中国皮肤罕见病相关孤儿药现状及展望

张姗; 吴超; 刘兆睿; 高祎濛; 刘洁; 晋红中

doi:10.12376/j.issn.2097-0501.2023.02.012

中国皮肤罕见病相关孤儿药现状及展望

doi: 10.12376/j.issn.2097-0501.2023.02.012

中国医学科学院北京协和医院皮肤科疑难重症及罕见病国家重点实验室国家皮肤与免疫疾病临床医学研究中心，北京 100730

基金项目:

中央高水平医院临床科研业务费 2022-PUMCH-B-092

国家自然科学基金 82173449

北京市自然科学基金 7232114

中国医学科学院医学与健康科技创新工程 2022-I2M-C&T-A-007

详细信息

通信作者:
刘洁，E-mail: Liujie04672@pumch.cn

晋红中，E-mail: jinhongzhong@263.net

中图分类号: R-1; R751
计量
- 文章访问数: 42
- HTML全文浏览量: 10
- PDF下载量: 16
- 被引次数: 0
出版历程
- 收稿日期: 2023-01-29
- 录用日期: 2023-02-18
- 网络出版日期: 2023-05-05

Current Status and Prospect of Orphan Drugs for Rare Skin Diseases in China

Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, National Clinical Research Center for Dermatologic and Immunologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China

Funding:

National High Level Hospital Clinical Research Funding 2022-PUMCH-B-092

National Natural Science Foundation of China 82173449

Beijing Natural Science Foundation 7232114

Chinese Academy of Medical Sciences(CAMS) Innovation Fund for Medical Sciences 2022-I2M-C&T-A-007

More Information

Corresponding author: LIU Jie, E-mail: Liujie04672@pumch.cn; JIN Hongzhong, E-mail: jinhongzhong@263.net

摘要

摘要: 罕见病是一类具有发病率极低、患者总数少等特点的疾病，治疗罕见病的药物称为孤儿药。目前已知的皮肤罕见病约450种，大多数疾病缺乏有效的治疗手段，在国家的政策支持和社会各界的积极推动下，近年来皮肤罕见病的治疗药物不断涌现，本文将梳理目前国内外已获批上市的皮肤孤儿药及中国用药可及性现状，以提高对皮肤罕见病及孤儿药的认识。
- 皮肤罕见病 /
- 孤儿药 /
- 罕见病用药 /
- 可及性
Abstract: Rare diseases are characterized by extremely low incidence rate and small number of patients in total. The drugs used to treat rare diseases are called orphan drugs. Currently, 450 kinds of rare skin diseases have been identified, most of which lack in effective treatments. Supported by the policy-making from the country and pushed by all sectors of the society, drugs for rare skin diseases have been emerging continuously recently in China. This paper reviews the current accessibility of the orphan drugs for skin rare diseases that have been approved in China and in other countries and regions for a better understanding of rare dermatosis and orphan drugs for the diseases.
- rare skin diseases /
- orphan drugs /
- rare disease drugs /
- accessibility
注释:

作者贡献：张姗负责文章撰写；吴超、刘兆睿、高祎濛对部分章节内容进行修订；刘洁负责设计文章选题和内容框架，对文章内容进行审阅修改；晋红中负责文章审阅及修改。

利益冲突：所有作者均声明不存在利益冲突。

HTML全文

表 1 生物制剂治疗化脓性汗腺炎相关临床研究

Table 1. Clinical researches on the treatment of hidradenitis suppurativa with biologics

药物名称	作用机制	疗程	疗效	参考文献
阿达木单抗	抗TNF-α	12周	HiSCR比例高于安慰剂组	[16]
乌司奴单抗	抗IL-12/IL-23	40周	82%获得mSS中度或显著改善	[18]
司库奇尤单抗	抗IL-17A	24周	70%达到临床缓解	[19]
HiSCR: 化脓性汗腺炎临床缓解；mSS: 改良Sartorius评分

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表 2 生物制剂治疗红皮病型银屑病相关临床研究

Table 2. Clinical researches on the treatment of erythrodermic psoriasis with biologics

