篇名

免疫療法在非癌症皮膚疾病之應用

並列篇名

Use of Immunotherapy in Non-Neoplastic Skin Diseases

DOI

10.6320/FJM.201807_22(4).0006

作者

蔡呈芳(Tsen-Fang Tsai)

關鍵字

乾癬 ; 異位性皮膚炎 ; 化膿性汗腺炎 ; 天疱瘡 ; 生物製劑 ; psoriasis ; atopic dermatitis ; hidradenitis suppurativa ; pemphigus ; biologics

出版品名稱

台灣醫學

卷期/出版年月

22卷4期

頁次

394 - 404

內容語文

繁體中文

中文摘要

免疫療法的進展,尤其是生物製劑的出現,讓許多皮膚病有了突破性的治療進展。乾癬就是其中的先行者,目前已有五代不同機轉的生物製劑被核准。除了第一代的alefacept及efalizumab,其他的生物製劑都仍在臨床使用中,作用於腫瘤壞死因子、介白素12/23、介白素17、介白素23。由於高度療效及相對良好的安全性,此類產品成為了中重度乾癬患者的黃金治療準則,除乾癬外,dupilumab也剛被核准用於異位性皮膚炎,這是一種介白素4/13的抑制劑,而IgE抑制劑omalizumab及adalimnmab則分別核准於慢性自發性蕁麻疹及化膿性汗腺炎。最近rituximab則在美國核准用於尋常性天疱瘡。生物製劑雖然療效佳,相對風險低,但是高昂的費用讓多數需要的患者無法負擔,健保基於財政負擔更無法全面給付。期待當這些藥品專利過期後,價格下降,能讓更多需要的患者可使用。也期待免疫學的進展,能夠繼續發現新的藥物及作用機轉,解決更多的皮膚疾病。

英文摘要

Advancement in immunotherapy, especially biologic agents, has revolutionized the treatment of many skin diseases. Psoriasis is at the forefront of this treatment paradigm change. Five generations of biologics have been approved for use in psoriasis. Except for the first generation (alefacept, efalizumab), all the other biologics are still in clinical use targeting tumor necrosis factor, interleukin 12/23, interleukin 17 and interleukin 23. Due to their high efficacy and favorable safety profiles, these biologics have become the gold standard in the treatment of moderate to severe psoriasis. Biologics have also been approved for atopic dermatitis, but only dupilumab, an interleukin 4/13 dual inhibitor, has recently been approved. However, the efficacy seems to lag behind that in psoriasis, and topical corticosteroid is often used concomitantly, which reflects the complexity in atopic dermatitis pathogenesis. For the other immune based skin disease, adalimumab is approved for hidradenitis suppurativa, omalizumab for chronic idiopathic urticaria and rituximab for pemphigus vulgaris (in United states). Despite the high efficacy and relative safety of these biologics, the high costs of these agents limit the accessibility to most patients, an important issue which hopefully can be resolved after the patents expire. Also, we hope more unsolved skin diseases can be better managed with the approval of novel agents and understanding of their pathogenesis.

