Generic placeholder image

Current Rheumatology Reviews


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

Research Article

Drug Levels and Antibodies Against TNF-blockers in Spondyloarthritis and Rheumatoid Arthritis are Associated with the Activity but they do Not Predict it

Author(s): Erika Marcela Padilla-Martínez, Consuelo Romero-Sanchez*, Juan Manuel Bello-Gualtero, Ana Maria Mesa-Betancourt, Wilson Bautista-Molano and Rafael Valle-O

Volume 15, Issue 4, 2019

Page: [329 - 335] Pages: 7

DOI: 10.2174/1573397115666190708113601

Price: $65


Background: Many patients may have resistance to TNF-blockers. These drugs may induce neutralizing antibodies. The determination of the drug levels of TNF-blockers and Anti-Drug Antibodies (ADAs) against TNF-blockers may help to make clinical decisions.

Objectives: The objective of this study was to associate and predict the drug levels of TNFblockers and ADAs in relation to disease activity in patients with Spondyloarthritis (SpA) and Rheumatoid Arthritis (RA).

Methods: Cross-sectional study including patients fulfilling ASAS classification criteria for SpA and 2010 ACR-EULAR classification criteria for RA. These patients were treated with Adalimumab (ADA), Infliximab (IFX), and Etanercept (ETN). A bivariate analysis and the chi-square test were performed to evaluate the association of ADAs and drug levels with activity measures for SpA and RA. Five regression models analyzing drug levels, ADAs and disease activity measures using a multiple linear regression were performed in order to evaluate the prediction of ADAs and drug levels in relation to disease activity.

Results: In SpA, IFX levels were associated with BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) (p=0.034). In RA, total drug levels were associated with DAS28-ESR (28 joint Disease activity Score-erythrocyte sedimentation rate), (p=0.008), DAS28-CRP (p=0.042), CDAI (Clinical Disease Activity Index) (p=0.047) and SDAI (Simple Disease activity index), (p=0.017). ADA levels had association with CDAI (p=0.002) and SDAI (p=0.002). IFX levels were associated with a DAS28-ESR (p=0.044), DAS28-CRP (p=0.022) and SDAI (p=0.022). ADAs were associated in SpA with BASDAI (p=0.027). Drug levels and ADAs did not predict disease activity in patients with SpA or RA.

Conclusion: ADAs and drug levels of anti-TNF are associated with disease activity measures in patients with SpA and RA. However, they cannot predict clinical activity in these conditions.

Keywords: Antibodies, tumoral necrosis factor, spondyloarthritis, rheumatoid arthritis, inflammatory bowel disease, peripheral arthritis.

