Ustekinumab (UST) is a monoclonal antibody targeting IL-12/23 p40, and Guselkumab (GUS) and Risankizumab(RIS) are monoclonal antibodies targeting IL-23 p19
March 1, 2022
Ustekinumab (UST) is a monoclonal antibody targeting IL-12/23 p40, and Guselkumab (GUS) and Risankizumab(RIS) are monoclonal antibodies targeting IL-23 p19. psoriasis patients were treated with anti-IL-17/23 biologics with mean follow-up of 21.1 months. Six patients developed DIIP at mean 14 months after initiation of the therapy. Older age, higher baseline KL-6 value and more frequent pre-existing IPs were associated with development of DIIP by univariate analysis. At the onset of DIIP, elevated serum KL-6 levels with concomitantly increased ground glass opacity (GGO) in Chest CT were demonstrated. DIIP was improved by only cessation of causative agents in five patients but steroid therapy was needed in one patient. Conclusions DIIP is a plausible complication of anti-IL-17/23 biologics. Age, baseline KL-6 level and underlying IP could be the risk factors for DIIP development. Serum KL-6 levels and chest CT are useful for not only predicting but also detecting DIIP caused by anti-IL-17/23 biologics. Introduction Psoriasis is a chronic inflammatory disease mainly affecting the skin . Increasing CUDC-907 (Fimepinostat) evidence suggests that IL-17/23 axis plays important roles in the pathogenesis of psoriasis [1C5]. Biologics inhibiting IL-17/23 axis has been developed to treat psoriasis, and currently, three anti-IL-23 and three anti-IL-17 biological agents are available for psoriasis in Japan . Ustekinumab (UST) is a monoclonal antibody targeting IL-12/23 p40, and Guselkumab (GUS) and Risankizumab(RIS) are monoclonal antibodies targeting IL-23 p19. Secukinumab (SEC) and ixekizumab (IXE) are monoclonal antibodies targeting IL-17A, and brodalumab (BRO) is a fully human monoclonal antibody targeting the IL-17 receptor A. All of them have demonstrated high efficacy for psoriasis in clinical settings . Interstitial pneumonia (IP) is one of frequent adverse events induced by a variety of drugs . KL-6 is a high molecular weight mucin-like glycoprotein produced by type 2 pneumocytes and respiratory bronchiolar epithelial cells . KL-6 is overproduced in regenerative epithelial cells following epithelial cell damage during IP progression, hence, the serum KL-6 levels have been considered a representative biomarker for IPs including drug-induced IP (DIIP) [10, 11]. Incidence, severity and prognosis of DIIP depend on not only the type of drug but also host specific reaction [8, 12C14]. There are several case reports showing DIIP by anti-IL-17/23 biologics [15C19] (Two cases of DIIP reported by Kikuchi et al  are also included in this study). Recently, association of noninfectious pneumonia with UST use was reported in JAMA dermatology, and a new warning for DIIP by UST was issued . Hence, careful attention should be paid for this adverse event CDH5 during treatment with anti-IL-17/23 biologics. However, the clinical characteristics of DIIP caused by anti-IL-17/23 biologics including UST remain to be determined. The aim of this study is to clarify the clinical characteristics of DIIP caused by anti-IL-17/23 biologics, including incidence, severity, and prognosis based on evaluation of KL-6 levels and chest CT findings. Methods Study subjects This study is a retrospective cohort study of confirmed cases of psoriasis treated with biologic CUDC-907 (Fimepinostat) agents targeting anti-IL-17/23 biologics at Jikei University Hospital from July 1, 2011 (07/01/2011) to August 31, 2019 (08/31/2019). Patients were eligible for the study if they met the following inclusion criteria 1) Age 20 years old, 2) Confirmed cases of psoriasis by specialists of the Japanese Dermatological Association, 3) Treated with one of anti-IL-17/23 biologics. The exclusion criteria were 1) Patients with progressive cancer or fatal disease. A total of 603 psoriasis patients (UST;256, GUS;53,SEC;183, IXE;39, BRO;72) were included in this study. This study was approved by the Ethics Committee of Jikei University (29C078 (8694)), and adhered to CUDC-907 (Fimepinostat) the tenets of the Declaration of Helsinki. Based on the ethical guidelines of Jikei University, informed consent was not necessary for this retrospective study, and we performed opt-out consent on the website of our hospital. All data were fully anonymized before statistical analysis. Patients medical records during July 1, 2011 (07/01/2011) to August 31, 2019 (08/31/2019) were accessed. Serum KL-6 levels were measured with a commercially available ELISA kit (Nanopia KL-6, 202138C005, Tokyo, Japan) before treatment (baseline) and during treatment. The intervals were determined by the attending doctors. Chest computed tomography (CT) was performed based on worsening of respiratory symptom and/or elevation of KL-6 levels. The chest CT findings of these patients were evaluated by two specialists of the Japanese Respiratory Society (H.H. and H.M.). The psoriasis area severity index (PASI) score and type of psoriasis were determined by specialists of the Japanese Dermatological Association (Y.U., H.N., and A.A.). Diagnosis of DIIP Diagnostic criteria for drug-induced lung injury by Camus P et al. has been widely used in.