Biologic therapies for psoriasis, targeting tumour necrosis factor-α and the interleukin (IL)-17/12/23 axes, can cause paradoxical eczema. The mechanisms underlying this phenomenon are unknown. We aimed to identify single nucleotide polymorphisms (SNPs) associated with paradoxical eczema in biologic-treated psoriasis patients and explored whether polygenic risk scores (PRS) for atopic disease were associated. We conducted a genome-wide association study (GWAS) of 3212 psoriasis patients in the U.K. and Ireland treated with biologic therapies, of whom 88 developed paradoxical eczema. Genome-wide significant (P <5x10-8) SNPs from published GWAS were used to generate PRS for atopic eczema, (PRSAE), general atopic disease (PRSAT) or a combination (PRSCO), which were tested for association with paradoxical eczema. Two lead SNPs reached genome-wide significance for association with paradoxical eczema: rs192705221 (mapping near UNC5B, P = 9.52 × 10-10) and rs72938898 (mapping to SLC1A2, P = 4.61 × 10-9). All three atopy PRS were associated with paradoxical eczema (P <0.05); PRSCO had the strongest association (OR 2.04, 95% CI 1.27-3.29, P = 0.003). Inclusion of PRSAE in a multivariable model including age, sex, atopic background, and psoriatic arthritis history improved model fit (P = 0.018) and diagnostic ability, with an increase in area under the curve from 0.67 to 0.69. Genetic burden for atopic disease is associated with paradoxical eczema occurring in biologic-treated psoriasis patients, which could indicate shared underlying mechanisms. Including genetic risk in multivariable models may have utility in adverse event prediction and precision medicine.

ESDR269 - Atopic polygenic risk score is associated with paradoxical eczema developing in psoriasis patients treated with biologics

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