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Dupilumab Use in Atopic Conditions and Its Side Effects

  • Cutaneous Drug Reactions (J Brieva, Section Editor)
  • Published:
Current Dermatology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

During the last years, dupilumab, a fully human monoclonal antibody directed against the IL-4 receptor α subunit has been investigated in several clinical trials with respect to efficacy, tolerability, and safety in different atopic diseases such as atopic dermatitis, asthma, and chronic sinusitis with nasal polyposis. The aim of this review is to summarize this study data with focus on efficacy and safety.

Recent Findings

In atopic dermatitis, three original publications (in total six phase 1, 2, and 3 studies) report consistently about a till today not known high grade of efficacy reducing disease activity. Significant improvement of disease burden has been also seen in two publications on asthma (two phase 2 trials) as well as on chronic sinusitis with nasal polyposis (phase 2 trial). Remarkable is the safety profile with only moderately increased rates for mild or moderate nasopharyngitis and injection site reactions (erythema). Organ toxicities, an increased cardiovascular risk or other health risks have not been described so far. However, a moderate increase of the rate of conjunctivitis in trials on atopic dermatitis remains unclear.

Conclusion

The reviewed studies on various atopic diseases have shown that dupilumab is an innovative, highly efficient, well-tolerated biological drug and has the potential to become the first biological cytokine-directed drug to be authorized for atopic diseases such as atopic dermatitis or asthma. The safety profile seems to be unique with an extremely good tolerability as detected so far.

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References

Papers of Particular Interest, Published Recently, Have Been Highlighted as:•• Of major importance

  1. Williams H, Flohr C. How epidemiology has challenged 3 prevailing concepts about atopic dermatitis. J Allergy Clin Immunol. 2006;118(1):209–13.

    Article  PubMed  Google Scholar 

  2. Bieber T. Atopic dermatitis. N Engl J Med. 2008;358(14):1483–94. doi:10.1056/NEJMra074081.

    Article  CAS  PubMed  Google Scholar 

  3. Maksimović N, Janković S, Marinković J, Sekulović LK, Zivković Z, Spirić VT. Health-related quality of life in patients with atopic dermatitis. J Dermatol. 2012;39(1):42–7. doi:10.1111/j.1346-8138.2011.01295.x.

    Article  PubMed  Google Scholar 

  4. Woodruff PG, Modrek B, Choy DF, Jia G, Abbas AR et al. T-helper type 2-driven inflammation defines major subphenotypes of asthma. Am J Respir Crit Care Med. 2009;180(5):388–95. doi: 10.1164/rccm.200903-0392OC. Erratum in: Am J Respir Crit Care Med. 2009 Oct 15;180(8):796.

  5. Suárez-Fueyo A, Ramos T, Galán A, Jimeno L, Wurtzen PA, et al. Grass tablet sublingual immunotherapy downregulates the TH2 cytokine response followed by regulatory T-cell generation. J Allergy Clin Immunol. 2014;133(1):130–8.e1-2. doi:10.1016/j.jaci.2013.09.043.

    Article  PubMed  Google Scholar 

  6. Jarvis D, Newson R, Lotvall J, Hastan D, Tomassen P, et al. Asthma in adults and its association with chronic rhinosinusitis: the GA2LEN survey in Europe. Allergy. 2012;67(1):91–8. doi:10.1111/j.1398-9995.2011.02709.x.

    Article  CAS  PubMed  Google Scholar 

  7. Brunner PM, Silverberg JI, Guttman-Yassky E, Paller AS, Kabashima K, et al. Councilors of the international eczema council. Increasing comorbidities suggest that atopic dermatitis is a systemic disorder. J Invest Dermatol. 2016; doi:10.1016/j.jid.2016.08.022.

    Google Scholar 

  8. Eyerich K, Novak N. Immunology of atopic eczema: overcoming the Th1/Th2 paradigm. Allergy. 2013;68(8):974–82. doi:10.1111/all.12184.

    Article  CAS  PubMed  Google Scholar 

  9. Mueller TD, Zhang JL, Sebald W, Duschl A. Structure, binding, and antagonists in the IL-4/IL-13 receptor system. Biochim Biophys Acta. 2002;1592(3):237–50.

    Article  CAS  PubMed  Google Scholar 

  10. National AWMF guideline Neurodermitis 2015: http://www.awmf.org/leitlinien/detail/ll/013-027.html

  11. Silverberg JI. Atopic dermatitis: an evidence-based treatment update. Am J Clin Dermatol. 2014;15(3):149–64. doi:10.1007/s40257-014-0062-z.

    Article  PubMed  Google Scholar 

  12. Simon D, Bieber T. Systemic therapy for atopic dermatitis. Allergy. 2014;69(1):46–55. doi: 10.1111/all.12339. Review.

