头皮银屑病外用药物的新选择——卡泊三醇倍他米松凝胶

头皮是银屑病最常见的好发部位之一.外用药物是治疗头皮银屑病的主要方法,维生素D3衍生物和糖皮质激素是目前最主要的外用药物.卡泊三醇倍他米松凝胶(赛美尔)(Xamiol)是一种含有卡泊三醇(50 μg/g)和二丙酸倍他米松(0.5 mg/g)的新型混合凝胶制剂.该文收集了国外赛美尔凝胶的临床试验及综述等文献资料,综述了赛美尔凝胶的作用机制、疗效和安全性,及其对患者依从性及生活质量的提高.赛美尔凝胶为头皮银屑病的外用药物治疗提供了新的选择.     

外用药物联合治疗银屑病的进展

银屑病的发病是多种因素共同作用的结果,其在病理上表现为角质形成细胞增生过度、炎症浸润和真皮乳头层的血管增生扩张,所以联合使用不同作用机制、不同作用靶位和不良反应无重叠的药物,可能会提高临床治疗效果和减少毒副作用。外用药物是治疗银屑病的主要手段之一,单独使用或配合其他治疗手段,可以使绝大多数银屑病患者的病情获得理想的临床控制。糖皮质激素(以下简称激素)、维生素D衍生物、维A酸和地蒽酚是目前国外治疗银屑病的最主要外用药物。将该4种药物相互联合外用,可以明显提高疗效和降低彼此的不良反应^[1]。     

面部、躯干屈侧部位和甲银屑病治疗进展

甲、面部和身体屈侧部位银屑病因发病部位特殊,往往对多种外用治疗药物耐受性差或治疗抵抗.因此选择安全有效的治疗方法尤为重要.这些部位银屑病的治疗以外用为主,甲损害可行局部注射、光疗和放疗,必要时联合系统治疗和生物疗法,但需要更多的随机、双肓临床试验资料指导临床治疗.     

蕈样肉芽肿的治疗进展

蕈样肉芽肿是常见的原发皮肤T细胞淋巴瘤,典型临床表现分为红斑期、斑块期、肿瘤期,病程呈慢性进行性.本病的病因及发病机制尚不清楚,其治疗和预后与疾病分期有关,早期以局部治疗为主,如局部外用糖皮质激素、氮芥、光疗法和放射疗法;晚期则以联合治疗为主,如联合干扰素、维A酸类、化疗药物等.治疗虽然可使蕈样肉芽肿患者得到缓解,但中位持续缓解时间一般较短,容易复发或进展.近年来,随着对蕈样肉芽肿发病机制的研究,出现了一些新的治疗方法,如新的外用制剂及剂型、单克隆抗体、免疫偶联物、组蛋白去乙酰化酶抑制剂、蛋白酶体抑制剂、免疫系统哨点抑制剂等.     

银屑病外用治疗现状

外用药物是治疗银屑病的主要手段之一,在银屑病治疗中占有举足轻重的地位,单独使用或配合其他治疗手段,可以使绝大多数银屑病患者的病情得到临床控制。现结合个人经验,介绍银屑病的外用治疗方法及注意事项。1银屑病的外用药物外用药物有多种,可根据病情单独应用,亦可联合应用。     

斑块状银屑病系统治疗的循证证据

系统评价或荟萃分析结果以及大样本多中心随机对照试验被认为是最佳证据。银屑病最常见的类型是斑块状银屑病，系统治疗斑块状银屑病的药物主要是甲氨蝶呤、环孢素和维A酸类药物。近几年生物制剂成为新的研究热点，已有多个随机对照试验为生物制剂的疗效和安全性提供了良好的证据。概括这些药物治疗斑块状银屑病的系统评价／荟萃分析和多中心随机对照试验结果，为临床提供最佳证据。     

