Original Article

Epidemiological and Clinical Factors Affecting the Response to Etanercept Among Patients with Rheumatoid Arthritis

Abstract

Background: This study aimed to inspect the association between the response to etanercept among patients with rheumatoid arthritis and several epidemiological and clinical variables and medication adherence, as measured by medication possession ratio (MPR). Methods: A cohort study that enrolls 120 active rheumatoid arthritis patients. The baseline values of disease activity score for 28 joints (DAS28) score,erythrocyte sedimmintation rate (ESR), WBC, tender joints count (TJC), swelling joints counts (SJC), and medication adherence, as measured by medication possession ratio (MPR), were identified. All patients received etanercept treatment for three months, and then the clinical response to etanercept was assessed after the end of the three months duration. Factors affecting clinical response were evaluated by univariate and multivariate logistic regression analysis. The predictive performance of a single independent predictor was then assessed using a receiver operating characteristic (ROC) curve. Results: The results of the univariate logistic regression model showed that the smoking, disease duration, baseline DAS28, and MPR could predict the patients' proclivity for being non-responder. The multivariate logistic regression model showed that only baseline DAS28 (P< 0.0001, OR=32.239, 95%CI: 4.941–210.338) and MPR (P=0.002, OR=0.00063, 95%CI: 0.00001–0.032) were independent predictive factors for the tendency of patients to be non-responder. ROC curve analysis disclosed that baseline ESR and DAS28 have a good area under the curve (AUC) with the optimal cut-off for the baseline ESR threshold was 52 mm/hr., whereas the baseline DAS28 threshold was 5.79. Conclusion: Current smoking is the main epidemiological factor that can predict the tendency for being non-responder. The potential of baseline ESR and DAS28 values as biomarkers for clinical response to etanercept in RA patients was identified by Receiver operating characteristic(ROC) analysis.

