Interleukin-6 Suppression by Different TNF Inhibitors in Rheumatoid Arthritis Patients During Maintenance Therapy

Authors

  • Sana Majid Mohammed Department of Pharmacology and Toxicology, College of Pharmacy, University of Sulaimani, Kurdistan Region, Iraq https://orcid.org/0009-0000-3849-8631
  • Hiwa Khidhir Saaed Department of Pharmacology and Toxicology, College of Pharmacy, University of Sulaimani, Kurdistan Region, Iraq https://orcid.org/0000-0003-1078-514X

DOI:

https://doi.org/10.54133/ajms.v5i.230

Keywords:

Biological therapy, DAS28, Interleukin-6, Maintenance therapy, Rheumatoid arthritis, TNF inhibitors

Abstract

in rheumatoid arthritis (RA). Objectives: To evaluate the effect of different TNF inhibitors on plasma IL-6 levels and disease activity in RA patients. Methods: A longitudinal, observational study included 65 adult RA patients receiving TNF inhibitors for at least six weeks in Sulaymaniyah, Iraq, between February and August 2022. Disease activity was assessed using the disease activity score 28 (DAS28). Plasma IL-6 levels, CRP, and ESR were measured at two time points over 14 weeks during maintenance therapy. Results: After 14 weeks, adalimumab lowered IL-6 levels to 31.92 ng/L (0.24), ESR to 15 mm/hr (16.8), and CRP to 8.4 mg/L (26.2). DAS28/ESR was also improved, it went from 4.7 (1.2) to 4.0 (1.3), which was the biggest change. Infliximab decreased IL-6 31.87 ng/L (0.29), ESR 10.1 mm/hr (15.0), and CRP 7 mg/L (13.5), but the smallest improvement was in DAS28/ESR 4.6 (1.6) to 4.5 (1.2). Etanercept exhibited the lowest decrease in IL-6, ESR, and CRP: 31.77 ng/L (0.39), 7.5 mm/hr (6.5), and 4.9 mg/L (4.9), respectively. However, it showed the second-greatest median improvement in DAS28/ESR, from 4·4 (1·8) to 4·0 (1·4). No correlation was found between plasma IL-6 levels and DAS28/ESR at either time point. Conclusion: TNF inhibitors differ in reducing plasma IL-6 levels and DAS28 during maintenance therapy in RA patients. Adalimumab was the most effective in reducing IL-6, CRP, ESR levels, and DAS28.

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References

Macgregor AJ, Snieder H, Rigby AS, Koskenvuo M, Kaprio J, Aho K, et al. Characterizing the quantitative genetic contribution to rheumatoid arthritis using data from twins. Arthr Rheum. 2000;43(1):30-37. doi: 10.1002/1529-0131

Mikhaylenko DS, Nemtsova MV, Bure I V, Kuznetsova EB, Alekseeva EA, Tarasov VV, et al. Genetic polymorphisms associated with rheumatoid arthritis development and antirheumatic therapy response. Int J Mol Sci. 2020;21(14):4911. doi: 10.3390/IJMS21144911.

Feldmann M, Brennan FM, Maini RN. Role of cytokines in rheumatoid arthritis. Annu Rev Immunol. 1996;14:397-440. doi: 10.1146/annurev.immunol.14.1.397.

Alam J, Jantan I, Bukhari SNA. Rheumatoid arthritis: Recent advances on its etiology, role of cytokines and pharmacotherapy. Biomed Pharmacother. 2017;92:615-633. doi: 10.1016/J.BIOPHA.2017.05.055.

Papadaki G, Goutakoli P, Tiniakou I, Grün JR, Grützkau A, Pavlopoulos GA, et al. IL-6 signaling attenuates TNF-α production by plasmacytoid dendritic cells in rheumatoid arthritis. J Immunol. 2022;209(10):1906-1917. doi: 10.4049/jimmunol.2100882.

Sanmartí R, Gómez-Centeno A, Ercilla G, Larrosa M, Viñas O, Vazquez I, et al. Prognostic factors of radiographic progression in early rheumatoid arthritis: A two year prospective study after a structured therapeutic strategy using DMARDs and very low doses of glucocorticoids. Clin Rheumatol. 2007;26(7):1111-1118. doi: doi: 10.1007/s10067-006-0462-4.

McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol. 2007;7(6):429-442. doi: 10.1038/nri2094.

Pasceri V, Willerson JT, Yeh ETH. Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation. 2000;102(18):2165-2168. doi: 10.1161/01.cir.102.18.2165.

Shrivastava AK, Singh HV, Raizada A, Singh SK, Pandey A, Singh N, et al. Inflammatory markers in patients with rheumatoid arthritis. Allergol Immunopathol (Madr). 2015;43(1):81-87. doi: 10.1016/j.aller.2013.11.003.

Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO, et al. 2010 Rheumatoid arthritis classification criteria: An American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis. 2010;69(9):1580-1588. doi: 10.1136/ard.2010.138461.

