Relationship Between Trough Levels of Anti-Infliximab and Serum Biomarkers in Patients With Rheumatoid Arthritis
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Abstract
Rheumatoid arthritis is a chronic condition, characterized by the expression of antibody against self-antigens. Inflammatory cell of synovial tissues secreted numerous cytokines, include tumor necrosis factor alpha. Infliximab was designed to treat several autoimmune diseases. However, a considerable number of patients fail to respond appropriately. To investigate the relationship between trough infliximab serum levels and infliximab antibody with C-reactive protein (CRP), Rheumatoid factor (RF), and Anticyclic citrullinated peptide (ACCP) status. This study examined 83 rheumatoid arthritis patients on infliximab for 6 months duration. Sampling was collected in Rheumatology Unit at (Baghdad Teaching Hospital) from September 2021 to April 2022. Each patient had 3 mL of blood drawn. before the next dosage of medication. Anti-infliximab antibody, trough infliximab, and ACCP levels were measured using ELISA, while RF and CRP status were determined using an agglutination test. Ages of the patients ranged between 30-75 years old, (66 females and 17 males), and 44.6% of patients were smokers. In this study, 41 out of 83 patients were responder for infliximab therapy. The seropositivity of anti-drug antibodies was 50% in non-responder and 48.80% in responder patients. In contrast, the infliximab trough level classification as low and high in responder and non-responder patients was high in 56.1 %, and 40.5% of patients respectively. The difference between the two groups was statistically non-significant P=0.114. In addition, 74 patients tested positive for anti-cyclic citrullinated peptide. (89.2%), abnormal CRP levels were found in 54 (65.1%) patients, and seropositivity of Rheumatoid factor was found in 52 (62.7 %) of the patients. There was a negative relationship between smoking and responsiveness to infliximab. (r= -0.295 P 0.007) while there was a positive correlation between anti-infliximab antibodies with CRP and RF (P=0.026). Likewise, ACCP and serum trough infliximab levels were correlated significantly (P=0.014). Antidrug antibody seropositivity correlates positively with CRP and RF status and between ACCP and serum trough infliximab in RA patients while there is a negative correlation between smoking and early response to infliximab.
2. Tabin S, Gupta RC, kamili AN, parray JA. Medical and medicinal importance of Rheum spp. collected from different altitudes of the Kashmir Himalayan range. Cell Mol Biomed Rep 2022;2:187-201.
3. Koch AE. The pathogenesis of rheumatoid arthritis. Am J Orthop (Belle Mead NJ) 2007;36:5-8.
4. Kallam SDM, Bodapati A, Reddy AS, Reddy KTK. Bioanalytical method development for monoclonal antibodies: advances and challenges. Cell Mol Biomed Rep 2025;5:48-62.
5. Barlow NL, Mohammed P, Berg JD. Serum trough infliximab and anti-infliximab antibodies in a cohort of gastroenterology and rheumatology patients' infliximab therapeutic drug monitoring. Ann Clin Biochem 2016;53:477-84.
6. Lim SH, Kim K, Choi CI. Pharmacogenomics of Monoclonal Antibodies for the Treatment of Rheumatoid Arthritis. J Pers Med 2022;12:1265.
7. Nozaki Y, Kotani T, Takeuchi T, Hidaka T, Miyake H, Hatta K, et al. The Impact of Early Optimization of Infliximab Blood Concentrations >1 mug/mL on Therapeutic Effectiveness in Rheumatoid Arthritis. Front Biosci (Landmark Ed) 2023;28(4):68.
8. Thudium CS, Frederiksen P, Karsdal MA, Bay-Jensen AC. Changes in type VI collagen degradation reflect clinical response to treatment in rheumatoid arthritis patients treated with tocilizumab. Arthritis Res Ther 2024;26:3.
9. Yang X, Cai Y, Xue B, Zhang B. Diagnostic value of anti-cyclic citrullinated peptide antibody combined with rheumatoid factor in rheumatoid arthritis in Asia: a meta-analysis. J Int Med Res 2021;49:03000605211047714.
10. Catrina AI, Joshua V, Klareskog L, Malmström V. Mechanisms involved in triggering rheumatoid arthritis. Immunol Rev 2016;269:162-74.
11. Al-Osami MH, Allawi A, Al-Saadawi TH. The association of smoking with the extra-articular manifestations in rheumatoid arthritis patients. Iraqi Postgrad Med J 2013;12:146-52.
12. Mattey DL, Hutchinson D, Dawes PT, Nixon NB, Clarke S, Fisher J, et al. Smoking and disease severity in rheumatoid arthritis: association with polymorphism at the glutathione S‐transferase M1 locus. Arthritis Rheum 2002;46:640-6.
13. Klareskog L, Malmström V, Lundberg K, Padyukov L, Alfredsson L. Smoking, citrullination and genetic variability in the immunopathogenesis of rheumatoid arthritis. Semin Immunol 2011;23:92-8.
