Pharmacotherapy of canine atopic dermatitis - current state and new trends

Abstract

This review offers a concise overview of current treatment options for canine atopic dermatitis and provide an outline of two promising new treatment options (phosphodiesterase 4 and histamine H4 receptor inhibitors). Glucocorticoids have been one of the first successful treatment options and are still part of the treatment regime. Ciclosporin was introduced more than 15 years ago and is also a main pharmacological treatment option. In 2013, the Janus kinase inhibitor oclacitinib was introduced as a first in class, which is then followed by the anti-canine IL-31 antibody lokivetmab in 2016. Thus, exciting new treatment options have found their way into clinical practice. Apart from these substance classes, antihistamines, essential fatty acids and lipid substitution will be discussed as add-on treatments.

Keywords

• Atopic dermatitis,pharmacotherapy,dog

References

1. 1. Bäumer W, Hoppmann J, Rundfeldt C, et al (2007): Highly selective phosphodiesterase 4 inhibitors for the treatment of allergic skin diseases and psoriasis. Inflamm Allergy Drug Targets, 6, 17-26.
2. 2. Bäumer, W, Kietzmann M (2007): Effects of cyclosporin A and cilomilast on activated canine, murine and human keratinocytes. Vet Dermatol, 18, 107-114.
3. 3. Bäumer W, Stahl J, Sander K, et al. (2011): Lack of preventing effect of systemically and topically administered histamine H(1) or H(4) receptor antagonists in a dog model of acute atopic dermatitis. Exp Dermatol, 20, 577-581.
4. 4. Bensignor E, Morgan DM, Nuttall T (2008): Efficacy of an essential fatty acid-enriched diet in managing canine atopic dermatitis: a randomized, single-blinded, cross-over study. Vet Dermatol, 19, 156-162.
5. 5. Bizikova P, Papich MG, Olivry T (2008): Hydroxyzine and cetirizine pharmacokinetics and pharmacodynamics after oral and intravenous administration of hydroxyzine to healthy dogs. Vet Dermatol, 19, 348-357.
6. 6. Callender VD, Alexis AF, Stein Gold LF, et al (2019): Efficacy and Safety of Crisaborole Ointment, 2%, for the Treatment of Mild-to-Moderate Atopic Dermatitis Across Racial and Ethnic Groups. Am J Clin Dermatol, 20, 711-723.
7. 7. Chermprapai S, Broere F, Gooris G, et al (2018): Altered lipid properties of the stratum corneum in Canine Atopic Dermatitis. Biochim Biophys Acta Biomembr, 1860, 526-533.
8. 8. Cosgrove SB, Wren JA, Cleaver DM, et al (2013): A blinded, randomized, placebo-controlled trial of the efficacy and safety of the Janus kinase inhibitor oclacitinib (Apoquel®) in client-owned dogs with atopic dermatitis. Vet Dermatol, 24, 587-597.

