Generic placeholder image

Current Rheumatology Reviews


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

Research Article

Antinuclear Antibodies and Lupus-like Manifestations in Rheumatoid Arthritis and Ankylosing Spondylitis Patients at 4 Months' Follow-up After Treatment with Infliximab and Etanercept

Author(s): Mir Amir Aghdashi, Mohsen Khadir and Roshan Dinparasti-Saleh*

Volume 16, Issue 1, 2020

Page: [61 - 66] Pages: 6

DOI: 10.2174/1573397115666190506152729

Price: $65


Background: Up to 44% of patients treated with infliximab and 7% of patients treated with etanercept reported to have anti-drug antibodies within the first 6 months of treatment. Recently, anti-TNF-α therapies have been reported to be employed in the induction of the druginduced lupus erythematous.

Objective: The aim of the present study was to investigate the relationship between anti-TNFα antibodies and various manifestations of lupus erythematous.

Methods: We enrolled a total of 56 cases divided into 28 known cases of rheumatoid arthritis and 28 cases of ankylosing spondylitis patients and 56 controls. The case group was divided into 4 groups according to the underlying disease (RA or AS) and treatment regimen (infliximab or etanercept). ANA and anti-dsDNA levels and lupus criteria were assessed at the beginning of the study and 4 months after the initiation of anti-TNFα.

Results: 36% and 21% of RA patients treated with infliximab, were ANA and anti-dsDNA positive after 4 months (P=0.003, P=0.025). 28% and 7% of RA patients treated with etanercept, were ANA and anti-dsDNA positive after 4 months (P=0.009, P=0.15). 21% and 7% of AS patients treated with infliximab, were ANA and anti-dsDNA positive, respectively (P=0.025, P=0.15). 14% and 7% of AS patients treated with etanercept, were ANA and anti-dsDNA positive, respectively (P=0.63, P=0.15). Three patients who were positive for auto-antibodies developed three criteria for SLE.

Conclusion: Infliximab potentially may increase both ANA and anti-dsDNA levels in rheumatoid arthritis, but only ANA in ankylosing spondylitis patients. In general, clinicians should consider different clinical symptoms of ATIL, which may be present as a lupus-like syndrome similar to idiopathic SLE or classical DIL.

Keywords: Lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis, infliximab, etanercept, anti-TNF-α therapies.

