How real is the long-lasting effect of tumor necrosis factor α inhibitors? Focus on immunogenicity
https://doi.org/10.14412/1996-7012-2014-2-35-40
Abstract
Tumor necrosis factor (TNF) α inhibitors are the most commonly used agents to treat rheumatoid arthritis (RA) and other inflammatory arthropathies. Five drugs belonging to the family of TNFα inhibitors have been certified in Russia for treating RA: infliximab (INF), adali- mumab (ADA), golimumab, certolizumab pegol, and etanercept (ETN). These drugs have different compositions. ETN does not belong to the family of monoclonal antibodies (mAbs) and has a different mechanism of action. It is a dimeric molecule of synthetic fusion protein contain- ing TNF receptor and bound to the Fc-fragment of human Ig1. ETN can inhibit both TNFα and lymphotoxin α. ETN contains only the pro- tein identical to human protein.
All TNFα inhibitors exhibit a virtually identical anti-inflammatory activity. The data from the registries show that the risk of discontinuation of therapy with TNFα during the first 2–3 years is appreciably high; there is a trend toward increased frequency of therapy discontinuation because of loss of effectiveness. It was found that the risk of therapy discontinuation because of insufficient effectiveness and adverse events (AEs) is minimal for ETN and maximal for INF. The structure of biological drugs (which also affects their immunogenicity) has the key neg- ative effect on maintaining the response to therapy and frequency of AEs. However, since ETN is a fusion molecule and contains less poten- tially immunogenic epitopes compared to mAbs, the frequency of detecting anti-drug antibodies (ADAbs) is appreciably lower.
The fact that ETN has a lower immunogenicity can be used to explain the significantly lower probability of discontinuing therapy using this drug as compared to INF and ADA. The risk that the need to increase the dose because of gradual loss of effectiveness of therapy with ADA and INF, was 4.9- and 28-fold higher, respectively, as compared to ETN.
Therapeutic algorithms make it possible to control therapy with TGFα inhibitors (development of ADAbs, blood concentration of drug), as well as to switch to using another biological drug. Currently, the main method for preventing ADAb formation is to strictly follow the recommenda- tions for using biological drugs in combination of disease-modifying anti-rheumatic drugs (first of all, with methotrexate). TNFα inhibitors hav- ing the lowest immunogenicity (ETN, etc.) are advisable to be used in this case.
About the Author
D.E. Karateev
V.A. Nasonova Research Institute of Rheumatology, Russian Academy of Medical Sciences, Moscow, Russia
Russian Federation
Russian Federation
References
1. Насонов ЕЛ. Фактор некроза опухоли α – новая мишень для противовоспалительной терапии ревматоидного артрита. Клиническая фармакология и терапия. 2001;10(1):64–70. [Nasonov EL. Factor of a necrosis of a tumor α – a new target for anti-inflammatory therapy of rheumatoid arthritis. Klinicheskaya farmakologiya i terapiya. 2001;10(1):64–70. (In Russ.)]
2. Smolen JS, Han C, Bala M, et al. Evidence of radiographic benefit of treatment with infliximab plus methotrexate in rheumatoid arthritis patients who had no clinical improvement: a detailed subanalysis of data from the anti-tumor necrosis factor trial in rheumatoid arthritis with concomitant therapy study. Arthritis Rheum. 2005;52(4):1020–30. DOI: http://dx.doi.org/10.1002/art.20982.
3. Каратеев ДЕ. Этанерцепт при ревматоидном артрите. Научно-практическая ревматология. 2009;47(5):52–7. [Karateev DE. Etanercept at rheumatoid arthritis. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2009;47(5):52Р7. (In Russ.)]. DOI: http://dx.doi.org/10.14412/1995-4484-2009-589.
4. Hetland ML, Christensen IJ, Tarp U, et al. Direct comparison of treatment responses, remission rates, and drug adherence in patients with rheumatoid arthritis treated with adalimumab, etanercept, or infliximab: results from eight years of surveillance of clinical practice in the nationwide Danish DANBIO registry. Arthritis Rheum. 2010;62(1):22–32. DOI: 10.1002/art.27227. 5. Iannone F, Gremese E, Atzeni F, et al. Longterm retention of tumor necrosis factor-α inhibitor therapy in a large italian cohort of patients with rheumatoid arthritis from the GISEA registry: an appraisal of predictors. J Rheumatol. 2012 Jun;39(6):1179–84. DOI: 10.3899/jrheum.111125.
5. Markenson JA, Gibofsky A, Palmer WR, et al. Persistence with anti-tumor necrosis factor therapies in patients with rheumatoid arthritis: observations from the RADIUS registry. J Rheumatol. 2011;38(7):1273–81. DOI: 10.3899/jrheum.101142.
