Reports

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

PRIORITY PRESS - American Academy of Dermatology (AAD) Summer Academy Meeting 2012

Boston, Massachusetts / August 15-19, 2012

Boston - The first treatments directed specifically at improving the mechanical properties of nail plates are reaching clinical practice. In data presented at the summer meeting of the AAD, these treatments appear to improve nail strength and appearance across multiple etiologies for abnormal nail growth. In the past, options for restoring the balance of water and keratin needed for healthy nails were extremely limited. Improvements in nail appearance were largely dependent on controlling the underlying pathologic process, such as psoriasis, or protecting nails from further exposures to external sources of injury. While these strategies remain important, the newer treatments directly targeting the nail appear to improve nail appearance more quickly and more effectively. Damaged nails, a significant cosmetic problem for those affected, can meaningfully limit occupational options in which hand appearance has an impact. A more effective option for restoring nail appearance has been a significant unmet medical need.

Chief Medical Editor: Dr. Léna Coïc, Montréal, Quebec

The list of causes of nail dystrophy is long and includes exposure to noxious agents, prolonged water immersion and systemic diseases, such as psoriasis. These can produce varying degrees of nail brittleness, splitting, discoloration, deformed growth and poor growth. Most of the disorders and abnormalities share a disturbance in the balance of water content to keratin. Until recently, there have been no treatments with a substantial effect on restoring this balance directly. Even topical corticosteroids for psoriatic nails are thought to address the inflammatory component rather than the key variables in nail matrix formation. A recently approved option in the United States (now approved in Canada under the name Veralac) appears to be the first among treatments that act specifically on nail mechanical properties.

“Many topical treatments are offered by dermatologists to improve nail growth and appearance with few or no data to support meaningful improvements. The current effort to evaluate newer therapies in double-blind trials has the potential to provide an evidence basis for managing these disorders,” stated Dr. C. Ralph Daniel, University of Mississippi Medical Center, Jackson. He suggested that improvements in nail appearance can be achieved with anti-inflammatory agents or antibacterial agents when inflammation or infection, respectively, are involved, but many treatments, such as application of petroleum jelly, are used on the level of home remedies.

New Clinical Findings

For psoriasis, double-blind data for a composite topically applied product that was recently approved for fragile nails by the U.S. Food and Drug Administration (FDA) was presented here at the summer meeting of the AAD. Although the agent—which is a hydrosoluble topical nail application containing hydroxypropyl chitosan (HPCH), Equisetum arvense (horsetail plant extract) and methylsulphonyl-methane (MSM)—became the only agent licensed by the FDA to directly treat nail abnormalities when it was approved last year, the new evidence of efficacy in psoriasis substantiates its versatility.

“The study confirmed that this agent is effective. Significant clinical benefit was observed even after 16 weeks on an intention-to-treat [ITT] analysis,” reported Dr. Franca Cantoresi, La Sapienza University, Rome, Italy. “Considering the poor clinical outcome of the available systemic and topical treatments for nail psoriasis, this [hydrosoluble] nail lacquer is a valid, effective and safe option in decreasing signs of [nail] dystrophy in psoriatic patients.”

In the study of nail psoriasis, 87 patients with mild to moderate involvement of the nail bed and/or matrix were randomized to apply the HPCH/MSM/E. arvense extract combination nail lacquer or a placebo once daily at night. Patients were not permitted to have received a systemic agent for psoriasis within the past 3 months or apply any other products to the nail, including polishes. Patients were also required to have negative mycology tests. Treatment efficacy was evaluated every 4 weeks by investigators blinded to the treatment using the modified Nail Psoriasis Severity Index (mNAPSI). The primary end point of clinical cure on mNAPSI, which has a scale of 1 to 96, was established as a score of ≤4. HPCH nail lacquer has no substantial odour and no colour and is applied like nail polish.

