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Immunogenicity of Biologic Agents in Psoriasis

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Biologic and Systemic Agents in Dermatology

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Abstract

Biologic immunotherapies for psoriasis are protein medications that use monoclonal antibody-binding sites or naturally occurring receptors to attain exquisite specificity for their target. However, by their very nature of being proteins that are made externally to the patient, there is a risk that the patient’s immune system will develop an immune reaction to these medications. It is clear that immune reactions to medications, generally manifested as antidrug antibodies (ADA), can impact the pharmacokinetics of biologics. What is less clear is the true impact of these reactions on the efficacy and safety of biologic immunotherapy. Additional confusion in the study of ADAs is generated by different methods of measurement of these antibodies which result in widely different results when measured. In this chapter we review the underpinnings of the development of immunogenicity, how it is measured, and how it may influence the success of biologic therapy. Additionally, we give a brief review of what is known about the immunogenicity of available biologic therapies for psoriasis.

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References

  1. Gottlieb A, Korman NJ, Gordon KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 2. Psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics. J Am Acad Dermatol. 2008;58(5):851–64.

    Article  PubMed  Google Scholar 

  2. Christophers E, Segaert S, Milligan G, Molta CT, Boggs R. Clinical improvement and satisfaction with biologic therapy in patients with severe plaque psoriasis: results of a European cross-sectional observational study. J Dermatolog Treat. 2013;24(3):193–8.

    Article  CAS  PubMed  Google Scholar 

  3. Baert F, Noman M, Vermeire S, et al. Influence of immunogenicity on the long-term efficacy of infliximab in Crohn's disease. N Engl J Med. 2003;348(7):601–8.

    Article  CAS  PubMed  Google Scholar 

  4. 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.

    Article  CAS  PubMed  Google Scholar 

  5. Garces S, Demengeot J, Benito-Garcia E. The immunogenicity of anti-TNF therapy in immune-mediated inflammatory diseases: a systematic review of the literature with a meta-analysis. Ann Rheum Dis. 2013;72(12):1947–55.

    Article  CAS  PubMed  Google Scholar 

  6. 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.

    Article  CAS  PubMed  Google Scholar 

  7. Wolbink GJ, Aarden LA, Dijkmans BA. Dealing with immunogenicity of biologicals: assessment and clinical relevance. Curr Opin Rheumatol. 2009;21(3):211–5.

    Article  PubMed  Google Scholar 

  8. Maneiro JR, Salgado E, Gomez-Reino JJ. Immunogenicity of monoclonal antibodies against tumor necrosis factor used in chronic immune-mediated inflammatory conditions: systematic review and meta-analysis. JAMA Intern Med. 2013;173(15):1416–28.

    Article  CAS  PubMed  Google Scholar 

  9. Jullien D, Prinz JC, Nestle FO. Immunogenicity of biotherapy used in psoriasis: the science behind the scenes. J Invest Dermatol. 2015;135(1):31–8.

    Article  PubMed  Google Scholar 

  10. van Schouwenburg PA, Rispens T, Wolbink GJ. Immunogenicity of anti-TNF biologic therapies for rheumatoid arthritis. Nat Rev Rheumatol. 2013;9(3):164–72.

    Article  PubMed  Google Scholar 

  11. Carrascosa JM. Immunogenicity in biologic therapy: implications for dermatology. Actas Dermosifiliogr. 2013;104(6):471–9.

    Article  CAS  PubMed  Google Scholar 

  12. Schellekens H. Immunogenicity of therapeutic proteins: clinical implications and future prospects. Clin Ther. 2002;24(11):1720–40. discussion 1719

    Article  CAS  PubMed  Google Scholar 

  13. Harding FA, Stickler MM, Razo J, DuBridge RB. The immunogenicity of humanized and fully human antibodies: residual immunogenicity resides in the CDR regions. MAbs. 2010;2(3):256–65.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Saravolatz LD, Wherry JC, Spooner C, et al. Clinical safety, tolerability, and pharmacokinetics of murine monoclonal antibody to human tumor necrosis factor-alpha. J Infect Dis. 1994;169(1):214–7.

    Article  CAS  PubMed  Google Scholar 

  15. Boulianne GL, Hozumi N, Shulman MJ. Production of functional chimaeric mouse/human antibody. Nature. 1984;312(5995):643–6.

    Article  CAS  PubMed  Google Scholar 

  16. LoBuglio AF, Wheeler RH, Trang J, et al. Mouse/human chimeric monoclonal antibody in man: kinetics and immune response. Proc Natl Acad Sci U S A. 1989;86(11):4220–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Scallon B, Cai A, Solowski N, et al. Binding and functional comparisons of two types of tumor necrosis factor antagonists. J Pharmacol Exp Ther. 2002;301(2):418–26.

