IXEKIZUMAB IMPROVES SIGNS, SYMPTOMS, AND QUALITY OF LIFE IN PATIENTS WITH AXIAL SPA IRRESPECTIVE OF DISEASE DURATION: RESULTS FROM THE COAST-V, COAST-W AND COAST-X TRIALS

BackgroundIxekizumab (IXE), a high-affinity monoclonal antibody selectively targeting interleukin-17A,1 has demonstrated superior efficacy to placebo (PBO) in the treatment of patients (pts) with radiographic axial spondyloarthritis (r-axSpA) (COAST-V [NCT02696785]; -W [NCT02696798]), and non-radiographic axial spondyloarthritis (nr-axSpA) (COAST-X [NCT02757352]).ObjectivesAssess treatment response to IXE categorised by disease duration since symptom onset (<5 years (yrs), ≥5yrs) in pts with r-axSpA and nr-axSpA up to 52 Weeks (Wks).MethodsPts fulfilled ASAS classification criteria for r-axSpA or nr-axSpA and were randomised to receive 80mg subcutaneous IXE every 2Wks or 4Wks, or PBO (16Wks COAST-V/W; 52Wks COAST-X). Data were summarized by disease duration and treatment in eligible intent-to-treat (ITT) pts. Wk16 treatment comparisons were conducted using Cochran-Haenszel-Mantel test and ANCOVA. Missing data were handled using non-responder imputation and modified baseline observation carried forward, for categorical and continuous endpoints, respectively.ResultsTable 1 presents pt demographics and baseline characteristics. Data is from pooled IXE pts. In pts with r-axSpA and <5yrs symptom duration, ASAS40 response was achieved by 51.5% at Wk16 and 60.6% at Wk52, compared to 36.9% at Wk16, significantly different to PBO (p<0.001), and 40.5% at Wk52, in pts with ≥5yrs symptom duration. In pts with nr-axSpA and <5yrs symptom duration, ASAS40 response was achieved by 42.5% at Wk16, significantly different to PBO (p=0.012), and 54.8% at Wk52, compared to 36.0% at Wk16 and 41.4% at Wk52 in pts with ≥5yrs symptom duration (Figure 1). In pts with r-axSpA and <5yrs symptom duration, ASDAS LDA <2.1 response was achieved by 39.4% at Wk16 and 48.5% at Wk52, compared to 27.5% at Wk16, significantly different to PBO (p<0.001), and 35.6% at Wk52 in pts with ≥5yrs symptom duration. In pts with nr-axSpA and <5yrs symptom duration, ASDAS LDA <2.1 response was achieved by 32.9% at Wk16, significantly different to PBO (p=0.003), and 49.3% at Wk52, compared to 23.9% at Wk16 and 36.9% at Wk52 in pts with ≥5yrs symptom duration. At Wk16, in pts with r-axSpA pts and <5yrs symptom duration, the Change from Baseline (CFB) in SF-36 Physical Component Summary (PCS) Score (LSM±SE) was 7.91 (±1.52), compared to 6.81 (±0.40) in pts with ≥5yrs symptom duration. In pts with nr-axSpA and <5yrs symptom duration, this score was 8.95 (±0.95) compared to 7.07 (±0.73) in pts with ≥5yrs symptom duration; both were significantly different to PBO (r-axSpA: p<0.001; nr-axSpA: p=0.037).Table 1.Patient demographics and Baseline CharacteristicsPts with r-axSpAPts with nr-axSpA<5yrs (Ns=33)≥5yrs (Ns=306)<5yrs (Ns=73)≥5yrs (Ns=111)Age (years)33.1 (8.15)45.1 (12.12)31.9 (10.07)46.4 (11.86)Male, n (%)26 (78.8)245 (80.1)40 (54.8)53 (47.7)Female, n (%)7 (21.2)61 (19.9)33 (45.2)58 (52.3)Age at axSpA onset (years)30.4 (8.29)27.0 (9.06)29.9 (10.22)29.5 (8.76)ASDAS score, mean (SD)3.87 (0.79)4.03 (0.82)3.79 (0.80)3.85 (0.78)BASDAI score, mean (SD)7.16 (1.64)7.25 (1.35)7.00 (1.33)7.30 (1.26)SF-36 PCS, mean (SD)34.02 (7.73)32.86 (7.63)32.84 (7.86)32.57 (6.97)Abbreviations: IXE=ixekizumab, n=number of pts in specified category, Ns=number of pts in each subgroup, SD=standard deviation.Figure 1.ASAS40 Response Rates for patients with r-axSpA (COAST-V/W) and nr-axSpA (COAST-X) Symptom Duration <5 and ≥5 years up to Week 52, ITT, NRI: Significantly greater response of IXE versus PBO at Week 16 denotated by * (p≤0.05), *** (p≤0.001). Abbreviations: PBO, placebo; IXE, Ixekizumab; NRI, nonresponder imputation; ITT, Intent-to-Treat (population), ASAS, Assessment of Spondyloarthritis International Society.ConclusionEfficacy response to the therapy with IXE was observed in both subgroups based on disease duration (<5 and ≥5yrs) with more robust responses in the <5 years subgroup.References[1]Paller AS, Br J Dermatol. 2020;183(2):231-241.Disclosure of InterestsVictoria Navarro-Compán Speakers bureau: AbbVie, Janssen, Eli Lilly and Company, Novartis, Pfizer and UCB, Paid instructor for: AbbVie, Janssen, Eli Lilly and Company, Novartis, Pfizer and UCB, Consultant of: AbbVie, Eli Lilly and Company, Novartis, Pfizer and UCB, Grant/research support from: ASAS: Research grant 2018 and 2021.Novartis: Research grant 2021 (Payment to institution), John D Reveille Speakers bureau: Eli Lilly and Company and UCB Pharma, Consultant of: UCB Pharma, Grant/research support from: Eli Lilly and Company, Proton Rahman Speakers bureau: Abbott, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, and Company Janssen, Novartis, and Pfizer., Paid instructor for: Advisory Board: Abbott, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Novartis, and Pfizer., Grant/research support from: Janssen and Novartis, José Maldonado-Cocco Speakers bureau: Pfizer, Merck Sharp Dohme, Wyeth, Sanofi Aventis, Novartis, Bristol Myers Squibb, Roche, Shering-Plough, Abbvie, UCB, Gilead., Consultant of: Pfizer, Merck Sharp Dohme, Wyeth, Sanofi Aventis, Novartis, Bristol Myers Squibb, Roche, Shering-Plough, Abbvie, UCB, Gilead., Grant/research support from: Pfizer, Merck Sharp Dohme, Wyeth, Sanofi Aventis, Novartis, Bristol Myers Squibb, Roche, Shering-Plough, Abbvie, UCB, Gilead., Marina Magrey Speakers bureau: Novartis, Abbvie, Eli Lilly and Company., Consultant of: Novartis, Eli Lilly and Comapny, Pfizer, Janssen, UCB Pharma, Abbvie, BMS., Rebecca Bolce Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, David Sandoval Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, So Young Park Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Andris Kronbergs Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Martin Rudwaleit Speakers bureau: Abbvie, BMS, Boehringer Ingelheim, Chugai, Eli Lilly and Company, Novartis, Pfizer, UCB., Paid instructor for: Abbvie, Eli Lilly, Novartis, UCB., Consultant of: UCB, Grant/research support from: Galapagos, UCB, Novartis.