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International Journal of Clinical Pharmacy

, Volume 37, Issue 2, pp 320–326 | Cite as

Infliximab drug and antibody levels in patients with dermatological conditions

  • L. ElberdínEmail author
  • M. Outeda
  • P. Salvador
  • S. Paradela
  • R. M. Fernández-Torres
  • R. Iglesias
  • E. Fonseca
  • I. Martín
Research Article

Abstract

Background In recent years, studies monitoring infliximab in rheumatoid arthritis and inflammatory bowel disease have confirmed the relationship between the clinical response and the infliximab and anti-infliximab antibodies serum levels. However, there is only limited evidence in the field of dermatology. Objective The aim of this study was to establish the correlation between plasma infliximab levels, the presence of anti-infliximab antibodies and the clinical response in dermatological conditions. Setting Retrospective observational study in a tertiary hospital (University Hospital of La Coruña, Spain). Method Patients with dermatological conditions being treated with infliximab (5 mg/kg/8 weeks after the induction dose) were included in the study. The concentrations of infliximab and anti-infliximab antibodies were quantified by two sandwich-type ELISA immunoassays. The patients were classified into three groups based on the efficacy: good, partial or non-efficacy at the time of each blood assessment. The development of adverse reactions was also evaluated. Main outcome measures Plasma levels of infliximab and anti-infliximab antibodies, clinical response and infusion reactions. Results 17 patients (45 assessments) were included. The good/partial efficacy rate was significantly higher in the case of >0.05 than <0.05 μg/mL infliximab concentration (93.3 vs. 40.0 %, p < 0.001). Anti-infliximab antibodies were only detected in five samples. Their presence was associated with a higher frequency of infusion reactions and a lower efficacy rate in comparison with the group without antiinfliximab antibodies (100.0 vs. 0.0 %, p < 0.001 and 0.0 vs. 85.0 %, p < 0.001 respectively). Conclusions The results obtained show that the presence of infliximab concentrations higher than 0.05 μg/mL are correlated with a good clinical response and the absence of toxicity. The incidence of anti-infliximab antibodies is low, although a correlation was observed between the presence of antibodies, absence of infliximab concentration, loss of clinical response and the development of infusion reactions.

Keywords

Anti-infliximab antibodies Dermatological conditions Drug levels Infliximab Tumor necrosis factor-alpha 

Notes

Conflicts of interest

Sabela Paradela, Rosa M. Fernandez-Torres and Eduardo Fonseca have participated in clinical trials sponsored by companies that manufacture drugs used for the treatment of psoriasis and in continuing medical education events supported by unrestricted educational grants from Abbvie, Celgene, Janssen-Cilag, Leo, MSD and Pfizer. The other authors have no conflicts of interest.