药物名称	作用机制	疗程	疗效	参考文献
英夫利西单抗	抗TNF-α	12周	48%达到PASI 75	[28]
依那西普	抗TNF-α	12周	40%达到PASI 75	[28]
阿达木单抗	抗TNF-α	12周	50%达到PASI 75	[28]
依奇珠单抗	抗IL-17A	12周	均达到PASI 75	[24]
司库奇尤单抗	抗IL-17A	16周	70%达到PASI 75	[29]
古塞奇尤单抗	抗IL-23	16周	90.9%获得临床总体印象评分改善	[30]
PASI 75:皮损面积和严重程度指数评分较基线下降75%

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表 3 生物制剂治疗大疱性类天疱疮相关临床研究

Table 3. Clinical researches on the treatment of bullous pemphigoid with biologics

药物名称	作用机制	样本量	疗效	参考文献
利妥昔单抗	抗CD20	122例	70.5%获得完全缓解	[46]
度普利尤单抗	抗IL-4/IL-13	13例	12/13病情改善且对疗效满意	[47]
奥马珠单抗	抗IgE	53例	67.9%实现病变完全消退	[46]

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参考文献(91)

[1]	Karas L, Lu CY, Agrawal PB, et al. The impact of the Orphan Drug Act on Food and Drug Administration-approved therapies for rare skin diseases and skin-related cancers[J]. J Am Acad Dermatol, 2019, 81(3): 867-877. doi: 10.1016/j.jaad.2019.05.025
[2]	Gong S, Wang Y, Pan X, et al. The availability and affordability of orphan drugs for rare diseases in China[J]. Orphanet J Rare Dis, 2016, 11: 20. doi: 10.1186/s13023-016-0392-4
[3]	马端, 李定国, 张学, 等. 中国罕见病防治的机遇与挑战[J]. 中国循证儿科杂志, 2011, 6(2): 81-82. https://www.cnki.com.cn/Article/CJFDTOTAL-XZEK201102003.htm
[4]	王雪, 赵聪, 许淑红, 等. 我国罕见病用药可及性现状分析[J]. 中国临床药理学杂志, 2021, 37(8): 1026-1032. doi: 10.13699/j.cnki.1001-6821.2021.08.024
[5]	刘鑫, 唐彦, 左玮, 等. 国外孤儿药综合评价概述及启示[J]. 临床药物治疗杂志, 2020, 18(6): 85-88. doi: 10.3969/j.issn.1672-3384.2020.06.017
[6]	张学军. 罕见性遗传性皮肤病的研究现状及展望[J]. 皮肤科学通报, 2020, 37(1): 1-5. https://www.cnki.com.cn/Article/CJFDTOTAL-ZYXW202001001.htm
[7]	国家卫生健康委办公厅. 罕见病诊疗指南(2019年版)[EB/OL]. (2019-02-27)[2022-12-10]. http://www.nhc.gov.cn/yzygj/s7659/201902/61d06b4916c348e0810ce1fceb844333.shtml.
[8]	Maurer M, Magerl M, Betschel S, et al. The international WAO/EAACI guideline for the management of hereditary angioedema-The 2021 revision and update[J]. Allergy, 2022, 77(7): 1961-1990. doi: 10.1111/all.15214
[9]	Zuraw B, Lumry WR, Johnston DT, et al. Oral once-daily berotralstat for the prevention of hereditary angioedema attacks: a randomized, double-blind, placebo-controlled phase 3 trial[J]. J Allergy Clin Immunol, 2021, 148(1): 164-172. e9. doi: 10.1016/j.jaci.2020.10.015
[10]	Wedner HJ, Aygören-Pürsün E, Bernstein J, et al. Randomized trial of the efficacy and safety of berotralstat (BCX7353) as an oral prophylactic therapy for hereditary angioedema: results of apeX-2 through 48 weeks (Part 2)[J]. J Allergy Clin Immunol Pract, 2021, 9(6): 2305-2314. e4. doi: 10.1016/j.jaip.2021.03.057
[11]	Banerji A, Riedl MA, Bernstein JA, et al. Effect of lanadelumab compared with placebo on prevention of hereditary angioedema attacks: a randomized clinical trial[J]. JAMA, 2018, 320(20): 2108-2121. doi: 10.1001/jama.2018.16773
[12]	Bissler JJ, Kingswood JC, Radzikowska E, et al. Everoli-mus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis (EXIST-2): a multicentre, randomised, double-blind, placebo-controlled trial[J]. Lancet, 2013, 381(9869): 817-824. doi: 10.1016/S0140-6736(12)61767-X
[13]	Wataya-Kaneda M, Ohno Y, Fujita Y, et al. Sirolimus gel treatment vs placebo for facial angiofibromas in patients with tuberous sclerosis complex: a randomized clinical trial[J]. JAMA Dermatol, 2018, 154(7): 781-788. doi: 10.1001/jamadermatol.2018.1408
