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Therapeutic New Era for Atopic Dermatitis: Part 2. Small Molecules

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초록

Atopic dermatitis (AD) is a chronic, inflammatory cutaneous disease driven by immune dysregulation and skin barrier dysfunction. Currently, we are experiencing a new era of understanding of the pathogenesis of AD and, as a consequence, a new era of innovation in therapeutics, including small molecules and biologic therapy. In contrast to biologics, small molecules are similar to conventional pharmacologic chemical agents used as drugs and are generally prepared by chemical synthesis. Unlike biologics, these drugs often are taken orally or formulated for topical use. The purpose of this review is to summarize the efficacy and safety of the current topical and systemic new therapies in AD by reviewing recently published papers on therapies currently in phase 2 or 3 clinical trials. In this review, it is important to note the characteristics of the study population, the primary endpoints, and whether or not there was concomitant topical therapy allowed. These study design elements may significantly alter the results of studies and should be taken into account. Targeted therapy help push AD treatment into a new era of personalized medicine.

Abstract

Atopic dermatitis (AD) is a chronic, inflammatory cutaneous disease driven by immune dysregulation and skin barrier dysfunction. Currently, we are experiencing a new era of understanding of the pathogenesis of AD and, as a consequence, a new era of innovation in therapeutics, including small molecules and biologic therapy. In contrast to biologics, small molecules are similar to conventional pharmacologic chemical agents used as drugs and are generally prepared by chemical synthesis. Unlike biologics, these drugs often are taken orally or formulated for topical use. The purpose of this review is to summarize the efficacy and safety of the current topical and systemic new therapies in AD by reviewing recently published papers on therapies currently in phase 2 or 3 clinical trials. In this review, it is important to note the characteristics of the study population, the primary endpoints, and whether or not there was concomitant topical therapy allowed. These study design elements may significantly alter the results of studies and should be taken into account. Targeted therapy help push AD treatment into a new era of personalized medicine.

참고문헌 (33)