References

  1. 1.
    Puig L, Carrascosa JM, Daudén E, Sánchez-Carazo JL, Ferrándiz C, Sánchez-Regaña M, et al. Spanish evidence-based guidelines on the treatment of moderate-to-severe psoriasis with biologic agents. Actas Dermosifiliogr. 2009;100:386–413.CrossRefPubMedGoogle Scholar
  2. 2.
    Mössner R, Schön MP, Reich K. Tumor necrosis factor antagonists in the therapy of psoriasis. Clin Dermatol. 2008;26:486–502.CrossRefPubMedGoogle Scholar
  3. 3.
    Doty JD, Mazur JE, Judson MA, et al. Treatment of sarcoidosis with infliximab. Chest. 2005;127:1064–71.CrossRefPubMedGoogle Scholar
  4. 4.
    White ES. Infliximab in sarcoidosis: more answers or more questions? Am J Respir Crit Care Med. 2006;174:732–3.CrossRefPubMedGoogle Scholar
  5. 5.
    Foster EN, Nguyen KK, Sheikh RA, Prindiville TP. Crohn’s disease associated with Sweet’s syndrome and Sjögren’s syndrome treated with infliximab. Clin Dev Immunol. 2005;12:145–9.CrossRefPubMedCentralPubMedGoogle Scholar
  6. 6.
    Karamlou K, Gorn AH. Refractory sweet syndrome with autoimmune organizing pneumonia treated with monoclonal antibodies to tumor necrosis factor. J Clin Rheumatol. 2004;10:331–5.CrossRefPubMedGoogle Scholar
  7. 7.
    Del Giacco SR, Firinu D, Lorrai MM, Serusi L, Meleddu R, Barca MP, et al. Idiopathic Pyoderma gangrenosum: successful resolution with infliximab therapy and proinflammatory cytokines assessment. Acta Derm Venereol. 2012;92:439–40.CrossRefPubMedGoogle Scholar
  8. 8.
    Brooklyn TN, Dunnill MGS, Shetty A, Bowden JJ, Williams JDL, Griffiths CEM, et al. Infliximab for the treatment of pyoderma gangrenosum: a randomized, double blind, placebo controlled trial. Gut. 2006;55:505–9.CrossRefPubMedCentralPubMedGoogle Scholar
  9. 9.
    Fardet L, Dupuy A, Kerob D, Levy A, Allez M, Begon E, et al. Infliximab for severe hidradenitis suppurativa: transient clinical efficacy in 7 consecutive patients. J Am Acad Dermatol. 2007;56:624–8.CrossRefPubMedGoogle Scholar
  10. 10.
    Paradela S, Rodríguez-Lojo R, Fernández-Torres R, Arévalo P, Fonseca E. Long-term efficacy of infliximab in hidradenitis suppurativa. J Dermatol Treat. 2012;23:278–83.CrossRefGoogle Scholar
  11. 11.
    Aikawa NE, de Carvalho JF, Almeida Silva CA, Bonfá E. Immunogenicity of anti-TNF-α agents in autoinmune diseases. Clin Rev Allergy Immunol. 2010;38:82–9.CrossRefGoogle Scholar
  12. 12.
    Van Schouwenburg PA, Rispens T, Wolbink GJ. Immunogenicity of anti-TNF biologic therapies for rheumatoid arthritis. Nat Rev Rheumatol. 2013;9:164–72.CrossRefPubMedGoogle Scholar
  13. 13.
    Hsu L, Snodgrass BT, Armstrong AW. Antidrug antibodies in psoriasis: a systematic review. Br J Dermatol. 2014;170:261–73.CrossRefPubMedGoogle Scholar
  14. 14.
    Haraoui B, Cameron L, Ouellet M, White B. Antiinfliximab antibodies in patients with rheumatoid arthritis who require higher doses of infliximab to achieve or maintain a clinical response. J Rheumatol. 2006;33:31–6.PubMedGoogle Scholar
  15. 15.
    Wolbink GJ, Vis M, Lems W, Voskuyl AE, de Groot E, Nurmohamed MT, et al. Development of anti-infliximab antibodies and relationship to clinical response in patients with rheumatoid arthritis. Arthritis Rheum. 2006;54:711–5.CrossRefPubMedGoogle Scholar
  16. 16.
    Svenson M, Geborek P, Saxne T, Bendtzen K. Monitoring patients treated with anti-TNF-alpha biopharmaceuticals: assessing serum infliximab and anti-infliximab antibodies. Rheumatology (Oxford). 2007;46:1828–34.CrossRefGoogle Scholar
  17. 17.
    Van der Bijl AE, Breedveld FC, Antoni CE, Kalden JR, Kary S, Burmester GR, 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;27:1021–8.CrossRefPubMedCentralPubMedGoogle Scholar