[14]	Phan K, Charlton O, Smith SD. Global prevalence of hidradenitis suppurativa and geographical variation—systematic review and meta-analysis[J]. Biomed Dermatol, 2020, 4(1): 1-6. doi: 10.1186/s41702-019-0053-z
[15]	Wang ZS, Li J, Ju Q, et al. Prevalence of acne inversa (Hidradenitis Suppurativa) in China: a nationwide cross-sectional epidemiological study[J]. Int J Dermatol Venereol, 2022, 5(1): 1-7. doi: 10.1097/JD9.0000000000000204
[16]	Kimball AB, Okun MM, Williams DA, et al. Two phase 3 Trials of adalimumab for hidradenitis suppurativa[J]. N Engl J Med, 2016, 375(5): 422-434. doi: 10.1056/NEJMoa1504370
[17]	Goldburg SR, Strober BE, Payette MJ. Hidradenitis suppurativa: current and emerging treatments[J]. J Am Acad Dermatol, 2020, 82(5): 1061-1082. doi: 10.1016/j.jaad.2019.08.089
[18]	Blok JL, Li K, Brodmerkel C, et al. Ustekinumab in hidradenitis suppurativa: clinical results and a search for potential biomarkers in serum[J]. Br J Dermatol, 2016, 174(4): 839-846. doi: 10.1111/bjd.14338
[19]	Casseres RG, Prussick L, Zancanaro P, et al. Secukinu-mab in the treatment of moderate to severe hidradenitis suppurativa: results of an open-label trial[J]. J Am Acad Dermatol, 2020, 82(6): 1524-1526. doi: 10.1016/j.jaad.2020.02.005
[20]	Marrakchi S, Guigue P, Renshaw BR, et al. Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis[J]. N Engl J Med, 2011, 365(7): 620-628. doi: 10.1056/NEJMoa1013068
[21]	Zhu T, Jin H, Shu D, et al. Association of IL36RN mutations with clinical features, therapeutic response to acitretin, and frequency of recurrence in patients with generalized pustular psoriasis[J]. Eur J Dermatol, 2018, 28(2): 217-224. doi: 10.1684/ejd.2018.3245
[22]	Bachelez H, Choon SE, Marrakchi S, et al. Trial of spesolimab for generalized pustular psoriasis[J]. N Engl J Med, 2021, 385(26): 2431-2440. doi: 10.1056/NEJMoa2111563
[23]	Imafuku S, Honma M, Okubo Y, et al. Efficacy and safety of secukinumab in patients with generalized pustular psoriasis: a 52-week analysis from phase Ⅲ open-label multicenter Japanese study[J]. J Dermatol, 2016, 43(9): 1011-1017. doi: 10.1111/1346-8138.13306
[24]	Saeki H, Nakagawa H, Ishii T, et al. Efficacy and safety of open-label ixekizumab treatment in Japanese patients with moderate-to-severe plaque psoriasis, erythrodermic psoriasis and generalized pustular psoriasis[J]. J Eur Acad Dermatol Venereol, 2015, 29(6): 1148-1155. doi: 10.1111/jdv.12773
[25]	Rosenbach M, Hsu S, Korman NJ, et al. Treatment of erythrodermic psoriasis: from the medical board of the National Psoriasis Foundation[J]. J Am Acad Dermatol, 2010, 62(4): 655-662. doi: 10.1016/j.jaad.2009.05.048
[26]	Ye F, Gui X, Wu C, et al. Severity evaluation and prognostic factors in erythrodermic psoriasis[J]. Eur J Dermatol, 2018, 28(6): 851-853.
[27]	Carrasquillo OY, Pabón-Cartagena G, Falto-Aizpurua LA, et al. Treatment of erythrodermic psoriasis with biologics: a systematic review[J]. J Am Acad Dermatol, 2020, 83(1): 151-158. doi: 10.1016/j.jaad.2020.03.073
[28]	Viguier M, Pagès C, Aubin F, et al. Efficacy and safety of biologics in erythrodermic psoriasis: a multicentre, retrospective study[J]. Br J Dermatol, 2012, 167(2): 417-423. doi: 10.1111/j.1365-2133.2012.10940.x
