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

<jats:title>Abstract</jats:title> <jats:p>Background/Aims </jats:p> <jats:p>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.</jats:p> <jats:p>Methods </jats:p> <jats:p>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.</jats:p> <jats:p>Results </jats:p> <jats:p>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 &lt;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.</jats:p> <jats:p>Conclusion </jats:p> <jats:p>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 Table 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 &lt;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 &lt;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 &lt;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&lt;0.05,†P&lt;0.01,‡P&lt;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 &lt; 0.05,†P &lt; 0.01,‡P &lt; 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 ...