生物制剂在治疗甲银屑病中的进展

银屑病是一种慢性炎症性皮肤病,常累及指（趾）甲。银屑病甲损害不仅影响美观,还会引起疼痛和（或）功能障碍,严重影响患者的生活质量,且是银屑病关节损害的独立预测因素。甲的结构及甲床的低渗透性使甲银屑病的治疗充满挑战。常规治疗包括局部外用药物、皮损内注射及系统药物治疗等,治疗周期较长,患者用药依从性差。近年来,随着生物制剂的问世,极大地提高了银屑病患者的临床疗效,同时也对银屑病甲损害有所改善,但在国内整体使用率不高,尚缺乏针对甲银屑病的疗效及安全性的循证医学证据。该文就国内外生物制剂在甲银屑病中的应用做一阐述,以期为临床医生提供帮助。     

银屑病的其他外用制剂

银屑病的其它外用药物种类较多,包括焦油类、蒽林和角质松解剂等,随着对银屑病治疗临床实践研究的深入,掌握这类药物的正确应用方法,并应用于临床,对加强银屑病的外用疗法具有重要意义。本文结合近年国内外相关文献,对治疗银屑病的其它类外用药物进行了归纳和总结,旨在为临床医生提供关于这类药物的较为全面的信息及最新研究进展。     

泽它洗剂治疗头皮银屑病及脂溢性皮炎的临床疗效观察

泽它洗剂治疗头皮银屑病及脂溢性皮炎的临床疗效观察吴建华①黄平②廖万清①银屑病及脂溢性皮炎是常见并易复发的慢性炎症性皮肤病，外用药物能够控制症状，但是头皮银屑病和头皮脂溢性皮炎，由于发病部位特殊，给患者外用药物带来不方便。最近我们用山东德美克制药有限公...     

局部应用血小板活化因子拮抗剂治疗寻常型银屑病的作用——临床和免疫组化研究

已证实血小板活化因子存在于免疫性皮肤反应和银屑病皮损中。为探讨血小板活化因子拮抗剂在治疗银屑病中的作用,本研究选择10例慢性斑块型银屑病患者,局部外用血小板活化因子拮抗剂进行双盲对照研究,治疗前、后评价临床反应和通过免疫组化了解局部炎症、分化和增殖程度变化。本研究证实,10％血小板活化因子拮抗剂溶液治疗银屑病4周后,临床和细胞生物学水平显示无效。对于这一阴性结果,最可能的解释是在银屑病发病机理中,血小板活化因子不是一个重要的作用因子。     

Novel Oral Therapies for Psoriasis and Psoriatic Arthritis

Several classes of new oral therapy are in use or in development for the treatment of psoriasis. Despite the high efficacy of biologics, new oral therapies remain important as patients generally prefer this mode of administration and they offer an alternative risk–benefit profile. In this review, we discuss the novel modes of action of these drugs, including modulation of cellular pathways involving diverse targets such as Janus kinase, phosphodiesterase 4, sphingosine 1-phosphate, A3 adenosine receptor and rho-associated kinase 2. We review the available evidence around licensed drugs (apremilast) and drugs that are advanced (tofacitinib) or early (ponesimod, baricitinib, peficitinib, INCB039110, CF101, KD025) in the development pipeline. The key limitations of these oral therapies are their modest efficacy profile (apremilast, ponesimod) and the limitations of their safety profile (tofacitinib, ponesimod), while the evidence for the early pipeline drugs are at phase II level only. Potential niches of current unmet needs include apremilast for patients with concomitant psoriatic arthritis, as combination treatments with biologic therapies, and/or for patients in whom multiple biologic therapies have failed due to immunogenicity and secondary inefficacy. The present knowledge gap regarding these novel drugs includes the need for longer clinical trials or observational studies to evaluate safety, and randomised phase III trials for the early pipeline drugs. We conclude that further research and data are necessary to conclusively establish the role of these agents in the current psoriasis treatment paradigm.     