[29]	Weng HJ, Wang TS, Tsai TF. Clinical experience of secukinumab in the treatment of erythrodermic psoriasis: a case series[J]. Br J Dermatol, 2018, 178(6): 1439-1440. doi: 10.1111/bjd.16252
[30]	Sano S, Kubo H, Morishima H, et al. Guselkumab, a human interleukin-23 monoclonal antibody in Japanese patients with generalized pustular psoriasis and erythrodermic psoriasis: efficacy and safety analyses of a 52-week, phase 3, multicenter, open-label study[J]. J Dermatol, 2018, 45(5): 529-539. doi: 10.1111/1346-8138.14294
[31]	中华医学会皮肤性病学分会, 中国医师协会皮肤科医师分会, 中国中西医结合学会皮肤性病专业委员会. 中国银屑病生物制剂治疗指南(2021)[J]. 中华皮肤科杂志, 2021, 54(12): 1033-1047.
[32]	高祎濛, 晋红中. 青斑样血管病发病机制[J]. 中华临床免疫和变态反应杂志, 2020, 14(5): 479-484. https://www.cnki.com.cn/Article/CJFDTOTAL-OZHL202005012.htm
[33]	Micieli R, Alavi A. Treatment for livedoid vasculopathy: a systematic review[J]. JAMA Dermatol, 2018, 154(2): 193-202. doi: 10.1001/jamadermatol.2017.4374
[34]	Gao Y, Jin H. Real-world data on pain management and effectiveness of anti-tumour necrosis factor agents in refractory livedoid vasculopathy[J]. J Eur Acad Dermatol Venereol, 2022, 36(1): e46-e48.
[35]	Gao Y, Jin H. Rivaroxaban for treatment of livedoid vasculopathy: a systematic review[J]. Dermatol Ther, 2021, 34(5): e15051.
[36]	Gao Y, Jin H. Efficacy and safety of intravenous immunoglobulin for treating refractory livedoid vasculopathy: a systematic review[J]. Ther Adv Chronic Dis, 2022, 13: 20406223221097331.
[37]	Huang XW, Zheng HX, Wang ML, et al. Adalimumab in treating refractory livedoid vasculopathy[J]. Vaccines(Basel), 2022, 10(4): 549.
[38]	Gao Y, Jin H. Efficacy of an anti-TNF-alpha agent in refractory livedoid vasculopathy: a retrospective analysis[J]. J Dermatol Treat, 2022, 33(1): 178-183. doi: 10.1080/09546634.2020.1737634
[39]	Dong L, Li Q, Yu Y, et al. Efficacy of adalimumab in the treatment of refractory livedoid vasculopathy: case report and literature review[J]. Dermatol Ther, 2022, 35(9): e15666.
[40]	Gao Y, Jin H. Plasminogen activator inhibitor-1: a potential etiological role in livedoid vasculopathy[J]. Int Wound J, 2020, 17(6): 1902-1908. doi: 10.1111/iwj.13480
[41]	Kneisel A, Hertl M. Autoimmune bullous skin diseases. Part 1: clinical manifestations[J]. J Dtsch Dermatol Ges, 2011, 9(10): 844-857.
[42]	Werth VP, Joly P, Mimouni D, et al. Rituximab versus mycophenolate mofetil in patients with pemphigus vulgaris[J]. N Engl J Med, 2021, 384(24): 2295-2305. doi: 10.1056/NEJMoa2028564
[43]	Joly P, Horvath B, Patsatsi Α, et al. Updated S2K guidelines on the management of pemphigus vulgaris and foliaceus initiated by the European Academy of Dermatology and Venereology(EADV)[J]. J Eur Acad Dermatol Venereol, 2020, 34(9): 1900-1913. doi: 10.1111/jdv.16752
[44]	中国医疗保健国际交流促进会皮肤科分会. 寻常型天疱疮诊断和治疗专家建议(2020)[J]. 中华皮肤科杂志, 2020, 53(1): 1-7. https://www.cnki.com.cn/Article/CJFDTOTAL-ZYXW202103012.htm
[45]	Persson MSM, Begum N, Grainge MJ, et al. The global incidence of bullous pemphigoid: a systematic review and meta-analysis[J]. Br J Dermatol, 2022, 186(3): 414-425. doi: 10.1111/bjd.20743
[46]	Cao P, Xu W, Zhang L. Rituximab, omalizumab, and dupilumab treatment outcomes in bullous pemphigoid: a systematic review[J]. Front Immunol, 2022, 13: 928621. doi: 10.3389/fimmu.2022.928621
