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Current Rheumatology Reviews

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ISSN (Print): 1573-3971
ISSN (Online): 1875-6360

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Research Article

No Correlation between Anti-drug Antibodies and Therapeutic Response in Tunisian Patients with Chronic Inflammatory Diseases Treated by TNF Blockers

Author(s): Selma Bouden, Lilia Laadhar, Jihene Soua*, Meriam Ben Messaoud, Leila Rouached, Imene Ayadi, Olfa Saidane, Aicha Ben Tekaya, Ines Mahmoud, Sonia Rekik, Héla Sahli Srairi, Rawdha Tekaya, Syrine Bellakhal, Monia Fekih, Leila Abdelmoula and Maryem Kallel

Volume 20, Issue 4, 2024

Published on: 02 January, 2024

Page: [435 - 443] Pages: 9

DOI: 10.2174/0115733971257151230919095431

Price: $65

Abstract

Introduction: Tumor necrosis factor alpha (TNF alpha) blockers such as infliximab (IFX) and adalimumab (ADA) had significantly changed the course of inflammatory diseases such as rheumatoid arthritis (RA), spondyloarthritis (SpA) and Crohn's disease (CD). However, about 30% of patients do not respond to these treatments. This lack of response may be due to the formation of antibodies against these drugs (anti-drug antibodies: ADAbs). The aim of this study was to determine the prevalence of ADAbs against IFX and ADA, and the trough serum concentration of IFX and ADA in RA, SpA or CD patients and to assess their impact on the therapeutic response.

Methods: A cross sectional, multi-centric study was conducted, including patients with RA, SpA or CD treated with IFX or ADA as a first biotherapy for at least 6 months. ADAbs and trough levels were measured by an Enzyme Linked Immunosorbent assay (ELISA).

Results: 197 patients were included (57 RA, 73 SpA and 67 CD). ADAbs were positive in 40% of cases for IFX and 25% for ADA. They were positive in 40% of SpA, 35% of RA, and 21% of CD. The presence of ADAbs was inversely correlated to the trough levels of IFX and ADA during RA (p = 0.01 and p < 0.0001), SpA (p < 0.01 and p < 0.0001) and CD (p = 0.001 and p = 0.04). For all pathologies, the presence of ADAbs was not correlated with disease activity. Concomitant methotrexate significantly reduced immunogenicity.

Conclusion: In our study, the presence of ADAb and low trough levels seem to not affect the therapeutic response in patients on TNF alpha antagonists. Other tracks more than immunogenicity should be investigated to explain the loss of response to these biotherapies.