Tofacitinib y otros inhibidores de las cinasas en el tratamiento de la psoriasis

Protein kinases play a crucial role in the intracellular signaling pathways involved in inflammation and cell proliferation. Advances in our understanding of these metabolic pathways and of the role played by intracellular signaling in the pathogenesis of psoriasis have led to research in this area and the development of a new class of drugs for the treatment of psoriasis and other inflammatory processes. Since kinase inhibitors are small molecules, oral and topical treatments are possible. The future role of these molecules in the therapeutic arsenal used to treat psoriasis is as yet unknown because in most cases they are still in the early stages of research. The fact that these drugs may cost much less than biologic therapies could favor their approval in coming years. Tofacitinib, a Janus kinase inhibitor, is the drug that has reached the most advanced stage of research and has shown the most promising results.     

Reformulations of well‐known active ingredients in the topical treatment of psoriasis vulgaris can improve clinical outcomes for patients

Although the majority of patients with psoriasis vulgaris are treated exclusively with topical therapies, research to develop more effective topical therapies that are associated with higher patient satisfaction has lagged behind the development of systemic agents. The aim of this literature review was to determine whether there is documented evidence that applying an innovative approach to improving the formulation of active ingredients commonly used in the topical treatment of psoriasis can have a positive effect on clinical outcomes and patient‐reported outcomes (PROs). The Embase and PubMed databases were searched for articles published between 2001 and 2016 that made direct head‐to‐head comparisons of different formulations of an active pharmaceutical ingredient (API), focusing on clinical outcomes and PROs. In total, 22 publications on APIs or API combinations met the eligibility criteria (19 head‐to‐head clinical trials, one pooled analysis, one health‐economic modelling study and one systematic review). Significant clinical benefit associated with the use of a reformulated API over an older formulation was reported in three trials of clobetasol propionate, one trial of calcipotriol, three trials of betamethasone and five trials/pooled analyses of calcipotriol/calcipotriene + betamethasone dipropionate (Cal/BD) formulations. Significantly improved PROs associated with the use of a reformulated API over an older formulation were reported in three trials of clobetasol propionate, one trial of betamethasone valerate and two trials of Cal/BD formulations. These results demonstrate that the innovative reformulation of APIs used in the treatment of psoriasis can produce therapies that attain significantly improved clinical outcomes and PROs. This suggests that improvement in topical therapy for psoriasis need not only to be achieved by the identification of new targets and the development of new APIs, but that improvement in the vehicle used to deliver existing APIs has the potential to result in significant clinical and patient benefits.     

痤疮药物治疗研究进展

痤疮药物治疗近年取得一定进展。多种新型药物的临床研究结果显示出良好的疗效及安全性, 如四环素类抗生素萨瑞环素(sarecycline)、第四代外用维A酸类药物曲法罗汀(trifarotene)、首个局部雄激素受体拮抗剂clascoterone、一氧化氮释放凝胶4% SB204和外用米诺环素泡沫制剂4% FMX101等。本文综述痤疮药物治疗研究的新进展。     

Combination therapy in the treatment of psoriasis

In addition to topical monotherapy for mild and systemic monotherapy for moderate to severe psoriasis, combination therapy plays an important role in daily practice. Although clinical trials almost exclusively evaluate monotherapy regimens, in real life psoriasis patients are usually treated with combination therapies. All combinations are used, topical/topical, topical/UV‐light, topical/systemic or UV‐light/systemic. Often not only two but more drugs/therapies are combined. Not every combination provides additive or synergistic effects. Some combinations are not possible and may be regarded as contraindications. Data on a benefit‐risk‐assessment are much more sparse in medical literature as compared to monotherapies. We summarize current knowledge about the use of combination therapies in psoriasis on the basis of published literature in the form of a table to show which combinations are possible, useful or which can not be recommended. This provides a quick overview of available options.     

