Withdrawal of Ixekizumab Results in Loss of Efficacy in Multiple Clinical Domains in Patients with Psoriatic Arthritis Who Had Achieved Minimal Disease Activity: Results from the SPIRIT-P3 Study

Laura Coates¹, Sreekumar Pillai ², Matthew M. Hufford ², Denise Alves ², So Young Park ², Gaia Gallo ², Beilei Wu ³, Ivo Valter ⁴, Hasan Tahir ⁵, Vinod Chandran ⁶, Arthur Kavanaugh ⁷ and Philip Mease ⁸, ¹University of Oxford, Oxford, United Kingdom, ²Eli Lilly and Company, Indianapolis, IN, ³GCE Solutions Inc., Bloomington, IL, ⁴Center for Clinical and Basic Research, Tallinn, Estonia, ⁵Department of Rheumatology, Whipps Cross University Hospital, London, United Kingdom, ⁶Division of Rheumatology, University of Toronto, Krembil Research Institute, University Health Network, Toronto, ON, Canada, ⁷University of California, San Diego School of Medicine, La Jolla, CA, ⁸Swedish Medical Center/Providence St Joseph Health, and University of Washington, Seattle, WA

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: MDA, psoriatic arthritis and relapse

Session Information

Date: Monday, November 11, 2019

Title: Spondyloarthritis Including Psoriatic Arthritis – Clinical Poster II: Treatment of Axial Spondyloarthritis & Psoriatic Arthritis

Session Type: Poster Session (Monday)

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

Background/Purpose: Ixekizumab (IXE), a high affinity monoclonal antibody that selectively targets interleukin-17A, has been demonstrated to improve the signs and symptoms, disease activity, and quality of life of patients with active PsA. SPIRIT-P3 was a randomized withdrawal (RW) phase 3b clinical trial that demonstrated that in patients who achieved sustained minimal disease activity (MDA) after open label (OL) IXE treatment, continued IXE treatment was superior to IXE withdrawal (placebo, PBO) in maintaining MDA. In this pre-specified and post-hoc analysis, we assessed the impact of IXE withdrawal on the individual components of MDA.

Methods: In SPIRIT-P3 (NCT02584855), patients with active PsA who were naïve to biologic DMARDs received OL treatment with IXE 80 mg every two weeks (Q2W) after a 160-mg starting dose for at least 36 weeks. Patients who achieved MDA (at least 5 out of 7 components [see table]) for three consecutive months between Weeks 36 and 64 were flexibly randomized 1:1 to IXE Q2W or placebo (PBO) and evaluated up to Week 104 in a double-blind manner. Patients were considered relapsed if they lost MDA at any point during the RW and received IXEQ2W thereafter. Kaplan-Meier product limit method was used to estimate time to loss of response of individual components in the RW intent-to-treat population. Treatment comparisons were done between groups using adjusted log-rank test stratified by geographic region and conventional synthetic DMARDs (cDMARD) use. A p-value < 0.05 was considered to be significant. Number of components of MDA met at randomization and at time of relapse in both PBO and IXE groups were assessed in the relapse population.

Results: A total of 394 patients entered into the OL treatment period; 158 (40%) of whom met three consecutive months of MDA and randomized to IXE (N=79) or PBO (N=79) in the RW period. At time of randomization, 77 patients (37 assigned to PBO; 40 assigned to IXEQ2W) had achieved very low disease activity (VLDA; i.e., meeting 7 out of 7 components). Overall, significantly more patients randomized to PBO than IXE relapsed during the RW period (data not shown). Among patients who had VLDA at randomization, 30 (81%) of PBO patients and 10 (25%) of IXE patients met relapse criteria. Time to relapse was significantly shorter in patients on PBO than IXE-treated patients for 5 out of 7 individual components (Tender joint count, Swollen joint count, PASI/BSA, patient pain VAS, Patient Global Disease Activity VAS) of MDA (p < 0.01, Table). Among patients who relapsed, 18 (60%) from IXEQ2W and 25 (37%) from PBO groups met 4 out of 7 components at time of relapse (figure).

Conclusion: In patients with sustained MDA, IXE withdrawal led to relapse in components of MDA, particularly tender and swollen joints, patient reported joint pain and disease activity, and psoriasis. IXE withdrawal, relative to continued treatment, was associated with relapse in multiple components of MDA within individual patients, even in patients who had achieved VLDA.

Table 91018

Time to loss of response of individual components of MDA in RW intent-to-treat population

Patients meeting number of components of MDA met at the time of relapse in PBO and IXE groups in relapse population

