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Rheumatology International
Published in: Rheumatology International 6/2014

01-06-2014 | Original Article

Candidate’s single-nucleotide polymorphism predictors of treatment nonresponse to the first anti-TNF inhibitor in ankylosing spondylitis

Authors: Ruxandra Schiotis, Alejandra Sánchez, Alejandro Escudero, Nerea Bartolomé, Magdalena Szczypiorska, Pilar Font, Antonio Martínez, Diego Tejedor, Marta Artieda, Juan Mulero, Anca Buzoianu, Eduardo Collantes-Estévez

Published in: Rheumatology International | Issue 6/2014

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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.
Literature
1.
2.
Braun J, Bollow M, Neure L et al (1995) Use of immunohistologic and in situ hybridization techniques in the examination of sacroiliac joint biopsy specimens from patients with ankylosing spondylitis. Arthritis Rheum 38:499–505PubMedCrossRef
3.
Braun J, Xiang J, Brandt J et al (2000) Treatment of spondyloarthropathies with antibodies against tumor necrosis factor α: first clinical and laboratory experiences. Ann Rheum Dis 59:i85–i89PubMedCrossRefPubMedCentral
4.
5.
van der Heijde D, Dijkmans B, Geusens P et al (2005) Efficacy and safety of infliximab in patients with ankylosing spondylitis: results of a randomized, placebo-controlled trial (ASSERT). Arthritis Rheum 52:582–591PubMedCrossRef
6.
Davis JC Jr, van der Heijde D, Braun J et al (2003) Recombinant human tumor necrosis factor receptor (etanercept) for treating ankylosing spondylitis: a randomized, controlled trial. Arthritis Rheum 48:3230–3236PubMedCrossRef
7.
van der Heijde D, Kivitz A, Schiff MH et al (2006) Efficacy and safety of adalimumab in patients with ankylosing spondylitis: results of a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 54:2136–2146PubMedCrossRef
8.
Braun J, Deodhar A, Inman RD et al (2012) Golimumab administered subcutaneously every 4 weeks in ankylosing spondylitis: 104-week results of the GO-RAISE study. Ann Rheum Dis 71:661–667PubMedCrossRefPubMedCentral
9.
Davis JC Jr, van der Heijde DM, Dougados M et al (2005) Baseline factors that influence ASAS 20 response in patients with ankylosing spondylitis treated with etanercept. J Rheumatol 32:1751–1754PubMed
10.
Rudwaleit M, Listing J, Brandt J, Braun J, Sieper J (2004) Prediction of a major clinical response (BASDAI 50) to tumour necrosis factor alpha blockers in ankylosing spondylitis. Ann Rheum Dis 63:665–670PubMedCrossRefPubMedCentral
11.
12.
Rudwaleit M, Claudepierre P, Wordsworth P et al (2009) Effectiveness, safety, and predictors of good clinical response in 1,250 patients treated with adalimumab for active ankylosing spondylitis. J Rheumatol 36:801–810PubMedCrossRef
13.
Lord PA, Farragher TM, Lunt M, Watson KD, Symmons DP, Hyrich KL (2010) Predictors of response to anti-TNF therapy in ankylosing spondylitis: results from the British Society for Rheumatology Biologics Register. Rheumatology (Oxford) 49:563–570CrossRef
14.
Arends S, Brouwer E, van der Veer E et al (2011) Baseline predictors of response and discontinuation of tumor necrosis factor-alpha blocking therapy in ankylosing spondylitis: a prospective longitudinal observational cohort study. Arthritis Res Ther 20(13):R94CrossRef
15.
Can M, Aydın SZ, Niğdelioğlu A, Atagündüz P, Direskeneli H (2012) Conventional DMARD therapy (methotrexate–sulphasalazine) may decrease the requirement of biologics in routine practice of ankylosing spondylitis patients: a real-life experience. Int J Rheum Dis 15:526–530PubMedCrossRef
16.
Chen J, Veras MM, Liu C, Lin J (2013) Methotrexate for ankylosing spondylitis. Cochrane Database Syst Rev 28(2):CD004524
17.