14. Frade-Sosa B, Ponce A, Ruiz-Esquide V, García-Yébenes MJ, Morlá R, Sapena N, et al. High sensitivity C reactive protein in patients with rheumatoid arthritis treated with antibodies against IL-6 or Jak inhibitors: a clinical and ultrasonographic study. Diagnostics (Basel) 2022;12:182.
15. de Hair MJ, Landewé RB, van de Sande MG, van Schaardenburg D, van Baarsen LG, Gerlag DM, et al. Smoking and overweight determine the likelihood of developing rheumatoid arthritis. Ann Rheum Dis 2013;72:1654-8.
16. Seror R, Henry J, Gusto G, Aubin HJ, Boutron-Ruault M-C, Mariette X. Passive smoking in childhood increases the risk of developing rheumatoid arthritis. Rheumatology (Oxford) 2019;58:1154-62.
17. Sugiyama D, Nishimura K, Tamaki K, Tsuji G, Nakazawa T, Morinobu A, et al. Impact of smoking as a risk factor for developing rheumatoid arthritis: a meta-analysis of observational studies. Ann Rheum Dis 2010;69:70-81.
18. Söderlin M, Petersson I, Geborek P. The effect of smoking on response and drug survival in rheumatoid arthritis patients treated with their first anti-TNF drug. Scand J Rheumatol 2012;41:1-9.
19. Song IS, Sohn HS, Kim H, Lim E, Kwon M, Ha JH, et al. Impact of smoking on the effectiveness of TNF-α inhibitors in patients with rheumatoid arthritis or Crohn’s disease. Transl Clin Pharmacol 2014;22:92-101.
20. Arnson Y, Shoenfeld Y, Amital H. Effects of tobacco smoke on immunity, inflammation and autoimmunity. J Autoimmun 2010;34:J258-J65.
21. Shrivastava AK, Singh H, Raizada A, Singh S, Pandey A, Singh N, et al. Inflammatory markers in patients with rheumatoid arthritis. Allergol Immunopathol (Madr) 2015;43:81-7.
22. Dessie G, Tadesse Y, Demelash B, Genet S, Malik T, Dejenie TA. Evaluation of C-reactive protein and associated factors among patients suffering from rheumatoid arthritis at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia. Open Access Rheumatol 2021;13:247-55.
23. Rocha SdB, Baldo DC, Andrade LEC. Clinical and pathophysiologic relevance of autoantibodies in rheumatoid arthritis. Adv Rheumatol 2019;59:2.
24. van Schouwenburg P. Antibodies against antibodies: immunogenicity of adalimumab as a model. Ann Rheum Dis 2012.
25. Bobbio-Pallavicini F, Caporali R, Alpini C, Avalle S, Epis OM, Klersy C, et al. High IgA rheumatoid factor levels are associated with poor clinical response to tumour necrosis factor α inhibitors in rheumatoid arthritis. Ann Rheum Dis 2007;66:302-7.
26. Albarzinji N, Ismael SA, Albustany D. Association of rheumatoid arthritis and its severity with human leukocytic antigen-DRB1 alleles in Kurdish region in North of Iraq. BMC Rheumatol 2022;6:1-5.
27. Alessandri C, Bombardieri M, Papa N, Cinquini M, Magrini L, Tincani A, et al. Decrease of anti-cyclic citrullinated peptide antibodies and rheumatoid factor following anti-TNFα therapy (infliximab) in rheumatoid arthritis is associated with clinical improvement. Ann Rheum Dis 2004;63:1218-21.
28. Kobak S, Bes C. An autumn tale: geriatric rheumatoid arthritis. Ther Adv Musculoskelet Dis 2018;10:3-11.
29. Quistrebert J, Hässler S, Bachelet D, Mbogning C, Musters A, Tak PP, et al., editors. Incidence and risk factors for adalimumab and infliximab anti-drug antibodies in rheumatoid arthritis: a European retrospective multicohort analysis. Semin Arthritis Rheum 2019;48:967-75.
30. Ingegnoli F, Castelli R, Gualtierotti R. Rheumatoid factors: clinical applications. Dis Markers 2013;35:727-34.
31. Perilla AMD, Vásquez GM, Rojas MX. ¿ Is seropositivity in patients with rheumatoid arthritis treated with adalimumab a factor to develop anti-adalimumab antibodies? Rev Cient Reumatologia (English Edition). 2019;26:24-30.
32. Larid G, Pancarte M, Offer G, Clavel C, Martin M, Pradel V, et al. In rheumatoid arthritis patients, HLA-DRB1* 04: 01 and rheumatoid nodules are associated with ACPA to a particular fibrin epitope. Front Immunol 2021;12:692041.
33. Eker YÖ, Pamuk ÖN, Pamuk GE, Dönmez S, Çakır N. The Frequency of anti-CCP antibodies in patients with rheumatoid arthritis and psoriatic arthritis and their relationship with clinical features and parameters of angiogenesis: A comparative study. Eur J Rheumatol 2014;1:67-71.
| Files | ||
| Issue | Vol 62 No 6 (2024) | |
| Section | Original Articles | |
| Keywords | ||
| Anti cyclic citrullinated protein C reactive protein Infliximab Rheumatoid arthritis Rheumatoid factor | ||
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