Martin L
Service de Dermatologie, CHU d'Angers, 4 rue Larrey, 49933 Angers cedex 9, France.
Ann Dermatol Venereol. 2010 Dec;137 Suppl 4:S165-76. doi: 10.1016/S0151-9638(10)70043-0.
Although the isolated clinical cases published are sometimes helpful in individual situations in which the therapeutic options have been exhausted, this type of publication cannot be generalized. For this reason, the selection presented covering the period from November 2009 to October 2010 is to a very large extent based on controlled trials, either because they contribute important information or because they raise great hope for a significant number of patients. For the first time in cutaneous oncology, a treatment (ipilimumab) has significantly increased overall survival in patients with metastatic melanoma (phase III), although this gain remains modest (4-6 months) and adverse immunological effects are frequent (30-40%). A phase I trial with treatment specifically targeting the mutant BRAF protein has shown an objective response in 81% of the patients treated in the metastatic phase of melanoma, thus allowing its development to be pursued. Grouping two studies in a rare tumor such as dermatofibrosarcoma also gives hope with imatinib as a neoadjuvant treatment when the initial tumor is inoperable, with, however, an inconsistent response of approximately 50% and only if the tumor presents reorganization of chromosomes 17 and 22. Cutaneous inflammatory diseases are still dominated by dual therapies in psoriasis, with, notably, an effectiveness trial on etanercept at different doses not showing a difference in efficacy depending on dose for the joint component of psoriasis, but also by the publication of a direct comparison of two dual therapies, ustekinumab versus etanercept. In atopic dermatitis, a controversial article invites one to reflect upon the progress made in the management of children by clinical nurses, as in the Netherlands and in Great Britain, in an attempt to contend with the shortage of dermatologists. Since the use of biotherapies is not the prerogative of psoriasis, infliximab was assessed in a phase II trial in Verneuil disease without demonstrating significant efficacy on the main criterion, but it did show a tendency to reduce the score used. This trial suffered from a weakness both in methodology and statistical power, thus precluding any conclusion. The rarity of therapeutic trials on drug eruptions warrants their mention. A French phase II study gives a glimpse of a trend toward efficacy in terms of survival in the treatment of toxic epidermal necrolysis with cyclosporine. As for infectious dermatosis and sexually transmitted infections, a French multicenter study has shown significantly higher efficacy with ivermectin than with malathion in treating pediculosis without increasing the side effects. Today, however, this systemic treatment cannot be a first-line treatment outside of certain specific situations. A large cohort study (somewhat unsatisfactory in its methodology) has not demonstrated the teratogenicity of antiherpes treatments in 830,000 infants. In prevention of HIV transmission, no microbicidal gel had shown efficacy to date. This has now been accomplished in South Africa with a 1% tenofovir gel. The results of a preliminary trial on therapeutic vaccination against HPV16 proposed to women who are carriers of cervical intraepithelial neoplasia opens the way for wide vaccine therapy of cutaneous virus-induced neoplasia. In conclusion, several articles analyzing the dermatology literature provide an opportunity to reflect on the quality of such articles, Boutron's being absolutely in-dis-pen-sa-ble!
尽管已发表的个别临床病例有时在治疗选择已穷尽的个别情况下有所帮助,但这类出版物不能一概而论。因此,本次呈现的涵盖2009年11月至2010年10月期间的内容在很大程度上基于对照试验,要么是因为它们提供了重要信息,要么是因为它们给大量患者带来了很大希望。在皮肤肿瘤学领域,一种治疗方法(伊匹单抗)首次显著提高了转移性黑色素瘤患者的总生存期(III期),尽管这种生存期的延长仍然有限(4 - 6个月),且免疫不良反应频繁(30 - 40%)。一项针对突变BRAF蛋白的特异性治疗的I期试验显示,在黑色素瘤转移阶段接受治疗的患者中,81%有客观反应,从而使其得以继续研发。将两项针对罕见肿瘤(如皮肤纤维肉瘤)的研究合并起来,对于伊马替尼作为初始肿瘤无法手术切除时的新辅助治疗也带来了希望,然而,其反应不一致,约为50%,且仅当肿瘤出现17号和22号染色体重排时有效。皮肤炎症性疾病在银屑病方面仍以联合治疗为主,特别是一项关于不同剂量依那西普的有效性试验表明,对于银屑病关节症状,疗效并不因剂量而异,同时还发表了两种联合治疗(优特克单抗与依那西普)的直接比较。在特应性皮炎方面,一篇有争议的文章促使人们思考荷兰和英国临床护士在儿童管理方面取得的进展,以应对皮肤科医生短缺的问题。由于生物疗法并非银屑病所特有,英夫利昔单抗在一项II期试验中用于治疗瘢痕性类天疱疮,但未在主要标准上显示出显著疗效,但确实显示出有降低所使用评分的趋势。该试验在方法学和统计效力方面都存在缺陷,因此无法得出任何结论。药物性皮疹的治疗试验很少见,因此值得一提。一项法国的II期研究显示,环孢素治疗中毒性表皮坏死松解症在生存方面有疗效趋势。至于感染性皮肤病和性传播感染,一项法国多中心研究表明,伊维菌素治疗头虱的疗效显著高于马拉硫磷,且未增加副作用。然而,如今这种全身治疗在某些特定情况之外不能作为一线治疗。一项大型队列研究(其方法学存在一定不足)未在83万名婴儿中证明抗疱疹治疗有致畸性。在预防HIV传播方面,迄今为止没有一种杀微生物凝胶显示出疗效。现在南非有一种1%替诺福韦凝胶已取得了成效。一项针对携带宫颈上皮内瘤变的女性进行的HPV16治疗性疫苗接种的初步试验结果为皮肤病毒诱导的肿瘤的广泛疫苗治疗开辟了道路。总之,几篇分析皮肤病学文献的文章为反思此类文章的质量提供了机会,布特龙的文章绝对不可或缺!