Graphical Abstract
McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med 2011; 365(23): 2205-19.
[] [PMID: 22150039]
Rudwaleit M, van der Heijde D, Landewé R, et al. The development of assessment of spondyloarthritis international society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis 2009; 68(6): 777-83.
[] [PMID: 19297344]
Atzeni F, Talotta R, Salaffi F, et al. Immunogenicity and autoimmunity during anti-TNF therapy. Autoimmun Rev 2013; 12(7): 703-8.
[] [PMID: 23207283]
Pecoraro V, De Santis E, Melegari A, Trenti T. The impact of immunogenicity of TNFα inhibitors in autoimmune inflammatory disease. A systematic review and meta-analysis. Autoimmun Rev 2017; 16(6): 564-75.
[] [PMID: 28411169]
Mok CC, van der Kleij D, Wolbink GJ. Drug levels, anti-drug antibodies, and clinical efficacy of the anti-TNFα biologics in rheumatic diseases. Clin Rheumatol 2013; 32(10): 1429-35.
[] [PMID: 23887439]
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: a real issue, a clinical perspective. Ann Rheum Dis 2013; 72(2): 165-78.
[] [PMID: 23178294]
Wolbink GJ, Aarden LA, Dijkmans BA. Dealing with immunogenicity of biologicals: assessment and clinical relevance. Curr Opin Rheumatol 2009; 21(3): 211-5.
[] [PMID: 19399992]
Arnett FC, Edworthy SM, Bloch DA, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988; 31(3): 315-24.
[] [PMID: 3358796]
Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 2010; 62(9): 2569-81.
[] [PMID: 20872595]
Rudwaleit M, van der Heijde D, Landewé R, et al. The assessment of spondyloarthritis international society classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general. Ann Rheum Dis 2011; 70(1): 25-31.
[] [PMID: 21109520]
Smolen JS, Breedveld FC, Schiff MH, et al. A simplified disease activity index for rheumatoid arthritis for use in clinical practice. Rheumatology (Oxford) 2003; 42(2): 244-57.
[] [PMID: 12595618]
Aletaha D, Smolen JS. The Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI) to monitor patients in standard clinical care. Best Pract Res Clin Rheumatol 2007; 21(4): 663-75.
[] [PMID: 17678828]
Zochling J. Measures of symptoms and disease status in ankylosing spondylitis: Ankylosing Spondylitis Disease Activity Score (ASDAS), Ankylosing Spondylitis Quality of Life Scale (ASQoL), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Global Score (BAS-G), Bath Ankylosing Spondylitis Metrology Index (BASMI), Dougados Functional Index (DFI), and Health Assessment Questionnaire for the Spondylarthropathies (HAQ-S). Arthritis Care Res (Hoboken) 2011; 63(Suppl. 11): S47-58.
[] [PMID: 22588768]
Singh JA, Furst DE, Bharat A, et al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken) 2012; 64(5): 625-39.
[] [PMID: 22473917]
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.
[] [PMID: 21540199]
Espiño-Lorenzo P, Manrique-Arija S, Ureña I, et al. Baseline comorbidities in patients with rheumatoid arthritis who have been prescribed biological therapy: a case control study. Reumatol Clin 2013; 9(1): 18-23.
[] [PMID: 22938792]
Machado-Alba JE, Ruiz A. The epidemiology of rheumatoid arthritis in a cohort of Colombian patients. Rev Colomb Reumatol 2015; 22: 148-52.
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 (Oxford) 2011; 50(8): 1445-52.
[] [PMID: 21427177]
Bartelds GM, Krieckaert CL, Nurmohamed MT, et al. Development of antidrug antibodies against adalimumab and association with disease activity and treatment failure during long-term follow-up. JAMA 2011; 305(14): 1460-8.
[] [PMID: 21486979]
Bartelds GM, Wijbrandts CA, Nurmohamed MT, et al. Clinical response to adalimumab: relationship to anti-adalimumab antibodies and serum adalimumab concentrations in rheumatoid arthritis. Ann Rheum Dis 2007; 66(7): 921-6.
[] [PMID: 17301106]
Keystone EC, Schiff MH, Kremer JM, et al. Once-weekly administration of 50 mg etanercept in patients with active rheumatoid arthritis: results of a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2004; 50(2): 353-63.
[] [PMID: 14872476]
Dore RK, Mathews S, Schechtman J, et al. The immunogenicity, safety, and efficacy of etanercept liquid administered once weekly in patients with rheumatoid arthritis. Clin Exp Rheumatol 2007; 25(1): 40-6.
[PMID: 17417989]
Jamnitski A, Krieckaert CL, Nurmohamed MT, et al. Patients non-responding to etanercept obtain lower etanercept concentrations compared with responding patients. Ann Rheum Dis 2012; 71(1): 88-91.
[] [PMID: 21914626]
Anderson J, Caplan L, Yazdany J, et al. Rheumatoid arthritis disease activity measures: American College of Rheumatology recommendations for use in clinical practice. Arthritis Care Res (Hoboken) 2012; 64(5): 640-7.
[] [PMID: 22473918]
Chen DY, Chen YM, Tsai WC, et al. Significant associations of antidrug antibody levels with serum drug trough levels and therapeutic response of adalimumab and etanercept treatment in rheumatoid arthritis. Ann Rheum Dis 2015; 74(3)e16
[] [PMID: 24442879]
Jung SM, Kim HS, Kim HR, et al. Immunogenicity of anti-tumour necrosis factor therapy in Korean patients with rheumatoid arthritis and ankylosing spondylitis. Int Immunopharmacol 2014; 21(1): 20-5.
[] [PMID: 24752013]
Paramarta JE, Baeten DL. Adalimumab serum levels and antidrug antibodies towards adalimumab in peripheral spondyloarthritis: no association with clinical response to treatment or with disease relapse upon treatment discontinuation. Arthritis Res Ther 2014; 16(4): R160.
[] [PMID: 25074046]
Deaconu C, Opris D, Mazilu D, et al. How useful is anti-TNF serum level and anti-drug antibodies detection in evaluating patients with spondyloarthritis. J Arthritis 2015; 4: 1-6.
Kneepkens EL, Krieckaert CL, van der Kleij D, et al. Lower etanercept levels are associated with high disease activity in ankylosing spondylitis patients at 24 weeks of follow-up. Ann Rheum Dis 2015; 74(10): 1825-9.
[] [PMID: 24812290]

Rights & Permissions Print Export Cite as
© 2024 Bentham Science Publishers | Privacy Policy