FRI0400 LONG-TERM SAFETY OF IXEKIZUMAB IN PATIENTS WITH RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS/ANKYLOSING SPONDYLITIS: AN INTEGRATED ANALYSIS OF COAST-V AND COAST-W
Authors: Helena Marzo-Ortega, Eduardo Mysler, Tetsuya Tomita, Jeffrey Lisse, Silvia Santisteban, Sandra Garces, Wen Xu, Martin Rudwaleit, Carlo Salvarani, Sergio Schwartzman
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> The efficacy and safety of ixekizumab (IXE) in patients with radiographic axial spondyloarthritis (r-axSpA) were investigated in the COAST trial program. <h3>Objectives</h3> To report the long-term safety of IXE in r-axSpA patients using integrated safety data from the COAST trials program. <h3>Methods</h3> Safety data for r-axSpA patients treated with IXE were integrated from COAST-V (biologic-naïve; NCT02696785) and COAST-W (Inadequate responders or intolerant to 1 or 2 TNF inhibitors; NCT02696798) studies. Patients fulfilled ASAS criteria for r-axSpA and mNY criteria for ankylosing spondylitis. Trial eligibility criteria were previously reported.<sup>1,2</sup> In these studies, participants were randomized to placebo (n=191), adalimumab (n=90, active reference arm, COAST-V only), or ixekizumab (n=376). Study participants initially randomized to IXE in both trials were treated with a starting dose (80-mg or 160-mg) and then 80-mg IXE every 2 weeks (IXEQ2W) or 4 weeks (IXEQ4W). Patients initially treated with placebo or adalimumab were re-randomized at Week 16 to receive either IXEQ2W or IXEQ4W following a 160-mg starting dose. The analysis population included all ixekizumab-exposed patients in both trials. Incidence rates (IR) per 100 person years with 95% confidence intervals (CI) and the number of patients are reported. Adverse Event (AE) codes were derived from MedDRA (v21.0). Integrated safety data presented here include all data collected between May 6. 2016 and Sept. 20, 2018. <h3>Results</h3> The integrated population consisted of 641 patients with 749.6 total patient-years of exposure to IXE. Mean follow up time was 427 days. Mean baseline age was 43.8±12.3 years. Mean and median baseline disease symptom duration (since onset) were 17.2±10.8 years and 15.5 years (Min: 1.1, Max: 56.2), respectively. Safety data are presented in Table 1. Among these patients, 489 (76.3%) reported ≥1 treatment emergent AEs with an IR of 65.2. Serious AEs (≥1) were reported for 51 (8.0%) patients with an IR of 6.8. Discontinuations due to AEs were reported for 38 (5.9%) patients with an IR of 5.1. One death was reported, a suicide, in a patient with a documented prior history of depression and judged by the blinded principal investigator to be unrelated to the investigational product. The overall infection IR was 39.4, with both serious and opportunistic infections reported with an IR of 1.7. Among opportunistic infections, no <i>Tuberculosis</i> infections or reactivations were reported and the <i>Candida</i> infection IR was 1.2. No infections were associated with grade 3 or 4 neutropenia. The confirmed major adverse cardiovascular events IR was 0.1. The malignancy IR was 0.4 with acute promyelocytic leukemia, bladder cancer, and ovarian cancer reported. The depression IR was 0.8. The adjudicated inflammatory bowel disease (IBD) IR was 1.5 with 4 of 11 patients having prior history of IBD. The Anterior uveitis (AU) IR was 3.9 with 24 of 29 patients having prior history of AU. The injection site reaction IR was 11.3. <h3>Conclusion</h3> The reported safety profile for IXE in r-axSpA is consistent with the profile reported for other indications. During the extension period, the overall safety profile of ixekizumab remained consistent with that observed during the double-blind period of COAST-V and COAST-W.<sup>1,2</sup> <h3>References</h3> [1 ] [Van der Heijde et al Lancet 2018 2Deodhar et al Arthritis Rheumatol 2018] <h3>Disclosure of Interests</h3> Helena Marzo-Ortega Grant/research support from: Janssen, Novartis and Pfizer, Consultant for: AbbVie, Celgene, Janssen, Eli-Lilly, Novartis and UCB, Speakers bureau: AbbVie, Celgene, Janssen, Eli-Lilly, Novartis and UCB, Eduardo Mysler Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly, Pfizer, Novartis, Janssen, Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lily, Janssen, Medimmune, Pfizer Inc, and Roche, Consultant for: AbbVie, Bristol-Myers Squibb, Eli Lily, Janssen, Medimmune, Pfizer Inc, and Roche, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, Pfizer, Novartis, Janssen, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lily, Janssen, Medimmune, Pfizer Inc, and Roche, Tetsuya Tomita Consultant for: AbbVie, Astellas, Bristol-Myers Squibb, Eisai, Eli Lilly and Company, Janssen, Mitsubishi Tanabe, Novartis, Takeda, and Pfizer, Speakers bureau: AbbVie, Astellas, Bristol-Myers Squibb, Eisai, Eli Lilly and Company, Janssen, Mitsubishi Tanabe, Novartis, Takeda, and Pfizer, Jeffrey Lisse Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Silvia Santisteban Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Sandra Garces Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Wen Xu Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Martin Rudwaleit Consultant for: AbbVie, BMS, Celgene, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB Pharma, Consultant for: AbbVie, BMS, Celgene, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB Pharma, Carlo Salvarani Grant/research support from: Roche, Consultant for: Eli Lilly and Company, Roche, Abbvie, Sergio Schwartzman Shareholder of: Amgen, Boston Scientific, Gilead, Medtronic, and Pfizer, Consultant for: AbbVie, Crescendo, Dermtech, Janssen, Gilead, Lilly, Myriad, Novartis, Regeneron, Samsung, Sanofi, and Union Chimique Belge, Speakers bureau: Abbott/AbbVie, Genentech, Janssen, Lilly, Novartis, Pfizer, Regeneron, Sanofi, and Union Chimique Belge