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Dermatitis

Oral small molecules for the treatment of atopic dermatitis: a systematic review

ORCID Icon, ORCID Icon, ORCID Icon, ORCID Icon & ORCID Icon
Pages 550-557 | Received 01 Oct 2018, Accepted 27 Oct 2018, Published online: 02 Dec 2018

References

  • Asher MI, Montefort S, Bjorksten B, et al. Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross-sectional surveys. Lancet. 2006;368:733–743.
  • Weidinger S, Novak N. Atopic dermatitis. Lancet. 2016;387:1109–1122.
  • Paller AS, McAlister RO, Doyle JJ, et al. Perceptions of physicians and pediatric patients about atopic dermatitis, its impact, and its treatment. Clin Pediatr (Phila). 2002;41:323–332.
  • Koblenzer CS, Koblenzer PJ. Chronic intractable atopic eczema. Its occurrence as a physical sign of impaired parent-child relationships and psychologic developmental arrest: improvement through parent insight and education. Arch Dermatol. 1988;124:1673–1677.
  • Kini SP, DeLong LK, Veledar E, et al. The impact of pruritus on quality of life: the skin equivalent of pain. Arch Dermatol. 2011;147:1153–1156.
  • Patel N, Strowd LC. The future of atopic dermatitis treatment. Adv Exp Med Biol. 2017;1027:185–210.
  • Boozalis E, Semenov YR, Kwatra SG. Food and drug administration approval process for dermatology drugs in the United States. J Dermatolog Treat. 2018;29:536–538.
  • Eichenfield LF, Stein Gold LF. Addressing the immunopathogenesis of atopic dermatitis: advances in topical and systemic treatment. Sem Cutan Med Surg. 2017;36:S45–S48.
  • Beck LA, Thaci D, Hamilton JD, et al. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med. 2014;371:130–139.
  • Bao L, Zhang H, Chan LS. The involvement of the JAK-STAT signaling pathway in chronic inflammatory skin disease atopic dermatitis. JAKSTAT. 2013;2:e24137.
  • Levy LL, Urban J, King BA. Treatment of recalcitrant atopic dermatitis with the oral Janus kinase inhibitor tofacitinib citrate. J Am Acad Dermatol. 2015;73:395–399.
  • Fridman JS, Scherle PA, Collins R, et al. Selective inhibition of JAK1 and JAK2 is efficacious in rodent models of arthritis: preclinical characterization of INCB028050. J Immunol. 2010;184:5298–5307.
  • Guttman-Yassky E, Silverberg JI, Nemoto O, et al. Baricitinib in adult patients with moderate-to-severe atopic dermatitis: a phase 2 parallel, double-blinded, randomized placebo-controlled multiple-dose study. J Am Acad Dermatol. 2018. doi: 10.1016/j.jaad.2018.01.018.
  • Craiglow BG, King BA. Killing two birds with one stone: oral tofacitinib reverses alopecia universalis in a patient with plaque psoriasis. J Invest Dermatol. 2014;134:2988–2990.
  • Vu M, Heyes C, Robertson SJ, et al. Oral tofacitinib: a promising treatment in atopic dermatitis, alopecia areata and vitiligo. Clin Exp Dermatol. 2017;42:942–944.
  • Grewe SR, Chan SC, Hanifin JM. Elevated leukocyte cyclic AMP-phosphodiesterase in atopic disease: a possible mechanism for cyclic AMP-agonist hyporesponsiveness. J Allergy Clin Immunol. 1982;70:452–457.
  • Chan SC, Reifsnyder D, Beavo JA, et al. Immunochemical characterization of the distinct monocyte cyclic AMP-phosphodiesterase from patients with atopic dermatitis. J Allergy Clin Immunol. 1993;91:1179–1188.
  • Dastidar SG, Rajagopal D, Ray A. Therapeutic benefit of PDE4 inhibitors in inflammatory diseases. Curr Opin Investig Drugs. 2007;8:364–372.
  • Schafer PH, Parton A, Gandhi AK, et al. Apremilast, a cAMP phosphodiesterase-4 inhibitor, demonstrates anti-inflammatory activity in vitro and in a model of psoriasis. Br J Pharmacol. 2010;159:842–855.
  • Wittmann M, Helliwell PS. Phosphodiesterase 4 inhibition in the treatment of psoriasis, psoriatic arthritis and other chronic inflammatory diseases. Dermatol Ther (Heidelb). 2013;3:1–15.