[47]	Abdat R, Waldman RA, de Bedout V, et al. Dupilumab as a novel therapy for bullous pemphigoid: a multicenter case series[J]. J Am Acad Dermatol, 2020, 83(1): 46-52. doi: 10.1016/j.jaad.2020.01.089
[48]	Feliciani C, Joly P, Jonkman MF, et al. Management of bullous pemphigoid: the European Dermatology Forum consensus in collaboration with the European Academy of Dermatology and Venereology[J]. Br J Dermatol, 2015, 172(4): 867-877. doi: 10.1111/bjd.13717
[49]	Jagasia MH, Greinix HT, Arora M, et al. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: Ⅰ. The 2014 Diagnosis and Staging Working Group report[J]. Biol Blood Marrow Transplant, 2015, 21(3): 389-401. e1. doi: 10.1016/j.bbmt.2014.12.001
[50]	Miklos D, Cutler CS, Arora M, et al. Ibrutinib for chronic graft-versus-host disease after failure of prior therapy[J]. Blood, 2017, 130(21): 2243-2250. doi: 10.1182/blood-2017-07-793786
[51]	Cutler C, Lee SJ, Arai S, et al. Belumosudil for chronic graft-versus-host disease after 2 or more prior lines of therapy: the ROCKstar study[J]. Blood, 2021, 138(22): 2278-2289. doi: 10.1182/blood.2021012021
[52]	Bradford PT, Devesa SS, Anderson WF, et al. Cutaneous lymphoma incidence patterns in the United States: a population-based study of 3884 cases[J]. Blood, 2009, 113(21): 5064-5073. doi: 10.1182/blood-2008-10-184168
[53]	Imam MH, Shenoy PJ, Flowers CR, et al. Incidence and survival patterns of cutaneous T-cell lymphomas in the United States[J]. Leuk Lymphoma, 2013, 54(4): 752-759. doi: 10.3109/10428194.2012.729831
[54]	Gilson D, Whittaker SJ, Child FJ, et al. British Associa-tion of Dermatologists and U.K. Cutaneous Lymphoma Group guidelines for the management of primary cutaneous lymphomas 2018[J]. Br J Dermatol, 2019, 180(3): 496-526. doi: 10.1111/bjd.17240
[55]	Liu J, Yu X, Liu Y, et al. Relative frequency and survival of primary cutaneous lymphomas: a retrospective analysis of 98 patients[J]. Chin Med J (Engl), 2014, 127(4): 645-650.
[56]	秦国敬, 张福仁, 卢宪梅, 等. 115例蕈样肉芽肿临床病理分析[J]. 中国麻风皮肤病杂志, 2015, 31(11): 673-678. https://www.cnki.com.cn/Article/CJFDTOTAL-MALA201511014.htm
[57]	Luo Y, Liu Z, Liu J, et al. Mycosis fungoides and variants of mycosis fungoides: a retrospective study of 93 patients in a Chinese population at a single center[J]. Ann Dermatol, 2020, 32(1): 14-20. doi: 10.5021/ad.2020.32.1.14
[58]	Leng L, Liu Z, Ma J, et al. Proteomic identification of new diagnostic biomarkers of early-stage cutaneous mycosis fungoides[J]. Cancer Commun (Lond), 2022, 42(6): 558-562. doi: 10.1002/cac2.12266
[59]	Garcia-Saleem TJ, Stonesifer CJ, Khaleel AE, et al. Management of mycosis fungoides with topical chlormethine/mechlorethamine gel: a Columbia University Cutaneous Lymphoma Center Experience[J]. Acta Derm Venereol, 2021, 101(9): adv00544. doi: 10.2340/00015555-3911
[60]	Duvic M, Martin AG, Kim Y, et al. Phase 2 and 3 clinical trial of oral bexarotene (Targretin capsules) for the treatment of refractory or persistent early-stage cutaneous T-cell lymphoma[J]. Arch Dermatol, 2001, 137(5): 581-593.
[61]	Che Y, Ding X, Song J, et al. Effective remission of chidamide on treatment of advanced mycosis fungoides: an unusual case report[J]. Dermatol Ther, 2019, 32(4): e12944.