6. Neovius M, Arkema EV, Olsson H, et al. Drug survival on TNF inhibitors in patients with rheumatoid arthritis comparison of adalimumab, etanercept and infliximab. Ann Rheum Dis. 2013 Nov 27. DOI: 10.1136/annrheumdis-2013-204128. [Epub ahead of print]
7. Scirе CA, Caporali R, Sarzi-Puttini P, et al. Drug survival of the first course of anti-TNF agents in patients with rheumatoid arthritis and seronegative spondyloarthritis: analysis from the MonitorNet database. Clin Exp Rheumatol. 2013;31(6):857–63. Epub 2013 Aug 26.
8. Flouri I, Markatseli TE, Voulgari PV, et al. Comparative effectiveness and survival of infliximab, adalimumab, and etanercept for rheumatoid arthritis patients in the Hellenic Registry of Biologics: Low rates of remission and 5-year drug survival. Semin Arthritis Rheum. 2014;43(3):447–57. DOI: 10.1016/j.semarthrit.2013.07.011.
9. Smolen J, Aletaha D, Bijlsma JWJ, et al. Treating rheumatoid arthritis to target: recommendations of an international task force. Ann Rheum Dis. 2010;69(4):631–7. DOI: 10.1136/ard.2009.123919. Epub 2010 Mar 9.
10. Schellekens H. Immunogenicity of therapeutic proteins: clinical implications and future prospects. Clin Ther.
11. ;24(11):1720–40. DOI: http://dx.doi.org/10.1016/S0149-2918(02)80075-3.
12. Cheifetz A, Mayer L. Monoclonal Antibodies, Immunogenicity, and Associated Infusion Reactions. Mount Sinai J Med. 2005;72(4):250–6.
13. Mirick GR, Bradt BM, Denardo SJ, Denardo GL. A review of human anti-globulin antibody (HAGA, HAMA, HACA, HAHA) responses to monoclonal antibodies. Q J Nucl Med Mol Imaging. 2004;48(4):251–7.
14. Waldmann T. Immunotherapy: past, present and future. Nature Medicine. 2003;9(3):269 –77. DOI: http://dx.doi.org/10.1038/nm0303-269.
15. Weiner LM. Fully human therapeutic monoclonal antibodies. J Immunother. 2006;29(1):1–9. DOI: http://dx.doi.org/10.1097/01.cji.0000192105. 24583.83.
16. Wolbink GJ, Vis M, Lems WF, et al. Development of anti-infliximab antibodies and relationship to clinical response in patients with rheumatoid arthritis. Arthritis Rheum. 2006;54(3):711–5. http://dx.doi.org/10.1002/art.21671.
17. Каратеев ДЕ. Вопросы иммуногенности биологических препаратов – теория и практика. Современная ревматология. 2009;1:67–72. [Karateev DE. The problems of the immunogenicity of biologicals: theory and practice. Sovremennaya revmatologiya. 2009;1:67–72. (In Russ.)]. DOI: http://dx.doi.org/10.14412/1996-7012-2009-527.
18. 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. DOI: 10.1093/rheumatology/ker124.
19. Vincent FB, Morand EF, Murphy K, et al. 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. DOI: 10.1136/annrheumdis-2012-202545.
20. Van Schouwenburg PA, Rispens T, Wolbink GJ. Immunogenicity of anti-TNF biologic therapies for rheumatoid arthritis. Nat Rev Rheumatol. 2013;9(3):164–72. DOI: 10.1038/nrrheum.2013.4.
21. Maini RN, Breedveld FC, Kalden JR, et al. Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. Arthritis Rheum. 1998;41(9):1552–63. DOI: http://dx.doi.org/10.1002/1529-0131(199809)41:9%3C1552::AID-ART5%3E3.0.CO;2-W.
22. Lovell DJ, Giannini EH, Reiff A, et al. Etanercept in children with polyarticular juvenile rheumatoid arthritis. Pediatric Rheumatology Collaborative Study Group. N Engl J Med. 2000;16(342):763–9. DOI: http://dx.doi.org/10.1056/NEJM2000031634 21103.
23. Maini RN, Breedveld FC, Kalden JR, et al. Sustained improvement over two years in physical function, structural damage, and signs and symptoms among patients with rheumatoid arthritis treated with infliximab and methotrexate. Arthritis Rheum. 2004;50(4):1051–65. DOI: http://dx.doi.org/10.1002/art.20159.