    Article  CAS  PubMed  Google Scholar 

  18. Hart MH, de Vrieze H, Wouters D, et al. Differential effect of drug interference in immunogenicity assays. J Immunol Methods. 2011;372(1-2):196–203.

    Article  CAS  PubMed  Google Scholar 

  19. 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.

    Article  CAS  PubMed  Google Scholar 

  20. van Schouwenburg PA, Krieckaert CL, Nurmohamed M, et al. IgG4 production against adalimumab during long term treatment of RA patients. J Clin Immunol. 2012;32(5):1000–6.

    Article  CAS  PubMed  Google Scholar 

  21. van Schouwenburg PA, Bartelds GM, Hart MH, Aarden L, Wolbink GJ, Wouters D. A novel method for the detection of antibodies to adalimumab in the presence of drug reveals "hidden" immunogenicity in rheumatoid arthritis patients. J Immunol Methods. 2010;362(1-2):82–8.

    Article  PubMed  Google Scholar 

  22. Hsu L, Snodgrass BT, Armstrong AW. Antidrug antibodies in psoriasis: a systematic review. Br J Dermatol. 2014;170(2):261–73.

    Article  CAS  PubMed  Google Scholar 

  23. Carrascosa JM, van Doorn MB, Lahfa M, Nestle FO, Jullien D, Prinz JC. Clinical relevance of immunogenicity of biologics in psoriasis: implications for treatment strategies. J Eur Acad Dermatol Venereol. 2014;28(11):1424–30.

    Article  PubMed  Google Scholar 

  24. Hsu L, Armstrong AW. Anti-drug antibodies in psoriasis: a critical evaluation of clinical significance and impact on treatment response. Expert Rev Clin Immunol. 2013;9(10):949–58.

    Article  CAS  PubMed  Google Scholar 

  25. Zhu Y SG, Yeilding N, et al. Immunogenicity assessment of ustekinumab in phase 3 studies in patients with moderate to severe plaque psoriasis. 19th annual congress of the European academy of dermatology and venereology; 6–10 Oct 2010; Gothenburg, Sweden.

    Google Scholar 

  26. Gottlieb AB, Evans R, Li S, et al. Infliximab induction therapy for patients with severe plaque-type psoriasis: a randomized, double-blind, placebo-controlled trial. J Am Acad Dermatol. 2004;51(4):534–42.

    Article  PubMed  Google Scholar 

  27. Parenky A, Myler H, Amaravadi L, et al. New FDA draft guidance on immunogenicity. AAPS J. 2014;16(3):499–503.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Reich K, Nestle FO, Papp K, et al. Infliximab induction and maintenance therapy for moderate-to-severe psoriasis: a phase III, multicentre, double-blind trial. Lancet. 2005;366(9494):1367–74.

    Article  CAS  PubMed  Google Scholar 

  29. 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.

    Article  CAS  Google Scholar 

  30. Menting SP, van Lumig PP, de Vries AC, et al. Extent and consequences of antibody formation against adalimumab in patients with psoriasis: one-year follow-up. JAMA Dermatol. 2014;150(2):130–6.

    Article  CAS  PubMed  Google Scholar 

  31. Bartelds GM, de Groot E, Nurmohamed MT, et al. Surprising negative association between IgG1 allotype disparity and anti-adalimumab formation: a cohort study. Arthritis Res Ther. 2010;12(6):R221.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Chirmule N, Jawa V, Meibohm B. Immunogenicity to therapeutic proteins: impact on PK/PD and efficacy. AAPS J. 2012;14(2):296–302.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. van der Bijl AE, Breedveld FC, Antoni CE, et al. An open-label pilot study of the effectiveness of adalimumab in patients with rheumatoid arthritis and previous infliximab treatment: relationship to reasons for failure and anti-infliximab antibody status. Clin Rheumatol. 2008;27(8):1021–8.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Jamnitski A, Bartelds GM, Nurmohamed MT, et al. The presence or absence of antibodies to infliximab or adalimumab determines the outcome of switching to etanercept. Ann Rheum Dis. 2011;70(2):284–8.

    Article  CAS  PubMed  Google Scholar 

  35. Menter A, Feldman SR, Weinstein GD, et al. A randomized comparison of continuous vs. intermittent infliximab maintenance regimens over 1 year in the treatment of moderate-to-severe plaque psoriasis. J Am Acad Dermatol. 2007;56(1):31.e31–15.

    Article  Google Scholar 

  36. De Simone C, Amerio P, Amoruso G, et al. Immunogenicity of anti-TNFalpha therapy in psoriasis: a clinical issue? Expert Opin Biol Ther. 2013;13(12):1673–82.

