POS1047 TRAF3IP2, HCP5 AND IL10 GENES POLYMORPHISMS INFLUENCE THE RESPONSE TO TNF-i IN PATIENTS WITH PSORIATIC ARTHRITIS

Abstract

BackgroundPsoriatic Arthritis (PsA) is a chronic inflammatory disease, characterized by both articular and periarticular manifestations, usually associated with psoriasis. The identification of the correct therapy for patients is still a critical issue, but the use of biological drugs, such as TNFi (Tumor Necrosis Factor Inhibitors), modified the outcome of PsA patients even if there is great variability in the clinical efficacy. Since the response to drugs is a complex trait, the identification of genetic factors could help to define new genomic biomarkers for more effective and personalized therapy.ObjectivesThe aim of this study was to evaluate the potential role of polymorphisms in genes already known to be involved in PsA susceptibility (ERAP1, HCP5, IL10, MIR146, PSORS1C1, STAT4, TNFAIP3 and TRAF3IP2) as predictors of efficacy of treatment, in a cohort of Italian PsA patients, treated with first-line TNF-i, in particular with Etanercept (ETN) and Adalimumab (ADA).MethodsPolymorphisms were analyzed in a cohort of 163 patients with peripheral PsA. For each patient was estimated the Disease Activity in Psoriatic Arthritis (DAPsA) score. Genotyping was performed by allelic discrimination by TaqMan assay. The possible association between the selected SNPs and mean values of DAPsA differences, at 22 (ΔT22) and 54 (ΔT54) weeks from the beginning of the TNF-i treatment, were evaluated by T-test. A multivariate logistic regression analysis was used to evaluate the contribution of each genetic variant investigated in the TNF-i treatment response.ResultsWe have observed that TRAF3IP2 SNP was associated with TNF-i treatment response in PsA patients. In particular, the patients carrying variant alleles seem to respond better to treatment, both at 22 (P = 0.032) and 54 weeks (P = 0.019). Moreover, the variant allele of TRAF3IP2 SNP resulted associated with a better response of joints involvement. Indeed, the number of tender and swollen joints decrease more in patients carrying variant allele (P = 0.006 and P = 0.024, respectively). We also observed that PsA patients carrying IL10 variant allele decrease their mean DAPsA value less than patients with wild-type genotype only at 54 weeks of treatment (P = 0.031). Also, HCP5 polymorphism showed a difference of mean difference of DAPsA values between genotypes for both follow up, even if these difference does not reach a statistical significance (P = 0.068 and P = 0.086). The multivariate regression analysis was performed with a stepwise method and it confirmed the involvement of TRAF3IP2 (P = 0.016) and HCP5 (P = 0.035) polymorphisms in the TNF-i response after 22 weeks and of TRAF3IP2 (P = 0.007), IL10 (P = 0.022) and HCP5 (P = 0.036) polymorphisms after 54 weeks. The two final models explain about 6% and 11% of the variability in TNF-i treatment response at 22 and 54 weeks respectively.ConclusionOur results suggest that some polymorphisms in genes associated to PsA susceptibility could also play a role in TNFi treatment response and could give a contribution in the definition of a genetic profile associated with the response to anti-TNF drugs.Figure 1.Mean differences of DAPsA values in the genotypic classes for TRAF3IP2, IL10 and HCP5 SNPs. DAPsA = Disease Activity Index for PsA; Wt = wild-type genotype; Hz = heterozygous genotype; Homo var = homozygous variant genotype.Disclosure of InterestsNone declared