Background Ankylosing Spondylitis (AS) is a chronic inflammatory arthritis characterised by sacroiliac/ lumbar spinal inflammation and extra-articular manifestations. Currently, TNF inhibitors (TNFi) are licensed for treatment-refractory AS; however, many patients do not respond to treatment and there is no way to predict Response/Non-Response (R/NR). The expression of several Interferon (IFN) signalling related genes (IRG) are associated with inflammatory diseases, including AS. Furthermore, an IRG expression signature has been used to predict treatment response in phase-Ia trials in systemic lupus erythematosus (1), demonstrating the feasibility of the use of IRG signatures as biomarkers in routine clinical practice.
Objectives To explore whether IRG signatures differentiate groups of AS patients, and can be associated with response to TNFi in AS.
Methods Twenty-six week-0 peripheral blood mononuclear cell (PBMC) samples from AS patients participating in a previously reported in-house clinical trial [infliximab (IFX), n=15 vs. placebo (P), n=11] (2) were selected from our tissue bank. R/NR was defined as a ≥1.1 point reduction in AS Disease Activity Score (ASDAS) at week-30, or a reduction in the number of sacroiliac/vertebral MRI lesions. Expression of 96 IRG was quantified from PBMCs using custom TaqMan assays and analysed using unsupervised hierarchical clustering, Chi-Squared, and Mann-Whitney U tests.
Results A total of 11 patients were clinical responders [IFX=7/15; P=4/11]. At week-0, patients clustered into 2 groups (C1/C2) based on expression of 14 IRG. Clinical/demographic characteristics were not significantly different between C1/C2 and groups were not biased for treatment (C1, IFX=8, P=4; C2, IFX=7, P=7, p=0.735). Improvement in ASDAS was weakly associated with C2 (C2, R=8/14, C1, R=7/12, p=0.098). Looking at IFX treated patients only (n=15), 2 cluster groups were observed (T1/T2) driven by 12 IRG. T2 was associated with a reduction in MRI lesions (T2 R=6/7, T1 R=3/8, p=0.057). Finally, paired week-0 and week-22 samples from 10 IFX-treated patients were analysed and clustered in 2 groups (H1/H2). Changes in IRG signature following treatment were observed towards segregating pre- and post- IFX treatment samples (H1, 6/8 week-0; H2, 8/12 week-22 p=?).
Conclusions This pilot study suggests a possible association between IRG and response to IFX treatment in AS. These results now require assessment in a larger cohort in order to determine statistical and possible clinical significance, and to refine the signature further to construct potential predictive algorithms.
Yao Y, et al. Arthritis Rheum 2009.
Marzo-Ortega H, et al. Ann Rheum Dis 2005.
Acknowledgements The authors would like to thank the George Drecler Foundation and BTCure EU/IMI for funding this project.
Disclosure of Interest None declared
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