A Randomized, Double-Blind, Active- and Placebo-Controlled Trial Evaluating a Novel Topical Treatment for Keloid Scars

September 2021 | Volume 20 | Issue 9 | Original Article | 964 | Copyright © September 2021


Published online August 25, 2021

Mark S. Nestor MD PhDa,b,c, Brian Berman MD PhDa,b, Daniel L. Fischer DOa, Haowei Han DOa, Anita Gade DOa, David Arnold DOa, Alec Lawson BAa

aCenter for Clinical and Cosmetic Research, Aventura, FL
bPhillip Frost Department of Dermatology and Cutaneous Surgery, Miami, FL
cDepartment of Surgery, Division of Plastic Surgery, Miami, FL; University of Miami, Miller School of Medicine, Miami, FL

Abstract
Keloid and hypertrophic scars are fibroproliferative disorders resulting from abnormal wound healing in genetically susceptible individuals. Current therapies are often ineffective. Kynurenine shows promise as a topical treatment for keloids and hypertrophic scars. In this study, healthy adult male and female subjects seeking treatment for mature keloid scars were enrolled. Subjects were randomized in double-blind fashion to receive kynurenic acid 0.5% (FS2) cream (Group 1), an active onion extract comparator treatment (Group 2), or the inactive vehicle (Group 3). Each treatment was applied twice-daily. Qualitative assessments were made using the Vancouver Scar Scale (VSS), as well as the Patient and Observer Scar Assessment Scales (POSAS). Among subjects in Group 1, there was a substantial decrease in mean PGSS scores after 30 days of treatment that continued to trend downward, becoming significant versus Group 2 at days 90 and 180 (P<0.05) and versus Group 3 at day 180 (P<0.01). Based on mean VSS scores, subjects in Group 1 achieved beneficial effects that became significant versus Group 2 at day 90 (P<0.01), day 120 (P<0.05), and day 180 (P<0.001) and versus Group 3 at day 180 (P<0.05). There were no significant improvements in Groups 2 or 3. There were no adverse events or local skin reactions. The twice-daily application of FS2 Cream represents a potentially new and effective treatment for mature keloid scars.

J Drugs Dermatol. 2021;20(9):964-968. doi:10.36849/JDD.6197

INTRODUCTION

Keloid and hypertrophic scars are fibroproliferative disorders resulting from abnormal wound healing in genetically susceptible individuals. They are characterized by chronic local inflammation and excessive deposition of extracellular matrix components, especially collagen, in the dermis and subcutaneous tissue that extend beyond the original site of injury.1,2

Although the pathophysiology of keloids is not well understood, they are associated with upregulated proinflammatory factors, such as interleukin-1α, IL-1β, IL-6, IL-8, IL-10, tumor necrosis factor-α, transforming growth factor-β, and platelet-derived growth factor.3-5 Hypertrophic scars demonstrate elevated levels collagen-I, collagen-III, and fibronectin expression associated with decreased collagenase activity that may be due to IGF-induced suppression of collagenase mRNA.6

Keloid scars can be disfiguring and are associated with significantly diminished quality of life,7 especially when they cause pain, pruritus, and functional disorders.8 Current therapies include excision, intralesional corticosteroids, verapamil and 5-fluorouracil,9-11 superficial and external beam radiation therapy,12,13 silicone sheeting,14 cryotherapy,15 nutraceuticals,16,17 alone or in combination,18 but often with limited efficacy.19 Recurrence rates as high as 80–100% are reported.20 Surgical excision alone may result in the recurrence of more severe keloids.21

The enzyme indoleamine 2,3-dioxygenase (IDO) is involved in the conversion of tryptophan to kynurenine.22 The local expression of IDO was shown to reduce scarring in an animal model by increasing matrix metalloproteinase (MMP)-1 and MMP-3 expression via kynurenine activation of dermal fibroblasts.23 These results suggest a potentially beneficial effect of kynurenine for treating keloid and hypertrophic scars.22

A previous phase 1 study assessed the safety and tolerability of a topical kynurenic acid formulation (FS2) in healthy adult human subjects.24 An investigational cream containing FS2 0.5% was applied to uninjured forearm skin daily for 30 days with no evidence of local or systemic adverse effects. Based on these results, 0.5% FS2 was chosen for further study. The primary object of this randomized comparator- and placebo-controlled study was to assess the ability of FS2 0.5% cream to diminish signs and symptoms of mature keloid scars. Secondary objectives were to assess the safety and tolerability of the FS2 moisturizer when applied to mature keloid scars.