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Clinical Trial
. 2018 Jun;37(6):1597-1604.
doi: 10.1007/s10067-018-4061-y. Epub 2018 Mar 15.

Age determines response to anti-TNFα treatment in patients with ankylosing spondylitis and is related to TNFα-producing CD8 cells

Agata Schramm-Luc  1 , Jolanta Schramm  2 , Mateusz Siedliński  1 , Tomasz J Guzik  1 , Bogdan Batko  3
Affiliations
Clinical Trial

Age determines response to anti-TNFα treatment in patients with ankylosing spondylitis and is related to TNFα-producing CD8 cells

Agata Schramm-Luc et al. Clin Rheumatol. 2018 Jun.

Abstract

Younger age is a predictor of good clinical response to treatment with tumour necrosis factor (TNF) α inhibitors in ankylosing spondylitis (AS) patients; therefore, the aim of the study was to determine age-related differences in cellular functions, which can predict the response. High disease activity AS patients were treated with TNFα inhibitors for 12 weeks. Based on the percentage of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) improvement, patients were divided into responding or non-responding groups. Cytometric and clinical assessment were determined at baseline, 4, and 12 weeks after initiation of anti-TNFα treatment. Expression of activation markers on T cells and intracellular cytokine staining was performed. Baseline percentage of TNFα-producing CD8 cells was lower in responders than in non-responders (20.8 ± 2.9 vs 40.7 ± 8.2; P = 0.04 in T test) and increased in the responding group during the first month of treatment (20.8 ± 2.9 vs 30.3 ± 2.5; P = 0.02). Moreover, its baseline level correlated with age (r = 0.7; P = 0.0009) but not with BASDAI improvement adjusted for age. There were no differences in the baseline percentage of IL-4, IL-17A, and IFNγ within CD4 and CD8 cells nor in the expression of CD25, CD28, and CD69 on these cells between responders and non-responders. However, baseline level of CD4+CD28null cells correlated with the percentage of BASDAI improvement while analysed as a continuous variable adjusted for age (r = - 0.4; P = 0.048). Clinical predictors of response were also determined. Influence of age on the response to anti-TNFα treatment in AS patients could be mediated by TNFα-producing CD8 cells.

Keywords: Activation markers; Ageing; Clinical improvement; Cytokines; Predictors; TNFα inhibitors.

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Conflict of interest statement

Ethics approval and consent to participate

This study is in accordance with ethical principles of the Helsinki declaration. The investigation protocol was approved by the Bioethics Committee of the Regional Chamber of Physicians in Cracow, Poland—investigation number 77/KBL/OIL/2013. Prior to enrolment, written consent was obtained from all patients.

Disclosures

None.

Figures

Fig. 1
Fig. 1
Differences in the intracellular TNFα staining of CD8 cells. Cytometric examples (a) and changes in the percentages of cells (b) in responding and non-responding groups at baseline, after 4, and 12 weeks from introducing anti-TNFα treatment. Data are shown as mean ± SEM; *P < 0.05. c Correlation between baseline percentage of TNFα-producing CD8 cells and patients’ age (r = 0.7; P = 0.0009)
See this image and copyright information in PMC

References

    1. van der Heijde D, Ramiro S, Landewe R, Baraliakos X, Van den Bosch F, Sepriano A, Regel A, Ciurea A, Dagfinrud H, Dougados M, van Gaalen F, Geher P, van der Horst-Bruinsma I, Inman RD, Jongkees M, Kiltz U, Kvien TK, Machado PM, Marzo-Ortega H, Molto A, Navarro-Compan V, Ozgocmen S, Pimentel-Santos FM, Reveille J, Rudwaleit M, Sieper J, Sampaio-Barros P, Wiek D, Braun J. 2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis. Ann Rheum Dis. 2017;76(6):978–991. doi: 10.1136/annrheumdis-2016-210770. - DOI - PubMed
    1. Chen JM, Veras MMS, Liu C, Lin JF (2013) Methotrexate for ankylosing spondylitis. Cochrane Db Syst Rev (2):Cd004524. doi:10.1002/14651858.Cd004524.Pub4 - PMC - PubMed
    1. Rudwaleit M, Claudepierre P, Wordsworth P, Cortina EL, Sieper J, Kron M, Carcereri-de-Prati R, Kupper H, Kary S. Effectiveness, safety, and predictors of good clinical response in 1250 patients treated with adalimumab for active ankylosing spondylitis. J Rheumatol. 2009;36(4):801–808. doi: 10.3899/jrheum.081048. - DOI - PubMed
    1. Arends S, Brouwer E, van der Veer E, Groen H, Leijsma MK, Houtman PM, Jansen TLTA, Kallenberg CGM, Spoorenberg A. 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. 2011;13(3):R94. doi: 10.1186/ar3369. - DOI - PMC - PubMed
    1. Rudwaleit M, Listing J, Brandt J, Braun J, Sieper J. Prediction of a major clinical response (BASDAI 50) to tumour necrosis factor alpha blockers in ankylosing spondylitis. Ann Rheum Dis. 2004;63(6):665–670. doi: 10.1136/ard.2003.016386. - DOI - PMC - PubMed

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