On the ITT analysis at 24 weeks, 55% of those randomized to the nail lacquer achieved the primary end point of clinical cure vs. 31.7% of those randomized to placebo (P<0.05). On the per-protocol analysis limited to those who completed all 24 weeks of treatment, the proportion of those cured climbed to 67.7% of those randomized to the active treatment vs. 40.6% of those on placebo (Figure 1). At the 16-week analysis, which was a predefined secondary end point, the clinical cure rates for active treatment and placebo were 41.9% and 18.7%, respectively (P<0.05).

Figure 1

There were no side effects associated with either active therapy or placebo. While most patients in both groups (96.8% and 78.1%, respectively) found their assigned treatment to have good or very good acceptability, it is notable that 21.9% of the placebo patients vs. only 3.2% of those receiving the HPCH nail lacquer characterized the acceptability as poor.

The objective clinical data leading up to the license dates back to a series of clinical trials that began to be published in 2006. Unlike nail softeners, which can reduce brittleness in dehydrated nails but do not increase strength, the 3 active ingredients in this hydrosoluble nail lacquer appear to provide a synergistic interaction that protects the nails while encouraging normal growth. According to experimental and clinical studies, the HCPH penetrates the nail to improve hydration, E. arvense provides silica that strengthens the nail and the sulfur content of the MSM encourages nail growth.

Other Study Results

The efficacy of the nail lacquer in psoriatic nails is a major extension of the evidence of efficacy against nail splitting and fragility. In one controlled and published trial of women with nail plate alterations of various etiologies, 90% of those on active therapy improved and 10% did not change. In contrast, 5% of controls improved, 90% were unchanged and 5% worsened (Sparavigna et al. J Plastic Derm 2006;2:31-8). Scanning electron microscopy in that study was able to demonstrate clear changes in nail characteristics before and after treatment relative to controls.

A study recently presented in abstract form associated the nail lacquer with objective changes in hardness, tensile strength and structure (Mailland et al. 2012, Abstract 35, Fourth Skin and Formulation Symposium, Lyon, France).

The primary end point of the study presented here at the AAD meeting was cure, but a large proportion of those not cured at 24 weeks chose to remain on therapy because of progressive improvement over the course of the study. It is notable that complete responses continued to accrue over time, according to Dr. Cantoresi. In one case of longstanding nail deformity, complete resolution took 27 months, suggesting that the affect of treatment on nail growth dynamics is cumulative.

“There really has not been much out there in terms of therapies specifically for nail psoriasis” commented Dr. Phoebe Rich, Oregon Health Sciences University, Portland. She was intrigued by the double-blind data presented here at the summer AAD meeting, where she led a review session on treatment of nail psoriasis. In her discussion, she suggested that systemic therapies, including biologics, are sometimes required to control severe nail involvement even when skin lesions have been controlled, but suggested that topical therapies with activity limited to the nails would be an important advance.

The difficulty of restoring a balance of water content and keratin has been the obstacle in the past to direct treatments to restore nail matrix and mechanical properties. While the HPCH nail lacquer is the only treatment approved for nail fragility, the growing understanding of molecular mechanisms in healthy nail production have led to other options that are now in development. Such treatments are expected to have a major impact on the quality of life for individuals with significant nail deformities.

“It is difficult to underestimate the burden imposed by disorders affecting the nails. This is a major quality-of-life issue. For those who are truly bothered or find that nail deformities are affecting their work, it is important to aggressively pursue an effective remedy,” Dr. Rich observed.

Summary

A treatment for relieving the signs and symptoms of onychodystrophy recently approved in Canada and in the United States has also been found effective for normalizing nail growth disrupted by psoriasis. This appears to be the first treatment to act specifically on nail plate mechanics and growth. Based on restoring the balance of water content and keratin to encourage matrix formation, the treatment demonstrates that the molecular processes that underlie nail formation can be addressed effectively for nail-specific benefits and improve the overall appearance of the nail.