[62]	Lesokhin AM, Ansell SM, Armand P, et al. Nivolumab in patients with relapsed or refractory hematologic malignancy: preliminary results of a phase Ⅰb study[J]. J Clin Oncol, 2016, 34(23): 2698-2704. doi: 10.1200/JCO.2015.65.9789
[63]	Khodadoust MS, Rook AH, Porcu P, et al. Pembrolizu-mab in relapsed and refractory mycosis fungoides and Sézary syndrome: a multicenter phase Ⅱ study[J]. J Clin Oncol, 2020, 38(1): 20-28. doi: 10.1200/JCO.19.01056
[64]	Ansell S, Gutierrez ME, Shipp MA, et al. A phase 1 study of nivolumab in combination with ipilimumab for relapsed or refractory hematologic nalignancies (CheckMate 039)[J]. Blood, 2016, 128(22): 183. doi: 10.1182/blood.V128.22.183.183
[65]	Chen C, Liu Z, Liu J, et al. Case report: outcome and adverse events of anti-PD-1 antibody plus chidamide for relapsed/refractory Sézary syndrome: case series and a literature review[J]. Front Oncol, 2022, 12: 842123. doi: 10.3389/fonc.2022.842123
[66]	Lundin J, Hagberg H, Repp R, et al. Phase 2 study of alemtuzumab (anti CD52 monoclonal antibody)in patients with advanced mycosis fungoides/Sézary syndrome[J]. Blood, 2003, 101(11): 4267-4272. doi: 10.1182/blood-2002-09-2802
[67]	Bagot M, Porcu P, Marie-Cardine A, et al. IPH4102, a first-in-class anti-KIR3DL2 monoclonal antibody, in patients with relapsed or refractory cutaneous T-cell lymphoma: an international, first-in-human, open-label, phase 1 trial[J]. Lancet Oncol, 2019, 20(8): 1160-1170. doi: 10.1016/S1470-2045(19)30320-1
[68]	Horwitz SM, Koch R, Porcu P, et al. Activity of the PI3K-δ, γ inhibitor duvelisib in a phase 1 trial and preclinical models of T-cell lymphoma[J]. Blood, 2018, 131(8): 888-898. doi: 10.1182/blood-2017-08-802470
[69]	Arnold M, Singh D, Laversanne M, et al. Global burden of cutaneous melanoma in 2020 and projections to 2040[J]. JAMA Dermatol, 2022, 158(5): 495-503. doi: 10.1001/jamadermatol.2022.0160
[70]	Atkins MB, Lotze MT, Dutcher JP, et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993[J]. J Clin Oncol, 1999, 17(7): 2105-2116. doi: 10.1200/JCO.1999.17.7.2105
[71]	Eggermont AM, Suciu S, Santinami M, et al. Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage Ⅲ melanoma: final results of EORTC 18991, a randomised phase Ⅲ trial[J]. Lancet, 2008, 372(9633): 117-126. doi: 10.1016/S0140-6736(08)61033-8
[72]	Andtbacka RH, Kaufman HL, Collichio F, et al. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma[J]. J Clin Oncol, 2015, 33(25): 2780-2788. doi: 10.1200/JCO.2014.58.3377
[73]	Chesney J, Puzanov I, Collichio F, et al. Randomized, open-label phase Ⅱ study evaluating the efficacy and safety of talimogene laherparepvec in combination with ipilimumab versus ipilimumab alone in patients with advanced, unresectable melanoma[J]. J Clin Oncol, 2018, 36(17): 1658-1667. doi: 10.1200/JCO.2017.73.7379
[74]	Eggermont AM, Chiarion-Sileni V, Grob JJ, et al. Prolonged survival in stage Ⅲ melanoma with ipilimumab adjuvant therapy[J]. N Engl J Med, 2016, 375(19): 1845-1855. doi: 10.1056/NEJMoa1611299
[75]	Weber J, Mandala M, Del Vecchio M, et al. Adjuvant nivolumab versus ipilimumab in resected stage Ⅲ or Ⅳ melanoma[J]. N Engl J Med, 2017, 377(19): 1824-1835. doi: 10.1056/NEJMoa1709030
