FRI0345 HEAD-TO-HEAD STUDY EVALUATING THE COMBINED ACR50/PASI100 TREATMENT RESPONSE OF IXEKIZUMAB VERSUS ADALIMUMAB: INDIVIDUAL PATIENT DATA FROM A RANDOMIZED, OPEN-LABEL STUDY IN BIOLOGIC-NAÏVE PATIENTS WITH PSORIATIC ARTHRITIS THROUGH WEEK 52

Background:Multiple biologic DMARDs (bDMARDs) are available for the treatment of psoriatic arthritis (PsA), but there are few direct comparisons of their efficacy and safety. In SPIRIT-H2H study, ixekizumab (IXE), a high-affinity monoclonal antibody selectively targeting IL-17A, was superior to adalimumab (ADA) at Week 24 for simultaneous achievement of ACR50 and 100% improvement from baseline in the Psoriasis Area and Severity Index (PASI 100) in patients (pts) with active PsA. Efficacy on other PsA domains was shown.1Objectives:To provide individual patient data demonstrating the simultaneous improvement in musculoskeletal and skin symptoms as assessed by American College of Rheumatology (ACR) response criteria and Psoriasis Area and Severity Index (PASI) percent improvement, respectively.Methods:Pts with active PsA fulfilling Classification for Psoriatic Arthritis (CASPAR) criteria, ≥3/66 tender and ≥3/68 swollen joints, ≥3% psoriasis body surface area (BSA) involvement, no prior treatment with bDMARDs, and prior inadequate response to ≥1 conventional synthetic DMARD (csDMARD), were randomized 1:1 to open-label IXE or ADA (label dosing according to presence/absence of moderate-to-severe psoriasis [baseline BSA≥10%, PASI≥12, and static Physician's Global Assessment≥3]) in Study I1F-MC-RHCF (NCT03151551). In this analysis, max ACRx was defined as the maximum ACRx response a patient can achieve where ACRx derivation follows the typical ACR response criteria: ≥x% improvement in both tender joint count (TJC) and swollen joint count (SJC) and ≥x% improvement in ≥3 of the 5 remaining components, Health Assessment Questionnaire-Disability Index total score (HAQ-DI), C-reactive protein (CRP), Patient Global Assessment (PatGA), Physician Global Assessment (PhyGA), and patient assessment of joint pain (patJP). Missing data were imputed using the last observation carried forward (LOCF) method.Results:At baseline, demographic and disease characteristics were similar across treatment groups. Mean baseline values for the ACR core data set were 20.2 (TJC), 10.4 (SJC), 63.8 (PatGA), 10.2 (CRP), 59.2 (PhyGA), 1.2 (HAQ-DI), and 61.0 (patJP). Mean PASI total score was 7.8. Figures 1 and 2 show the maximum ACR response by PASI percent improvement at Weeks 24 and 52, respectively. Independent of joint improvement, more ixekizumab-treated patients compared to adalimumab-treated patients achieved ≥PASI 90 (76.6% vs. 57.5% at week 24 and 83.0% vs. 59.6% at Week 52). Evaluation of patient-level data shows that while very few patients had joint improvement but little skin improvement (max ACRx≥50 and PASI<50; Figures 1 and 2) in both treatment arms (IXE: 1.8%; ADA: 1.4%), fewer patients treated with IXE had no to little improvement in both joint and skin symptoms (PASI<50 and max ACRx<50) than those treated with ADA at Week 24 (IXE: 3.6%; ADA: 13.3%). A similar pattern was observed at Week 52 (Figure 2).Conclusion:Ixekizumab treatment was superior to adalimumab when evaluating the combination of musculoskeletal and skin symptoms of PsA as measured by ACR response and PASI response.References:[1]Mease PJ, Smolen JS, Behrens F et al., Ann Rheum Dis 2019; 79(1):123-131.Disclosure of Interests:Arthur Kavanaugh Grant/research support from: AbbVie, Amgen, Eli Lilly, Novartis, Janssen, Pfizer, Gilead, UCB, Consultant of: AbbVie, Amgen, Eli Lilly, Novartis, Janssen, Pfizer, Gilead, UCB, Ennio Lubrano: None declared, Talia Muram Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Chen-Yen Lin Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Soyi Liu Leage Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Filip van den Bosch Consultant of: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Speakers bureau: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Lars Erik Kristensen Consultant of: UCB Pharma (Advisory Board), Sannofi (Advisory Board), Abbvie (Advisory Board), Biogen (Advisory Board), Speakers bureau: AbbVie, Amgen, Biogen, Bristol-Myers Squibb,Celgene, Eli Lilly, Gilead, Forward Pharma, Janssen Pharmaceuticals, MSD, Novartis, Pfizer, and UCB Pharm

Continuing versus withdrawing ixekizumab treatment in patients with axial spondyloarthritis who achieved remission : efficacy and safety results from a placebo-controlled, randomised withdrawal study (COAST-Y)

