Ixekizumab Improves Signs and Symptoms of Patients with Radiographic and Non-radiographic Axial Spondyloarthritis and Extra-articular Manifestation of Enthesitis Through 16 Weeks

Georg Schett¹, Filip Van den Bosch², Xenofon Baraliakos³, David Sandoval⁴, Vladimir Geneus⁴, Rebecca Bolce⁴, Soyi Liu-Leage⁵, Andris Kronbergs⁴ and Philip Mease⁶, ¹Friedrich-Alexander-Universität Erlangen- Nuremberg, Erlangen, Germany, ²Ghent University Hospital, Ghent, Belgium, ³Rheumazentrum Ruhrgebiet Herne, Ruhr-University Bochum, Bochum, Germany, ⁴Eli Lilly and Company, Indianapolis, ⁵Eli Lilly and Company, Indianapolis, IN, ⁶Seattle Rheumatology Associates, P.L.L.C., Seattle, WA

Meeting: ACR Convergence 2020

Keywords: Biologicals, clinical trial, Disease-Modifying Antirheumatic Drugs (Dmards), Interleukins, spondyloarthritis

Session Information

Date: Saturday, November 7, 2020

Title: Spondyloarthritis Including Psoriatic Arthritis – Treatment Poster II

Session Type: Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Axial SpA (axSpA) is a chronic inflammatory disease affecting the spine and sacroiliac (SI) joints and has two subtypes that represent the spectrum of disease: radiographic axSpA (r-axSpA) and non-radiographic axSpA (nr-axSpA). The distinction between the two is defined by the presence or absence of radiographic changes at the SI joints. Both subtypes may have extra-articular manifestations such as peripheral enthesitis, increasing the disease burden and decreasing quality of life (QoL). Ixekizumab is a high-affinity monoclonal antibody that selectively targets IL-17A. It has shown efficacy in clinical trials for r- and nr-axSpA as well as psoriasis and PsA. This post-hoc analysis explores the efficacy of ixekizumab in improving enthesitis, overall disease activity and QoL in patients with r-axSpA, who are biologic DMARD-naïve (COAST-V) or previously exposed to TNF inhibitors (COAST-W), or patients with nr-axSpA (COAST-X).

Methods: Patients with enthesitis at baseline from three Phase 3, randomized, double-blind, placebo (PBO)-controlled studies [COAST-V (NCT02696785), COAST-W (NCT02696798), and COAST-X (NCT02757352)] examining the efficacy and safety of ixekizumab in patients with r-axSpA or nr-axSpA. Ixekizumab (80 mg) or PBO were given SC every 2 (Q2W) or 4 (Q4W) weeks during a double-blind 16-week treatment period, with a starting dose of 80 mg or 160 mg at Week 0. Here, we explore the efficacy of ixekizumab at week 16 in resolving peripheral enthesitis in patients as assessed by Spondyloarthritis Research Consortium of Canada (SPARCC). We also compare the % patients achieving Assessment of Spondyloarthritis International Society 40 (ASAS40), Ankylosing Spondylitis Disease Activity Score (ASDAS) < 2.1 and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50), change from baseline (CFB) in BASFI and 36-Item Short Form Health Survey (SF36-PCS) in patients achieving and not achieving SPARCC=0. Missing data were imputed using non-responder imputation for categorical data and modified baseline observation carried forward for continuous data.

Results: 543 Patients had enthesitis at baseline. In patients with r-axSpA, 48.6% and 67.6% achieved resolution of peripheral enthesitis (SPARCC=0) at week 16 in the IXE80Q4W and IXE80Q2W groups, respectively, compared to only 22.9% in the PBO group. For the patients with nr-axSpA, resolution of peripheral enthesitis at week 16 was observed in 52.2% and 57.7% in the IXE80Q4W and IXE80Q2W groups, respectively, while enthesitis resolved in 31.3% of PBO patients. The % of patients achieving ASDAS < 2.1 and BASDAI50 were also greater for the IXE80Q4W and IXE80Q2W groups vs PBO for both r-axSpA and nr-axSpA (Table 2). Patients with enthesitis resolution with ixekizumab showed improvements in BASFI and SF36-PCS compared to PBO for both r-axSpA and nr-axSpA (Table 3). Improvements were also seen in patients with SPARCC >0 at week 16.

Conclusion: Ixekizumab is effective in resolving enthesitis and improvements in overall disease activity and QoL in patients with r-axSpA and nr-axSpA.

Table 1. ASAS40, ASDAS-LDA and BASDAI50 responses in all patients, patients with remission of peripheral enthesitis (SPARCC=0) or patients with no remission of peripheral enthesitis (SPARCC>0) at Week 16

Table 2. BASFI and SF-36 responses in all patients, patients with remission of peripheral enthesitis (SPARCC=0) or patients with no remission of peripheral enthesitis (SPARCC>0) at Week 16

Disclosure: G. Schett, None; F. Van den Bosch, AbbVie, 5, 8, Celgene, 5, 8, Eli Lilly, 5, 8, Galapagos, 5, 8, Novartis, 5, 8, Pfizer, 5, 8, UCB, 5, 8, Gilead, 5, Merck, 5, 8; X. Baraliakos, AbbVie, 2, 5, 8, Novartis, 2, 5, 8, Celgene, 5, 8, Chugai, 5, 8, Pfizer, 5, 8, UCB, 5, 8, BMS, 5, 8, Merck, 5, 8, Galapagos, 5; D. Sandoval, Eli Lilly and Company, 3; V. Geneus, Eli Lilly and Company, 3, 4; R. Bolce, Eli Lilly and Company, 1, 3; S. Liu-Leage, Eli Lilly and Company, 3, 4; A. Kronbergs, Eli Lilly and Company, 1, 3; P. Mease, Amgen, 2, 5, 8, Bristol-Myers Squibb, 2, 5, Novartis, 2, 5, 8, Pfizer Inc, 2, 5, 8, Sun, 2, 5, UCB, 2, 5, 8, AbbVie, 2, 5, 8, Gilead, 2, 5, Janssen, 2, 5, 8, Eli Lilly, 2, 5, 8, Galapagos, 5, GlaxoSmithKline, 5.

To cite this abstract in AMA style:

Schett G, Van den Bosch F, Baraliakos X, Sandoval D, Geneus V, Bolce R, Liu-Leage S, Kronbergs A, Mease P. Ixekizumab Improves Signs and Symptoms of Patients with Radiographic and Non-radiographic Axial Spondyloarthritis and Extra-articular Manifestation of Enthesitis Through 16 Weeks [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/ixekizumab-improves-signs-and-symptoms-of-patients-with-radiographic-and-non-radiographic-axial-spondyloarthritis-and-extra-articular-manifestation-of-enthesitis-through-16-weeks/. Accessed .

« Back to ACR Convergence 2020

ACR Meeting Abstracts - https://acrabstracts.org/abstract/ixekizumab-improves-signs-and-symptoms-of-patients-with-radiographic-and-non-radiographic-axial-spondyloarthritis-and-extra-articular-manifestation-of-enthesitis-through-16-weeks/