主題分類 醫藥衛生 > 醫藥衛生綜合
參考文獻
  1. Ellis CN, Krueger GG: Treatment of chronic plaque psoriasis by selective targeting of memory effector T lymphocytes. N Engl J Med 2001;345:248-55. doi: 10.1056/NEJM200107263450403
    連結:
  2. Huang PH, Liao YH, Wei CC, et al: Clinical effectiveness and safety experience with alefacept in the treatment of patients with moderate-to-severe chronic plaque psoriasis in Taiwan: results of an open-label, single-arm, multicentre pilot study. J Eur Acad Dermatol Venereol 2008;22:923-30. doi: 10.1111/j.1468-3083.2007.02575.x
    連結:
  3. Gordon KB, Papp KA, Hamilton TK, et al: Efalizumab for patients with moderate to severe plaque psoriasis: a randomized controlled trial. JAMA 2003;290:3073-80. doi: 10.1001/jama.290.23.3073
    連結:
  4. Tsai TF, Liu MT, Liao YH, et al: Clinical effectiveness and safety experience with efalizumab in the treatment of patients with moderate-to-severe plaque psoriasis in Taiwan: results of an open-label, single-arm pilot study. J Eur Acad Dermatol Venereol 2008;22:345-52. doi: 10.1111/j.1468-3083.2007.02430.x
    連結:
  5. Seminara NM, Gelfand JM: Assessing long-term drug safety: lessons (re) learned from raptiva. Semin Cutan Med Surg 2010;29:16-9. doi: 10.1016/j.sder.2010.01.001
    連結:
  6. Leonardi CL, Powers JL, Matheson RT, et al: Etanercept as monotherapy in patients with psoriasis. N Engl J Med 2003;349:2014-22. doi: 10.1056/NEJMoa030409
    連結:
  7. Menter A, Tyring SK, Gordon K, et al: Adalimumab therapy for moderate to severe psoriasis: A randomized, controlled phase III trial. J Am Acad Dermatol 2008;58:106-15. doi: 10.1016/j.jaad.2007.09.010
    連結:
  8. Asahina A, Nakagawa H, Etoh T, et al: Adalimumab in Japanese patients with moderate to severe chronic plaque psoriasis: efficacy and safety results from a Phase II/III randomized controlled study. J Dermatol 2010;37:299-310. doi: 10.1111/j.1346-8138.2009.00748.x
    連結:
  9. Cai L, Gu J, Zheng J, et al: Efficacy and safety of adalimumab in Chinese patients with moderate-to-severe plaque psoriasis: results from a phase 3, randomized, placebo-controlled, double-blind study. J Eur Acad Dermatol Venereol 2017;31:89-95. doi: 10.1111/jdv.13746
    連結:
  10. Chiu HY, Wang TS, Chan CC, et al: Risk Factor Analysis for the Immunogenicity of Adalimumab Associated with Decreased Clinical Response in Chinese Patients with Psoriasis. Acta Derm Venereol 2015;95:711-6. doi: 10.2340/00015555-2069
    連結:
  11. Leonardi CL, Kimball AB, Papp KA, et al: Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1). Lancet 2008;371:1665-74. doi: 10.1016/S0140-6736(08)60725-4
    連結:
  12. Tsai TF, Ho JC, Song M, et al: Efficacy and safety of ustekinumab for the treatment of moderate-to-severe psoriasis: a phase III, randomized, placebo-controlled trial in Taiwanese and Korean patients (PEARL). J Dermatol Sci 2011;63:154-63. doi: 10.1016/j.jdermsci.2011.05.005
    連結:
  13. Igarashi A, Kato T, Kato M, et al: Efficacy and safety of ustekinumab in Japanese patients with moderate-to-severe plaque-type psoriasis: long-term results from a phase 2/3 clinical trial. J Dermatol 2012;39:242-52. doi: 10.1111/j.1346-8138.2011.01347.x
    連結:
  14. Kim BS, Lee WK, Pak K, et al: Ustekinumab treatment is associated with decreased systemic and vascular inflammation in patients with moderate to severe psoriasis: Feasibility study using 18F-fluorodeoxyglucose positron emission tomography-computed tomography. J Am Acad Dermatol 2018;pii: S0190-9622 (18)30461-4. doi: 10.1016/j.jaad.2018.03.011
    連結:
  15. Tsai TF, Ho V, Song M, et al: The safety of ustekinumab treatment in patients with moderate-to-severe psoriasis and latent tuberculosis infection. Br J Dermatol 2012;167: 1145-52. doi: 10.1111/j.1365-2133.2012.11142.x
    連結:
  16. Griffiths CE, Strober BE, van de Kerkhof P, et al: Comparison of ustekinumab and etanercept for moderate-to-severe psoriasis. N Engl J Med 2010;362:118-28. doi: 10.1056/NEJMoa0810652
    連結:
  17. Papp KA, Griffiths CE, Gordon K, et al: Long-term safety of ustekinumab in patients with moderate-to-severe psoriasis: final results from 5 years of follow-up. Br J Dermatol 2013;168:844-54. doi: 10.1111/bjd.12214
    連結:
  18. Langley RG, Elewski BE, Lebwohl M, et al: Secukinumab in plaque psoriasis--results of two phase 3 trials. N Engl J Med 2014;371: 326-38. doi: 10.1056/NEJMoa1314258
    連結:
  19. Blauvelt A, Prinz JC, Gottlieb AB, et al: Secukinumab administration by pre-filled syringe: efficacy, safety and usability results from a randomized controlled trial in psoriasis (FEATURE). Br J Dermatol 2015;172:484-93. doi: 10.1111/bjd.13348
    連結:
