhar, Atulya (Atul)

AU - Maksymowych, Walter P.

AU - Van den Bosch, Filip

AU - Sieper, Joachim

AU - Tomita, Tetsuya

AU - Landewé, Robert

AU - Zhao, Fangyi

AU - Krishnan, Eswar

AU - Adams, David H.

AU - Pangallo, Beth

AU - Carlier, Hilde

AU - Churchill, Melvin

AU - Flint, Kathleen

AU - Gladstein, Geoffrey

AU - Greenwald, Maria

AU - Howell, Mary

AU - Ince, Akgun

AU - Kaine, Jeffrey

AU - Mehta, Daksha

AU - Peters, Eric

AU - Querubin, Roel

AU - Reveille, John

AU - Roseff, Richard

AU - Diegel, Roger

AU - Thai, Christine

AU - Bessette, Louis

AU - Morin, Frederic

AU - Rahman, Proton

AU - Barrera Rodriguez, Aaron Alejandro

AU - Cons-Molina, Fidencio

AU - Duran Barragan, Sergio

AU - Skinner, Cassandra

AU - Pacheco Tena, Cesar

AU - Ramos Remus, Cesar

AU - Rizo Rodriguez, Juan Cruz

AU - Hong, Seung Jae

AU - Lee, Yeon Ah

AU - Ju, Ji Hyeon

AU - Kang, Seong Wook

AU - Kim, Tae Hwan

AU - Lee, Chang Keun

AU - Lee, Eun Bong

AU - Lee, Sang Heon

AU - Park, Min Chan

AU - Shin, Kichul

AU - Lee, Sang Hoon

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: Biological disease-modifying anti-rheumatic drugs (bDMARDs) are recommended for radiographic axial spondyloarthritis, otherwise known as ankylosing spondylitis, when conventional therapies are not effective. We report efficacy and safety data on ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A (IL-17A), in patients with radiographic axial spondyloarthritis who have not previously been treated with bDMARDs. Methods: In this phase 3, randomised, double-blind, placebo-controlled superiority study of ixekizumab, adult patients with inadequate response or intolerance to non-steroidal anti-inflammatory drugs, an established diagnosis of radiographic axial spondyloarthritis, radiographic sacroiliitis centrally defined by modified New York criteria, and at least one spondyloarthritis feature according to the Assessment of SpondyloArthritis international Society (ASAS) criteria, were recruited from 84 sites (12 countries) in Europe, Asia, and North America. By use of a computer-generated random sequence, patients were randomly assigned (1:1:1:1) to 80 mg subcutaneous ixekizumab every two (Q2W) or four (Q4W) weeks, 40 mg adalimumab Q2W (active reference group), or placebo. The primary objective was to compare the proportion of patients achieving an ASAS40 response, a composite measure of clinical improvement in axial spondyloarthritis, at week 16 for both ixekizumab treatment groups versus the placebo group. The adalimumab reference group was included as an in-study active reference for comparison with placebo to provide additional context to interpretation of the ixekizumab study results. Findings: Between June 20, 2016, and Aug 22, 2017, 341 patients were randomly assigned to either the placebo group (n=87), adalimumab group (n=90), ixekizumab Q2W (n=83), or ixekizumab Q4W (n=81). At week 16, compared with placebo (16 [18%] of 87), more patients achieved ASAS40 with ixekizumab Q2W (43 [52%] of 83; p<0·0001), ixekizumab Q4W (39 [48%] of 81; p<0·0001), and adalimumab (32 [36%] of 90; p=0·0053). One serious infection occurred in each of the ixekizumab Q2W (1%), ixekizumab Q4W (1%), and adalimumab (1%) groups; none were reported with placebo. One (1%) Candida infection occurred in the adalimumab group and one (1%) patient receiving ixekizumab Q2W was adjudicated as having probable Crohn's disease. No treatment-emergent opportunistic infections, malignancies, or deaths occurred. Interpretation: Each dosing regimen of ixekizumab was superior to placebo for improving radiographic axial spondyloarthritis signs and symptoms in patients not previously treated with bDMARDs; the safety profile was consistent with previous indications of ixekizumab. Funding: Eli Lilly and Company

AB - Background: Biological disease-modifying anti-rheumatic drugs (bDMARDs) are recommended for radiographic axial spondyloarthritis, otherwise known as ankylosing spondylitis, when conventional therapies are not effective. We report efficacy and safety data on ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A (IL-17A), in patients with radiographic axial spondyloarthritis who have not previously been treated with bDMARDs. Methods: In this phase 3, randomised, double-blind, placebo-controlled superiority study of ixekizumab, adult patients with inadequate response or intolerance to non-steroidal anti-inflammatory drugs, an established diagnosis of radiographic axial spondyloarthritis, radiographic sacroiliitis centrally defined by modified New York criteria, and at least one spondyloarthritis feature according to the Assessment of SpondyloArthritis international Society (ASAS) criteria, were recruited from 84 sites (12 countries) in Europe, Asia, and North America. By use of a computer-generated random sequence, patients were randomly assigned (1:1:1:1) to 80 mg subcutaneous ixekizumab every two (Q2W) or four (Q4W) weeks, 40 mg adalimumab Q2W (active reference group), or placebo. The primary objective was to compare the proportion of patients achieving an ASAS40 response, a composite measure of clinical improvement in axial spondyloarthritis, at week 16 for both ixekizumab treatment groups versus the placebo group. The adalimumab reference group was included as an in-study active reference for comparison with placebo to provide additional context to interpretation of the ixekizumab study results. Findings: Between June 20, 2016, and Aug 22, 2017, 341 patients were randomly assigned to either the placebo group (n=87), adalimumab group (n=90), ixekizumab Q2W (n=83), or ixekizumab Q4W (n=81). At week 16, compared with placebo (16 [18%] of 87), more patients achieved ASAS40 with ixekizumab Q2W (43 [52%] of 83; p<0·0001), ixekizumab Q4W (39 [48%] of 81; p<0·0001), and adalimumab (32 [36%] of 90; p=0·0053). One serious infection occurred in each of the ixekizumab Q2W (1%), ixekizumab Q4W (1%), and adalimumab (1%) groups; none were reported with placebo. One (1%) Candida infection occurred in the adalimumab group and one (1%) patient receiving ixekizumab Q2W was adjudicated as having probable Crohn's disease. No treatment-emergent opportunistic infections, malignancies, or deaths occurred. Interpretation: Each dosing regimen of ixekizumab was superior to placebo for improving radiographic axial spondyloarthritis signs and symptoms in patients not previously treated with bDMARDs; the safety profile was consistent with previous indications of ixekizumab. Funding: Eli Lilly and Company

UR - http://www.scopus.com/inward/record.url?scp=85055119391&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85055119391&partnerID=8YFLogxK

U2 - 10.1016/S0140-6736(18)31946-9

DO - 10.1016/S0140-6736(18)31946-9

M3 - Article

C2 - 30360964

AN - SCOPUS:85055119391

JO - The Lancet

JF - The Lancet

SN - 0140-6736

ER -