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HLA-C*06:02 Does Not Predispose to Clinical Response Following Long-Term Adalimumab Treatment in Psoriatic Patients: A Retrospective Cohort Study

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Abstract

Background

The genetic basis of predisposition to psoriasis is recognised; however, the response to psoriasis treatment in patients with different genetic predisposition is poorly understood.

Objective

To analyse the presence of the HLA-C*06:02 polymorphism in psoriatic patients treated with adalimumab.

Methods

Genomic DNA was extracted from whole blood of 122 patients with moderate-to-severe psoriasis treated with adalimumab for 3 years. Genotyping was performed using PCR. Disease severity was assessed by the Psoriasis Area and Severity Index (PASI) at day 0 and after 1, 3, 6, 12, 24 and 36 months. Logistic regression was used to evaluate the association between dependent variables (including HLA-C*06:02 status) and achievement of PASI 50, 75 and 90.

Results

No difference was observed after adalimumab treatment between C*06:02 positive (HLA-C*06:02-POS) patients (n = 46) and C*06:02 negative (HLA-C*06:02-NEG) patients (n = 76) over the 3-year follow-up period in terms of PASI response or time-course when PASI response was achieved. However, a small, but non-statistically significant difference was noted between genotypes for PASI 50 at 1 month (HLA-C*06:02-NEG: 44.7% vs. HLA-C*06:02-POS: 56.5%) and at 3 months (HLA-C*06:02-NEG: 71.1% vs. HLA-C*06:02-POS: 80.4%). Simple logistic regression analysis did not reveal an association between independent variables (including C*06:02 status) and PASI response; however, multivariate regression revealed that gender (females better than males) was associated with achievement of PASI 50 at month 1 (OR 0.34, 95% CI 0.16–0.72, p = 0.005) and of PASI 75 at 3 months (OR 0.36, 95% CI 0.16–0.8, p = 0.012).

Conclusion

Adalimumab reduced long-term severity in patients with moderate-severe psoriasis, independent of their HLA-C*06:02 status.

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References

  1. Parisi R, Symmons DP, Griffiths CE, et al. Global epidemiology of psoriasis: a systematic review of incidence and prevalence. J Invest Dermatol. 2013;133:377–85.

    Article  CAS  PubMed  Google Scholar 

  2. Sampogna F, Gisondi P, Melchi CF, et al. Prevalence of symptoms experienced by patients with different clinical types of psoriasis. Br J Dermatol. 2004;151:594–9.

    Article  CAS  PubMed  Google Scholar 

  3. Nickoloff BJ, Qin JZ, Nestle FO. Immunopathogenesis of psoriasis. Clin Rev Allergy Immunol. 2007;33:45–56.

    Article  CAS  PubMed  Google Scholar 

  4. Bowcock AM, Krueger JG. Getting under the skin: the immunogenetics of psoriasis. Nat Rev Immunol. 2005;5:699–711.

    Article  CAS  PubMed  Google Scholar 

  5. Griffiths CE, Barker JN. Pathogenesis and clinical features of psoriasis. Lancet. 2007;370:263–71.

    Article  CAS  PubMed  Google Scholar 

  6. Lowes MA, Bowcock AM, Krueger JG. Pathogenesis and therapy of psoriasis. Nature. 2007;445:866–73.

    Article  CAS  PubMed  Google Scholar 

  7. Warren RB, Griffiths CE. The potential of pharmacogenetics in optimizing the use of methotrexate for psoriasis. Br J Dermatol. 2005;153:869–73.

    Article  CAS  PubMed  Google Scholar 

  8. Tzu J, Kerdel F. From conventional to cutting edge: the new era of biologics in treatment of psoriasis. Dermatol Ther. 2008;21:131–41.

    Article  PubMed  Google Scholar 

  9. Hebert HL, Ali FR, Bowes J, et al. Genetic susceptibility to psoriasis and psoriatic arthritis: implications for therapy. Br J Dermatol. 2012;166:474–82.

    Article  CAS  PubMed  Google Scholar 

  10. Nair RP, Stuart PE, Nistor I, et al. Sequence and haplotype analysis supports HLA-C as the psoriasis susceptibility 1 gene. Am J Hum Genet. 2006;78:827–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Gulliver W. HLA-Cw6 polymorphism predict response to the biologic therapy efalizumab in patients with chronic plaque psoriasis. J Am Acad Dermatol. 2009;60(Suppl. 1):AB162.

  12. Costanzo A, Spallone G, Talamonti M, et al. New developments in the pharmacogenetics of psoriasis: HLA-Cw6 as a marker for the treatment of psoriasis with biological therapies. Adv Psoriasis Inflam Skin Dis. 2011;1:125–30.

    Google Scholar 

  13. Caldarola G, Sgambato A, Fanali C, et al. HLA-Cw6 allele, NFkB1 and NFkBIA polymorphisms play no role in predicting response to etanercept in psoriatic patients. Pharmacogenet Genomics. 2016;26:423–7.

    Article  CAS  PubMed  Google Scholar 

  14. Talamonti M, Botti E, Galluzzo M, et al. Pharmacogenetics of psoriasis: HLA-Cw6 but not LCE3B/3C deletion nor TNFAIP3 polymorphism predisposes to clinical response to interleukin 12/23 blocker ustekinumab. Br J Dermatol. 2013;169:458–63.

    Article  CAS  PubMed  Google Scholar 

  15. Talamonti M, Galluzzo M, Chimenti S, Costanzo A. HLA-C*06 and response to ustekinumab in Caucasian patients with psoriasis: Outcome and long-term follow-up. J Am Acad Dermatol. 2016;74:374–5.

    Article  CAS  PubMed  Google Scholar 

  16. Galluzzo M, Boca AN, Botti E, et al. IL12B (p40) gene polymorphisms contribute to ustekinumab response prediction in psoriasis. Dermatology. 2016;232:230–6.

    Article  CAS  PubMed  Google Scholar 

  17. Finlay AY. Current severe psoriasis and the rule of tens. Br J Dermatol. 2005;152:861–7.

    Article  CAS  PubMed  Google Scholar 

  18. Blandizzi C, Gionchetti P, Armuzzi A, et al. The role of tumour necrosis factor in the pathogenesis of immune-mediated diseases. Int J Immunopathol Pharmacol. 2014;27(1 Suppl):1–10.

  19. Burmester GR, Panaccione R, Gordon KB, McIlraith MJ, Lacerda AP. Adalimumab: long-term safety in 23,458 patients from global clinical trials in rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis and Crohn’s disease. Ann Rheum Dis. 2013;72:517–24.

    Article  CAS  PubMed  Google Scholar 

  20. Papp KA, Armstrong AW, Reich K, Karunaratne M, Valdecantos W. Adalimumab efficacy in patients with psoriasis who received or did not respond to prior systemic therapy: a pooled post hoc analysis of results from three double-blind, placebo-controlled clinical trials. Am J Clin Dermatol. 2016;17:79–86.

    Article  PubMed  Google Scholar 

  21. Gallo E, Cabaleiro T, Román M, et al. The relationship between tumour necrosis factor (TNF)-α promoter and IL12B/IL-23R genes polymorphisms and the efficacy of anti-TNF-α therapy in psoriasis: a case-control study. Br J Dermatol. 2013;169:819–29.

    Article  CAS  PubMed  Google Scholar 

  22. Lande R, Botti E, Jandus C, et al. The antimicrobial peptide LL37 is a T-cell autoantigen in psoriasis. Nat Commun. 2014;5:5621.

    Article  CAS  PubMed  Google Scholar 

  23. Mabuchi T, Hirayama N. Binding affinity and interaction of LL-37 with HLA-C*06:02 in psoriasis. J Invest Dermatol. 2016;136:1901–3.

