ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1864

Ixekizumab Significantly Improves Signs, Symptoms, and Spinal Inflammation of Active Ankylosing Spondylitis/Radiographic Axial Spondyloarthritis: 16-Week Results of a Phase 3 Randomized, Active and Placebo-Controlled Trial

Désirée van der Heijde1, James Cheng-Chung Wei2, Maxime Dougados3, Philip J. Mease4, Atul A. Deodhar5, Walter P. Maksymowych6, Filip van Den Bosch7, Joachim Sieper8, Tetsuya Tomita9, Robert B.M. Landewé10, Lotus Mallbris11, Fangyi Zhao11, David Adams11, Beth Pangallo11 and Hilde Carlier11, 1Leiden University Medical Centre, Leiden, Netherlands, 2Allergy/Immunology/Rheumatology, Chung Shan Med Univ Hospital, Taichung, Taiwan, 3Rheumatology Department, Cochin Hospital, AP-HP, Paris Descartes University, Paris, France, Paris, France, 4Swedish Medical Center and University of Washington, Seattle, WA, 5Oregon Health & Science U, Portland, OR, 6University of Alberta, Edmonton, AB, Canada, 7Ghent University Hospital, Ghent, Belgium, Ghent, Belgium, 8Charité University Hospital, Berlin, Germany, 9Department of Orthopedics, Osaka University Graduate School of Medicine, Suita Osaka, Japan, 10Amsterdam Rheumatology & Clinical Immunology Center and Zuyderland Medical Center, Amsterdam; Heerlen, Netherlands, 11Eli Lilly and Company, Indianapolis, IN

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: , ,

Session Information

Date: Monday, October 22, 2018

Title: 4M089 ACR Abstract: Spondyloarthritis Incl PsA–Clinical III: Treatment of Axial SpA (1864–1869)

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose: COAST-V (NCT02696785) is the first phase 3 study of ixekizumab (IXE), a high-affinity anti-IL-17A monoclonal antibody, in patients (pts) with active radiographic axial SpA (r-axSpA) who are biologic DMARD (bDMARD) naive. We report the Week (Wk) 16 primary outcome and key efficacy and safety data from this ongoing 52-wk study.

Methods: Adults with active r-axSpA per Assessment of SpA international Society (ASAS) criteria (sacroiliitis centrally defined by modified New York Criteria and ≥1 SpA feature), BASDAI ≥4, back pain ≥4, and inadequate response or intolerance to NSAID therapy, were randomized 1:1:1:1 to subcutaneous placebo (PBO), 80 mg IXE every 4 (Q4W) or 2 wks (Q2W), or 40 mg Q2W adalimumab (ADA; active reference arm) up to Wk 16. The primary endpoint was ASAS40 response at Wk 16. Major secondary endpoints included ASAS20, BASDAI50, AS Disease Activity Score (ASDAS) Inactive Disease, and change from baseline (CFB) in ASDAS, BASFI, MRI spine SpA Research Consortium of Canada (SPARCC) score, Short Form 36-item Physical Component Summary (SF-36 PCS) and ASAS-Health Index (HI). All images were centrally read.

Results: Of 341 subjects randomized, 97% completed Wk 16. Baseline demographics and disease characteristics were comparable among study arms: mean age was 41.7 years; mean time since r-axSpA symptoms onset was 16.0 years, and mean BASDAI was 6.7. Significantly more patients achieved ASAS40 at Wk 16 (primary endpoint) with IXE Q2W (52%) and IXE Q4W (48%) than with PBO (18%, p<.001). Compared to PBO, both IXE regimens had significantly higher improvements at Wk 16 for disease activity, functional disability, and spinal and SIJ inflammation. Significant improvements were first observed at Wk 1 for ASAS20, BASFI CFB, and ASDAS CFB, at Wk 2 for ASAS40, and at Wk 4 (first time of assessment) for SF36-PCS CFB and ASAS-HI CFB. At Wk 16, ADA (active reference arm) showed significant improvements versus PBO (ASAS40 effect size vs. PBO 17.2% [95% CI 4.4, 30.0]). The frequency of treatment-emergent adverse events and serious adverse events are provided in the table below. No opportunistic infections were reported in any arm; one Candida infection was reported in the ADA active reference arm. One case of inflammatory bowel disease was reported in the IXE Q2W study arm. No malignancies or deaths occurred in any study arm.

Conclusion: The primary and all major secondary endpoints for IXE were met at Wk 16 with no unexpected safety findings. IXE was superior to PBO for improving r-axSpA signs and symptoms, health-related quality of life, and inflammation on MRI in pts with r-axSpA naïve to bDMARDS.



Efficacy and Safety Results at Week 16

 

Placebo

(N=87)

Adalimumab

(N=90)

Ixekizumab Q4W

(N=81)

Ixekizumab Q2W

(N=83)

Responder Rate, n (%), Intent-to-treat population

ASAS40a,b

16 (18%)

32 (36%)†

39 (48%)‡

43 (52%)‡

ASAS20a,b

35 (40%)

53 (59%)†

52 (64%)†

57 (69%)‡

BASDAI50a,b

15 (17%)

29 (32%)*

34 (42%)‡

36 (43%)‡

ASDAS Inactive Diseasea,b

2 (2%)

14 (16%)†

13 (16%)†

9 (11%)*

Change From Baseline, Least Squares Mean (Standard Error), Intent-to-treat population

ASDASb,c

-0.5 (0.1)

-1.3 (0.1)‡

-1.4 (0.1)‡

-1.4 (0.1)‡

BASFIb,c

-1.2 (0.2)