Prevoo MLL, Van’T Hof MA, Kuper HH, Van Leeuwen MA, Van De Putte LBA, Van Riel PLCM. Modified disease activity scores that include twenty-eight-joint counts development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum1995;38(1):44-48. doi: 10.1002/art.1780380107.

Al-Jabi SW, Seleit DI, Badran A, Koni A, Zyoud SH. Impact of socio-demographic and clinical characteristics on functional disability and health-related quality of life in patients with rheumatoid arthritis: a cross-sectional study from Palestine. Health Qual Life Outcomes. 2021;19(1). doi: 10.1186/S12955-021-01874-X.

Othman MA, Wan Ghazali WS, Yahya NK, Wong KK. Correlation of demographic and clinical characteristics with rheumatoid factor seropositivity in rheumatoid arthritis patients. Malaysian J Med Sci. 2016;23(6):52-59. doi: 10.21315/mjms2016.23.6.6.

Ataman S, Sunar I, Bodur H, Melikoglu MA, Cay HF, Capkin E, et al. Demographic and clinical characteristics of patients with sustained and switching treatments using biological and targeted synthetic disease-modifying antirheumatic drugs: a multicenter, observational cross-sectional study for rheumatoid arthritis. Rheumatol Ther. 2022;9(1):223-241. doi: 10.1007/s40744-021-00403-y.

Bazzani C, Filippini M, Caporali R, Bobbio-Pallavicini F, Favalli EG, Marchesoni A, et al. Anti-TNFα therapy in a cohort of rheumatoid arthritis patients: Clinical outcomes. Autoimmun Rev. 2009;8(3):260-265. doi: 10.1016/j.autrev.2008.11.001.

Krishna Priya EK, Srinivas L, Rajesh S, Sasikala K, Banerjee M. Pro-inflammatory cytokine response pre-dominates immuno-genetic pathway in development of rheumatoid arthritis. Mol Biol Rep. 2020;47(11):8669-8677. doi: 10.1007/s11033-020-05909-2.

Ramos-Remus C, Ramirez-Gomez A, Brambila-Barba V, Barajas-Ochoa A, Castillo-Ortiz JD, Adebajo AO, et al. Latitude gradient influences the age of onset of rheumatoid arthritis: a worldwide survey. Clin Rheumatol. 2017;36(3):485-497. doi: 10.1007/s10067-016-3481-9.

Strand V, Boklage SH, Kimura T, Joly F, Boyapati A, Msihid J. High levels of interleukin-6 in patients with rheumatoid arthritis are associated with greater improvements in health-related quality of life for sarilumab compared with adalimumab. Arthritis Res Ther. 2020;22(1). doi: 10.1186/s13075-020-02344-3.

Linauskas A, Overvad K, Symmons D, Johansen MB, Stengaard-Pedersen K, de Thurah A. Body fat percentage, waist circumference, and obesity as risk factors for rheumatoid arthritis: A Danish cohort study. Arthritis Care Res. 2019;71(6):777-786. doi: 10.1002/acr.23694.

Liu Y, Hazlewood GS, Kaplan GG, Eksteen B, Barnabe C. Impact of obesity on remission and disease activity in rheumatoid arthritis: a systematic review and meta-analysis. Arthritis Care Res. 2017;69(2):157-165. doi: 10.1002/acr.22932.

Singh S, Proudfoot J, Xu R, Sandborn WJ. Obesity and response to infliximab in patients with inflammatory bowel diseases: pooled analysis of individual participant data from clinical trials. Am J Gastroenterol. 2018;113(6):883-889. doi: 10.1038/S41395-018-0104-X.

Peluso I, Palmery M. The relationship between body weight and inflammation: Lesson from anti-TNF-α antibody therapy. Hum Immunol. 2016;77(1):47-53. doi: 10.1016/J.humimm.2015.10.008.

Üstünsoy S, tezcan D, keskin G, Bilgetekin İ. A three-year retrospective analysis of anti-tnf treatment outcomes in rheumatoid arthritis and ankylosing spondylitis patients. J Contemp Med. 2020;10(3):324-330. doi: 10.16899/jcm.645326.

Güngör Olçum G. Relation between disease activation, and serum erythrocyte sediment level and c-reactive protein levels in rheumatoid arthritis patients receiving anti tumor necrosis factor alpha treatment. Eurasian J Med Oncol. 2017;1(2):69-75. doi: 10.14744/ejmo.2017.47955.

Favalli EG, Pregnolato F, Biggioggero M, Becciolini A, Penatti AE, Marchesoni A, et al. Twelve-year retention rate of first-line tumor necrosis factor inhibitors in rheumatoid arthritis: real-life data from a local registry. Arthritis Care Res. 2016;68(4):432-439. .doi: 10.1002/acr.22788.

