A Single-Blinded Randomized Controlled Study to Assess the Efficacy of Twice Daily Application of Sinecatechins 15% Ointment When Used Sequentially With Cryotherapy in the Treatment of External Genital Warts

November 2014 | Volume 13 | Issue 11 | Original Article | 1400 | Copyright © November 2014

Shelbi C. Jim On MD,a Rita V. Linkner MD,a Madelaine Haddican MD,a Alex Yaroshinsky PhD,b
Matthew Gagliotti BA,a Giselle Singer BS,a and Gary Goldenberg MDa

aIcahn at Mount Sinai School of Medicine, Department of Dermatology, New York, NY
bVital Systems, Inc. Rolling Meadows, IL

Abstract
OBJECTIVE: To evaluate the efficacy of sequential therapy of cryotherapy and sinecatechins 15% ointment BID versus cryotherapy alone in treatment of external genital warts (EGW).
METHODS: Forty-two subjects with at least two EGW lesions underwent cryotherapy to all lesions. One week following cryotherapy, subjects were randomized 1:1 to receive either no additional treatment or treatment with sinecatechins 15% ointment BID up to 16 weeks or until complete clearance. The total number of visible baseline and new EGW were recorded at each visit. Subjects were followed for a total of 65 weeks post-treatment.
RESULTS: There was a significant reduction in mean number of lesions from baseline after 16 weeks of treatment in the cryotherapy-sinecatechins ointment group compared to cryotherapy alone (-5.0 lesions vs -2.1 lesions respectively, P=0.07).
CONCLUSION: Cryotherapy plus sinecatechins 15% ointment BID resulted in a significant improvement in the reduction of EGW compared to cryotherapy alone. Clinicaltrials.gov registration identifier: NCT02147353

J Drugs Dermatol. 2014;13(11):1400-1405.

INTRODUCTION

External genital warts (EGW) are the most common sexually transmitted disease associated with more than 30 types of the Human Papillomavirus (HPV). It is estimated that 360,000 Americans are diagnosed with genital warts each year.1 Visible EGW present as asymptomatic flat, sessile, or lobulated papules (condyloma) found on the external genitalia (eg, penis, scrotum, vulva), pubic area, perineal area, and/or crural folds. However, EGW can be associated with itching, burning, tenderness, and/or discomfort. To date, no effective virus-specific agents exist for the treatment of HPV. However, various modalities are available for the treatment of visible EGW, each having significant failure and recurrence rates. Treatments are classified as either provider- or patient-applied. Provider-applied therapies are further classified into surgical (eg, cryotherapy, excision, electrosurgery, and laser ablation) and non-surgical (eg, podophyllin resin, interferons, and trichloroacetic acid). Patient-applied therapies include podophyllotoxin 0.5% solution, imiquimod 5% and 3.75% creams, and sinecatechins 15% ointment.
Cryotherapy is an effective method of EGW treatment. However, multiple sessions may be required with reported clearance rates ranging between 27% and 88%.2 Cryotherapy has various limiting factors. Clearance rates with cryotherapy can be improved by increasing the freeze time; however, this is often associated with increased discomfort, severe skin necrosis, and a greater risk of post-treatment hypopigmentation.3 Additionally, as with other lesion-directed therapies, cryotherapy does not treat sub-clinical lesions in the surrounding skin. The recurrence rate associated with this provider-applied methodology has been estimated to be between 25-39%.4,5
Sinecatechins 15% ointment is Food and Drug Administration approved for three times daily application in immunocompetent subjects 18 years and older for the treatment of EGW and perianal warts. While the exact mechanism of action is unknown, the drug is a botanical with antioxidant, antiviral, and immune-stimulatory properties. In two phase III studies, each involving 500 subjects, sinecatechins ointment demonstrated statistically significant rates of clearance with 53.6% clearance rate at Week 16 compared to vehicle, 35.5%.6 Additionally, sinecatechins demonstrated an early onset of action compared to vehicle alone. The recurrence rate of EGW 12 weeks post-treatment was 6.8% with sinecatechins.7,8 The overall incidence of subjects with local adverse events leading to discontinuation was 2.3% with the maximal severity of erythema, erosion, edema, and induration occurring at Week 2 and declining thereafter.8-10 To date, no trial has evaluated the efficacy of the combination of cryotherapy and sinecatechins ointment for genital warts.
Treatment of EGW with cryotherapy followed by sinecatechins appears to be logical. Cryotherapy has direct cytodestructive effects