-2.1 (0.2)†

-2.4 (0.2)‡

-2.4 (0.2)‡

Spine SPARCC Scoreb,d

-1.5 (1.1)

-11.6 (1.1)‡

-11.0 (1.2)‡

-9.6 (1.2)‡

Sacroiliac joint SPARCC Scored,e

0.9 (0.6)

-4.2 (0.6)‡

-4.0 (0.6)‡

-4.3 (0.6)‡

SF-36 PCSb,c

3.6 (0.8)

6.9 (0.7)†

7.7 (0.8)‡

8.0 (0.8)‡

ASAS-Health Indexb,c

-1.3 (0.3)

-2.3 (0.3)*

-2.4 (0.3)*

-2.7 (0.3)‡

High sensitivity C-reactive protein (mg/L)c,f

1.4 (1.9)

-7.2 (1.9)†

-5.2 (2.0)*

-6.6 (2.0)†

Safety Overview, n (%), Safety population

Placebo

(N=86)

Adalimumab

(N=90)

Ixekizumab Q4W

(N=81)

Ixekizumab Q2W

(N=83)

Treatment-emergent adverse events

34 (40%)

44 (49%)

34 (42%)

36 (43%)

Serious adverse events

0

3 (3%)

1 (1%)

1 (1%)

Discontinued due to adverse event

0

1 (1%)

0

3 (4%)

aLogistic regression analysis with nonresponder imputation for missing data. bA primary or major secondary endpoint. Comparisons between each of the ixekizumab treatment arms and placebo for primary and major secondary endpoints were all statistically significant as calculated using a graphical multiplicity testing method. cMixed effects model of repeated measures analysis. dAnalysis of covariance model based on observed case. eSacroiliac joint SPARCC score at baseline was 5.2. fAt baseline, 64% of patients had CRP>5 mg/L. *p<.05; †p<.01; ‡p<.001
All statistical comparisons were made between placebo and active treatment arms. Adalimumab represents an active reference; the study was not powered to test equivalence or noninferiority of active treatment arms to each other, including ixekizumab versus adalimumab.
Intention-to-treat population: All randomized patients, analyzed according to the treatment to which they were assigned.
Safety population: All randomized patients who received ≥1 dose of study treatment, analyzed according to the treatment to which they were assigned.

 

Disclosure: D. van der Heijde, Imaging Rheumatology BV, 3,AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi and UCB Pharma, 5; J. C. C. Wei, Pfizer, Inc., 2, 5, 8,Celgene Corporation, UCB, TSH Taiwan, 5,Chugai, 5, 8,BMS, Janssen, 2, 8,Sanofi-Aventis, Novartis, 2,Abbott, Eisai, 8; M. Dougados, Eli Lilly and Co., Pfizer, AbbVie, UCB, 2, 5; P. J. Mease, AbbVie, Amgen, Bristol Myers Squibb, Celgene, Janssen, Novartis, Pfizer, UCB, 2, 5, 8,Genentech, Inc., 8,Eli Lilly and Co., Sun Pharma, 2, 5; A. A. Deodhar, AbbVie Inc., Eli Lilly and Co., Janssen, Novartis, Pfizer, UCB, 2, 5; W. P. Maksymowych, AbbVie Inc., Pfizer, 2, 5, 9,Eli Lilly and Co., UCB, 5,Novartis, Janssen, 5, 9; F. van Den Bosch, AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Co., Janssen, Merck, Novartis, Pfizer, Sanofi, UCB, 2, 5, 8; J. Sieper, AbbVie Inc., Novartis, Merck, Janssen, Pfizer, 5, 8,Eli Lilly and Co., 5,UCB, Inc., 8; T. Tomita, Abbvie, Astellas, Bristol Myers Squibb, Eisai, Eli Lilly and Co., Janssen, Mitsubishi Tanabe, Novartis, Takeda, Pfizer, 5, 8; R. B. M. Landewé, AbbVie Inc., Amgen, Pfizer, Roche, Schering, UCB, 2, 5, 8,Ablynx, Astra-Zeneca, Celgene, Eli Lilly and Co., Gilead, Galapagos, Glaxo-Smith-Kline, Novo-Nordisk, TiGenix, 5,Bristol Myers Squibb, Janssen, Merck, 5, 8,Novartis, 2, 5,Centocor, 2, 8,Rheumatology Consultancy BV, 3; L. Mallbris, Eli Lilly and Company, 1, 3; F. Zhao, Eli Lilly and Company, 1, 3; D. Adams, Eli Lilly and Company, 1, 3; B. Pangallo, Eli Lilly and Co., 1; H. Carlier, Eli Lilly and Company, 1, 3.

To cite this abstract in AMA style:

van der Heijde D, Wei JCC, Dougados M, Mease PJ, Deodhar AA, Maksymowych WP, van Den Bosch F, Sieper J, Tomita T, Landewé RBM, Mallbris L, Zhao F, Adams D, Pangallo B, Carlier H. Ixekizumab Significantly Improves Signs, Symptoms, and Spinal Inflammation of Active Ankylosing Spondylitis/Radiographic Axial Spondyloarthritis: 16-Week Results of a Phase 3 Randomized, Active and Placebo-Controlled Trial [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/ixekizumab-significantly-improves-signs-symptoms-and-spinal-inflammation-of-active-ankylosing-spondylitis-radiographic-axial-spondyloarthritis-16-week-results-of-a-phase-3-randomized-active-a/. Accessed .

« Back to 2018 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/ixekizumab-significantly-improves-signs-symptoms-and-spinal-inflammation-of-active-ankylosing-spondylitis-radiographic-axial-spondyloarthritis-16-week-results-of-a-phase-3-randomized-active-a/