Cooper GS, Bynum ML, Somers EC. Recent insights in the epidemiology of autoimmune diseases: improved prevalence estimates and understanding of clustering of diseases. J Autoimmun 2009; 33(3-4): 197-207.
[] [PMID: 19819109]
Zhu B, Zhu Q, Li N, Wu T, Liu S, Liu S. Association of serum/plasma high mobility group box 1 with autoimmune diseases: A systematic review and meta-analysis. Medicine (Baltimore) 2018; 97(29)e11531
[] [PMID: 30024540]
McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med 2011; 365(23): 2205-19.
[] [PMID: 22150039]
Carmona L, Villaverde V, Hernández-García C, Ballina J, Gabriel R, Laffon A. EPISER Study Group.The prevalence of rheumatoid arthritis in the general population of Spain. Rheumatology (Oxford) 2002; 41(1): 88-95.
[] [PMID: 11792885]
Silman AJ, Pearson JE. Epidemiology and genetics of rheumatoid arthritis. Arthritis Res 2002; 4(Suppl. 3): S265-72.
[] [PMID: 12110146]
Hanson A, Brown MA. Genetics and the causes of ankylosing spondylitis. Rheum Dis Clin North Am 2017; 43(3): 401-14.
[] [PMID: 28711142]
Hinze AM, Louie GH. Osteoporosis management in ankylosing spondylitis. Curr Treatm Opt Rheumatol 2016; 2(4): 271-82.
[] [PMID: 28620575]
Gran JT, Husby G. The epidemiology of ankylosing spondylitis. Semin Arthritis Rheum 1993; 22(5): 319-34.
[] [PMID: 8511596]
Beutler B, Cerami A. The biology of cachectin/TNF--a primary mediator of the host response. Annu Rev Immunol 1989; 7: 625-55.
[] [PMID: 2540776]
Choy EH, Panayi GS. Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med 2001; 344(12): 907-16.
[] [PMID: 11259725]
Shingu M, Nagai Y, Isayama T, Naono T, Nobunaga M, Nagai Y. The effects of cytokines on metalloproteinase inhibitors (TIMP) and collagenase production by human chondrocytes and TIMP production by synovial cells and endothelial cells. Clin Exp Immunol 1993; 94(1): 145-9.
[] [PMID: 8403497]
Klareskog L, Catrina AI, Paget S. Rheumatoid arthritis. Lancet 2009; 373(9664): 659-72.
[] [PMID: 19157532]
Lim H, Lee SH, Lee HT, et al. Structural biology of the TNFα antagonists used in the treatment of rheumatoid arthritis. Int J Mol Sci 2018; 19(3)E768
[] [PMID: 29518978]
Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American college of rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol 2016; 68(1): 1-26.
[] [PMID: 26545940]
Sieper J, Poddubnyy D. Axial spondyloarthritis. Lancet 2017; 390(10089): 73-84.
[] [PMID: 28110981]
Knight DM, Trinh H, Le J, et al. Construction and initial characterization of a mouse-human chimeric anti-TNF antibody. Mol Immunol 1993; 30(16): 1443-53.
[] [PMID: 8232330]
Chen X, DuBois DC, Almon RR, Jusko WJ. Biodistribution of etanercept to tissues and sites of inflammation in arthritic rats. Drug Metab Dispos 2015; 43(6): 898-907.
[] [PMID: 25834031]
Gamarra RM, McGraw SD, Drelichman VS, Maas LC. Serum sickness-like reactions in patients receiving intravenous infliximab. J Emerg Med 2006; 30(1): 41-4.
[] [PMID: 16434333]
Radstake TR, Svenson M, Eijsbouts AM, et al. Formation of antibodies against infliximab and adalimumab strongly correlates with functional drug levels and clinical responses in rheumatoid arthritis. Ann Rheum Dis 2009; 68(11): 1739-45.
[] [PMID: 19019895]
Moots RJ, Xavier RM, Mok CC, et al. The impact of anti-drug antibodies on drug concentrations and clinical outcomes in rheumatoid arthritis patients treated with adalimumab, etanercept, or infliximab: Results from a multinational, real-world clinical practice, non-interventional study. PLoS One 2017; 12(4)e0175207
[] [PMID: 28448562]
Bendtzen K, Geborek P, Svenson M, Larsson L, Kapetanovic MC, Saxne T. Individualized monitoring of drug bioavailability and immunogenicity in rheumatoid arthritis patients treated with the tumor necrosis factor alpha inhibitor infliximab. Arthritis Rheum 2006; 54(12): 3782-9.
[] [PMID: 17133559]
Quaresma MV, Bernardes Filho F, Oliveira FB, Pockstaller MP, Dias MF, Azulay DR. Anti-TNF-α and hydralazine drug-induced lupus. An Bras Dermatol 2015; 90(3)(Suppl. 1): 125-9.
