Topical Cyclosporine Versus Emulsion Vehicle for the Treatment of Brittle Nails: A Randomized Controlled Pilot Study
October 2014 | Volume 13 | Issue 10 | Original Article | 1232 | Copyright © October 2014
Julian Mackay-Wiggan MD MS,a Jackleen Marji MD PhD,a John G. Walt MBA,b Angela Campbell,a Carol
Coppola,a Bibhas Chakraborty PhD,c David A. Hollander MD MBA,b and Scott M. Whitcup MDb
aColumbia University Medical Center, Department of Dermatology, New York, NY
bAllergan, Inc., Irvine, CA
cColumbia University Medical Center, Department of Biostatistics, New York, NY
Abstract
BACKGROUND: Limited options are available for the treatment of brittle nail syndrome.
OBJECTIVE: To assess the efficacy and safety of topical cyclosporine emulsion (CsAE) versus emulsion (vehicle) alone in the treatment of brittle nail syndrome.
RESULTS: Twenty-four patients were randomized to topical CsAE emulsion or emulsion (vehicle) for 24 weeks. Four fingernails of each patient were included; the 2 most severe brittle nails and the second most normal nail were treated with the same medication. The fourth nail, the most normal nail, remained untreated and was used to assess nail growth. The prespecified primary endpoint was change from baseline in Physician Global Assessment (PGA) score (0 to 5 scale) at each follow-up visit. Safety evaluations were conducted at each visit.
RESULTS: In the intent-to-treat population (n=12 for each treatment arm), the PGA score for treated nails improved from baseline (CsAE, 0.7 to 1.4; emulsion, 0.7 to 1.5;
P<0.05 for each), with no significant between-group differences. Untreated nails did not improve in overall appearance (0.0 to 0.3 grade;
P>0.05). Statistically and clinically significant improvement from baseline was reported for nail length/appearance in both CsAE and vehicle groups.
LIMITATIONS: Sample size was relatively small. The difference in PGA between treated and untreated nails was not analyzed. Baseline disease severity may have been too mild, limiting detection of efficacy.
CONCLUSIONS: Both CsAE and emulsion vehicle applied topically appeared to improve signs and symptoms of brittle nail syndrome and were well tolerated. These findings warrant corroboration in a larger population and inclusion of comparison with an inactive control and a higher concentration of CsAE, the former which may help in distinguishing the efficacy of vehicle emulsion from CsAE.
J Drugs Dermatol. 2014;13(10):1232-1239.
INTRODUCTION
The term “brittle nail syndrome†refers to nails that tend to peel, chip, split, crack, fray, or layer, and are fragile, thin, ragged, rough, dull, brittle, and/or break easily. This common medical condition affects approximately 30% of women (twice the percentage of men), with a higher prevalence among the elderly.1
Several factors, including anemia, biotin deficiency, or cysteine deficiency,2,3 have been postulated as causes of nail brittleness. Another proposed causative or exacerbating factor is nail plate dehydration,4,5 either from repetitive cycles of hydration and dehydration related to hand washing or from dehydrating chemicals, such as those found in nail enamel and cuticle removers.6,7 Characteristic features of brittle nail syndrome demonstrated by electron microscopy have been reproduced in normal nail clippings repeatedly exposed to cycles of wetting and drying.8 Treatment of brittle nails currently involves restoration and maintenance of nail plate hydration by minimizing exposure to dehydrating chemicals and by use of moisturizers, such as alpha hydroxy acids.
Chronic inflammation also is believed to be a possible cause or contributor.9 Supporting this hypothesis is the fact that nail pathology associated with psoriasis, a T-cell–mediated inflammatory disorder, may manifest with similar features. Topical cyclosporine, a T-cell inhibitor and topical immunomodulator with anti-inflammatory effects, has been used successfully at concentrations of 10%10 and 70%11 to improve signs and symptoms of nail psoriasis.10,11 Topical cyclosporine ophthalmic emulsion is approved by the US Food and Drug Administration (FDA) to increase tear production in patients with tear suppression presumed to be due to ocular inflammation. Because nail psoriasis is caused by chronic inflammation, and brittle nail syndrome has similar clinical features that may be due (at least in part) to chronic inflammation, we hypothesized that topical cyclosporine may improve signs and symptoms of brittle nail syndrome.
The objective of this study was to assess the efficacy and safety of topical cyclosporine emulsion 0.05% (CsAE; Restasis Ophthalmic Emulsion, Allergan, Inc., Irvine, CA) versus emulsion (CsAE vehicle) alone (Refresh Dry Eye Therapy®, Allergan, Inc.,
