Gupta A K, Fleckman P, Baran R
Department of Medicine, Sunnybrook and Women's College Health Sciences Center, University of Toronto, Ontario, Canada.
J Am Acad Dermatol. 2000 Oct;43(4 Suppl):S70-80. doi: 10.1067/mjd.2000.109071.
Onychomycosis is a relatively common condition affecting toenails more than fingernails. It is caused predominantly by dermatophytes. Onychomycosis can cause pain and discomfort and has the potential to be a source of morbidity.
We evaluated the efficacy and safety of ciclopirox nail lacquer solution 8% used to treat onychomycosis of the toe in the United States and in centers worldwide.
Two identically designed, double-blind, vehicle controlled, parallel group multicenter studies were performed in the United States to evaluate the use of ciclopirox nail lacquer to treat mild to moderate toe onychomycosis caused by dermatophytes. In the first study, 223 patients were randomized to treatment (ciclopirox group: 112, vehicle group: 111), and in the second study, 237 subjects were randomized (ciclopirox group: 119, vehicle group: 118). Before randomization, patients were to have clinical features of onychomycosis in at least one great toe with positive light microscopic examination and a positive dermatophyte culture. The test material was applied daily for a period of 48 weeks to all toenails and affected fingernails, covering the entire nail plate and approximately 5 mm of surrounding skin. At baseline, subjects had between 20% to 65% area of target nail involved. Physician's assessments were carried out every 4 weeks, and mycologic evaluation and photographic planimetry using standardized photographs were performed every 12 weeks during the 48 weeks of treatment. In studies conducted outside the United States, patients were also to have clinical, microscopic, and culture evidence of onychomycosis. However, these studies included some patients infected with nondermatophyte organisms (eg, Candida species), and the area of nail involvement was generally greater than observed in the US studies. Treatment regimens also varied in the non-US studies with lacquer applications that were sometimes less frequent than the once daily treatment used in the US studies (eg, alternate day or twice weekly). In addition, the typical duration of treatment was 6 months in the non-US studies as compared with 48 weeks in the United States. Outcome measures were similar to those used in the US trials, although a non-photographic planimetric method was used to quantify disease extent.
Data from the pivotal US trials have demonstrated that ciclopirox nail lacquer 8% topical solution is significantly more effective than placebo in the treatment of onychomycosis caused by Trichophyton rubrum, and of mild to moderate toe onychomycosis without lunula involvement. At the end of the 48-week treatment period, the mycologic cure rate (negative culture and negative light microscopy) in study I was 29% vs 11% in the ciclopirox and vehicle groups, respectively. Similarly, the mycologic cure rate for study II was 36% vs 9%, respectively. In the non-US studies, the mycologic cure rates ranged from 46.7% to 85.7%. In addition, ciclopirox nail lacquer has demonstrated a broad spectrum of activity with efficacy against Candida species and some nondermatophytes in non-US studies. Ciclopirox nail lacquer is considered extremely safe regarding causally related treatment emergent adverse-effects (TEAEs), with most TFAEs transient and localized to the site of action (eg, erythema and application site reaction). In the US studies, TFAEs were generally mild and cleared while the patient continued to use the nail lacquer.
Studies conducted worldwide demonstrate the efficacy of ciclopirox nail lacquer for the treatment of finger and toe onychomycosis. Both controlled and open-label studies confirm the excellent safety profile of this topical therapy. Thus, the nail lacquer provides a treatment choice with a favorable benefit-to-risk ratio. With its novel mechanism of action and its topical route of administration, ciclopirox nail lacquer offers an innovative approach to the treatment of this often difficult-to-manage disease
甲癣是一种相对常见的疾病，对趾甲的影响比对指甲更为常见。它主要由皮肤癣菌引起。甲癣可导致疼痛和不适，并有引发发病的可能性。
我们评估了8%环吡酮甲涂剂溶液在美国及全球各中心用于治疗趾甲甲癣的疗效和安全性。
在美国进行了两项设计相同、双盲、赋形剂对照、平行组多中心研究，以评估环吡酮甲涂剂治疗由皮肤癣菌引起的轻至中度趾甲甲癣的效果。在第一项研究中，223例患者被随机分组接受治疗（环吡酮组：112例，赋形剂组：111例），在第二项研究中，237例受试者被随机分组（环吡酮组：119例，赋形剂组：118例）。在随机分组前，患者至少有一个拇趾具有甲癣的临床特征，且光学显微镜检查和皮肤癣菌培养呈阳性。将受试材料每日应用于所有趾甲和受累指甲，覆盖整个甲板及周围约5毫米的皮肤。基线时，受试者目标指甲受累面积在20%至65%之间。每4周进行一次医生评估，在48周的治疗期间，每12周进行一次真菌学评估，并使用标准化照片进行图像平面测量。在美国以外进行的研究中，患者也需有甲癣的临床、显微镜检查和培养证据。然而，这些研究包括一些感染非皮肤癣菌的患者（如念珠菌属），且指甲受累面积通常大于美国研究中观察到的情况。非美国研究中的治疗方案也有所不同，甲涂剂的应用频率有时低于美国研究中每日一次的治疗频率（如隔日或每周两次）。此外，非美国研究中的典型治疗疗程为6个月，而美国为48周。结局指标与美国试验中使用的指标相似，尽管使用了非图像平面测量方法来量化疾病范围。
美国关键试验的数据表明，8%环吡酮甲涂剂外用溶液在治疗红色毛癣菌引起的甲癣以及无甲半月受累的轻至中度趾甲甲癣方面明显比安慰剂更有效。在48周治疗期结束时，研究I中环吡酮组和赋形剂组的真菌学治愈率（培养阴性且光学显微镜检查阴性）分别为29%和11%。同样，研究II的真菌学治愈率分别为36%和9%。在非美国研究中，真菌学治愈率在46.7%至85.7%之间。此外，在非美国研究中环吡酮甲涂剂已显示出广泛的活性，对念珠菌属和一些非皮肤癣菌有效。就因果相关的治疗突发不良事件（TEAE）而言，环吡酮甲涂剂被认为极其安全，大多数TEAE是短暂的，且局限于作用部位（如红斑和用药部位反应）。在美国研究中，TEAE一般较轻，在患者继续使用甲涂剂时会消退。
全球范围内进行的研究证明了环吡酮甲涂剂治疗手指甲和趾甲甲癣的疗效。对照研究和开放标签研究均证实了这种局部治疗的良好安全性。因此，甲涂剂提供了一种具有良好效益风险比的治疗选择。凭借其新颖的作用机制和局部给药途径，环吡酮甲涂剂为治疗这种通常难以管理的疾病提供了一种创新方法。
