P178\u2003The impact of peripheral articular manifestations on the efficacy of ixekizumab in patients with radiographic axial spondyloarthritis

Abstract

\n Background/Aims\u2002\n Axial spondyloarthritis (axSpA) is characterised by chronic inflammation of the axial skeleton and is commonly associated with peripheral articular manifestations (PA), which further increases disease burden. Ixekizumab (IXE), a high-affinity monoclonal antibody that selectively targets IL-17A, is approved for treating both nonradiographic and radiographic (r-) forms of axSpA. We explored the efficacy of IXE in patients with raxSpA with (PA+) and without (PA−) PA at baseline.\n Methods\u2002\n Week 16 data from two Phase 3, randomized, double-blind, placebo (PBO)-controlled trials, with patients who fulfilled the Assessment of Spondylo-Arthritis International Society (ASAS) criteria for r-axSpA and were either biologic-naïve (COAST-V, NCT02696785) or TNFi-experienced (COAST-W, NCT02696798), were analysed. Patients were randomly assigned 1:1:1:1 to subcutaneous PBO, 80 mg IXE every 4 (Q4W) or 2 (Q2W) weeks (80 mg or 160 mg starting dose, assigned 1:1) or 40 mg adalimumab (ADA) Q2W in COAST-V or 1:1:1 in COAST-W. We present a post-hoc analysis of data from COAST-V and -W and an integrated dataset, with patients categorized by baseline PA status. Presence of PA was defined as a 44-joint swollen joint count (SJC) ≥1 or a 46-joint tender joint count (TJC) ≥1. Efficacy and health-related quality of life (HRQoL) outcomes were analysed at week 16.\n Results\u2002\n Data from 656 patients (COAST-V: N = 146 PA−/194 PA+; COAST-W: N = 93 PA−/223 PA+) were analyzed. At baseline, PA+ patients had a higher mean age, more enthesitis (higher Spondyloarthritis Research Consortium of Canada [SPARCC] scores), and higher disease activity (higher CRP levels, Ankylosing Spondylitis Disease Activity Score [ASDAS] and BASDAI). ASAS40, ASDAS <2.1, and BASDAI50 responder rates (Table, section a) were all significantly higher for both IXE dose regimens versus PBO in both PA− and PA+ patients in the integrated dataset and numerically higher in the separate datasets. Furthermore, short-form-36 physical component summary (Table, section b) showed significantly greater improvements from baseline in both IXE groups vs PBO in the separate and integrated datasets, regardless of baseline PA status.\n Conclusion\u2002\n IXE led to significant improvements versus PBO in all efficacy and HRQoL endpoints at Week 16 in the integrated dataset, irrespective of PA manifestations at baseline. P178\u2003Table 1:a) Responder rates at Week 16 for the intent-to-treat population, number (%)No peripheral articular manifestations at baselinePeripheral articular manifestations at baselinePBOADAQ2WIEQ4WIXEQ2WPBOADAQ2WIXEQ4WIXEQ2WIntegrated datasetaN=71N/AN=63N=66N=119N/AN=132N=115ASAS4011.5N/A29 (46.0)‡28 (42.4)‡18 (15.1)N/A39 (29.5)†45 (39.1)‡ASDAS <2.18 (11.3)N/A24 (38.1)‡23 (34.8)†8 (6.7)N/A31 (23.5)‡28 (24.3)‡BASDAI5010 (14.1)N/A21 (33.3)*26 (39.4)†15 (12.6)N/A38 (28.8)‡33 (28.7)†COAST-VbN=34N=39N=35N=38N=52N=51N=46N=45ASAS408 (23.5)17 (43.6)18 (51.4)*18 (47.4)8 (15.4)15 (29.4)21 (45.7)†25 (55.6)‡ASDAS <2.17 (20.6)18 (46.2)*14 (40.0)17 (44.7)*4 (7.7)16 (31.4)†21 (45.7)†18 (40.0)‡BASDAI507 (20.6)16 (41.0)13 (37.1)16 (42.1)8 (15.4)13 (25.5)21 (45.7)†20 (44.4)†COAST-WbN=37N/AN=28N=28N=67N/AN=86N=70ASAS403 (8.1)N/A11 (39.3)†10 (35.7)*10 (35.7)*N/A18 (20.9)20 (28.6)ASDAS <2.11 (2.7)N/A10 (35.7)‡6 (21.4)*4 (6.0)N/A10 (11.6)10 (14.3)BASDAI503 (8.1)N/A8 (28.6)*10 (35.7)*7 (10.4)N/A17 (19.8)13 (18.6)Non-responder imputation was used for missing responses.P-values vs. PBO (aCochran-Mantel-Haenszel test, adjusted by study;bFisher’s exact test):*P<0.05,†P<0.01,‡P<0.001.b) Change from baseline in SF-36 PCS scores at Week 16 for the intent-to-treat population, LSM (SE)No peripheral articular manifestations at baselinePeripheral articular manifestations at baselinePBOADAQ2WIXEQ4WIXEQ2WPBOADAQ2WIXEQ4WIXEQ2WIntegrated dataseta1.6 (0.90)N/A7.2 (0.95)‡6.1 (0.92)‡3.8 (0.69)N/A7.7 (0.67)‡8.2 (0.71)‡COAST-Vb2.3 (1.15)7.0 (1.10)†6.9 (1.13)†6.4 (1.07)*4.6 (1.00)6.9 (1.01)8.3 (1.07)*9.3 (1.10)†COAST-Wc0.64 (1.57)N/A7.1 (1.75)†5.4 (1.72)*1.9 (0.96)N/A6.4 (0.85)‡6.3 (0.97)‡P-values vs. PBO (MMRM analysis with treatment,a,b,c study,a baseline value,a,b,c visit,a,b,c baseline value-by-visit,a,b,c treatment-by-visit interaction,a,b,c geographic region,b,c baseline CRP status,b,c and number of prior TNF inhibitorsc included as fixed factors):*P < 0.05,†P < 0.01,‡P < 0.001.ADAQ2W = adalimumab every 2 weeks; ASAS = Assessment of Spondyloarthritis International Society criteria; ASDAS = ankylosing spondylitis disease activity score; BASDAI = Bath Ankylosing Spondylitis Disease Activity Index; CRP = c reactive protein; IXEQ2W = ixekizumab every 2 weeks; IXEQ4W = ixekizumab every 4 weeks; MMRM = mixed-effects model of repeated measures; N/A = not applicable; PBO = placebo; PCS = physical component summary; SE = standard error; SF-36 = short-form-36; TNF = tumour necrosis factor.\n Disclosure\u2002\n R. Sengupta: None. P. Bird: Grants/research support; Pfizer, Eli Lilly, Gilead, Abbvie, Novartis. D. Aletaha: Consultancies; Abbvie, Amgen, Celgene, Eli Lilly, Medac, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, Genzyme. Grants/research support; Abbvie, Novartis, Roche. M. Magrey: Consultancies; Novartis, Pfizer, Eli Lilly, Abbvie, UCB. Other; Clinical trials with: Abbvie and UCB. Y. Kadono: Member of speakers’ bureau; Abbie, Lilly, Novartis. E. Soriano: Consultancies; Abbvie, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, Sandoz. Member of speakers’ bureau; Abbvie, Amber, Bristol-Myers Squibb, Eli Lilly, Novartis, Pfizer, Roche, UCB. Grants/research support; Abbvie, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, Sandoz, UCB. A.J. Bradley: Shareholder/stock ownership; Eli Lilly. Other; Employee of Eli Lilly and Company. S. Liu-Leage: Shareholder/stock ownership; Eli Lilly. Other; Employee of Eli Lilly and Company. Y. Schymura: Other; Employee of Eli Lilly and Company. M.J. Nissen: Corporate appointments; Abbvie, Celgene, Lilly, Novartis, Pfizer. Member of speakers’ bureau; Abbvie, Celgene, Novartis, Pfizer. Other; Member of EuroSpA (supported by Novartis).