1. Kobelt G, Lekander I, Lang A, Raffeiner B, Botsios C, Geborek P. Cost-effectiveness of etanercept treatment in early active rheumatoid arthritis followed by dose adjustment. Int J Technol Assess Health Care 2011;27(3):193–200.
2. Moelants EAV, Mortier A, Van Damme J, Proost P. Regulation of TNF-α with a focus on rheumatoid arthritis. Immunol Cell Biol 2013;91(6):393–401.
3. Fassio A, Adami G, Gatti D, et al. Inhibition of tumor necrosis factor-alpha (TNF-alpha) in patients with early rheumatoid arthritis results in acute changes of bone modulators. Int Immunopharmacol 2019;67:487-489.
4. Rutherford AI, Patarata E, Subesinghe S, Hyrich KL, Galloway JB. Opportunistic infections in rheumatoid arthritis patients exposed to biologic therapy: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis. Rheumatology (Oxford) 2018 1;57(6):997-1001.
5. Aletaha D, Smolen JS. Diagnosis and Management of Rheumatoid Arthritis: A Review. JAMA 2018;320(13):1360-1372.
6. Atzeni F, Benucci M, Sallì S, Bongiovanni S, Boccassini L, Sarzi-Puttini P. Different effects of biological drugs in rheumatoid arthritis. Autoimmun Rev 2013r;12(5):575-9.
7. Zhao S, Mysler E, Moots RJ. Etanercept for the treatment of rheumatoid arthritis. Immunotherapy 2018;10(6):433-445.
8. Van Vollenhoven RF, Østergaard M, Leirisalo-Repo M, et al. Full dose, reduced dose or discontinuation of etanercept in rheumatoid arthritis. Ann Rheum Dis 2016;75(1):52-8.
9. Bendtzen K. Is there a need for immunopharmacologic guidance of anti-tumor necrosis factor therapies? Arthritis Rheum 2011;63(4):867-70.
10. Landewé R, Van Der Heijde D, Klareskog L, Van Vollenhoven R, Fatenejad S. Disconnect between inflammation and joint destruction after treatment with etanercept plus methotrexate: Results from the trial of etanercept and methotrexate with radiographic and patient outcomes. Arthritis Rheum 2006;54(10):3119–25.
11. 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. Inflammopharmacology 2019;27(6):1123-1130.
12. Daïen CI, Morel J. Predictive factors of response to biological disease modifying antirheumatic drugs: Towards personalized medicine. Mediators Inflamm 2014;2014:386148.
13. Fransen J, van Riel PLCM. The Disease Activity Score and the EULAR Response Criteria. Rheum Dis Clin North Am 2009;35(4):745-57, vii-viii.
14. van Riel PLCM, Renskers L. The Disease Activity Score (DAS) and the Disease Activity Score using 28 joint counts (DAS28) in the management of rheumatoid arthritis. Clin Exp Rheumatol 2016;34(4):40–4.
15. Tracey D, Klareskog L, Sasso EH, Salfeld JG, Tak PP. Tumor necrosis factor antagonist mechanisms of action: A comprehensive review. Pharmacol Ther 2008;117(2):244-79.
16. Katchamart W, Johnson S, Lin HJL, Phumethum V, Salliot C, Bombardier C. Predictors for remission in rheumatoid arthritis patients: A systematic review. Arthritis Care Res (Hoboken) 2010;62(8):1128-43.
17. Callaghan CA, Boyter AC, Mullen AB, Mcrorie ER. Biological therapy for rheumatoid arthritis: Is personalised medicine possible? European Journal of Hospital Pharmacy 2014;21:229-237.
18. Ma MHY, Kingsley GH, Scott DL. A systematic comparison of combination DMARD therapy and tumour necrosis inhibitor therapy with methotrexate in patients with early rheumatoid arthritis. Rheumatology (Oxford) 2010;49(1):91-8.
19. Teaha DIM, Pascalău NA, Lazăr L. Comparative study of the clinical response of patients to different treatment regimens in rheumatoid arthritis. Farmacia 2019;67(3):411–7.
20. Tao W, Concepcion AN, Vianen M, et al. Multiomics and Machine Learning Accurately Predict Clinical Response to Adalimumab and Etanercept Therapy in Patients With Rheumatoid Arthritis. Arthritis Rheumatol 2021;73(2):212–22.
21. Park SJ, Shin JI. The effect of smoking on response and drug survival in rheumatoid arthritis patients treated with their first anti-TNF drug: Comments on the article by Soderlin et al. Scand J Rheumatol. 2012 Oct;41(5):411-2.
22. Abhishek A, Butt S, Gadsby K, Zhang W, Deighton CM. Anti-TNF-α agents are less effective for the treatment of rheumatoid arthritis in current smokers. J Clin Rheumatol 2010;16(1):15–8.
23. Hyrich KL, Watson KD, Silman AJ, Symmons DPM. Predictors of response to anti-TNF-α therapy among patients with rheumatoid arthritis: Results from the British Society for Rheumatology Biologics Register. Rheumatology 2006;45(12):1558–65.
24. Turesson C, Schaid DJ, Weyand CM, et al. Association of HLA-C3 and smoking with vasculitis in patients with rheumatoid arthritis. Arthritis Rheum 2006;54(9):2776–83.
25. Källberg H, Padyukov L, Plenge RM, et al. Gene-gene and gene-environment interactions involving HLA-BRB1, PTPN22, and smoking in two subsets of rheumatoid arthritis. Am J Hum Genet 2007;80(5):867–75.
26. Gordon K, Korman N, Frankel E, et al. Efficacy of etanercept in an integrated multistudy database of patients with psoriasis. J Am Acad Dermatol 2006;54(3 SUPPL. 2):S101–11.
27. Papp KA, Langley RG, Lebwohl M, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet 2008;371(9625):1675–84.
28. Naldi L, Chatenoud L, Linder D, et al. Cigarette smoking, body mass index, and stressful life events as risk factors for psoriasis: Results from an Italian case-control study. J Invest Dermatol 2005;125(1):61–7.
29. Hetland ML, Christensen IJ, Tarp U, et al. Direct comparison of treatment responses, remission rates, and drug adherence in patients with rheumatoid arthritis treated with adalimumab, etanercept, or infliximab: Results from eight years of surveillance of clinical practice in the nationwide Danish . Arthritis Rheum 2010;62(1):22–32.
30. Van der Heijde DMFM, Van’t Hof MA, Van Riel PLCM, Van Leeuwen MA, Van Rijswijk MH, Van de Putte LBA. Validity of single variables and composite indices for measuring disease activity in rheumatoid arthritis. Ann Rheum Dis 1992;51(2):177–81.
31. De Geest S, Sabaté E. Adherence to long-term therapies: Evidence for action. Eur J Cardiovasc Nurs 2003;2(4):323.
32. Smolen JS, Landewé RBM, Bijlsma JWJ, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis 2020;79(6):S685–99.
33. Bluett J, Morgan C, Thurston L, et al. Impact of inadequate adherence on response to subcutaneously administered anti-tumour necrosis factor drugs: Results from the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate cohort. Rheumatol (United Kingdom) 2015;54(3):494–9.
Files
IssueVol 10, No 2 (Spring 2022) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/jpc.v10i2.9975
Keywords
Epidemiology Etanercept Rheumatoid Arthritis

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
Mohammed S, Zalzala M, Gorial F. Epidemiological and Clinical Factors Affecting the Response to Etanercept Among Patients with Rheumatoid Arthritis. J Pharm Care. 2022;10(2):55-62.