    Article  PubMed  Google Scholar 

  37. Menter A, Tyring SK, Gordon K, et al. Adalimumab therapy for moderate to severe psoriasis: a randomized, controlled phase III trial. J Am Acad Dermatol. 2008;58(1):106–15.

    Article  PubMed  Google Scholar 

  38. Papp K, Crowley J, Ortonne JP, et al. Adalimumab for moderate to severe chronic plaque psoriasis: efficacy and safety of retreatment and disease recurrence following withdrawal from therapy. Br J Dermatol. 2011;164(2):434–41.

    Article  CAS  PubMed  Google Scholar 

  39. 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.

    Article  CAS  PubMed  Google Scholar 

  40. Takahashi H, Tsuji H, Ishida-Yamamoto A, Iizuka H. Plasma trough levels of adalimumab and infliximab in terms of clinical efficacy during the treatment of psoriasis. J Dermatol. 2013;40(1):39–42.

    Article  CAS  PubMed  Google Scholar 

  41. 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.

    Article  PubMed  Google Scholar 

  42. Leonardi CL, Powers JL, Matheson RT, et al. Etanercept as monotherapy in patients with psoriasis. N Engl J Med. 2003;349(21):2014–22.

    Article  CAS  PubMed  Google Scholar 

  43. Papp KA, Tyring S, Lahfa M, et al. A global phase III randomized controlled trial of etanercept in psoriasis: safety, efficacy, and effect of dose reduction. Br J Dermatol. 2005;152(6):1304–12.

    Article  CAS  PubMed  Google Scholar 

  44. Tyring S, Gottlieb A, Papp K, et al. Etanercept and clinical outcomes, fatigue, and depression in psoriasis: double-blind placebo-controlled randomised phase III trial. Lancet. 2006;367(9504):29–35.

    Article  CAS  PubMed  Google Scholar 

  45. 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.

    CAS  PubMed  Google Scholar 

  46. 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.

    Article  CAS  PubMed  Google Scholar 

  47. Langley RG, Elewski BE, Lebwohl M, et al. Secukinumab in plaque psoriasis--results of two phase 3 trials. N Engl J Med. 2014;371(4):326–38.

    Article  PubMed  Google Scholar 

  48. Gordon KB, Blauvelt A, Papp KA, et al. Phase 3 trials of Ixekizumab in moderate-to-severe plaque psoriasis. N Engl J Med. 2016;375(4):345–56.

    Article  CAS  PubMed  Google Scholar 

  49. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Plasencia C, Pascual-Salcedo D, Nuno L, et al. Influence of immunogenicity on the efficacy of longterm treatment of spondyloarthritis with infliximab. Ann Rheum Dis. 2012;71(12):1955–60.

    Article  CAS  PubMed  Google Scholar 

  51. Gordon KB, Gottlieb AB, Leonardi CL, et al. Clinical response in psoriasis patients discontinued from and then reinitiated on etanercept therapy. J Dermatolog Treat. 2006;17(1):9–17.

    Article  CAS  PubMed  Google Scholar 

  52. Korswagen LA, Bartelds GM, Krieckaert CL, et al. Venous and arterial thromboembolic events in adalimumab-treated patients with antiadalimumab antibodies: a case series and cohort study. Arthritis Rheum. 2011;63(4):877–83.

    Article  CAS  PubMed  Google Scholar 

  53. Noiles K, Vender R. Biologic survival. J Drugs Dermatol. 2009;8(4):329–33.

    PubMed  Google Scholar 

  54. Esposito M, Gisondi P, Cassano N, et al. Survival rate of antitumour necrosis factor-alpha treatments for psoriasis in routine dermatological practice: a multicentre observational study. Br J Dermatol. 2013;169(3):666–72.

    Article  CAS  PubMed  Google Scholar 

  55. 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.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

    Alexandra G. Florek MD

  2. Department of Dermatology, Medical College of Wisconsin, 9200 W. Wisconsin Ave., Milwaukee, WI, 53226, USA

    Kennethk B. Gordon MD

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  1. Alexandra G. Florek MD
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  2. Kennethk B. Gordon MD
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Correspondence to Kennethk B. Gordon MD .

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Editors and Affiliations

  1. Division of Dermatology, David Geffen School of Medicine a UCLA, Los Angeles, California, USA

    Paul S. Yamauchi

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Florek, A.G., Gordon, K.B. (2018). Immunogenicity of Biologic Agents in Psoriasis. In: Yamauchi, P. (eds) Biologic and Systemic Agents in Dermatology. Springer, Cham. https://doi.org/10.1007/978-3-319-66884-0_11

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  • DOI: https://doi.org/10.1007/978-3-319-66884-0_11

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