Soubrier M, Pereira B, Frayssac T, Fan A, Couderc M, Malochet-Guinamand S, et al. Retention rates of adalimumab, etanercept and infliximab as first-line biotherapy agent for rheumatoid arthritis patients in daily practice: Auvergne experience. Int J Rheum Dis. 2018;21(11):1924-1932. doi: 10.1111/1756-185X.13156.

Soubrier M, Pereira B, Fan A, Frayssac T, Couderc M, Malochet-Guinamand S, et al. Retention rates of adalimumab, etanercept, and infliximab as first- or second-line biotherapies for spondyloarthritis patients in daily practice in Auvergne (France). Int J Rheum Dis. 2018;21(11):1986-1992. doi: 10.1111/1756-185X.13375.

Kaneko K, Miyabe Y, Takayasu A, Fukuda S, Miyabe C, Ebisawa M, et al. Chemerin activates fibroblast-like synoviocytes in patients with rheumatoid arthritis. Arthritis Res Ther. 2011;13(5):R158. doi: 10.1186/ar3475.

Wu JF, Yang YH, Wang LC, Lee JH, Shen EY, Chiang BL. Comparative usefulness of C-reactive protein and erythrocyte sedimentation rate in juvenile rheumatoid arthritis. Clin Exp Rheumatol. 2007;25(5):782-785.

Hsu CT, Lin YT, Yang YH, Chiang BL. Factors affecting clinical and therapeutic outcomes of patients with juvenile rheumatoid arthritis. Scand J Rheumatol. 2004;33(5):312-317. doi: 10.1080/03009740410005854.

Keenan RT, Swearingen CJ, Yazici Y. Erythrocyte sedimentation rate and C-reactive protein levels are poorly correlated with clinical measures of disease activity in rheumatoid arthritis, systemic lupus erythematosus and osteoarthritis patients. Clin Exp Rheumatol. 2008;26(5):814-819.

Mohammed AM, Zayni SM, AL-Anee MM, Gorial FI, Al-Rubaee A. Diagnostic and predictive values of IL-6 in a group of Iraqi patients with rheumatoid arthritis. J Fac Med Baghdad. 2023;65(2). doi: 10.32007/jfacmedbagdad.2044.

Shaban SA. Study the serum IL-6 level between rheumatoid arthritis patients and control. Tikrit J Pure Sci. 2015;20:38-341. doi: 10.25130/tjps.v20i4.1210.

Ma J, Zhang Y, Gong Y, Zhu Y, Li M, Zhao J. Correlation between plasma levels of D-dimer and IL-1, IL-6, and TNF-α in patients with rheumatoid arthritis. Int J Clin Exp Med. 2018;11(9):9865-9871.

Wei ST, Sun YH, Zong SH, Xiang YB. Serum levels of IL-6 and TNF-α may correlate with activity and severity of rheumatoid arthritis. Med Sci Monit. 2015;21:4030-4038. doi: 10.12659/MSM.895116.

Eng GP, Bouchelouche P, Bartels EM, Bliddal H, Bendtzen K, Stoltenberg M. Anti-drug antibodies, drug levels, interleukin-6 and soluble TNF receptors in rheumatoid arthritis patients during the first 6 months of yreatment with adalimumab or infliximab: A descriptive cohort study. PLoS One. 2016;11(9):e0162316. doi: 10.1371/journal.pone.0162316.

Knudsen LS, Hetland ML, Johansen JS, Skjødt H, Peters ND, Colic A, et al. Changes in plasma Il-6, plasma VEGF and serum YKL-40 during treatment with etanercept and methotrexate or etanercept alone in patients with active rheumatoid arthritis despite methotrexate therapy. Biomark Insights. 2009;4:91-95. doi: 10.4137/bmi.s2300.

Milman N, Karsh J, Booth RA. Correlation of a multi-cytokine panel with clinical disease activity in patients with rheumatoid arthritis. Clin Biochem. 2010;43(16-17):1309-1314. doi: 10.1016/j.clinbiochem.2010.07.012.

Greenberg JD, Reed G, Decktor D, Harrold L, Furst D, Gibofsky A, et al. A comparative effectiveness study of adalimumab, etanercept and infliximab in biologically naive and switched rheumatoid arthritis patients: Results from the US CORRONA registry. Ann Rheum Dis. 2012;71(7):1134-1142. doi: 10.1136/annrheumdis-2011-150573.

Schippe LG, van Hulst LTC, Grol R, van Riel PLCM, Hulscher MEJL, Fransen J. Meta-analysis of tight control strategies in rheumatoid arthritis: protocolized treatment has additional value with respect to the clinical outcome. Rheumatology. 2010;49(11):2154-2164. doi: 10.1093/rheumatology/keq195.

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Published

2023-09-04

How to Cite

Mohammed, S. M., & Saaed, H. K. (2023). Interleukin-6 Suppression by Different TNF Inhibitors in Rheumatoid Arthritis Patients During Maintenance Therapy. Al-Rafidain Journal of Medical Sciences ( ISSN 2789-3219 ), 5, 184–191. https://doi.org/10.54133/ajms.v5i.230

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