[开放获取] 小分子靶向药物：银屑病治疗的新选择

【摘要】 随着免疫学和分子生物学的飞速发展，银屑病发病机制研究取得了显著的进步，靶向发病机制中关键分子的治疗策略也取得了很大的成功。除生物制剂外，银屑病小分子靶向药物日益受到关注，以磷酸二酯酶4、Janus激酶、酪氨酸激酶2等为主要靶分子，越来越多的候选药物在研究中观察到较好的疗效，部分药物已获批用于临床，在银屑病的治疗中发挥独特的作用。     

Diet and psoriasis: experimental data and clinical evidence

Psoriasis is considered as a T-cell-mediated inflammatory skin disease which is characterized by hyperproliferation and poor differentiation of epidermal keratinocytes. While susceptibility to psoriasis is inherited, the disease is influenced by environmental factors such as infections and stress. Diet has been suggested to play a role in the aetiology and pathogenesis of psoriasis. Fasting periods, low-energy diets and vegetarian diets improved psoriasis symptoms in some studies, and diets rich in n-3 polyunsaturated fatty acids from fish oil also showed beneficial effects. All these diets modify the polyunsaturated fatty acid metabolism and influence the eicosanoid profile, so that inflammatory processes are suppressed. Some patients with psoriasis show an elevated sensitivity to gluten. In patients with IgA and/or IgG antigliadin antibodies the symptoms have been shown to improve on a gluten-free diet. The active form of vitamin D, 1,25-dihydroxyvitamin D(3), exhibits antiproliferative and immunoregulatory effects via the vitamin D receptor, and thus is successfully used in the topical treatment of psoriasis. In this review, dietary factors which play a role in psoriasis are assessed and their potential benefit is evaluated. Furthermore, the risk of drug-nutrient interactions in psoriasis therapy is discussed.     

Topical calcitriol – studies on local tolerance and systemic safety

Calcitriol 3 μg g⁻¹ ointment (Silkis ointment®, Galderma Laboratories) is a new treatment for psoriasis. Calcitriol is the biologically active metabolite of vitamin D₃. It induces keratinocyte differentiation, inhibits keratinocyte, T-cell and fibroblast proliferation, and inhibits the production of some inflammatory mediators, all contributors to the pathogenesis of psoriasis. Preclinical studies have shown an effect of topical calcitriol on calcium homeostasis at doses higher than those in clinical use. No adverse local events were observed when calcitriol was applied to animal skin. Phase I clinical studies confirmed that calcitriol 3 μg g⁻¹ ointment is well tolerated in humans. These studies have demonstrated that at the minimal effective concentration of 3 μg g⁻¹, calcitriol ointment has no discernible photosensitizing or phototoxic potential and no skin irritant or allergic potential in healthy volunteers. Its low systemic absorption through human skin is unlikely to significantly affect calcium homeostasis. This paper summarizes the findings of the preclinical and early clinical studies that provided the foundation of the later Phase II and III clinical trials on efficacy and safety with topical calcitriol 3 μg g⁻¹ ointment for the treatment of plaque psoriasis.     

Calcipotriol plus Betamethasondipropionat-Gel in der Behandlung der Kopfhautpsoriasis

Scalp psoriasis has a significant psychosocial impact on individuals affecting their quality of life. It occurs in 50–80% of patients with psoriasis and may be the only affected area of the body. Current topical therapies for scalp psoriasis are difficult or unpleasant to apply, resulting in decreased adherence and efficacy. A combination of calcipotriol and betamethasone dipropionate in a gel formulation has been developed and approved in Germany for the treatment of scalp psoriasis. Multiple randomized controlled clinical trials have confirmed the efficacy and safety of the new formulation. After two weeks, 60% of patients showed significant improvement; this climbed to 70%, after eight weeks. It may be safely used for up to 52 weeks. No cases of atrophy, striae, or steroid purpura were noted in two 52-week studies. Although scalp psoriasis can often be adequately treated with topical therapy, there is a need for treatment recommendations and algorithms for severe forms and for patients with extended body involvement, taking the combination of systemic and topical treatment and the presence of comorbidities into account.