Disclosure: L. Coates, Abbvie, 2, 5, 8, AbbVie, 2, 5, 8, AbbVie, Amgen, BMS, Celgene Corporation, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Prothena, Sun Pharma, UCB, 5, Abbvie, Amgen, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB, 5, Abbvie, Amgen, Lilly, Novartis, Pfizer, UCB, 8, AbbVie, Celgene Corporation, Eli Lilly, Janssen, Novartis, UCB, 8, AbbVie, Celgene Corporation, Eli Lilly, Novartis, Pfizer, 2, AbbVie, Celgene Corporation, Novartis, Pfizer, 2, Abbvie, Celgene, Novartis, Pfizer, Lilly, 2, Amgen, 5, 8, Biogen, 8, Bristol-Myers Squibb, 5, Celgene, 2, 5, 8, Eli Lilly, 2, 5, 8, Galapagos, 5, Gilead, 5, Janssen, 2, 5, 8, Janssen Research & Development, LLC, Lilly, 2, 5, 8, MSD, 5, Novartis, 2, 5, 8, Pfizer, 2, 5, 8, Pfizer Inc, 2, 5, 8, Prothena, 5, Sun Pharma, 5, UCB, 5, 8, UCB Pharma, 5; S. Pillai, Eli Lilly, 1, 3, Eli Lilly and Company, 3; M. Hufford, Eli Lilly and Company, 1, 3; D. Alves, Eli Lilly, 1, 3; S. Young Park, Eli Lilly and Company, 1, 3; G. Gallo, Eli Lilly, 1, 3, 4, Eli Lilly and Company, 1, 3, 4; B. Wu, None; I. Valter, Eli Lilly, 9, Eli Lilly and Company, 9; H. Tahir, AbbVie, Janssen, Eli Lilly, and Novartis, 8, Novartis, Eli-Lilly, 2; V. Chandran, Abbvie, 1, AbbVie, 1, 5, Abbvie, Amgen, Celgene, BMS, Eli Lilly, Janssen, Novartis, Pfizer, UCB, 5, Amgen, 5, Bristol Myers Squibb, 5, Celgene, 5, Eli Lilly, 3, Eli Lilly and Company, 5, 9, Janssen Pharmaceutica, 5, Novartis, 5, 8, Pfizer, 5, UCB, 5; A. Kavanaugh, Abbott, 2, Abbott, Amgen, AstraZeneca, BMS, Celgene Corporation, Centocor-Janssen, Pfizer, Roche, UCB, 2, Amgen, 2, Bristol-Myers Squibb, 2, Eli Lilly, 5, Eli Lilly and Company, 5, Gilead Sciences, Inc., 2, Janssen, 2, Janssen Research & Development, LLC, 2, Novartis, 2, 5, Pfizer, 2, Pfizer Inc, 2, Roche, 2, UCB Pharma, 2; P. Mease, Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Genentech, Janssen, Novartis, Pfizer, Roche, UCB, 2, 5, Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB, 8, AbbVie, 2, 5, 8, Abbvie, 2, 5, 8, Abbvie, Amgen, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Sun, UCB, 5, Abbvie, Amgen, Bristol Myers Squibb, Celgene, Genentech, Janssen, Lilly, Novartis, Pfizer, UCB, 8, Abbvie, Amgen, Bristol Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer, Sun, UCB, 2, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Janssen, Leo, Merck, Novartis, Pfizer and UCB., 5, 8, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Leo, Eli Lilly, Merck, Novartis, Pfizer, Sun Pharmaceutical Industries, Inc., and UCB, 2, Abbvie, Amgen, Brsitol Myers Squibb, Boehringer Ingelheim, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Sun, UCB, 5, Abbvie, Amgen, Brsitol Myers Squibb, Celgene, Genentech, Janssen, Lilly, Novartis, Pfizer, UCB, 8, Abbvie, Amgen, Brsitol Myers Squibb,Celgene, Janssen, Lilly, Novartis, Pfizer, Sun, UCB, 2, Amgen, 2, 5, 6, 8, Amgen, Bristol-Myers Squibb, Celgene, Galapagos, Gilead, GSK, Janssen, Leo, Eli Lilly, Merck, Novartis, Pfizer, Sun Pharmaceutical Industries, and UCB, 5, BMS, 2, 5, 8, Boehringer Ingelheim, 2, 5, Boerhinger Ingelheim, 5, Bristol Myers Squibb, 2, 5, 8, Bristol Myers Squibb Co., 2, 5, 8, Bristol-Myers Squibb, 2, 5, 6, 8, Celgene, 2, 5, 6, 8, Celgene Corp., 2, 5, 8, CORRONA, 5, Eli Lilly, 2, 5, 8, Galapagos, 2, 5, 8, Genentech, 2, 5, 6, 8, Gilead, 2, 5, 8, Janssen, 2, 5, 6, 8, Janssen Inc, 2, 5, 8, Leo, 2, 5, 8, Lilly, 2, 5, 6, 8, Merck, 2, 5, 8, Novartis, 2, 5, 6, 8, Pfizer, 2, 5, 8, Pfizer Inc, 2, 5, 6, Sun, 2, 5, SUN, 2, 5, Sun Pharma, 2, 5, Sun Pharmaceutical Industries, 2, 5, Sun Pharmaceutical Industries, Inc., 2, 5, 8, UCB, 2, 5, 6, 8, UCB Pharma, 2, 5, 8.

To cite this abstract in AMA style:

Coates L, Pillai S, Hufford M, Alves D, Young Park S, Gallo G, Wu B, Valter I, Tahir H, Chandran V, Kavanaugh A, Mease P. Withdrawal of Ixekizumab Results in Loss of Efficacy in Multiple Clinical Domains in Patients with Psoriatic Arthritis Who Had Achieved Minimal Disease Activity: Results from the SPIRIT-P3 Study [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/withdrawal-of-ixekizumab-results-in-loss-of-efficacy-in-multiple-clinical-domains-in-patients-with-psoriatic-arthritis-who-had-achieved-minimal-disease-activity-results-from-the-spirit-p3-study/. Accessed .

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