title: Candidate's single-nucleotide polymorphism predictors of treatment nonresponse to the first anti-TNF inhibitor in ankylosing spondylitis.
abstract: The objective of this study is to identify single-nucleotide polymorphisms (SNPs) predictors of treatment nonresponse to the first anti-TNF-alpha agent in ankylosing spondylitis (AS). Patients were classified as "nonresponders" if they failed to achieve improvement ≥50 % of the initial BASDAI. We selected candidate SNPs previously reported, associated with susceptibility or pathogenesis of AS and with other spondylarthropaties (SpAs). The predictors of nonresponse were modeled with multiple logistic regression. The predictive power of the genetic model of nonresponse to treatment was tested with AUC-ROC. One hundred and twenty-one (121) AS patients fulfilled the inclusion criteria. Of the candidate SNPs tested for association with treatment effectiveness, five independent predictors were identified: rs917997, rs755622, rs1800896, rs3740691, and rs1061622. The genetic model of nonresponse to treatment had a predictive power of 0.77 (95 % CI 0.68-0.86). Our study identified several polymorphisms which could be the useful genetic biomarkers in predicting nonresponse to anti-TNF-alpha therapy.
authors: Department of Pharmacology, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania, Elena.Schiotis@umfcluj.ro.
authors: Ruxandra
authors: R
authors: Schiotis
authors: Alejandra
authors: A
authors: Sánchez
authors: Alejandro
authors: A
authors: Escudero
authors: Nerea
authors: N
authors: Bartolomé
authors: Magdalena
authors: M
authors: Szczypiorska
authors: Pilar
authors: P
authors: Font
authors: Antonio
authors: A
authors: Martínez
authors: Diego
authors: D
authors: Tejedor
authors: Marta
authors: M
authors: Artieda
authors: Juan
authors: J
authors: Mulero
authors: Anca
authors: A
authors: Buzoianu
authors: Eduardo
authors: E
authors: Collantes-Estévez
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D019540:Area Under Curve; D015331:Cohort Studies; D000068800:Etanercept; D005260:Female; D005838:Genotype; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D000069285:Infliximab; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D012372:ROC Curve; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D013167:Spondylitis, Ankylosing / Q000188:drug therapy* / Q000235:genetics; D017211:Treatment Failure; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept