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Alitretinoin: A Review in Severe Chronic Hand Eczema

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Abstract

Chronic hand eczema is a common but frequently disabling skin condition which poses a significant social and economic burden. Although skin protection measures and topical therapies are fundamental in its management, some patients are refractory to first-line therapy with topical corticosteroids and require systemic treatment. Alitretinoin (9-cis-retinoic acid; Toctino®) is an endogenous vitamin A derivative with high binding affinity for both retinoic acid receptors and retinoid X receptors. Alitretinoin is the first systemic treatment to be approved in the EU for use in patients with severe chronic hand eczema unresponsive to potent topical corticosteroids. This article updates an earlier review of alitretinoin in this indication, focusing on recently published data. In clinical trials, treatment with alitretinoin 10 or 30 mg once daily for up to 24 weeks improved the severity and extent of severe chronic hand eczema in adults, with significantly more alitretinoin than placebo recipients achieving ratings of ‘clear’ or ‘almost clear’ hands on the Physician Global Impression of Change scale. For the most part, data obtained in real-world studies were consistent with those observed in clinical trials. Alitretinoin was generally well tolerated, with most adverse events being reversible, dose-dependent and of mild or moderate severity. Thus, oral alitretinoin is a useful treatment option for patients with severe chronic hand eczema unresponsive to potent topical corticosteroids.

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References

  1. Diepgen TL, Andersen KE, Chosidow O, et al. Guidelines for diagnosis, prevention and treatment of hand eczema. J Dtsch Dermatol Ges. 2015;13(1):e1–22.

    Article  PubMed  Google Scholar 

  2. Diepgen TL, Agner T, Aberer W, et al. Management of chronic hand eczema. Contact Dermat. 2007;57(4):203–10.

    Article  Google Scholar 

  3. Bissonnette R, Diepgen TL, Elsner P, et al. Redefining treatment options in chronic hand eczema (CHE). J Eur Acad Dermatol Venereol. 2010;24(Suppl 3):1–20.

    Article  PubMed  Google Scholar 

  4. Feldman SR, Phelps KC, Verzino KC. Anticancer and immunosuppressant drugs. Handbook of dermatologic drug therapy. UK: Taylor & Francis; 2005. p. 61.

  5. Garnock-Jones KP, Perry CM. Alitretinoin: in severe chronic hand eczema. Drugs. 2009;69(12):1625–34.

    Article  CAS  PubMed  Google Scholar 

  6. Xu J, Drew PD. 9-cis-retinoic acid suppresses inflammatory responses of microglia and astrocytes. J Neuroimmunol. 2006;171(1–2):135–44.

    Article  CAS  PubMed  Google Scholar 

  7. Stiefel. Summary of product characteristics: Toctino® soft capsules. 2013. http://www.mhra.gov.uk. Accessed 13 July 2016.

  8. Gottardis MM, Lamph WW, Shalinsky DR, et al. The efficacy of 9-cis retinoic acid in experimental models of cancer. Breast Cancer Res Treat. 1996;38(1):85–96.

    Article  CAS  PubMed  Google Scholar 

  9. Heyman RA, Mangelsdorf DJ, Dyck JA, et al. 9-cis retinoic acid is a high affinity ligand for the retinoid X receptor. Cell. 1992;68(2):397–406.

    Article  CAS  PubMed  Google Scholar 

  10. Zhang XK, Lehmann J, Hoffmann B, et al. Homodimer formation of retinoid X receptor induced by 9-cis retinoic acid. Nature. 1992;358(6387):587–91.

    Article  CAS  PubMed  Google Scholar 

  11. Kislat A, Meller S, Mota R, et al. Alitretinoin, a dual RAR and RXR agonist, modulates leukocyte recruitment pathways and suppresses dendritic cell functions in vitro and in vivo. [abstract no. 409]. J Invest Dermatol. 2014;134:S72.

    Article  Google Scholar 

  12. Scheuermann J, Kraus LF, Frenzel DF, et al. 9-cis-retinoic acid modulates dendritic cell differentiation to generate a Treg inducing phenotype. [abstract no. P116]. Exp Dermatol. 2015;24(3):E21.

    Google Scholar 

  13. Schindler M, Drozdenko G, Kuhl AA, et al. Immunomodulation in patients with chronic hand eczema treated with oral alitretinoin. Int Arch Allergy Immunol. 2014;165(1):18–26.

    Article  CAS  PubMed  Google Scholar 

  14. Jungersted JM, Hogh JK, Hellgren LI, et al. Changes in skin barrier during treatment with systemic alitretinoin: focus on skin susceptibility and stratum corneum ceramides. Arch Dermatol Res. 2010;302(9):653–6.

    Article  CAS  PubMed  Google Scholar 

  15. Schmitt-Hoffmann AH, Roos B, Sauer J, et al. Pharmacokinetics, efficacy and safety of alitretinoin in moderate or severe chronic hand eczema. Clin Exp Dermatol. 2011;36(Suppl 2):29–34.

    Article  PubMed  Google Scholar 

  16. Schmitt-Hoffmann AH, Roos B, Sauer J, et al. Low levels of alitretinoin in seminal fluids after repeated oral doses in healthy men. Clin Exp Dermatol. 2011;36(Suppl 2):12–7.

    Article  PubMed  Google Scholar 

  17. Thyssen JP, Vester L, Gronhoj Larsen C, et al. The single-dose pharmacokinetics of alitretinoin and its metabolites are not significantly altered in patients with cirrhosis. Br J Dermatol. 2014;170(2):408–14.

    Article  CAS  PubMed  Google Scholar 

  18. Schmitt-Hoffmann AH, Roos B, Sauer J, et al. Influence of alitretinoin on the pharmacokinetics of the oral contraceptive ethinyl estradiol/norgestimate. Clin Exp Dermatol. 2011;36(Suppl 2):4–11.

    Article  PubMed  Google Scholar 

  19. Ruzicka T, Lynde CW, Jemec GB, et al. Efficacy and safety of oral alitretinoin (9-cis retinoic acid) in patients with severe chronic hand eczema refractory to topical corticosteroids: results of a randomized, double-blind, placebo-controlled, multicentre trial. Br J Dermatol. 2008;158(4):808–17.

    Article  CAS  PubMed  Google Scholar 

  20. Fowler JF, Graff O, Hamedani AG. A phase 3, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of alitretinoin (BAL4079) in the treatment of severe chronic hand eczema refractory to potent topical corticosteroid therapy. J Drugs Dermatol. 2014;13(10):1198–204.

    CAS  PubMed  Google Scholar 

  21. Dirschka T, Reich K, Bissonnette R, et al. An open-label study assessing the safety and efficacy of alitretinoin in patients with severe chronic hand eczema unresponsive to topical corticosteroids. Clin Exp Dermatol. 2011;36(2):149–54.

    Article  CAS  PubMed  Google Scholar 

  22. Bissonnette R, Worm M, Gerlach B, et al. Successful retreatment with alitretinoin in patients with relapsed chronic hand eczema. Br J Dermatol. 2010;162(2):420–6.

    Article  CAS  PubMed  Google Scholar 

  23. Lynde C, Cambazard F, Ruzicka T, et al. Extended treatment with oral alitretinoin for patients with chronic hand eczema not fully responding to initial treatment. Clin Exp Dermatol. 2012;37(7):712–7.

    Article  CAS  PubMed  Google Scholar 

  24. Diepgen TL, Pfarr E, Zimmermann T. Efficacy and tolerability of alitretinoin for chronic hand eczema under daily practice conditions: results of the TOCCATA open study comprising 680 patients. Acta Derm Venereol. 2012;92(3):251–5.

    Article  CAS  PubMed  Google Scholar 

  25. Augustin M, Thaci D, Noone M, et al. Early use of alitretinoin in accordance with standard guidelines in patients with severe, refractory CHE–effect on the quality of life [abstract no. 2999892]. In: 23rd World Congress of Dermatology. 2015.

  26. Thaci D, Augustin M, Noone M, et al. A focus on patients with severe CHE: influential factors on the quality of life, work productivity and progression of treatment while taking alitretinoin [abstract no. 2999752]. In: 23rd World Congress of Dermatology. 2015.

  27. Morris M, Schifano L, Fong R, et al. Safety of alitretinoin for severe refractory chronic shand eczema: clinical studies and postmarketing surveillance. J Dermatolog Treat. 2015;27(1):54-8.

    Article  PubMed  Google Scholar 

  28. National Institute for Health and Care Excellence. Alitretinoin for the treatment of severe chronic hand eczema. 2009. http://www.nice.org.uk/guidance/ta177. Accessed 13 July 2016.

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Acknowledgments

During the peer review process, the manufacturer of alitretinoin (GlaxoSmithKline) was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

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Correspondence to Hannah A. Blair.

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The preparation of this review was not supported by any external funding.

Conflict of interest

Hannah Blair and Lesley Scott are salaried employees of Adis/Springer, are responsible for the article content and declare no relevant conflicts of interest.

Additional information

The manuscript was reviewed by: T. Agner, Department of Dermatology, University of Copenhagen, Bispebjerg Hospital, Copenhagen, Denmark; S. Feldman, Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC, USA; T. Ruzicka, Department of Dermatology and Allergology, Ludwig Maximilian University, Munich, Germany.

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Blair, H.A., Scott, L.J. Alitretinoin: A Review in Severe Chronic Hand Eczema. Drugs 76, 1271–1279 (2016). https://doi.org/10.1007/s40265-016-0621-0

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