Objectives: The objective of COAST-Y was to evaluate the effect of continuing versus withdrawing ixekizumab (IXE) in patients with axial spondyloarthritis (axSpA) who had achieved remission. Methods: COAST-Y is an ongoing, phase III, long-term extension study that included a double-blind, placebo (PBO)-controlled, randomised withdrawal-retreatment period (RWRP). Patients who completed the originating 52-week COAST-V, COAST-W or COAST-X studies entered a 24-week lead-in period and continued either 80 mg IXE every 2 (Q2W) or 4 weeks (Q4W). Patients who achieved remission (an Ankylosing Spondylitis Disease Activity Score (ASDAS)3.5 at any visit) after the 40-week RWRP, with time-to-flare as a major secondary endpoint. Results: Of 773 enrolled patients, 741 completed the 24-week lead-in period and 155 entered the RWRP. Forty weeks after randomised withdrawal, 83.3% of patients in the combined IXE (85/102, p<0.001), IXE Q4W (40/48, p=0.003) and IXE Q2W (45/54, p=0.001) groups remained flare-free versus 54.7% in the PBO group (29/53). Continuing IXE significantly delayed time-to-flare versus PBO, with most patients remaining flare-free for up to 20 weeks after IXE withdrawal. Conclusions: Patients with axSpA who continued treatment with IXE were significantly less likely to flare and had significantly delayed time-to-flare compared with patients who withdrew to PBO

A head-to-head comparison of the efficacy and safety of ixekizumab and adalimumab in biological-naive patients with active psoriatic arthritis: 24-week results of a randomised, open-label, blinded-assessor trial

Objectives To compare efficacy and safety of ixekizumab (IXE) to adalimumab (ADA) in biological disease-modifying antirheumatic drug-naive patients with both active psoriatic arthritis (PsA) and skin disease and inadequate response to conventional synthetic disease-modifying antirheumatic drug (csDMARDs).Methods Patients with active PsA were randomised (1:1) to approved dosing of IXE or ADA in an open-label, head-to-head, blinded assessor clinical trial. The primary objective was to evaluate whether IXE was superior to ADA at week 24 for simultaneous achievement of a >= 50% improvement from baseline in the American College of Rheumatology criteria (ACR50) and a 100% improvement from baseline in the Psoriasis Area and Severity Index (PASI100). Major secondary objectives, also at week 24, were to evaluate whether IXE was: (1) non-inferior to ADA for achievement of ACR50 and (2) superior to ADA for PASI100 response. Additional PsA, skin, treat-to-target and quality-of-life outcome measures were assessed at week 24.Results The primary efficacy endpoint was met (IXE: 36%, ADA: 28%; p=0.036). IXE was non-inferior for ACR50 response (IXE: 51%, ADA: 47%; treatment difference: 3.9%) and superior for PASI100 response (IXE: 60%, ADA: 47%; p=0.001). IXE had greater response versus ADA in additional PsA, skin, nail, treat-to-target and quality-of-life outcomes. Serious adverse events were reported in 8.5% (ADA) and 3.5% (IXE) of patients.Conclusions IXE was superior to ADA in achievement of simultaneous improvement of joint and skin disease (ACR50 and PASI100) in patients with PsA and inadequate response to csDMARDs. Safety and tolerability for both biologicals were aligned with established safety profiles.</div

A head-to-head comparison of the efficacy and safety of ixekizumab and adalimumab in biological-naïve patients with active psoriatic arthritis: 24-week results of a randomised, open-label, blinded-assessor trial

Objectives: To compare efficacy and safety of ixekizumab (IXE) to adalimumab (ADA) in biological disease-modifying antirheumatic drug-naïve patients with both active psoriatic arthritis (PsA) and skin disease and inadequate response to conventional synthetic disease-modifying antirheumatic drug (csDMARDs). Methods: Patients with active PsA were randomised (1:1) to approved dosing of IXE or ADA in an open-label, head-to-head, blinded assessor clinical trial. The primary objective was to evaluate whether IXE was superior to ADA at week 24 for simultaneous achievement of a ≥50% improvement from baseline in the American College of Rheumatology criteria (ACR50) and a 100% improvement from baseline in the Psoriasis Area and Severity Index (PASI100). Major secondary objectives, also at week 24, were to evaluate whether IXE was: (1) non-inferior to ADA for achievement of ACR50 and (2) superior to ADA for PASI100 response. Additional PsA, skin, treat-to-target and quality-of-life outcome measures were assessed at week 24. Results: The primary efficacy endpoint was met (IXE: 36%, ADA: 28%; p=0.036). IXE was non-inferior for ACR50 response (IXE: 51%, ADA: 47%; treatment difference: 3.9%) and superior for PASI100 response (IXE: 60%, ADA: 47%; p=0.001). IXE had greater response versus ADA in additional PsA, skin, nail, treat-to-target and quality-of-life outcomes. Serious adverse events were reported in 8.5% (ADA) and 3.5% (IXE) of patients. Conclusions: IXE was superior to ADA in achievement of simultaneous improvement of joint and skin disease (ACR50 and PASI100) in patients with PsA and inadequate response to csDMARDs. Safety and tolerability for both biologicals were aligned with established safety profiles