AB0262 PTPN22 1858C>T polymorphism is a negative biomarker of (eular good) response to methotrexate in a cohort of early rheumatoid arthritis

Abstract

Background A tight control strategy is necessary for an optimal management of early rheumatoid arthritis (ERA). However, it is not sufficient because there is a huge need of biomarkers in order to predict drug responsiveness and improve assessment of both disease activity and structural damage. Objectives To identify possible biomarkers predictors of response to Methotrexate (MTX) treatment in a cohort of ERA treated according to a tight control protocol. Methods A total of 286 consecutive patients with ERA were enrolled in the study. All patients were treated with MTX for three months, then with a combination with Tumor Necrosis Factor (TNF) blockers if they had an incomplete response after 3-month treatment period. At baseline and every 3 months demographic and immunological data and the ACR/EULAR core data set [erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), swollen joint count (SJC), tender joint count (TJC), physician and patient global assessment, pain, health assessment questionnaire (HAQ)] were recorded. Moreover, DNA from all patients was genotyped for the PTPN22 1858C>T by polymerase chain restriction fragment length polymorphism method. The EULAR response criteria were used as the primary outcome measure at 3- and 6-month follow-up visits. The likelihoods of achieving a good EULAR response (defined as a disease activity score (DAS) <2.4 and a fall in this score from baseline by >1.2) at the third month and a sustained remission at the sixth month follow-up visits (defined as a DAS value of <1.6 for at least two consecutive visits 3 months apart) were evaluated using univariate and multivariate logistic regression and the results were expressed as ORs with 95% CI. Results 45.7% of the patients reached a good EULAR response at the third month and 21.8% reached a sustained remission at the sixth month of follow-up. A lower percentage of ERA patients carrying the PTPN22 1858 CT/TT genotype reached a good EULAR response to MTX treatment after 3 month follow-up (22.6%) and a sustained remission at the sixth month of follow-up (6.7%) compared to subjects with the CC genotype (good EULAR response at the third month: 49.1% (OR 0.30, 95%CI 0.13-0.73); sustained remission at the sixth month 24.1% (OR 0.23, 95%CI 0.05-0.98)). The influence of each baseline parameter (demographic, genetic and immunological) on the likelihood of reaching a good EULAR response was evaluated and the PTPN22 CT/TT genotype arose as a significant predictor of good response to MTX at the third month (OR 0.30, 95%CI 0.13-0.75). When considering the sustained remission at the sixth month, the PTPN22 CT/TT genotype again proved as a “negative” predictor of this target (OR 0.19, 95%CI 0.04-0.86), together with female sex (OR 0.47, 95%CI 0.23-0.96) and “having at onset an ESR>30 mm/h” (OR 0.28, 95%CI 0.14-0.55). Conclusions The PTPN22 CT/TT genotype predicts a worse response to MTX therapy at the third month of follow-up and a lower likelihood of reaching sustained remission at the sixth month, together with female sex and h...