Candidate’s single-nucleotide polymorphism predictors of treatment nonresponse to the first anti-TNF inhibitor in ankylosing spondylitis
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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.
KeywordsAnkylosing spondylitis Anti-TNF-alpha agents SNPs Treatment response
Authors would like to thank Pedro Zarco Montejo, Hospital FUNDACION ALCORCÓN, Jordi Gratacós Masmitjá, Hospital PARC TAULÍ, Xavier Juanola Roura Hospital BELLVITGE, Enrique Batlle Gualda, University Hospital ALICANTE, Pilar Fernández Dapica Hospital DOCE DE OCTUBRE, Luis F. Linares Ferrando Hospital VIRGEN DE LA ARRIXACA, Mª Elia Brito Brito Hospital RAMÓN Y CAJAL, Eduardo Cuende Quintana University Hospital PRÍNCIPE DE ASTURIAS, Carlos Vázquez Galeano Hospital SAN JORGE, Enrique Calero Secall University Hospital CARLOS HAYA, Carlos Rodríguez Lozano Hospital DOCTOR NEGRÍN, Rubén Queiro Silva University Hospital CENTRAL DE ASTURIAS, Antonio Juan Más Hospital. FUNDACIÓN SON LLATZER, Cristina Medrano Le Quement Hospital. INTERNACIONAL MERIMAR, Enrique Ornilla University Hospital NAVARRA, Carlos Montilla Morales University Hospital VIRGEN DE LA VEGA, Teresa Clavaguera Poch Hospital PALAMÓS, Mª Cruz Fernández Espartero Hospital MÓSTOLES, for providing helpful information about the patients included in REGISPONSER-AS cohort. This work was supported by the Spanish Ministry of Science and Innovation (Project PSE-01000-2006-1) and by Progenika Biopharma S.A. The author SR wishes to thank Prof. Simion Simon, PhD at University Babes Bolyai, Cluj-Napoca, for the internship at University Hospital, “Reina Sofia”, Cordoba, Spain provided from program cofinanced by The SECTORAL OPERATIONAL PROGRAMME HUMAN RESOURCES DEVELOPMENT, Contract POSDRU 6/1.5/S/3— “Doctoral studies: through science toward society”.
Conflict of interest
MS., N.B., M.A., A.M. and D.T. are currently employees of Progenika Biopharma, SA. A.S. is supported by an unrestricted Grant from Pfizer. This does not alter our compliance with all the policies on sharing data and materials. All the other authors have no conflicts of interest to declare.
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