  18. 18.
    Miele E, Markowitz JE, Mamula P, Baldassano RN. Human antichimeric antibody in children and young adults with inflammatory bowel disease receiving infliximab. J Pediatr Gastroenterol Nutr. 2004;38:502–8.CrossRefPubMedGoogle Scholar
  19. 19.
    Vermeire S, Noman M, Van Assche G, Baert F, D’Haens G, Rutgeerts P. Effectiveness of concomitant immunosuppressive therapy in suppressing the formation of antibodies to infliximab in Crohn’s disease. Gut. 2007;56:1226–31.CrossRefPubMedCentralPubMedGoogle Scholar
  20. 20.
    Hanauer SB, Wagner CL, Bala M, Mayer L, Travers S, Diamond RH, et al. Incidence and importance of antibody responses to infliximab after maintenance or episodic treatment in Crohn’s disease. Clin Gastroenterol Hepatol. 2004;2:542–53.CrossRefPubMedGoogle Scholar
  21. 21.
    Shankar G, Devanarayan V, Amaravadi L, Barrett YC, Bowsher R, Finco-Kent D, et al. Recommendations for the validation of immunoassays used for detection of host antibodies against biotechnology products. J Pharm Biomed Anal. 2008;48:1267–81.CrossRefPubMedGoogle Scholar
  22. 22.
    Llinares-Tello F, de Salazar JR, Gallego JM, Soler GS, Ramírez CS, Heredia ES, et al. Analytical and clinical evaluation of a new immunoassay for therapeutic drug monitoring of infliximab and adalimumab. Clin Chem Lab Med. 2012;50:1845–7.CrossRefPubMedGoogle Scholar
  23. 23.
    Sartorius K, Lapins J, Emtestam L, Jemec GB. Suggestions for uniform outcome variables when reporting treatment effects in hidradenitis suppurativa. Br J Dermatol. 2003;149:211–3.CrossRefPubMedGoogle Scholar
  24. 24.
    Reich K, Nestle FO, Papp K, Ortonne JP, Evans R, Guzzo C, et al. Infliximab induction and maintenance therapy for moderate-to-severe psoriasis: a phase III, multicentre, double-blind trial. Lancet. 2005;366:1367–74.CrossRefPubMedGoogle Scholar
  25. 25.
    Matsumoto Y, Maeda T, Tsuboi R, Okubo Y. Anti-adalimumab and anti-infliximab antibodies developed in psoriasis vulgaris patients reduced the efficacy of biologics: report of two cases. J Dermatol. 2013;40:389–92.CrossRefPubMedGoogle Scholar
  26. 26.
    Klotz U, Teml A, Schwab M. Clinical pharmacokinetics and use of infliximab. Clin Pharmacokinet. 2007;46:645–60.CrossRefPubMedGoogle Scholar
  27. 27.
    Adisen E, Aral A, Aybay C, Gürer MA. Anti-infliximab antibody status and its relation to clinical response in psoriatic patients. A pilot study. J Dermatol. 2010;37:708–13.CrossRefPubMedGoogle Scholar
  28. 28.
    Meyer MW, Zachariae C, Bendtzen K, Skov L. Lack of anti-drug antibodies in patients with psoriasis well-controlled on long-term treatment with tumour necrosis factor inhibitors. Acta Derm Venereol. 2012;92:362–4.CrossRefPubMedGoogle Scholar
  29. 29.
    Pascual-Salcedo D, Plasencia C, Ramiro S, Nuño L, Bonilla G, Nagore D, et al. Influence of immunogenicity on the efficacy of long term treatment with infliximab in rheumatoid arthritis. Rheumatology (Oxford). 2011;50:1445–52.CrossRefGoogle Scholar
  30. 30.
    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;40:39–42.CrossRefPubMedGoogle Scholar

Copyright information

© Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie 2015

Authors and Affiliations

  • L. Elberdín
    • 1
    Email author
  • M. Outeda
    • 1
  • P. Salvador
    • 1
  • S. Paradela
    • 2
  • R. M. Fernández-Torres
    • 2
  • R. Iglesias
    • 2
  • E. Fonseca
    • 2
  • I. Martín
    • 1
  1. 1.Department of PharmacyUniversity Hospital of La CoruñaLa CoruñaSpain
  2. 2.Department of DermatologyUniversity Hospital of La CoruñaLa CoruñaSpain

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