  • Giustina TA, Chan SC, Thiel ML, et al. Increased leukocyte sensitivity to phosphodiesterase inhibitors in atopic dermatitis: tachyphylaxis after theophylline therapy. J Allergy Clin Immunol. 1984;74:252–257.
  • Souness JE, Aldous D, Sargent C. Immunosuppressive and anti-inflammatory effects of cyclic AMP phosphodiesterase (PDE) type 4 inhibitors. Immunopharmacology. 2000;47:127–162.
  • Griffiths CE, Van Leent EJ, Gilbert M, et al. Randomized comparison of the type 4 phosphodiesterase inhibitor cipamfylline cream, cream vehicle and hydrocortisone 17-butyrate cream for the treatment of atopic dermatitis. Br J Dermatol. 2002;147:299–307.
  • Hanifin JM, Chan SC, Cheng JB, et al. Type 4 phosphodiesterase inhibitors have clinical and in vitro anti-inflammatory effects in atopic dermatitis. J Invest Dermatol. 1996;107:51–56.
  • Hoppmann J, Galetzka C, Höfgen N, et al. The phosphodiesterase 4 inhibitor AWD 12-281 is active in a new guinea-pig model of allergic skin inflammation predictive of human skin penetration and suppresses both Th1 and Th2 cytokines in mice. J Pharm Pharmacol. 2005;57:1609–1617.
  • Seldon PM, Giembycz MA. Suppression of granulocyte/macrophage colony-stimulating factor release from human monocytes by cyclic AMP-elevating drugs: role of interleukin-10. Br J Pharmacol. 2001;134:58–67.
  • Walter M, Kottke T, Stark H. The histamine H4 receptor: targeting inflammatory disorders. Eur J Pharmacol. 2011;668:1–5.
  • Gutzmer R, Mommert S, Gschwandtner M, et al. The histamine H4 receptor is functionally expressed on T(H)2 cells. J Allergy Clin Immunol. 2009;123:619–625.
  • Raap U, Wichmann K, Bruder M, et al. Correlation of IL-31 serum levels with severity of atopic dermatitis. J Allergy Clin Immunol. 2008;122:421–423.
  • Glatzer F, Gschwandtner M, Ehling S, et al. Histamine induces proliferation in keratinocytes from patients with atopic dermatitis through the histamine 4 receptor. J Allergy Clin Immunol. 2013;132:1358–1367.
  • Cowden JM, Zhang M, Dunford PJ, et al. The histamine H4 receptor mediates inflammation and pruritus in Th2-dependent dermal inflammation. J Invest Dermatol. 2010;130:1023–1033.
  • Seike M, Furuya K, Omura M, et al. Histamine H(4) receptor antagonist ameliorates chronic allergic contact dermatitis induced by repeated challenge. Allergy. 2010;65:319–326.
  • Suwa E, Yamaura K, Oda M, et al. Histamine H(4) receptor antagonist reduces dermal inflammation and pruritus in a hapten-induced experimental model. Eur J Pharmacol. 2011;667:383–388.
  • Matsushita A, Seike M, Okawa H, et al. Advantages of histamine H4 receptor antagonist usage with H1 receptor antagonist for the treatment of murine allergic contact dermatitis. Exp Dermatol. 2012;21:714–715.
  • Ohsawa Y, Hirasawa N. The antagonism of histamine H1 and H4 receptors ameliorates chronic allergic dermatitis via anti-pruritic and anti-inflammatory effects in NC/Nga mice. Allergy. 2012;67:1014–1022.
  • Volf EM, Au SC, Dumont N, et al. A phase 2, open-label, investigator-initiated study to evaluate the safety and efficacy of apremilast in subjects with recalcitrant allergic contact or atopic dermatitis. J Drugs Dermatol. 2012;11:341–346.
  • Samrao A, Berry TM, Goreshi R, et al. A pilot study of an oral phosphodiesterase inhibitor (apremilast) for atopic dermatitis in adults. Arch Dermatol. 2012;148:890–897.
  • Farahnik B, Beroukhim K, Nakamura M, et al. Use of an oral phosphodiesterase-4 inhibitor (apremilast) for the treatment of chronic, severe atopic dermatitis: a case report. Dermatol Online J. 2017;23(5):1–5.
  • Abrouk M, Farahnik B, Zhu TH, et al. Apremilast treatment of atopic dermatitis and other chronic eczematous dermatoses. J Am Acad Dermatol. 2017;77:177–180.