  20. Lacour JP, Paul C, Jazayeri S, et al: Secukinumab administration by autoinjector maintains reduction of plaque psoriasis severity over 52 weeks: results of the randomized controlled JUNCTURE trial. J Eur Acad Dermatol Venereol 2017;31:847-56. doi: 10.1111/jdv.14073
    連結:
  21. Blauvelt A, Reich K, Tsai TF, et al: Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate-to-severe plaque psoriasis up to 1 year: Results from the CLEAR study. J Am Acad Dermatol 2017;76:60-9. doi: 10.1016/j.jaad.2016.08.008
    連結:
  22. Wu NL, Hsu CJ, Sun FJ, Tsai TF: Efficacy and safety of secukinumab in Taiwanese patients with moderate to severe plaque psoriasis: Subanalysis from ERASURE phase III study. J Dermatol 2017;44:1129-37. doi: 10.1111/1346-8138.13900
    連結:
  23. Bissonnette R, Luger T, Thaçi D, et al: Secukinumab demonstrates high sustained efficacy and a favourable safety profile in patients with moderate-to-severe psoriasis through 5 years of treatment (SCULPTURE Extension Study). J Eur Acad Dermatol Venereol 2018. doi: 10.1111/jdv. doi: 10.1111/jdv.14878
    連結:
  24. Egeberg A, Ottosen MB, Gniadecki R, et al: Safety, efficacy and drug survival of biologics and biosimilars for moderate-to-severe plaque psoriasis. Br J Dermatol 2018;178:509-19. doi: 10.1111/bjd.16102
    連結:
  25. Kammüller M, Tsai TF, Griffiths CE, et al: Inhibition of IL-17A by secukinumab shows no evidence of increased Mycobacterium tuberculosis infections. Clin Transl Immunol 2017;6:e152. doi: 10.1038/cti.2017.34
    連結:
  26. Papp KA, Leonardi CL, Blauvelt A, et al: Ixekizumab treatment for psoriasis: integrated efficacy analysis of three double-blinded, controlled studies (UNCOVER-1, UNCOVER-2, UNCOVER-3). Br J Dermatol 2018;178:674-81. doi: 10.1111/bjd.16050
    連結:
  27. Reich K, Pinter A, Lacour JP, et al: Comparison of ixekizumab with ustekinumab in moderate-to-severe psoriasis: 24-week results from IXORA-S, a phase III study. Br J Dermatol 2017;177:1014-23. doi: 10.1111/bjd.15666
    連結:
  28. Lebwohl MG, Papp KA, Marangell LB, et al: Psychiatric adverse events during treatment with brodalumab: Analysis of psoriasis clinical trials. J Am Acad Dermatol 2018;78:81-9. doi: 10.1016/j.jaad.2017.08.024
    連結:
  29. Blauvelt A, Papp KA, Griffiths CE, et al: Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis: Results from the phase III, double-blinded, placebo- and active comparator-controlled VOYAGE 1 trial. J Am Acad Dermatol 2017;76:405-17. doi: 10.1016/j.jaad.2016.11.041
    連結:
  30. Reich K, Armstrong AW, Foley P, et al: Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: Results from the phase III, double-blind, placebo- and active comparator-controlled VOYAGE 2 trials. J Am Acad Dermatol 2017;76:418-31. doi: 10.1016/j.jaad.2016.11.042
    連結:
  31. Langley RG, Tsai TF, Flavin S, et al: Efficacy and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: results of the randomized, double-blind, phase III NAVIGATE trial. Br J Dermatol 2018;178:114-23. doi: 10.1111/bjd.15750
    連結:
  32. Simpson EL, Bieber T, Guttman-Yassky E, et al: Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis. N Engl J Med 2016;375:2335-48. doi: 10.1056/NEJMoa1610020
    連結:
  33. Blauvelt A, de Bruin-Weller M, Gooderham M, et al: Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a 1-year, randomised, double-blinded, placebo-controlled, phase 3 trial. Lancet 2017;389:2287-303. doi: 10.1016/S0140-6736(17)31191-1
    連結:
  34. de Bruin-Weller M, Thaçi D, Smith CH, et al: Dupilumab with concomitant topical corticosteroid treatment in adults with atopic dermatitis with an inadequate response or intolerance to ciclosporin A or when this treatment is medically inadvisable: a placebo-controlled, randomized phase III clinical trial (LIBERTY AD CAFÉ). Br J Dermatol 2017 Nov 28. doi: 10.1111/bjd.16156. [Epub ahead of print]
    連結:
  35. Kimball AB, Okun MM, Williams DA, et al: Two Phase 3 Trials of Adalimumab for Hidradenitis Suppurativa. N Engl J Med 2016;375:422-34. doi: 10.1056/NEJMoa1504370
    連結:
  36. Joly P, Maho-Vaillant M, Prost-Squarcioni C, et al: First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial. Lancet 2017;389:2031-40. doi: 10.1016/S0140-6736(17)30070-3
    連結:
  37. Zhu X, Zheng M, Song M, et al: Efficacy and safety of ustekinumab in Chinese patients with moderate to severe plaque-type psoriasis: results from a phase 3 clinical trial (LOTUS). J Drugs Dermatol 2013;12:166-74.
  38. Langley RG, Papp K, Gottlieb AB, et al: Safety results from a pooled analysis of randomized, controlled phase II and III clinical trials and interim data from an open-label extension trial of the interleukin-12/23 monoclonal antibody, briakinumab, in moderate to severe psoriasis. J Eur Acad Dermatol Venereol 2013;27:1252-61.