P172 An integrated safety analysis of treatment-emergent fungal infections in patients with psoriasis, psoriatic arthritis, or axial spondyloarthritis treated with ixekizumab from 26 clinical studies

Abstract

Abstract Background/Aims Interleukin (IL)-17 plays a role in host defense against common extracellular pathogens, including fungi. Treatment with IL-17 inhibitors has been associated with fungal infections. Ixekizumab (IXE) is an anti-IL-17A monoclonal antibody approved for the treatment of psoriasis (PsO) in adults and children, psoriatic arthritis (PsA) in adults, and axial spondyloarthritis (axSpA) in adults. This integrated post-hoc analysis investigates treatment-emergent fungal infections in IXE-treated patients across the approved indications. Methods Safety data on fungal infections were pooled from the IXE paediatric and adult clinical trial programs, comprising 26 clinical studies. Here, we describe the types of fungal infections, number of infections, recurrence (defined by at least two separate events irrespective of location), severity (defined at the investigator’s discretion), events that lead to discontinuation, and anti-fungal medications. Data are presented as frequency or incidence rate per 100 person-years (IR). Results Fungal infections were reported in patients with PsO (IR = 4.0), PsA (IR = 4.1), and axSpA (IR = 2.7). Across indications, most fungal infections were not recurrent and were classified as mild or moderate in severity. There were few severe fungal infections in patients with PsO (IR = 0.1), PsA (IR = 0.0), and axSpA (IR = 0.0). Most fungal infections in patients with PsO, PsA, and axSpA were candidiasis (IR = 1.9, IR = 2.5, IR = 1.4, respectively) and superficial dermatophytosis (IR = 1.5, IR = 1.0, IR = 1.0, respectively). No cases of subcutaneous and systemic mycosis infections were reported. The proportions of patients with PsO, PsA, and axSpA who received a topical vs systemic anti-fungal medication were 53.6% vs 1.1%, 47.8% vs 0.0%, and 45.6% vs 3.5%, respectively (Table 1). Most fungal infections did not lead to discontinuation of IXE (Table 1). Conclusion Consistent with previously disclosed IXE data, the majority of treatment-emergent fungal infections observed in patients with PsO, PsA, or axSpA treated with IXE were: (i) not recurrent; (ii) mild or moderate in severity, (iii) associated with candidiasis and superficial dermatophytosis, (iv) managed with topical anti-fungal medications or no treatment reported, and (v) not leading to drug discontinuation. Disclosure S. Schwartzman: Corporate appointments; SS reports being a board member of the National Psoriasis Foundation. Consultancies; S. Schwartzman has served as a speaker and/or consultant for AbbVie, Janssen, Eli Lilly and Company, Pfizer, UCB, Myriad, Novartis, Regeneron, Sanofi, Stelexis, Jubilant, Teijin. L. Puig: Corporate appointments; Board member of the International Psoriasis Council. Consultancies; AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Leo Pharma, Eli Lilly and Company, Novartis, Pfizer, Sandoz, Sanofi, UCB. Honoraria; Boehringer Ingelheim, Janssen, Eli Lilly and Company, Novartis, UCB, travel support from Janssen, Eli Lilly and Company, Pfizer, UCB. Grants/research support; L. Puig reports receiving grants from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Leo Pharma, Eli Lilly and Company, Novartis, Pfizer, Sanofi, UCB. A.D. Cohen: Honoraria; AbbVie, Amgen, Boehringer Ingelheim, Dexcel Pharma; Janssen, Eli Lilly and Company, Neopharm, Novartis, Perrigo, Pfizer, Rafa. Grants/research support; A. D. Cohen has served on advisory board for Samsung, and reports receiving grants from AbbVie, Janssen, Novartis, Pfizer, travel support from AbbVie. S. Khattri: Consultancies; S. Khattri reports being part of Eli Lilly and Company speaker’s bureau, receiving consulting fees and honoraria from Eli Lilly and Company, AbbVie, UCB, Janssen, BI, Regeneron, Leo Pharma. C. Jossart: Shareholder/stock ownership; C. Jossart is a stockholder of Eli Lilly and Company and was an employee of Eli Lilly and Company when this study was conducted. C. Diaz: Shareholder/stock ownership; C. Diaz is employee and stockholder of Eli Lilly and Company. A. Garrelts: Shareholder/stock ownership; A. Garrelts is employee and stockholder of Eli Lilly and Company. D. Zhu: Shareholder/stock ownership; D. Zhu is employee and stockholder of Eli Lilly and Company. N. Eberhart: Shareholder/stock ownership; N. Eberhart is employee and stockholder of Eli Lilly and Company. A. Eleftheriadi: Shareholder/stock ownership; A. Eleftheriadi is employee and stockholder of Eli Lilly and Company. N. Tangsirisap: Shareholder/stock ownership; N. Tangsirisap is employee and stockholder of Eli Lilly and Company. C. Schuster: Shareholder/stock ownership; C. Schuster is an employee and stockholder of Eli Lilly and Company. A.B. Gottlieb: Consultancies; Xbiotech (stock options for an RA project). Honoraria; Amgen, AnaptysBio, Avotres Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Dice Therapuetics, Dermavant, Lilly, Janssen, Leo, Pharma, Novartis, Pfizer, Sanofi, Sun Pharma, UCB Pharma. Grants/research support; AnaptysBio, Moonlake Immunotherapeutics, Novartis, BMS, and UCB Pharma; all funds go to the Icahn School of Medicine at Mount Sinai. M. Sheesh: Shareholder/stock ownership; MS is a full-time employee and minor share holder of Eli-Lilly and Company.