9. 9. Cosgrove SB, Wren JA, Cleaver DM, et al (2013): Efficacy and safety of oclacitinib for the control of pruritus and associated skin lesions in dogs with canine allergic dermatitis. Vet Dermatol, 24, 479-e114.
10. 10. Ehling S, Bäumer W, Papich MG (2019): Diphenhydramine pharmacokinetics after oral and intravenous administration of diphenhydramine and oral administration of dimenhydrinate to healthy dogs, and pharmacodynamic effect on histamine-induced wheal formation: a pilot study. Vet Dermatol, 30, 91-e24.
11. 11 Ferrer L, Alberola J, Queralt M, et al (1999): Clinical anti-inflammatory efficacy of arofylline, a new selective phosphodiesterase-4 inhibitor, in dogs with atopic dermatitis. Vet Rec, 145, 191-194.
12. 12. Fukuyama T, Ganchingco JR, Mishra SK et al (2017): Janus kinase inhibitors display broad anti-itch properties: A possible link through the TRPV1 receptor. J Allergy Clin Immunol, 140, 306-309.
13. 13. Gadeyne C, Little P, King VL, et al (2014): Efficacy of oclacitinib (Apoquel®) compared with prednisolone for the control of pruritus and clinical signs associated with allergic dermatitis in client-owned dogs in Australia. Vet Dermatol, 25, 512-518.
14. 14. Hillier A, Griffin CE (2001): The ACVD task force on canine atopic dermatitis (I): incidence and prevalence. Vet Immunol Immunopathol, 81, 147-151.
15. 15. Kabashima K, Furue M, Hanifin JM, et al (2018): Nemolizumab in patients with moderate-to-severe atopic dermatitis: Randomized, phase II, long-term extension study. J Allergy Clin Immunol, 142, 1121-1130.
16. 16. Köchling H, Schaper K, Wilzopolski J, et al (2017): Combined treatment with H1 and H4 receptor antagonists reduces inflammation in a mouse model of atopic dermatitis. J Dermatol Sci, 87, 130-137.
17. 17. Lourenço AM, Schmidt V, São Braz B, et al (2016): Efficacy of proactive long-term maintenance therapy of canine atopic dermatitis with 0.0584% hydrocortisone aceponate spray: a double-blind placebo controlled pilot study. Vet Dermatol, 27, 88-92.
18. 18. Martel BC, Lovato P, Bäumer W, et al (2017): Translational Animal Models of Atopic Dermatitis for Preclinical Studies. Yale J Biol Med, 90, 389-402.
19. 19. Moyaert H, Van Brussel L, Borowski S, et al (2017): A blinded, randomized clinical trial evaluating the efficacy and safety of lokivetmab compared to ciclosporin in client-owned dogs with atopic dermatitis. Vet Dermatol, 28, 593-e145.
20. 20. Nuttall T, Mueller R, Bensignor E, et al (2009): Efficacy of a 0.0584% hydrocortisone aceponate spray in the management of canine atopic dermatitis: a randomised, double blind, placebo-controlled trial. Vet Dermatol, 20, 191-198.
21. 21. Olivry T, Banovic F (2019): Treatment of canine atopic dermatitis: time to revise our strategy? Vet Dermatol, 30, 87-90.
22. 22. Olivry T, DeBoer DJ, Favrot C, et al (2015): Treatment of canine atopic dermatitis: 2015 updated guidelines from the International Committee on Allergic Diseases of Animals (ICADA). BMC Vet Res, 11, 210.
23. 23. Olivry T, Hill P (2001): The ACVD task force on canine atopic dermatitis (XVIII): histopathology of skin lesions. Vet Immunol Immunopathol, 81, 305-309.
24. 24. Olivry T, Mueller RS (2003): Evidence-based veterinary dermatology: a systematic review of the pharmacotherapy of canine atopic dermatitis. Vet Dermatol, 14, 121-146.
25. 25. Piekutowska A, Pin D, Reme CA, et al (2008): Effects of a topically applied Preparation of epidermal lipids on the stratum corneum barrier of atopic dogs. J Comp Pathol 138, 197-203.
26. 26. Reiter L, Torres, S, Wertz, P (2009): Characterization and quantification of ceramides in the nonlesional skin of canine patients with atopic dermatitis compared with controls. Vet Dermatol, 20, 260-266.
27. 27. Rossbach K, Nassenstein C, Gschwandtner M et al (2011): Histamine H1, H3 and H4 receptors are involved in pruritus. Neuroscience, 190, 89-102.
28. 28. Rossbach K, Schaper K, Kloth Ch et al (2016): Histamine H4 receptor knockout mice display reduced inflammation in a chronic model of atopic dermatitis. Allergy, 71, 189-197.
29. 29. Rossbach K, Wendorff S, Sander K, et al (2009): Histamine H4 receptor antagonism reduces hapten-induced scratching behaviour but not inflammation. Exp Dermatol, 18, 57-63.
30. 30. Saridomichelakis MN, Olivry T (2016): An update on the treatment of canine atopic dermatitis. Vet J, 207, 29-37.
31. 31. Simpson EL, Bieber T, Guttman-Yassky E, et al (2016): Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis. N Engl J Med, 375, 2335-2348.
32. 32. Stahl J, Paps J, Bäumer W et al (2012): Dermatophagoides farinae house dust mite allergen challenges reduce stratum corneum ceramides in an experimental dog model of acute atopic dermatitis. Vet Dermatol, 23, 497-e97.
33. 33. Thurmond RL (2015): The histamine H4 receptor: from orphan to the clinic. Front Pharmacol, 31, 65.
34. 34. Werfel T, Layton G, Yeadon M, et al (2019): Efficacy and safety of the histamine H(4) receptor antagonist ZPL-3893787 in patients with atopic dermatitis. J Allergy Clin Immunol, 143, 1830-1837.