SAT0405 Clinical, biological and genetic factors, predictors of treatment nonresponse to tnf inhibitors (TNFI), in ankylosing spondylitis (AS) and psoriatic arthritis (PSA)

Abstract

BackgroundTNF inhibitors (TNFi), are effective in controlling the activity of spondyloarthritis. But, there is a proportion of patients, who have to stop treatment due to its ineffectiveness or to the appearance of adverse events. In addition, these therapies imply high economic costs. To identify predictors of response, would help us to make decisions and to improve the risk/benefit ratio, in patients candidates who are candidates to initiate TNFiObjectivesTo determine clinical, biological and genetic predictors of nonresponse to treatment with TNFi in patients with AS and PsA.MethodsWe analyzed 118 patients [49 AS and 69 PsA (24 axial and peripheral involvement and 45 only peripheral)], under treatment or who were to start treatment with TNFi. Data were collected, prior to the start of the TNFi and at the last scheduled visit to the Rheumatology Service of the Hospital Puerta de Hierro, during the period 2013–2014. A clinical response was defined as the reduction ≥50% of the initial BASDAI, in patient with axial involvement, and if the final DAS 28 PCR was <2.6, in those patients with only peripheral involvement. A total of 73 men and 45 woman, mean age 53±11.2 years, and a median duration of illness of 15 years (IQR 10–23) were included. The baseline ESR and CRP were (10mm/hr IQR 5.0–27.0 and 2mg/l IQR 0.0–9.0) respectively. The mean and SD of BASDAI, DAS28 CPR and BASFI were (6.0±1.9, 3.0±0.6 and 5.4±2.5) respectively. A univariate analysis was performed using a Cox proportional hazard regression model which included: Smoker status, axial pain, peripheral arthritis, sacroiliitis, IBD, uveitis, psoriasis, HLA B27, VSG, PCR, BASDAI, BASFI, VGP, the number of TNFi and 45 single nucleotide polymorphism (SNPs) previously reported to be associated with response to TNFi. SNP genotyping was performed using de Sequenom MassARRAY plataform.Variables with a P-value <0.1 were included in a multivariate analysis. The discrimination capacity of the model was assessed using the Harrell C index. P-values <0.05 were considered statistically significant. Statistical analysis was performed with the SPSS v.17 software.ResultsThe median duration of treatment was 62.9 months (IQR 40.7–96.5), the response to TNFi was 79.7% of patients, with mean and SD of BASDAI, BASFI and DAS 28 PCR (2.7±2.2, 4.2±2.8, 1.5±0.6) respectively. The factors that increased the non-response rate, were: the group of peripheral PsA versus AS (HR 2.94, P=0.023), VGP (HR 1.47, P<0.001), BASDAI (HR 1.80, P=0.001), BASFI (HR 1.52, P=0.001) and the number of TNFi used (P<0.001). There was a trend of significance (P <0.10) for females, with a 2.13-fold lower response rate than males (P=0.065). The SNPs associated were: rs4240847 of the MAPKAPK2 gene (allele A, HR 1.63, P=0.019), rs11096957 of the TLR-10 gene (T allele, HR 1.49, P=0.011), rs11541076 of the IRAK-3 (allele T, HR 1.47, P=0.050), rs916344 of the MAPK14 gene, in a recessive form,since CC alleles against CG or GG increased 10.12 times the non-response rate (HR 10,12; P=0.027) and rs11591741 of the CHUK ...