[] [PMID: 26312694]
Vaz JL, Fernandes V, Nogueira F, Arnóbio A, Levy RA. Infliximab-induced autoantibodies: a multicenter study. Clin Rheumatol 2016; 35(2): 325-32.
[] [PMID: 26676808]
Aletaha D, Neogi T, Silman AJ, et al. 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]
Petri M, Orbai AM, Alarcón GS, et al. Derivation and validation of the systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 2012; 64(8): 2677-86.
[] [PMID: 22553077]
van Gestel AM, Prevoo ML, van ’t Hof MA, van Rijswijk MH, van de Putte LB, van Riel PL. Development and validation of the European League Against Rheumatism response criteria for rheumatoid arthritis. Comparison with the preliminary American College of Rheumatology and the World Health Organization/International League Against Rheumatism Criteria. Arthritis Rheum 1996; 39(1): 34-40.
[] [PMID: 8546736]
Lukas C, Landewé R, Sieper J, et al. Assessment of SpondyloArthritis international Society. Development of an ASAS-endorsed disease activity score (ASDAS) in patients with ankylosing spondylitis. Ann Rheum Dis 2009; 68(1): 18-24.
[] [PMID: 18625618]
Monaco C, Nanchahal J, Taylor P, Feldmann M. Anti-TNF therapy: past, present and future. Int Immunol 2015; 27(1): 55-62.
[] [PMID: 25411043]
Corbett M, Soares M, Jhuti G, Rice S, Spackman E, Sideris E, et al. Tumour necrosis factor-alpha inhibitors for ankylosing spondylitis and non-radiographic axial spondyloarthritis: a systematic review and economic evaluationHealth technology assessment (Winchester, England) 2016 Feb; 20(9): 1-334 v-vi
[PMID: 26847392]
Lopetuso LR, Gerardi V, Papa V, et al. Can We Predict the Efficacy of Anti-TNF-α Agents? Int J Mol Sci 2017; 18(9)E1973
[] [PMID: 28906475]
Ziolkowska M, Maslinski W. Laboratory changes on anti-tumor necrosis factor treatment in rheumatoid arthritis. Curr Opin Rheumatol 2003; 15(3): 267-73.
[] [PMID: 12707580]
Beigel F, Schnitzler F, Paul Laubender R, et al. Formation of antinuclear and double-strand DNA antibodies and frequency of lupus-like syndrome in anti-TNF-α antibody-treated patients with inflammatory bowel disease. Inflamm Bowel Dis 2011; 17(1): 91-8.
[] [PMID: 20564536]
Charles PJ, Smeenk RJ, De Jong J, Feldmann M, Maini RN. Assessment of antibodies to double-stranded DNA induced in rheumatoid arthritis patients following treatment with infliximab, a monoclonal antibody to tumor necrosis factor alpha: findings in open-label and randomized placebo-controlled trials. Arthritis Rheum 2000; 43(11): 2383-90.
[<2383:AID-ANR2>3.0.CO;2-D] [PMID: 11083258]
De Bandt M, Sibilia J, Le Loët X, et al. Club Rhumatismes et Inflammation. Systemic lupus erythematosus induced by anti-tumour necrosis factor alpha therapy: a French national survey. Arthritis Res Ther 2005; 7(3): R545-51.
[] [PMID: 15899041]
Ramos-Casals M. Roberto-Perez-Alvarez, Diaz-Lagares C, Cuadrado MJ, Khamashta MA. BIOGEAS study group. Autoimmune diseases induced by biological agents: a double-edged sword? Autoimmun Rev 2010; 9(3): 188-93.
[] [PMID: 19854301]
Borchers AT, Keen CL, Gershwin ME. Drug-induced lupus. Ann N Y Acad Sci 2007; 1108: 166-82.
[] [PMID: 17893983]
Ramos-Casals M, Brito-Zerón P, Muñoz S, et al. Autoimmune diseases induced by TNF-targeted therapies: analysis of 233 cases. Medicine (Baltimore) 2007; 86(4): 242-51.
[] [PMID: 17632266]
Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25(11): 1271-7.
[] [PMID: 7138600]
Akgül Ö, Kılıç G, Kılıç E, Cüce İ, Özgöçmen S. A patient with ankylosing spondylitis who developed infliximab-induced lupus and treated with etanercept. Rheumatol Int 2014; 34(3): 443-4.
[] [PMID: 23263496]
Williams VL, Cohen PR. TNF alpha antagonist-induced lupus-like syndrome: report and review of the literature with implications for treatment with alternative TNF alpha antagonists. Int J Dermatol 2011; 50(5): 619-25.
[] [PMID: 21506984]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy