P25 Genome-wide association study and predictive models for the efficacy and safety of NB-UVB phototherapy in psoriasis

Abstract Background Psoriasis is a chronic inflammatory skin disease affecting ∼125 million individuals worldwide. Although the treatment of psoriasis has entered an era of biological agents and small molecule drugs, narrowband ultraviolet B (NB-UVB) phototherapy still represents an effective, cost-efficient, and safe therapeutic option for patients with plaque psoriasis. However, the clinical and genetic predictors of NB-UVB treatment response remain limited. Objective We aimed to detect single nucleotide polymorphisms (SNPs) associated with the efficacy of NB-UVB in treating psoriasis and its adverse events (AEs), in order to establish predictive models for the efficacy and safety of NB-UVB phototherapy. Methods A total of 252 patients with moderate-to-severe plaque psoriasis were enrolled in this study and underwent 12 weeks of NB-UVB phototherapy. Psoriasis area and severity index (PASI) and the AEs of NB-UVB treatment were recorded during follow-up. Whole blood samples were collected from the participants, and extracted DNA was genotyped using Infinium Global Screening Array-24 v3.0 BeadChip. Genome-wide association studies (GWASs) were performed to identify SNPs related to NB-UVB treatment response. Predictive models for the efficacy and safety of NB-UVB therapy, which involved SNPs along with clinical parameters, were developed utilizing logistic regression and further validated by receiver operating characteristic (ROC) curve and calibration curve. Results After 4 weeks of NB-UVB phototherapy, 40.8% of patients achieved PASI50. Through GWASs, we discovered that SLC7A13 rs35314286 TA allele [odds ratio (OR) = 2.631, P = 5.96 × 10−6] and DYNC1H1 rs941636 A allele (OR = 3.066, P = 3.15 × 10−6) were significantly correlated with better efficacy of 4-week NB-UVB treatment. After 12 weeks of treatment, 61.4% of patients achieved PASI75. Seven ATP2B2 SNPs and 11 PSMB7 SNPs significantly impacted 12-week PASI75 achievement. During the treatment, 29.8% of patients experienced AEs that included pruritus, sting, numbness, erythema, vesicles, desquamation, hyperpigmentation, and photosensitivity. Two KCNA2 SNPs, seven THSD7B SNPs and one TENM4 SNP were considerably associated with the occurrence of AEs. Based on the clinical parameters (body mass index, smoking history, PASI score, and the percentage of PASI improvement at Week 4) and NB-UVB relevant SNPs, predictive models for the efficacy and safety of NB-UVB phototherapy were established, demonstrating excellent predictive capacities with area under the curve (AUC) value being 0.81 for 4-week efficacy, 0.80 for 12-week efficacy, and 0.85 for AE development. Conclusion Multiple gene SNPs were identified to be correlated with the efficacy and safety of NB-UVB phototherapy. Moreover, predictive models of NB-UVB treatment response were subsequently established. Our findings might contribute to the advancement of precision phototherapy in psoriasis. Clinical trial registration (www.chictr.org.cn), identifier (ChiCTR2000036186).