    Article  CAS  PubMed  Google Scholar 

  24. Hsu L, Snodgrass BT, Armstrong AW. Anti-drug antibodies in psoriasis: a systematic review. Br J Dermatol. 2014;170:261–73.

    Article  CAS  PubMed  Google Scholar 

  25. (European Medicines Agency. Guideline on immunogenicity assessment of biotechnology-derived therapeutic proteins. 2007. http://www.ema.europa.eu/docs/en:GB/document:library/Scientific:guideline/2009/09/WC500003946.pdf.

  26. Zhu Y, Shankar G, Yeilding N, et al. Immunogenicity assessment of ustekinumab in phase 3 studies in patients with moderate to severe plaque psoriasis. In: 19th Annual Congress of the European Academy of Dermatology and Venereology; 6–10 October 2010; Gothenburg. 2010. p. 563.

  27. 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;R221.

  28. 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:R105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. 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;71:1955–60.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  32. Gudjónsson JE, Kárason A, Antonsdóttir AA, et al. HLA-Cw6-positive and HLA-Cw6-negative patients with psoriasis vulgaris have distinct clinical features. J Invest Dermatol. 2002;118:362–5.

    Article  PubMed  Google Scholar 

  33. Generali E, Sciré CA, Cantarini L, Selmi C. Sex differences in the treatment of psoriatic arthritis: a systematic literature review. Isr Med Assoc J. 2016;18:203–8.

    PubMed  Google Scholar 

  34. Gniadecki R, Kragballe K, Dam TN, Skov L. Comparison of drug survival rates for adalimumab, etanercept and infliximab in patients with psoriasis vulgaris. Br J Dermatol. 2011;164:1091–6.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  36. De Simone C, Caldarola G, Maiorino A, et al. Clinical predictors of nonresponse to anti-TNF-α agents in psoriatic patients: a retrospective study. Dermatol Ther. 2016;29:372–6.

    Article  PubMed  Google Scholar 

  37. Batalla A, Coto E, González-Fernández D, et al. The Cw6 and late-cornified envelope genotype plays a significant role in anti-tumor necrosis factor response among psoriatic patients. Pharmacogenet Genomics. 2015;25:313–6.

    CAS  PubMed  Google Scholar 

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Author notes

    Authors and Affiliations

    1. Department of Dermatology, University of Rome Tor Vergata, Rome, Italy

      Marina Talamonti, Marco Galluzzo, Arianna Zangrilli, Mauro Bavetta & Luca Bianchi

    2. Third Department of Dermatology, A. Syggros Hospital, Athens, Greece

      Marina Papoutsaki

    3. Primula Multimedia SRLOspedaletto, Pisa, Italy

      Colin Gerard Egan

    4. Department of Dermatology, University of L’Aquila, L’Aquila, Italy

      Sara Tambone & Maria Concetta Fargnoli

    Authors
    1. Marina Talamonti
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    2. Marco Galluzzo
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    Correspondence to Marina Talamonti.

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    Conflict of interest

    MT., M.G, A.Z, M.P, C.G.E., M.B., S.T., M.C. F., L. B. have anything to declare.

    Funding

    No sources of financial assistance were received to conduct the study described in the manuscript.

    Ethical approval and informed consent

    This study was conducted in accordance with the Helsinki Declaration. All patients gave written informed consent to draw a vial of blood for DNA analyses as approved by ‘‘Tor Vergata Ethics Committee’’ (Approval No. 20745, v. 25 Mar 2005).

    Additional information

    M. Talamonti and M. Galluzzo contributed equally to this paper.

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    Talamonti, M., Galluzzo, M., Zangrilli, A. et al. HLA-C*06:02 Does Not Predispose to Clinical Response Following Long-Term Adalimumab Treatment in Psoriatic Patients: A Retrospective Cohort Study. Mol Diagn Ther 21, 295–301 (2017). https://doi.org/10.1007/s40291-017-0261-4

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    • DOI: https://doi.org/10.1007/s40291-017-0261-4

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