Chen J, Liu C (2005) Sulfasalazine for ankylosing spondylitis. Cochrane Database Syst Rev 18(2):CD004800
18.
Baraliakos X, Brandt J, Listing J et al (2005) Outcome of patients with active ankylosing spondylitis after two years of therapy with etanercept: clinical and magnetic resonance imaging data. Arthritis Rheum 53:856–863PubMedCrossRef
19.
Baraliakos X, Listing J, Fritz C et al (2011) Persistent clinical efficacy and safety of infliximab in ankylosing spondylitis after 8 years-early clinical response predicts long-term outcome. J Rheumatol (Oxford) 50:1690–1699CrossRef
20.
Poddubnyy DA, Märker-Hermann E, Kaluza-Schilling W et al (2011) Relation of HLA-B27, tumor necrosis factor-α promoter gene polymorphisms, and T cell cytokine production in ankylosing spondylitis—a comprehensive genotype-phenotype analysis from an observational cohort. J Rheumatol 38:2436–2441PubMedCrossRef
21.
Seitz M, Wirthmu¨ ller U, Moller B, Villiger PM (2007) The −308 tumour necrosis factor-gene polymorphismpredicts therapeutic response to TNF-blockers in rheumatoid arthritis and spondyloarthritis patients. Rheumatology 46:93–96PubMedCrossRef
22.
Collantes E, Zarco P, Munoz E et al (2007) Disease pattern of spondyloarthropathies in Spain: description of the first national registry (REGISPONSER) extended report. Rheumatology (Oxford) 46:1309–1315CrossRef
23.
Schiotis R, Font P, Escudero E et al (2011) Usefulness of a centralized system of data collection for the development of an international multicentre registry of spondyloarthritis. Rheumatology (Oxford) 50:132–136CrossRef
24.
Van der Linden S, Valkenburg HA, Cats A (1984) Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 27:361–368PubMedCrossRef
25.
Fan JB, Oliphant A, Shen R et al (2003) Highly parallel SNP genotyping. Cold Spring Harb Symp Quant Biol 68:69–78PubMedCrossRef
26.
Paynter RA, Skibola DR, Skibola CF et al (2006) Accuracy of multiplexed Illumina platform-based single-nucleotide polymorphism genotyping compared between genomic and whole genome amplified DNA collected from multiple sources. Cancer Epidemiol Biomarkers Prev 15:2533–2536PubMedCrossRef
27.
Reich D, Patterson N, De Jager PL et al (2005) A whole-genome admixture scan finds a candidate locus for multiple sclerosis susceptibility. Nat Genet 37:1113–1118PubMedCrossRef
28.
Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 15(21):263–265CrossRef
29.
Glintborg B, Østergaard M, Krogh NS et al (2013) Clinical response, drug survival and predictors thereof in 432 ankylosing spondylitis patients after switching tumour necrosis factor α inhibitor therapy: results from the Danish nationwide DANBIO registry. Ann Rheum Dis 72:1149–1155PubMedCrossRef
30.
Okamura H, Tsutsui H, Kashiwamura S, Yoshimoto T, Nakanishi K (1998) Regulation of interferon-_ production by IL-12 and IL-18. Curr Opin Immunol 10:259–264PubMedCrossRef
31.
de Jager W, Vastert SJ, Beekman JM et al (2009) Defective phosphorylation of interleukin-18 receptor beta causes impaired natural killer cell function in systemic-onset juvenile idiopathic arthritis. Arthritis Rheum 60:2782–2793PubMedCrossRef
32.
Hunt KA, Zhernakova A, Turner G et al (2008) Newly identified genetic risk variants for celiac disease related to the immune response. Nat Genet 40:395–402PubMedCrossRefPubMedCentral
33.
Zhernakova A, Festen EM, Franke L et al (2008) Genetic analysis of innate immunity in Crohn’s disease and ulcerative colitis identifies two susceptibility loci harboring CARD9 and IL18RAP. Am J Hum Genet 82:1202–1210PubMedCrossRefPubMedCentral
34.
Eder L, Chandran V, Ueng J et al (2010) Predictors of response to intra-articular steroid injection in psoriatic arthritis. Rheumatology (Oxford) 49:1367–1373CrossRef
35.