  1. Fleischmann R, "Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis", N Engl J Med, 367, pp.495~507 (2012)
  2. Guttman-Yassky E, "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, 80, pp.913~921 (2019)
  3. Mariette X, "Lymphoma in the tofacitinib rheumatoid arthritis clinical development program", Arthritis Care Res(Hoboken), 70, pp.685~694 (2018)
  4. Renert-Yuval Y, "What’s new in atopic dermatitis", Dermatol Clin, 37, pp.205~213 (2019)
  5. Riese RJ, "Inhibition of JAK kinases in patients with rheumatoid arthritis : scientific rationale and clinical outcomes", Best Pract Res Clin Rheumatol, 24, pp.513~526 (2010)
  6. Guttman-Yassky E, "Upadacitinib in adults with moderate to severe atopic dermatitis: 16-week results from a randomized, placebocontrolled trial", J Allergy Clin Immunol, 145, pp.877~884 (2020)
  7. "A Study to Evaluate Upadacitinib in Adolescent and Adult Subjects with Moderate to Severe Atopic Dermatitis (Measure Up 2)" (2018)[URL]
  8. Simpson EL, "Efficacy and safety of abrocitinib in patients with moderate-to-severe atopic dermatitis (AD): results from the phase 3, JADE MONO-1 study", Proceedings of European Academy of Dermatology and Venereology 28th Congress (2019)
  9. Simpson EL, "Efficacy and safety of baricitinib in moderate to severe atopic dermatitis: results of two phase 3monotherapy randomized, double-blind, placebo-controlled 16-week trials (BREEZE-AD1 and BREEZE-AD2)", Proceedings of the 24th Congress of World Congress of Dermatology (2019)
  10. Kim BS, "Treatment of atopic dermatitis with ruxolitinib cream (JAK1", JAK2 inhibitor) or triamcinolone cream, 2020, pp.145, 572~582
  11. Kim BS, "Effects of ruxolitinib cream on pruritus and quality of life in atopic dermatitis: results from a phase 2, randomized, dose-ranging, vehicle- and active-controlled study", J Am Acad Dermatol, 82, pp.1305~1313 (2020)
  12. Papp K, "Efficacy and safety of ruxolitinib cream for the treatment of atopic dermatitis: results from two phase 3, randomized, double-blind studies", Proceedings of the 2nd Annual Revolutionizing Atopic Dermatitis Conference (2020)
  13. Nguyen HL, "New and emerging therapies for pediatric atopic dermatitis", Paediatr Drugs, 21, pp.239~260 (2019)
  14. Levy LL, "Treatment of recalcitrant atopic dermatitis with the oral Janus kinase inhibitor tofacitinib citrate", J Am Acad Dermatol, 73, pp.395~399 (2015)
  15. Bissonnette R, "Topical tofacitinib for atopic dermatitis : a phase IIa randomized trial", Br J Dermatol, 175, pp.902~911 (2016)
  16. Zammit D, "ASN002, a novel dual SYK", JAK inhibitor, demonstrates strong efficacy in a rat model of collagen-induced arthritis, ARHP Annual Meeting, pp.2017[DOI]
  17. Bissonnette R, "The oral Janus kinase", spleen tyrosine kinase inhibitor ASN002 demonstrates efficacy and improves associated systemic inflammation in patients with moderate-to-severe atopic dermatitis : results from a randomized double-blind placebo-controlled study, 2019, pp.181, 733~742
  18. Nakagawa H, "Efficacy and safety of topical JTE-052, a Janus kinase inhibitor, in Japanese adult patients with moderate-to-severe atopic dermatitis: a phase II, multicentre, randomized, vehicle-controlled clinical study", Br J Dermatol, 178, pp.424~432 (2018)
  19. Oetjen LK, "Sensory neurons co-opt classical immune signaling pathways to mediate chronic itch", Cell, 171, pp.217~228 (2017)
  20. Nakagawa H, "Phase 2 clinical study of delgocitinib ointment in pediatric patients with atopic dermatitis", J Allergy Clin Immunol, 144, pp.1575~1583 (2019)
  21. Nakagawa H, "Delgocitinib ointment, a topical Janus kinase inhibitor, in adult patients with moderate to severe atopic dermatitis: a phase 3, randomized, double-blind, vehicle-controlled study and an open-label, long-term extension study", J Am Acad Dermatol, 82, pp.823~831 (2020)
  22. Howell MD, "JAK", STAT inhibitors and other small molecule cytokine antagonists for the treatment of allergic disease, 2018, pp.120, 367~375
  23. Simpson EL, "A phase 2 randomized trial of apremilast in patients with atopic dermatitis", J Invest Dermatol, 139, pp.1063~1072 (2019)
  24. "Topical Roflumilast in Adults with Atopic Dermatitis" (2013)[URL]
  25. Hajar T, "New and developing therapies for atopic dermatitis", An Bras Dermatol, 93, pp.104~107 (2018)
  26. Paller AS, "Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults", J Am Acad Dermatol, 75, pp.494~503 (2016)
  27. Schlessinger J, "Safety, effectiveness, and pharmacokinetics of crisaborole in infants aged 3 to < 24 months with mild-to-moderate atopic dermatitis: a phase IV open-label study (CrisADe CARE 1)", Am J Clin Dermatol, 21, pp.275~284 (2020)
  28. Silverberg JI, "Evaluating the efficacy of crisaborole using the atopic dermatitis severity index and percentage of affected body surface area", Acta Derm Venereol, 100, pp.adv00170~ (2020)
  29. Abuabara K, "Is new better than tried and tested? Topical atopic dermatitis treatment in context", Br J Dermatol, 178, pp.583~584 (2018)
  30. Hanifin JM, "OPA-15406, a novel, topical, nonsteroidal, selective phosphodiesterase-4 (PDE4) inhibitor, in the treatment of adult and adolescent patients with mild to moderate atopic dermatitis (AD): a phase-II randomized, double-blind, placebo-controlled study", J Am Acad Dermatol, 75, pp.297~305 (2016)
  31. "Comparison Trial of OPA-15406 Ointment in Pediatric Patients with Atopic Dermatitis" (2019)[URL]
  32. "A Safety and Efficacy of DRM02 in Subjects with Atopic Dermatitis" (2013)[URL]
  33. "LEO 29102 Cream in the Treatment of Atopic Dermatitis" (2009)[URL]

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