DOI: 10.6084/m9.figshare.26946032
title: Treatment-emergent Candida infections in patients with psoriasis, psoriatic arthritis, and axial spondyloarthritis treated with ixekizumab: an integrated safety analysis of 25 clinical studies

description: This safety analysis investigates treatment-emergent mucosal/cutaneous Candida infections in patients treated with ixekizumab (IXE), an anti-interleukin-17A monoclonal antibody, across the approved indications: psoriasis (PsO), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA). Safety data were pooled from 25 clinical studies. Incidence rates (IRs) are expressed as per 100 patient-years (PY), using the entire duration of exposure. Candida infections had an IR of 1.9 per 100 PY in patients with PsO (<i>N</i> = 6892; total PY = 18025.7), 2.0 per 100 PY in patients with PsA (<i>N</i> = 1401; total PY = 2247.7), and 1.2 per 100 PY in patients with axSpA (<i>N</i> = 932; total PY = 2097.7). The majority of treatment-emergent Candida infections were: (i) experienced only once by patients (IR = 1.3;IR = 1.6;IR = 1.0), (ii) mild/moderate in severity (IR = 0.8/0.9;IR = 1.5/0.4;IR = 0.8/0.5) as opposed to severe (IR = 0.0; IR = 0.0; IR = 0.0), (iii) oral Candida or genital Candida (IR = 0.9/0.6;IR = 1.0/0.7;IR = 0.4/0.6), (iv) marked as recovered/resolved during the studies (89.3%;93.8%;90.3%), (v) not leading to IXE discontinuation (0.0%;0.0%;0.1% discontinued), (vi) managed with topical (34.7%;22.2%;11.5%) or no anti-fungal medications (63.5%;77.8%;80.8%) as opposed to systemic therapies (1.5%;0.0%;7.7%), (vii) typically resolved before next visit. This integrated safety analysis shows that the risk of developing Candida infections is low with IXE, and the severity is mild-to-moderate in most instances across the approved IXE indications. A comprehensive list of the clinical trials and their registration numbers is reported in Table S1 of the supplemental material. Ixekizumab (IXE) is a drug approved for the treatment of psoriasis, psoriatic arthritis, and axial spondyloarthritis. IXE belongs to the class of molecules that blocks a protein called interleukin-17A. Since interleukin-17A is involved in the defense against fungi, the clinical use of this class of drug has the potential to increase the risk of developing fungal infections, such as Candida infections. Therefore, researchers collected safety data from 25 clinical studies comprising 9225 adult patients treated with IXE: 6892 with psoriasis, 1401 with psoriatic arthritis, and 932 with axial spondyloarthritis. Researchers looked at the rate of new cases of Candida infections, the so-called incidence rate, and found that 1.9 per 100 patient-years experienced at least 1 Candida infection in the psoriasis group, 2.0 per 100 patient-years in the psoriatic arthritis group, and 1.2 per 100 patient-years in the axial spondyloarthritis group. Across indications, the majority of Candida infections (<i>i</i>) were experienced only once by patients, (<i>ii</i>) were mild or moderate in severity, (<i>iii</i>) involved infections caused by superficial skin fungus in the mouth or genitals, (<i>iv</i>) were considered recovered/resolved during the studies, (<i>v</i>) did not lead to IXE discontinuation, (<i>vi</i>) were managed with topical anti-fungal medications or no medications, and (<i>vii</i>) were typically resolved before next visit. In conclusion, this safety analysis shows that the risk of developing Candida infections is low with IXE, and the severity is mild-to-moderate in most instances across the approved IXE indications.