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[1]
Vincent FB, Morand EF, Murphy K, Mackay F, Mariette X, Marcelli C. Antidrug antibodies (ADAb) to tumour necrosis factor (TNF)-specific neutralising agents in chronic inflammatory diseases: R real issue, a clinical perspective. Ann Rheum Dis 2013; 72(2): 165-78.
[http://dx.doi.org/10.1136/annrheumdis-2012-202545] [PMID: 23178294]
[2]
Stas P, Lasters I. Immunogenicity of therapeutic antibodies. Med Sci 2009; 25(12): 1070-7.
[http://dx.doi.org/10.1051/medsci/200925121070] [PMID: 20035681]
[3]
van Schouwenburg PA, van de Stadt LA, de Jong RN, et al. Adalimumab elicits a restricted anti-idiotypic antibody response in autoimmune patients resulting in functional neutralisation. Ann Rheum Dis 2013; 72(1): 104-9.
[http://dx.doi.org/10.1136/annrheumdis-2012-201445] [PMID: 22759910]
[4]
Sethu S, Govindappa K, Alhaidari M, Pirmohamed M, Park K, Sathish J. Immunogenicity to biologics: Rechanisms, prediction and reduction. Arch Immunol Ther Exp 2012; 60(5): 331-44.
[http://dx.doi.org/10.1007/s00005-012-0189-7] [PMID: 22930363]
[5]
Garcês S, Demengeot J, Benito-Garcia E. The immunogenicity of anti-TNF therapy in immune-mediated inflammatory diseases: R systematic review of the literature with a meta-analysis. Ann Rheum Dis 2013; 72(12): 1947-55.
[http://dx.doi.org/10.1136/annrheumdis-2012-202220] [PMID: 23223420]
[6]
Tamas MM, Felea I, Rednic S. How much difference does the age at onset make in early arthritis patients? Comparison between the ACR 1987 and the ACR/EULAR 2010 classification criteria for rheumatoid arthritis at the time of diagnosis. Rheumatol Int 2013; 33(11): 2881-4.
[http://dx.doi.org/10.1007/s00296-012-2515-0] [PMID: 22955876]
[7]
Braun J, van den Berg R, Baraliakos X, et al. 2010 update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis 2011; 70(6): 896-904.
[http://dx.doi.org/10.1136/ard.2011.151027] [PMID: 21540199]
[8]
Satsangi J, Silverberg MS, Vermeire S, Colombel JF. The Montreal classification of inflammatory bowel disease: Rontroversies, consensus, and implications. Gut 2006; 55(6): 749-53.
[http://dx.doi.org/10.1136/gut.2005.082909] [PMID: 16698746]
[9]
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 Rheum 1995; 38(1): 44-8.
[http://dx.doi.org/10.1002/art.1780380107] [PMID: 7818570]
[10]
Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P, Calin A. A new approach to defining disease status in ankylosing spondylitis: Rhe bath ankylosing spondylitis disease activity index. J Rheumatol 1994; 21(12): 2286-91.
[PMID: 7699630]
[11]
Lukas C, Landewé R, Sieper J, et al. Development of an ASAS-endorsed disease activity score (ASDAS) in patients with ankylosing spondylitis. Ann Rheum Dis 2009; 68(1): 18-24.
[http://dx.doi.org/10.1136/ard.2008.094870] [PMID: 18625618]
[12]
Best WR. Predicting the Crohnʼs disease activity index from the harvey-bradshaw index. Inflamm Bowel Dis 2006; 12(4): 304-10.
[http://dx.doi.org/10.1097/01.MIB.0000215091.77492.2a] [PMID: 16633052]
[13]
Hock BD, Stamp LK, Hayman MW, Keating PE, Helms ETJ, Barclay ML. Development of an ELISA-based competitive binding assay for the analysis of drug concentration and antidrug antibody levels in patients receiving adalimumab or infliximab. Ther Drug Monit 2016; 38(1): 32-41.
[http://dx.doi.org/10.1097/FTD.0000000000000229] [PMID: 26222874]
[14]
Wolbink GJ, Aarden LA, Dijkmans BAC. Dealing with immunogenicity of biologicals: Rssessment and clinical relevance. Curr Opin Rheumatol 2009; 21(3): 211-5.
[http://dx.doi.org/10.1097/BOR.0b013e328329ed8b] [PMID: 19399992]
[15]
Wadhwa M, Knezevic I, Kang HN, Thorpe R. Immunogenicity assessment of biotherapeutic products: Rn overview of assays and their utility. Biologicals 2015; 43(5): 298-306.
[http://dx.doi.org/10.1016/j.biologicals.2015.06.004] [PMID: 26144595]
[16]
Komaki Y, Komaki F, Sakuraba A, Cohen R. Approach to optimize anti-TNF-α therapy in patients with IBD. Curr Treat Options Gastroenterol 2016; 14(1): 83-90.
[http://dx.doi.org/10.1007/s11938-016-0079-x] [PMID: 26872815]
[17]
Mahmoud I, Rouached L, Ben Tekaya A, Saidane O, Bouden S, Jradi S, et al. Immunogenicity of antitumor necrosis factor therapy in patients with spondyloarthritis. Drug Metab Pers Ther 2020; 0139
[http://dx.doi.org/10.1515/dmdi-2020-0139] [PMID: 33155988]
[18]
Schellekens H. Immunogenicity of therapeutic proteins: Rlinical implications and future prospects. Clin Ther 2002; 24(11): 1720-40.
[http://dx.doi.org/10.1016/S0149-2918(02)80075-3] [PMID: 12501870]
[19]
Mohanan D, Slütter B, Henriksen-Lacey M, et al. Administration routes affect the quality of immune responses: R cross-sectional evaluation of particulate antigen-delivery systems. J Control Release 2010; 147(3): 342-9.
[http://dx.doi.org/10.1016/j.jconrel.2010.08.012] [PMID: 20727926]
[20]
Maini RN, Breedveld FC, Kalden JR, et al. Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor? monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. Arthritis Rheum 1998; 41(9): 1552-63.
[http://dx.doi.org/10.1002/1529-0131(199809)41:9<1552::AID-ART5>3.0.CO;2-W] [PMID: 9751087]
[21]
Plasencia C, Pascual-Salcedo D, Nuño L, et al. Influence of immunogenicity on the efficacy of longterm treatment of spondyloarthritis with infliximab. Ann Rheum Dis 2012; 71(12): 1955-60.