  • Murata Y, Song M, Kikuchi H, et al. Phase 2a, randomized, double-blind, placebo-controlled, multicenter, parallel-group study of a H4 R-antagonist (JNJ-39758979) in Japanese adults with moderate atopic dermatitis. J Dermatol. 2015;42:129–139.
  • Hay RJ, Johns NE, Williams HC, et al. The global burden of skin disease in 2010: an analysis of the prevalence and impact of skin conditions. J Invest Dermatol. 2014;134:1527–1534.
  • Drucker AM. Atopic dermatitis: burden of illness, quality of life, and associated complications. Allergy Asthma Proc. 2017;38:3–8.
  • Brunner PM, Guttman-Yassky E, Leung DY. The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies. J Allergy Clin Immunol. 2017;139:S65–S76.
  • Schmitt J, Schakel K, Schmitt N, et al. Systemic treatment of severe atopic eczema: a systematic review. Acta Derm Venereol. 2007;87:100–111.
  • ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29, Identifier: NCT02087943, Efficacy and Safety Study of Apremilast in Subjects With Moderate to Severe Atopic Dermatitis. 2017 Apr 26 [cited 2018 Apr 12]; Available from: https://clinicaltrials.gov/ct2/show/NCT02087943
  • Damsky W, King BA. JAK inhibitors in dermatology: the promise of a new drug class. J Am Acad Dermatol. 2017;76:736–744.
  • ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29, Identifier: NCT02780167, Study To Evaluate Pf-04965842 In Subjects With Moderate To Severe Atopic Dermatitis. 2018 May 16 [cited 2018 July 15]; Available from: https://clinicaltrials.gov/ct2/show/NCT02780167
  • Wollenhaupt J, Silverfield J, Lee EB, et al. Safety and efficacy of tofacitinib, an oral janus kinase inhibitor, for the treatment of rheumatoid arthritis in open-label, longterm extension studies. J Rheumatol. 2014;41:837–852.
  • ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29, Identifier: NCT03559270, A Study of Baricitinib (LY3009104) in Participants With Moderate to Severe Atopic Dermatitis. 2018 July 6 [cited 2018 July 15]; Available from: https://clinicaltrials.gov/ct2/show/NCT03559270
  • ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29, Identifier: NCT03435081, A Study of Baricitinib (LY3009104) in Adult Participants With Moderate to Severe Atopic Dermatitis. 2018 Feb 15 [cited 2018 July 15]; Available from: https://clinicaltrials.gov/ct2/show/NCT03435081
  • ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29, Identifier: NCT03334422, Study of Baricitinib (LY3009104) in Adults With Moderate to Severe Atopic Dermatitis. 2017 Nov 7 [cited 2018 July 15]; Available from: https://clinicaltrials.gov/ct2/show/NCT03334422
  • ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29, Identifier: NCT03334396, A Study of Baricitinib (LY3009104) in Adults With Moderate to Severe Atopic Dermatitis. 2017 Nov 7 [cited 2018 July 15]; Available from: https://clinicaltrials.gov/ct2/show/NCT03334396
  • ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29, Identifier: NCT03334435, A Study of Long-term Baricitinib (LY3009104) Therapy in Atopic Dermatitis. 2017 Nov 7 [cited 2018 July 15]; Available from: https://clinicaltrials.gov/ct2/show/NCT03334435
  • ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29, Identifier: NCT03428100, A Long-term Study of Baricitinib (LY3009104) With Topical Corticosteroids in Adults With Moderate to Severe Atopic Dermatitis That Are Not Controlled With Cyclosporine or for Those Who Cannot Take Oral Cyclosporine Because it is Not Medically Advisable. 2018 Feb 9 [cited 2018 July 15]; Available from: https://clinicaltrials.gov/ct2/show/NCT03428100
  • Miyano K, Matsushita S, Tsuchida T, et al. Inhibitory effect of a histamine 4 receptor antagonist on CCL17 and CCL22 production by monocyte-derived Langerhans cells in patients with atopic dermatitis. J Dermatol. 2016;43:1024–1029.
  • ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29, Identifier: NCT02424253, A Study to Determine the Efficacy of ZPL-3893787 in Subjects With Atopic Dermatitis. 2017 July 17 [cited 2018 July 15]; Available from: https://clinicaltrials.gov/ct2/show/NCT02424253
  • Yanes DA, Mosser-Goldfarb JL. Emerging therapies for atopic dermatitis: the prostaglandin/leukotriene pathway. J Am Acad Dermatol. 2018;78:S71–S75.
  • ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29, Identifier: NCT02002208, Effect of OC000459 on Moderate to Severe Atopic Dermatitis. 2018 Mar 26 [cited 2018 Apr 12]; Available from: https://clinicaltrials.gov/ct2/show/NCT02002208
  • ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29, Identifier: NCT01785602, Efficacy and Safety Study of QAW039 in the Treatment of Patients With Moderate to Severe Atopic Dermatitis. 2015 Dec 15 [cited 2018 Apr 12]; Available from: https://clinicaltrials.gov/ct2/show/NCT01785602
  • ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29, Identifier: NCT02590289, A Pharmacokinetic Study to Evaluate BBI-5000 Capsules and Food Effect in Healthy Adult Subjects. 2015 Dec 2 [cited 2018 July 15]; Available from: https://clinicaltrials.gov/ct2/show/NCT02590289
  • Romeo SP. Atopic dermatitis: the itch that rashes. Pediatr Nurs. 1995;21:157–163.
  • Yosipovitch G, Stander S, Kerby MB, et al. Serlopitant for the treatment of chronic pruritus: results of a randomized, multicenter, placebo-controlled phase 2 clinical trial. J Am Acad Dermatol. 2018;78:882–891.
  • Nygaard U, Vestergaard C, Deleuran M. Emerging treatment options in atopic dermatitis: systemic therapies. Dermatology. 2017;233:344–357. 201
  • ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29, Identifier: NCT02475447, Safety, Pharmacokinetics and Preliminary Efficacy of Asimadoline in Pruritus Associated With Atopic Dermatitis. 2017 Dec 13 [cited 2018 July 15]; Available from: https://clinicaltrials.gov/ct2/show/NCT02475447
  • ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29, Identifier: NCT02975206, Study of the Efficacy, Safety, and Tolerability of Serlopitant for Pruritus (Itch) in Atopic Dermatitis. 2018 Mar 6 [cited 2018 July 15]; Available from: https://clinicaltrials.gov/ct2/show/NCT02975206
  • ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29, Identifier: NCT02651714, Tradipitant in Treatment-resistant Pruritus Associated With Atopic Dermatitis. 2017 Nov 6 [cited 2018 July 15]; Available from: https://clinicaltrials.gov/ct2/show/NCT02651714
  • Nalaskowski MM, Metzner A, Brehm MA, et al. The inositol 5-phosphatase SHIP1 is a nucleo-cytoplasmic shuttling protein and enzymatically active in cell nuclei. Cell Signal. 2012;24:621–628.
  • Aquinox Pharmaceuticals Announces Results From Phase 2 KINSHIP Trial With AQX-1125 in Patients With Atopic Dermatitis. 2015, Available from: http://investor.aqxpharma.com/news-releases/news-release-details/aquinox-pharmaceuticals-announces-results-phase-2-kinship-trial (accessed 2018 May 5).
  • ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29, Identifier: NCT03160248, An Investigator-initiated Study of Apremilast to Demonstrate Efficacy Nummular Eczema. 2017 Aug 21 [cited 2018 July 15]; Available from: https://clinicaltrials.gov/ct2/show/NCT03160248
  • ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29, Identifier: NCT03349060, Study to Evaluate Efficacy and Safety of PF-04965842 in Subjects Aged 12 Years And Older With Moderate to Severe Atopic Dermatitis. 2018 July 13 [cited 2018 July 15]; Available from: https://clinicaltrials.gov/ct2/show/NCT03349060
  • ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29, Identifier: NCT02925117, A Study to Evaluate ABT-494 (Upadacitinib) in Adult Subjects With Moderate to Severe Atopic Dermatitis. 2018 Apr 27 [cited 2018 July 15]; Available from: https://clinicaltrials.gov/ct2/show/NCT02925117
  • ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29, Identifier: NCT03139981, A Study To Evaluate ASN002 In Subjects With Atopic Dermatitis. 2018 Jan 2 [cited 2018 July 15]; Available from: https://clinicaltrials.gov/ct2/show/NCT03139981
  • ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29, Identifier: NCT02004119, Phase 2 Study of KHK4577. 2016 Mar 17 [cited 2018 July 15]; Available from: https://clinicaltrials.gov/ct2/show/NCT02004119
  • ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29, Identifier: NCT00455429, An Efficacy and Safety Study of JNJ-26113100 in the Treatment of Adult Atopic Dermatitis. 2014 Mar 12 [cited 2018 Apr 12]; Available from: https://clinicaltrials.gov/ct2/show/NCT00455429

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