24. Farrell RJ, Alsahli M, Jeen YT, et al. Intravenous hydrocortisone premedication reduces antibodies to infliximab in Crohn's disease: a randomized controlled trial. Gastroenterology. 2003;124(4):917–24. DOI: http://dx.doi.org/10.1053/gast.2003.50145. 25. Keystone EC, Schiff MH, Kremer JM,
25. 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(20:353–63.
26. 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. DOI: http://dx.doi.org/10.1136/ard.2007.072397. Epub 2007 May 1.
27. Bartelds GM, Wijbrandts CA, Nurmohamed MT, et al. Clinical response to adalimumab: relationship to anti-adalimum-ab antibodies and serum adalimumab concentrations in rheumatoid arthritis. Ann Rheum Dis. 2007;66(7):921–6. DOI: http://dx.doi.org/10.1136/ard.2006.065615. Epub 2007 Feb 14.
28. Tyring S, Gordon KB, Poulin Y, et al. Long-term safety and efficacy of 50 mg of etanercept twice weekly in patients with psoriasis. Arch Dermatol. 2007;143(6):719–26. DOI: http://dx.doi.org/10.1001/arch-derm.143.6.719.
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. Epub 2010 Oct 22.
30. West RL, Zelinkova Z, Wolbink GJ, et al. Immunogenicity negatively influences the outcome of adalimumab treatment in Crohn's disease. Aliment Pharmacol Ther. 2008;28(9):1122–6. DOI: 10.1111/j.1365-2036.2008.03828.x.
31. Van Kuijk AW, de Groot M, Stapel SO, et al. Relationship between the clinical response to adalimumab treatment and serum levels of adalimumab and anti-adalimumab antibodies in patients with psoriatic arthritis. Ann Rheum Dis. 2010;69(3):624–5. DOI: 10.1136/ard.2009.108787.
32. Lecluse LL, Driessen RJ, Spuls PI, et al. Extent and clinical consequences of antibody formation against adalimumab in patients with plaque psoriasis. Arch Dermatol. 2010;146(2):127–32. DOI: 10.1001/archdermatol.2009.347.
33. Bartelds GM, Wijbrandts CA, Nurmohamed MT, et al. Anti-infliximab and anti-adalimumab antibodies in relation to response to adalimumab in infliximab switchers and anti-tumour necrosis factor naive patients: a cohort study. Ann Rheum Dis. 2010;69(5):817–21. DOI: 10.1136/ard.2009.112847. Epub 2009 Jul 5.
34. De Vries MK, van der Horst-Bruinsma IE, Nurmohamed MT, et al. Immunogenicity does not influence treatment with etanercept in patients with ankylosing spondylitis. Ann Rheum Dis. 2009;68(4):531-5. DOI: 10.1136/ard.2008.089979.
35. Adisen E, Aral A, Aybay C, Gü rer MA. Anti-infliximab antibody status and its relation to clinical response in psoriatic patients: A pilot study. J Dermatol. 2010;37(8):708–13. DOI: 10.1111/j.1346-8138.2010.00882.x.
36. Bendtzen K. Is there a need for immunopharmacologic guidance of anti-tumor necrosis factor therapies? Arthritis Rheum. 2011 Apr;63(4):867–70. DOI: 10.1002/art.30207.
37. Moots RJ, Haraoui B, Matucci-Cerinic M, et al. Differences in biologic dose-escalation, non-biologic and steroid intensification among three anti-TNF agents: evidence from clinical practice. Clin Exp Rheumatol. 2011;29(1):26–34. Epub 2011 Feb 23.
38. Daien CI, Morel J. Predictive factors of response to biological disease modifying antirheumatic drugs: towards personalized medicine. Mediators Inflamm. 2014;2014:386148. DOI: 10.1155/2014/386148.
39. Bartelds GM, Krieckaert CL, Nurmohamed MT, et al. Development of antidrug antibodies against adalimumab and association with disease activity and treat-ment failure during long-term follow-up. JAMA. 2011;305(14):1460–8. DOI: 10.1001/jama.2011.406.
40. Jani M, Barton A, Warren RB, Griffiths CE, Chinoy H. The role of DMARDs in reducing the immunogenicity of TNF inhibitors in chronic inflammatory diseases. Rheumatology (Oxford). 2014;53(2):213–22. DOI: 10.1093/rheumatology/ket260.
Review
For citations:
Karateev D. How real is the long-lasting effect of tumor necrosis factor α inhibitors? Focus on immunogenicity. Sovremennaya Revmatologiya=Modern Rheumatology Journal. 2014;8(2):35-40. (In Russ.) https://doi.org/10.14412/1996-7012-2014-2-35-40
Views:
9106
Email this article 