Abstract
ObjectiveRheumatoid Arthritis (RA) is a progressive autoimmune disease characterized by chronic joint inflammation and structural damage. Remission or at least low disease activity (LDA) represent potentially desirable goals of RA treatment. Single nucleotide polymorphisms (SNPs) in several genes might be useful for prediction of response to therapy. We aimed at exploring 4 SNPs in candidate genes (STAT4, PTPN2, PSORS1C1 and TRAF3IP2) in order to investigate their potential role in the response to therapy with tumor necrosis factor inhibitors (TNF-i) in RA patients.MethodsIn 171 RA patients we investigated the following SNPs: rs7574865 (STAT4), rs2233945 (PSORS1C1), rs7234029 (PTPN2) and rs33980500 (TRAF3IP2). Remission, LDA, and EULAR response were registered at 6 months and 2 years after initiation of first line TNF-i [Adalimumab (ADA) and Etanercept (ETN)].ResultsSTAT4 variant allele was associated with the absence of a good/moderate EULAR response at 2 years of treatment in the whole RA group and in ETN treated patients. The PTPN2 SNP was associated with no good/moderate EULAR response at 6 months in ADA treated patients. Patients carrying PSORS1C1 variant allele did not reach LDA at 6 months in both the whole RA group and ETN treated patients. TRAF3IP2 variant allele was associated with the lack of LDA and remission achievement at 6 months in all RA cohort while an association with no EULAR response at 2 years of treatment occurred only in ETN treated patients.ConclusionsFor the first time, we reported that SNPs in STAT4, PTPN2, PSORS1C1, and TRAF3IP2 are associated with response to TNF-i treatment in RA patients; however, these findings should be validated in a larger population.
Highlights
Rheumatoid Arthritis (RA) is a progressive autoimmune disease characterized by chronic joint inflammation and structural damage [1]
TRAF3IP2 variant allele was associated with the lack of low disease activity (LDA) and remission achievement at 6 months in all RA cohort while an association with no European League Against Rheumatism (EULAR) response at 2 years of treatment occurred only in ETN treated patients
We reported that single nucleotide polymorphisms (SNPs) in signal transducer and activator of transcription 4 (STAT4), protein tyrosine phosphatase non-receptor 2 (PTPN2), PSORS1C1, and TRAF3IP2 are associated with response to tumor necrosis factor inhibitors (TNF-i) treatment in RA patients; these findings should be validated in a larger population
Summary
Rheumatoid Arthritis (RA) is a progressive autoimmune disease characterized by chronic joint inflammation and structural damage [1]. The introduction of biological disease modifying anti-rheumatic drugs (bDMARDs) has changed the face of RA with remission or at least low disease activity (LDA) as achievable goals [3, 4]. Predictive biomarkers of response to therapy with bDMARDs could enable selection of the optimal treatment for the individual patients. Evidence assessed the value of age, gender, concomitant drugs, body mass index, or smoking status for predicting response to treatment [5,6,7]. RA disease duration, disease activity, functional status, presence of autoantibodies [rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA)], and previous therapies can influence drug response [8,9,10,11]. Genetic interindividual variability can contribute to the differences in the response to treatment: some single nucleotide polymorphisms (SNPs) showed an association with bDMARDs response and might be useful for prediction, few associations have been replicated [12,13,14,15]
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