[http://dx.doi.org/10.1136/annrheumdis-2011-200828] [PMID: 22563028]
[22]
Krieckaert CLM, Bartelds GM, Lems WF, Wolbink GJ. The effect of immunomodulators on the immunogenicity of TNF-blocking therapeutic monoclonal antibodies: R review. Arthritis Res Ther 2010; 12(5): 217.
[http://dx.doi.org/10.1186/ar3147] [PMID: 21029481]
[23]
Arstikyte I, Kapleryte G, Butrimiene I, Venalis A. influence of immunogenicity on the efficacy of long-term treatment with tnf α blockers in rheumatoid arthritis and spondyloarthritis patients. BioMed Res Int 2015; 2015: 1-10.
[http://dx.doi.org/10.1155/2015/604872] [PMID: 26064930]
[24]
Pascual-Salcedo D, Plasencia C, Ramiro S, et al. Influence of immunogenicity on the efficacy of long-term treatment with infliximab in rheumatoid arthritis. Rheumatology 2011; 50(8): 1445-52.
[http://dx.doi.org/10.1093/rheumatology/ker124] [PMID: 21427177]
[25]
de Vries MK, Wolbink GJ, Stapel SO, et al. Decreased clinical response to infliximab in ankylosing spondylitis is correlated with anti-infliximab formation. Ann Rheum Dis 2007; 66(9): 1252-4.
[http://dx.doi.org/10.1136/ard.2007.072397] [PMID: 17472991]
[26]
Kneepkens EL, Wei JCC, Nurmohamed MT, et al. Immunogenicity, adalimumab levels and clinical response in ankylosing spondylitis patients during 24 weeks of follow-up. Ann Rheum Dis 2015; 74(2): 396-401.
[http://dx.doi.org/10.1136/annrheumdis-2013-204185] [PMID: 24326011]
[27]
Ducourau E, Mulleman D, Paintaud G, et al. Antibodies toward infliximab are associated with low infliximab concentration at treatment initiation and poor infliximab maintenance in rheumatic diseases. Arthritis Res Ther 2011; 13(3): R105.
[http://dx.doi.org/10.1186/ar3386] [PMID: 21708018]
[28]
Krintel SB, Grunert VP, Hetland ML, et al. The frequency of anti-infliximab antibodies in patients with rheumatoid arthritis treated in routine care and the associations with adverse drug reactions and treatment failure. Rheumatology 2013; 52(7): 1245-53.
[http://dx.doi.org/10.1093/rheumatology/ket017] [PMID: 23459699]
[29]
Arends S, Lebbink HR, Spoorenberg A, et al. The formation of autoantibodies and antibodies to TNF-α blocking agents in relation to clinical response in patients with ankylosing spondylitis. Clin Exp Rheumatol 2010; 28(5): 661-8.
[PMID: 20822711]
[30]
Hoxha A, Calligaro A, Tonello M, et al. The clinical relevance of early anti-adalimumab antibodies detection in rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis: R prospective multicentre study. Joint Bone Spine 2016; 83(2): 167-71.
[http://dx.doi.org/10.1016/j.jbspin.2015.04.020] [PMID: 26750762]
[31]
Vande Casteele N, Ferrante M, Van Assche G, et al. Trough concentrations of infliximab guide dosing for patients with inflammatory bowel disease. Gastroenterology 2015; 148(7): 1320-1329.e3.
[http://dx.doi.org/10.1053/j.gastro.2015.02.031] [PMID: 25724455]
[32]
Pallagi-Kunstár É, Farkas K, Szepes Z, et al. Utility of serum TNF-α, infliximab trough level, and antibody titers in inflammatory bowel disease. World J Gastroenterol 2014; 20(17): 5031-5.
[http://dx.doi.org/10.3748/wjg.v20.i17.5031] [PMID: 24833846]
[33]
Senabre Gallego JM, Rosas J, Marco-Mingot M, et al. Clinical relevance of monitoring serum adalimumab levels in axial spondyloarthritis. Rheumatol Int 2019; 39(5): 841-9.
[http://dx.doi.org/10.1007/s00296-019-04288-7] [PMID: 30899987]
[34]
Paramarta JE, Baeten DL. Adalimumab serum levels and antidrug antibodies towards adalimumab in peripheral spondyloarthritis: Ro association with clinical response to treatment or with disease relapse upon treatment discontinuation. Arthritis Res Ther 2014; 16(4): R160.
[http://dx.doi.org/10.1186/ar4675] [PMID: 25074046]
[35]
Cludts I, Spinelli FR, Morello F, Hockley J, Valesini G, Wadhwa M. Reprint of Anti-therapeutic antibodies and their clinical impact in patients treated with the TNF antagonist adalimumab. Cytokine 2018; 101: 70-7.
[http://dx.doi.org/10.1016/j.cyto.2017.11.007] [PMID: 29174881]
[36]
Bandrés Ciga S, Salvatierra J, López-Sidro M, et al. An examination of the mechanisms involved in secondary clinical failure to adalimumab or etanercept in inflammatory arthropathies. J Clin Rheumatol 2015; 21(3): 115-9.
[http://dx.doi.org/10.1097/RHU.0000000000000229] [PMID: 25807089]
[37]
Kuang B, King L, Wang HF. Therapeutic monoclonal antibody concentration monitoring: Rree or total? Bioanalysis 2010; 2(6): 1125-40.
[http://dx.doi.org/10.4155/bio.10.64] [PMID: 21083212]
[38]
O’Meara S, Nanda KS, Moss AC. Antibodies to infliximab and risk of infusion reactions in patients with inflammatory bowel disease: R systematic review and meta-analysis. Inflamm Bowel Dis 2014; 20(1): 1-6.
[http://dx.doi.org/10.1097/01.MIB.0000436951.80898.6d] [PMID: 24280879]
[39]
Casteele N, Gils A, Singh S, et al. Antibody response to infliximab and its impact on pharmacokinetics can be transient. Am J Gastroenterol 2013; 108(6): 962-71.
[http://dx.doi.org/10.1038/ajg.2013.12] [PMID: 23419382]
[40]
Mehta P, Manson JJ. What is the clinical relevance of TNF inhibitor immunogenicity in the management of patients with rheumatoid arthritis? Front Immunol 2020; 11: 589.
[http://dx.doi.org/10.3389/fimmu.2020.00589] [PMID: 32318070]

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