  13. National AWMF guideline Asthma 2013: http://www.awmf.org/uploads/tx_szleitlinien/nvl-002l_S3_Asthma_2013-abgelaufen.pdf

  14. Bateman ED, Boushey HA, Bousquet J, Busse WW, Clark TJ, et al. GOAL investigators group. Can guideline-defined asthma control be achieved? The gaining optimal asthma ControL study. Am J Respir Crit Care Med. 2004;170(8):836–44.

    Article  PubMed  Google Scholar 

  15. Humbert M, Beasley R, Ayres J, Slavin R, Hébert J, et al. Benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment): INNOVATE. Allergy. 2005;60(3):309–16.

    Article  CAS  PubMed  Google Scholar 

  16. •• Beck LA, Thaçi D, Hamilton JD, Graham NM, Bieber T, Rocklin R, et al. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med. 2014;371(2):130–9. doi:10.1056/NEJMoa1314768. This article contains the first presentation of clinical data of dupilumab in atopic dermatitis and was the basis for future trials and publications.

    Article  PubMed  Google Scholar 

  17. Tsianakas A, Luger TA. The anti-IL-4 receptor alpha antibody dupilumab: facing a new era in treating atopic dermatitis. Expert Opin Biol Ther. 2015;15(11):1657–60.

    Article  CAS  PubMed  Google Scholar 

  18. Barbier N, Paul C, Luger T, Allen R, De Prost Y, et al. Validation of the eczema area and severity index for atopic dermatitis in a cohort of 1550 patients from the pimecrolimus cream 1% randomized controlled clinical trials programme. Br J Dermatol. 2004;150(1):96–102.

    Article  CAS  PubMed  Google Scholar 

  19. Thaçi D, Simpson EL, Beck LA, Bieber T, Blauvelt A, et al. Efficacy and safety of dupilumab in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical treatments: a randomised, placebo-controlled, dose-ranging phase 2b trial. Lancet. 2016;387(10013):40–52. doi:10.1016/S0140-6736(15)00388-8.

    Article  PubMed  Google Scholar 

  20. Tsianakas A, Ständer S. Dupilumab: a milestone in the treatment of atopic dermatitis. Lancet. 2016;387(10013):4–5.

    Article  PubMed  Google Scholar 

  21. Simpson EL, Gadkari A, Worm M, Soong W, Blauvelt A, et al. Dupilumab therapy provides clinically meaningful improvement in patient-reported outcomes (PROs): a phase IIb, randomized, placebo-controlled, clinical trial in adult patients with moderate to severe atopic dermatitis (AD). J Am Acad Dermatol. 2016;75(3):506–15. doi:10.1016/j.jaad.2016.04.054.

    Article  CAS  PubMed  Google Scholar 

  22. •• Simpson EL, Bieber T, Guttman-Yassky E, Beck LA, Blauvelt A, et al. Two phase 3 trials of Dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016; This article presents the phase 3 data of dupilumab in atopic dermatitis which will lead to FDA approval in atopic dermatitis.

  23. Wenzel S, Ford L, Pearlman D, Spector S, Sher L, et al. Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med. 2013;368(26):2455–66. doi:10.1056/NEJMoa1304048.

    Article  CAS  PubMed  Google Scholar 

  24. Wenzel S, Castro M, Corren J, Maspero J, Wang L, et al. Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist: a randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial. Lancet. 2016;388(10039):31–44. doi:10.1016/S0140-6736(16)30307-5.

    Article  CAS  PubMed  Google Scholar 

  25. Bachert C, Mannent L, Naclerio RM, Mullol J, Ferguson BJ, et al. Effect of subcutaneous Dupilumab on nasal polyp burden in patients with chronic sinusitis and nasal polyposis: a randomized clinical trial. JAMA. 2016;315(5):469–79. doi:10.1001/jama.2015.19330.

    Article  CAS  PubMed  Google Scholar 

  26. Thiel MA, Coster DJ, Standfield SD, Brereton HM, Mavrangelos C, et al. Penetration of engineered antibody fragments into the eye. Clin Exp Immunol. 2002;128(1):67–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Dermatology, University Hospital Muenster, Von-Esmarch-Str. 58, 48149, Muenster, Germany

    Athanasios Tsianakas & Thomas A. Luger

Authors
  1. Athanasios Tsianakas
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  2. Thomas A. Luger
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Correspondence to Athanasios Tsianakas.

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Conflict of Interest

T.A. Luger participated as investigators in multiple clinical trials on dupilumab sponsored by Regeneron.

A. Tsianakas participated as investigator in multiple clinical trials on dupilumab sponsored by Regeneron.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Cutaneous Drug Reactions

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Tsianakas, A., Luger, T.A. Dupilumab Use in Atopic Conditions and Its Side Effects. Curr Derm Rep 6, 43–47 (2017). https://doi.org/10.1007/s13671-017-0179-4

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  • DOI: https://doi.org/10.1007/s13671-017-0179-4

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