Abstract
This study aimed to explore the predictive value of 10 serum cytokines for clinical response to etanercept (ETN) in rheumatoid arthritis (RA) patients. Totally 128 active RA patients were enrolled, and their serum cytokines levels were detected by enzyme-linked immune sorbent assay at baseline. All patients received ETN treatment for 24 weeks, and clinical response to ETN was assessed at week 4 (W4), week 12 (W12) and week 24 (W24). There were 40 (31.3%), 74 (57.8%) and 94 (73.4%) patients who achieved clinical response at W4, W12 and W24, respectively. Based on the clinical response status at W24, patients were divided into responders and non-responders. Baseline levels of interleukin (IL)-1β and IL-17A were higher in responders, while baseline levels of tumor necrosis factor (TNF)-α, IL-6, 1L-8, IL-21, IL-23, intercellular cell adhesion molecule-1 (ICAM-1) and vascular endothelial growth factor (VEGF) were similar in responders compared with non-responders. Responders had less of a history of biologics, and higher baseline level of C-reactive protein (CRP) compared with non-responders. Further analysis revealed that CRP and IL-1β were independent factors predicting increased clinical response. Subsequent receiver operating characteristics (ROC) curve analysis illustrated that the combination of CRP and IL-1β (AUC: 0.730, 95% CI 0.636–0.824) well distinguished responders from non-responders. In conclusion, IL-1β, IL-17A, CRP and biologics history would serve as potential markers for clinical response to ETN in RA patients.
Similar content being viewed by others
References
Aletaha D, Smolen JS (2018) Diagnosis and management of rheumatoid arthritis: a review. JAMA 320:1360–1372. https://doi.org/10.1001/jama.2018.13103
Bendtzen K (2011) Is there a need for immunopharmacologic guidance of anti-tumor necrosis factor therapies? Arthritis Rheum 63:867–870. https://doi.org/10.1002/art.30207
Benedetti G, Miossec P (2014) Interleukin 17 contributes to the chronicity of inflammatory diseases such as rheumatoid arthritis. Eur J Immunol 44:339–347. https://doi.org/10.1002/eji.201344184
Brennan FM, McInnes IB (2008) Evidence that cytokines play a role in rheumatoid arthritis. J Clin Invest 118:3537–3545. https://doi.org/10.1172/JCI36389
Buch MH, Seto Y, Bingham SJ, Bejarano V, Bryer D, White J, Emery P (2005) C-reactive protein as a predictor of infliximab treatment outcome in patients with rheumatoid arthritis: defining subtypes of nonresponse and subsequent response to etanercept. Arthritis Rheum 52:42–48. https://doi.org/10.1002/art.20711
Burmester GR, Pope JE (2017) Novel treatment strategies in rheumatoid arthritis. Lancet 389:2338–2348. https://doi.org/10.1016/S0140-6736(17)31491-5
Chen DY, Chen YM, Chen HH, Hsieh CW, Lin CC, Lan JL (2011) Increasing levels of circulating Th17 cells and interleukin-17 in rheumatoid arthritis patients with an inadequate response to anti-TNF-alpha therapy. Arthritis Res Ther 13:R126. https://doi.org/10.1186/ar3431
Eastgate JA, Symons JA, Wood NC, Grinlinton FM, di Giovine FS, Duff GW (1988) Correlation of plasma interleukin 1 levels with disease activity in rheumatoid arthritis. Lancet 2:706–709. https://doi.org/10.1016/s0140-6736(88)90185-7
Eudy AM, Vines AI, Dooley MA, Cooper GS, Parks CG (2014) Elevated C-reactive protein and self-reported disease activity in systemic lupus erythematosus. Lupus 23:1460–1467. https://doi.org/10.1177/0961203314543915
Haraoui B, Bykerk V (2007) Etanercept in the treatment of rheumatoid arthritis. Ther Clin Risk Manag 3:99–105. https://doi.org/10.2147/tcrm.2007.3.1.99
Kawashiri SY et al (2009) Proinflammatory cytokines synergistically enhance the production of chemokine ligand 20 (CCL20) from rheumatoid fibroblast-like synovial cells in vitro and serum CCL20 is reduced in vivo by biologic disease-modifying antirheumatic drugs. J Rheumatol 36:2397–2402. https://doi.org/10.3899/jrheum.090132
Kayakabe K et al (2012) Interleukin-1beta measurement in stimulated whole blood cultures is useful to predict response to anti-TNF therapies in rheumatoid arthritis. Rheumatology (Oxford) 51:1639–1643. https://doi.org/10.1093/rheumatology/kes094
Metawi SA, Abbas D, Kamal MM, Ibrahim MK (2011) Serum and synovial fluid levels of interleukin-17 in correlation with disease activity in patients with RA. Clin Rheumatol 30:1201–1207. https://doi.org/10.1007/s10067-011-1737-y
Niu X, Chen G (2014) Clinical biomarkers and pathogenic-related cytokines in rheumatoid arthritis. J Immunol Res. 2014:698192. https://doi.org/10.1155/2014/698192
O'Dell JR et al (2013) Therapies for active rheumatoid arthritis after methotrexate failure. N Engl J Med 369:307–318. https://doi.org/10.1056/NEJMoa1303006
Rooney M, Symons JA, Duff GW (1990) Interleukin 1 beta in synovial fluid is related to local disease activity in rheumatoid arthritis. Rheumatol Int 10:217–219
Rosu A, Margaritescu C, Stepan A, Musetescu A, Ene M (2012) IL-17 patterns in synovium, serum and synovial fluid from treatment-naive, early rheumatoid arthritis patients. Rom J Morphol Embryol 53:73–80
Shi R, Chen M, Litifu B (2018) Serum interleukin-6 and survivin levels predict clinical response to etanercept treatment in patients with established rheumatoid arthritis. Mod Rheumatol 28:126–132. https://doi.org/10.1080/14397595.2017.1317384
Sikorska D, Rutkowski R, Luczak J, Samborski W, Witowski J (2018) No effect of anti-TNF-alpha treatment on serum IL-17 in patients with rheumatoid arthritis. Cent Eur J Immunol 43:270–275. https://doi.org/10.5114/ceji.2018.80045
Smolen JS, Aletaha D, McInnes IB (2016) Rheumatoid arthritis. Lancet 388:2023–2038. https://doi.org/10.1016/S0140-6736(16)30173-8
van Vollenhoven RF et al (2016) Full dose, reduced dose or discontinuation of etanercept in rheumatoid arthritis. Ann Rheum Dis 75:52–58. https://doi.org/10.1136/annrheumdis-2014-205726
Acknowledgements
This study supported by National Natural Science Foundation of China (No. 81501888).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no competing interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Zhang, B., Jiang, W. IL-1β, IL-17A, CRP and biologics history might serve as potential markers for clinical response to etanercept in rheumatoid arthritis patients. Inflammopharmacol 27, 1123–1130 (2019). https://doi.org/10.1007/s10787-019-00624-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10787-019-00624-2