[76]	Eggermont AMM, Blank CU, Mandalà M, et al. Adjuvant pembrolizumab versus placebo in resected stage Ⅲ melanoma (EORTC 1325-MG/KEYNOTE-054): distant metastasis-free survival results from a double-blind, randomised, controlled, phase 3 trial[J]. Lancet Oncol, 2021, 22(5): 643-654. doi: 10.1016/S1470-2045(21)00065-6
[77]	Long GV, Menzies AM, Nagrial AM, et al. Prognostic and clinicopathologic associations of oncogenic BRAF in metastatic melanoma[J]. J Clin Oncol, 2011, 29(10): 1239-1246. doi: 10.1200/JCO.2010.32.4327
[78]	Long GV, Flaherty KT, Stroyakovskiy D, et al. Dabrafenib plus trametinib versus dabrafenib monotherapy in patients with metastatic BRAF V600E/K-mutant melanoma: long-term survival and safety analysis of a phase 3 study[J]. Ann Oncol, 2017, 28(7): 1631-1639. doi: 10.1093/annonc/mdx176
[79]	Ascierto PA, Dummer R, Gogas HJ, et al. Update on tolerability and overall survival in COLUMBUS: landmark analysis of a randomised phase 3 trial of encorafenib plus binimetinib vs vemurafenib or encorafenib in patients with BRAF V600-mutant melanoma[J]. Eur J Cancer, 2020, 126: 33-44. doi: 10.1016/j.ejca.2019.11.016
[80]	Paulson KG, Park SY, Vandeven NA, et al. Merkel cell carcinoma: current US incidence and projected increases based on changing demographics[J]. J Am Acad Dermatol, 2018, 78(3): 457-463. e2. doi: 10.1016/j.jaad.2017.10.028
[81]	D'Angelo SP, Lebbé C, Mortier L, et al. First-line avelu-mab in a cohort of 116 patients with metastatic Merkel cell carcinoma (JAVELIN Merkel 200): primary and biomarker analyses of a phase Ⅱ study[J]. J Immunother Cancer, 2021, 9(7): e002646. doi: 10.1136/jitc-2021-002646
[82]	Nghiem P, Bhatia S, Lipson EJ, et al. Three-year survival, correlates and salvage therapies in patients receiving first-line pembrolizumab for advanced Merkel cell carcinoma[J]. J Immunother Cancer, 2021, 9(4): e002478. doi: 10.1136/jitc-2021-002478
[83]	Kreicher KL, Kurlander DE, Gittleman HR, et al. Incid-ence and survival of primary dermatofibrosarcoma protuberans in the United States[J]. Dermatol Surg, 2016, 42 Suppl 1: S24-S31.
[84]	Llombart B, Serra-Guillén C, Monteagudo C, et al. Dermatofibrosarcoma protuberans: a comprehensive review and update on diagnosis and management[J]. Semin Diagn Pathol, 2013, 30(1): 13-28. doi: 10.1053/j.semdp.2012.01.002
[85]	Navarrete-Dechent C, Mori S, Barker CA, et al. Imatinib treatment for locally advanced or metastatic dermatofibrosarcoma protuberans: a systematic review[J]. JAMA Dermatol, 2019, 155(3): 361-369. doi: 10.1001/jamadermatol.2018.4940
[86]	中华医学会血液学分会红细胞疾病(贫血)学组. 中国卟啉病诊治专家共识(2020年)[J]. 中华医学杂志, 2020, 100(14): 1051-1056. doi: 10.3760/cma.j.cn112137-20200219-00349
[87]	Langendonk JG, Balwani M, Anderson KE, et al. Afamelanotide for erythropoietic protoporphyria[J]. N Engl J Med, 2015, 373(1): 48-59. doi: 10.1056/NEJMoa1411481
[88]	《中华传染病杂志》编辑委员会. 中国利什曼原虫感染诊断和治疗专家共识[J]. 中华传染病杂志, 2017, 35(9): 513-518.
[89]	卞星晨, 刘笑芬. 两性霉素B脂质体作为一线治疗药物: 巴西内脏利什曼病[J]. 中国感染与化疗杂志, 2018, 18(4): 364. https://www.cnki.com.cn/Article/CJFDTOTAL-KGHL201804006.htm
[90]	袁传杰, 杨雪, 朱渝. 内脏利什曼病临床药物治疗研究现状[J/OL]. 中华妇幼临床医学杂志(电子版), 2022, 18(4): 387-392.
[91]	So JY, Nazaroff J, Iwummadu CV, et al. Long-term safety and efficacy of gene-corrected autologous keratinocyte grafts for recessive dystrophic epidermolysis bullosa[J]. Orphanet J Rare Dis, 2022, 17(1): 377. doi: 10.1186/s13023-022-02546-9