Improvement seen in both groups at weeks 6 and 12 but no significant intergroup difference. ANCOVA indicates analysis of covariance; ANOVA, analysis of variance; PLE, Polypodium leucotomos extract.
Improvement seen in both groups at weeks 6 and 12 but no significant intergroup difference. ANCOVA indicates analysis of covariance; PLE, Polypodium leucotomos extract.
Ahmed AM, Lopez I, Perese F, Vasquez R, Hynan LS, Chong B, Pandya AG. A Randomized, Double-Blinded, Placebo-Controlled Trial of Oral Polypodium leucotomos Extract as an Adjunct to Sunscreen in the Treatment of Melasma. JAMA Dermatol. 2013;149(8):981-983. doi:10.1001/jamadermatol.2013.4294
Treatments for melasma include photoprotection in conjunction with topical agents such as hydroquinone, retinoids, or combinations. These regimens, while reasonably effective, are hindered by adverse effects such as irritation and ochronosis.1,2 Aggressive topical sunscreen use improves melasma as monotherapy.3 However, compliance with frequent sunscreen application is difficult; a more convenient and effective photoprotective regimen is needed. We assessed the effectiveness of Polypodium leucotomos extract (PLE), an oral, commercially available UV radiation protectant, as an adjunct to once-daily topical sunscreen application in the treatment of melasma.
The sample size was calculated from results of a previous study using topical hydroquinone in which patients with melasma improved significantly with daily application of hydroquinone, 4%, cream with or without 4 salicylic acid peels over a period of 8 weeks.4 The primary end point was improvement in the melanin index, defined as the difference between pigmented and adjacent normal skin using narrowband reflectance spectrophotometry (Mexameter; Courage and Khazaka Inc). For our treatment group, we estimated the mean (SD) improvement in the melanin index compared with that in those receiving placebo to be 11.7 (13.0) points, based on the reported findings of Kodali et al.4 A sample size of 20 patients per study arm was required to detect this difference, assuming a type I error of 0.05 and 80% power, using a 2-sided, 2–independent sample t test.
We recruited Hispanic women with melasma via announcement on a Spanish-language news station in Dallas, Texas. Approximately 125 subjects were screened, and 40 were enrolled. Subjects were required to have a diagnosis of moderate to severe facial melasma, defined as a melanin index of 30 or greater. Pregnant and lactating subjects and those who recently used other treatments for melasma were excluded. The study protocol was approved by our university institutional review board.
The 40 subjects were randomized to receive either 240-mg doses of oral PLE or placebo 3 times daily for 12 weeks. All subjects were given a standard, broad-spectrum, topical sunscreen (sun-protection factor, 55) to use every morning. The primary outcome measure was change in melanin index from baseline at weeks 6 and 12. Assessment of melasma area and severity index (MASI) and melasma-related quality-of-life (MelasQOL) were performed as secondary end points. All assessments were performed by blinded investigators. All subjects commenced study participation in May 2010 and completed the study in August 2010.
Thirty-three of 40 subjects completed the study (16 in the PLE group and 17 in the placebo group). There was no significant difference between the 2 groups regarding age, duration of melasma, or Fitzpatrick skin type. Both the PLE and placebo groups showed significant improvement in melanin index between weeks 0 and 12, with 28.8% improvement in the PLE group, and 13.8% improvement in the placebo group (Figure 1). However, the intergroup difference was not statistically significant (P = .14). The MASI scores (Figure 2) similarly showed improvement in both groups between weeks 0 and 12, without significant intergroup difference (P = .62). The MelasQOL scores (data not shown) showed minimal change in either group. Both groups tolerated the treatments well.
The results of our study do not support the premise that oral PLE is effective as an adjunct to topical sunscreen in the treatment of melasma in Hispanic women. Both the primary and secondary outcome measures failed to show a significant difference from placebo. Using a clinically meaningful effect size, this study was powered to detect a difference of 11.7 points in melanin index in the PLE group compared with placebo. The actual difference between the groups was less than half of the original estimate (5.1 points) and not statistically significant. We do not believe this small improvement is enough for most patients to be interested in purchasing and ingesting an oral medication 3 times daily.
To our knowledge, the efficacy of sunscreen alone in the treatment of melasma has never been quantified. From evaluation of the placebo group, we conclude that once-daily use of topical, broad-spectrum sunscreen for 12 weeks results in a 14% improvement in the darkness component of melasma.
In sum, we conclude that oral PLE is well tolerated but not significantly better than placebo as an adjunct to topical sunscreen in the treatment of melasma in Hispanic women. Topical sunscreen alone, even with just once-daily application during summer months, results in mild improvement of melasma.
Corresponding Author: Ammar M. Ahmed, MD, Department of Dermatology, University of Texas Southwestern Medical Center at Austin, CEC C2.443, Austin, TX 78701 (firstname.lastname@example.org).
Accepted for Publication: February 12, 2013.
Published Online: June 5, 2013. doi:10.1001/jamadermatol.2013.4294.
Author Contributions: Dr Ahmed had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Ahmed, Pandya.
Acquisition of data: Ahmed, Lopez, Perese, Vasquez.
Analysis and interpretation of data: Ahmed, Hynan, Chong, Pandya.
Drafting of the manuscript: Ahmed, Lopez, Perese, Vasquez.
Critical revision of the manuscript for important intellectual content: Ahmed, Hynan, Chong, Pandya.
Statistical analysis: Hynan.
Obtained funding: Ahmed, Chong.
Administrative, technical, and material support: Ahmed, Lopez, Perese, Vasquez, Pandya.
Study supervision: Ahmed, Perese, Chong, Pandya.
Conflict of Interest Disclosures: None reported.
Funding/Support: This study was supported by a grant from the Skin of Color Society. Polypodium leucotomos extract capsules and placebo were donated by Industrial Farmaceutica Cantabria SA, Madrid, Spain. Sunscreen was donated by Aveeno, Johnson & Johnson Consumer Companies Inc.
Role of the Sponsors: The sponsors had no role in the design and conduct of the study; in the collection, analysis, and interpretation of data; or in the preparation, review, or approval of the manuscript.
Additional Contributions: We are indebted to Heidi Jacobe, MD, for advice regarding study design, and Mia Ashe-Randolph and Memoree Lee for administrative assistance.
Trial Registration: clinicaltrials.gov Identifier: NCT01092884.