Radstake TR, Sweep FC, Welsing P et al (2005) Correlation of rheumatoid arthritis severity with the genetic functional variants and circulating levels of macrophage migration inhibitory factor. Arthritis Rheum 52:3020–3029PubMedCrossRef
36.
Lauten M, Matthias T, Stanulla M, Beger C, Welte K, Schrappe M (2002) Association of initial response to prednisone treatment in childhood acute lymphoblastic leukaemia and polymorphisms within the tumor necrosis factor and the interleukin-10 genes. Leukemia 16:1437–1442PubMedCrossRef
37.
Middleton PG, Taylor PR, Jackson G, Proctor SJ, Dickinson AM (1998) Cytokine gene polymorphisms associating with severe acute graft-versus-host disease in HLA-identical sibling transplants. Blood 92:3943–3948PubMed
38.
de Paz B, Alperi-López M, Ballina-García FJ, Prado C, Mozo L, Gutiérrez C, Suárez A (2010) Interleukin 10 and tumor necrosis factor-alpha genotypes in rheumatoid arthritis-association with clinical response to glucocorticoids. J Rheumatol 37:503–511PubMedCrossRef
39.
Wajant H, Pfizenmaier K, Scheurich P (2003) Tumor necrosis factor signaling. Cell Death Differ 10:45–65PubMedCrossRef
40.
Grell M, Douni E, Wajant H et al (1995) The transmembrane form of tumor necrosis factor is the prime activating ligand of the 80 kDa tumor necrosis factor receptor. Cell 83:793–802PubMedCrossRef
41.
Kim EY, Priatel JJ, Teh SJ, Teh HS (2006) TNF receptor type 2 (p75) Functions as a costimulator for antigen-driven T cell responses in vivo. J Immunol 176:1026–1035PubMedCrossRef
42.
Cope AP, Aderka D, Doherty M et al (1992) Increased levels of soluble tumor necrosis factor receptors in the sera and synovial fluid of patients with rheumatic diseases. Arthritis Rheum 35:1160–1169PubMedCrossRef
43.
Deleuran BW, Chu C-Q, Field M et al (1992) Localization of tumor necrosis factor receptors in the synovial tissue and cartilage-pannus junction in patients with rheumatoid arthritis: implications for local actions of tumor necrosis factor. Arthritis Rheum 35:1170–1178PubMedCrossRef
44.
Tolusso B, Sacco S, Gremese E, La Torre G, Tomietto P, Ferraccioli GF (2004) Relationship between the tumor necrosis factor receptor II (TNF-RII) gene polymorphism and sTNF-RII plasma levels in healthy controls and in rheumatoid arthritis. Hum Immunol 65:1420–1426PubMedCrossRef
45.
Glossop JR, Dawes PT, Nixon NB, Mattey DL (2005) Polymorphism in the tumour necrosis factor receptor II gene is associated with circulating levels of soluble tumour necrosis factor receptors in rheumatoid arthritis. Arthritis Res Ther 7:R1227–R1234PubMedCrossRefPubMedCentral
46.
Fabris M, Tolusso B, Di Poi E, Assaloni R, Sinigaglia L, Ferraccioli G (2002) Tumor necrosis factor-alpha receptor II polymorphism in patients from southern Europe with mild-moderate and severe rheumatoid arthritis. Rheumatology 29:1847–1850
47.
Pedersen SJ, Sørensen IJ, Garnero P et al (2011) ASDAS, BASDAI and different treatment responses and their relation to biomarkers of inflammation, cartilage and bone turnover in patients with axial spondyloarthritis treated with TNFα inhibitors. Ann Rheum Dis 70:1375–1381PubMedCrossRef
Metadata
Title
Candidate’s single-nucleotide polymorphism predictors of treatment nonresponse to the first anti-TNF inhibitor in ankylosing spondylitis
Authors
Ruxandra Schiotis
Alejandra Sánchez
Alejandro Escudero
Nerea Bartolomé
Magdalena Szczypiorska
Pilar Font
Antonio Martínez
Diego Tejedor
Marta Artieda
Juan Mulero
Anca Buzoianu
Eduardo Collantes-Estévez
Publication date
01-06-2014
Publisher
Springer Berlin Heidelberg
Published in
Rheumatology International / Issue 6/2014
Print ISSN: 0172-8172
Electronic ISSN: 1437-160X
DOI
https://doi.org/10.1007/s00296-013-2913-y

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