IL23 Receptor Polymorphism Is a Predictor of Anti‐Tumour Necrosis Factor‐α‐Induced Paradoxical Psoriasis in Inflammatory Bowel Disease

ABSTRACT Background Paradoxical psoriasis (PP) is an adverse drug reaction associated with anti‐tumour necrosis factor (TNF)‐α therapy leading to disfiguring skin lesions that may impact an individual's quality of life and affect their inflammatory bowel disease (IBD) care. To date, there are no tools to identify individuals at risk for PP. IL‐23 receptor (IL23R) gene polymorphisms have been linked to psoriasis and may be implicated in PP. Aims To evaluate the association between the IL23R1142G>A single nucleotide variant and the occurrence of PP in an anti‐TNFα‐treated IBD population and assess other clinical variables associated with PP development. Methods In a retrospective cohort study conducted in anti‐TNFα‐exposed adult patients with IBD, participants were screened for the IL23R1142G>A variant genotype and the occurrence of PP was assessed. Participants were additionally assessed for clinical variables associated with PP development and for the impact of PP on IBD treatment. Results Among 499 patients, the incidence of PP was 5.1% (29/570) with 570 unique anti‐TNFα exposures. Most patients had severe PP (69.0%) and required treatment cessation (69.0%), which resulted in complete resolution of PP. An IL23R1142G>A variant genotype was highly associated with PP development (46.2% vs. 5.1%, OR = 17.8, 95% CI 7.8–40.0; p < 0.0001). No other clinical variables were associated with the occurrence of PP. Conclusions Variation in the IL23R gene may identify those at risk of anti‐TNFα‐induced PP, beyond clinical variables. Further validation of this finding may promote its utility as a clinically actionable tool for the safe delivery of IBD medical therapy.