Polyphenon E®: a new treatment for external anogenital warts

Background External genital warts (EGWs, condylomata acuminata) are a common, highly contagious disease caused by human papillomavirus (HPV), predominantly HPV 6 and HPV 11. Green tea catechins have been identified for their immunostimulatory, antiproliferative and antitumour properties. Two phase III trials evaluated treatment of EGWs with ointment containing a mixture of green tea catechins (Polyphenon E^®, U.S. adopted name: sinecatechins). Objectives To obtain additional data on the efficacy and safety of Polyphenon E^® ointment in the treatment of EGWs from two randomized, double‐blind, vehicle‐controlled trials. Methods Men and women aged ≥ 18 years (n = 1005), with two to 30 EGWs (12–600 mm² total area) applied vehicle (G_Veh; n = 207), Polyphenon E^® ointment 10% (G_10%; n = 401) or Polyphenon E^® ointment 15% (G_15%; n = 397) three times daily until complete clearance of all EGWs (baseline + new EGWs) or for a maximum of 16 weeks. Results A total of 1004 patients were evaluable for safety and 986 for efficacy; 838 completed treatment after 16 weeks. Complete clearance of all EGWs was obtained in 53·6% (G_10%) and 54·9% (G_15%) of patients with Polyphenon E^® vs. vehicle (35·4%) (P < 0·001). Statistically significant differences in clearance rates appeared after 6 weeks of active treatment. Odds ratios vs. G_Veh for G_10% [2·10; 95% confidence interval (CI) 1·49–2·98] and G_15% (2·22; 95% CI 1·57–3·14) indicated about a twofold higher chance of complete clearance under active treatment. Time to complete clearance was shorter with active treatment (hazard ratios 1·57 and 1·87, respectively, for G_10% and G_15% vs. G_Veh groups; P < 0·001). Recurrence rates during follow‐up were low and similar across groups: 5·8%, 6·8% and 6·5% (G_Veh, G_10% and G_15% groups, respectively). Adverse events were evenly distributed across groups (～ 30% of patients). Severe local signs were more frequent but moderate in the active treatment groups (1·5%, 9·2% and 13·5% for G_Veh, G_10% and G_15% groups, respectively). Conclusions Polyphenon E^® ointment is effective and well tolerated in the treatment of EGWs.     

Topical Polyphenon E in the treatment of external genital and perianal warts: a randomized controlled trial

Background Benign external genital and perianal warts (condylomata acuminata) are disfiguring, displeasing skin tumours caused by human papillomavirus that may vitally burden affected patients and their partners. Current treatment options are still unsatisfactory due to low efficacy, high recurrence rates or an unfavourable side‐effect profile. Although most recently prophylactic vaccines have been recommended for adolescent women, appropriate treatment modalities for anogenital warts are still needed. Green tea catechins exert antiviral, antioxidative, antiproliferative and immunostimulatory activity. Polyphenon^® E (MediGene AG, Munich, Germany), a proprietary extract of green tea leaves, was therefore investigated for the topical treatment of this frequent viral disease. Objectives To investigate Polyphenon^® E 15% and 10% ointment for efficacy and safety in the treatment of anogenital warts in immunocompetent men and women. Methods Five hundred and three patients were randomized to receive either Polyphenon^® E 15% or 10% ointment or matching vehicle. The topical treatment was self‐applied by the patients three times daily to all warts. Assessment of response and of adverse events was performed biweekly until complete clearance of all (baseline and new) anogenital warts or for up to 16 weeks. Recurrence was evaluated during a 12‐week treatment‐free follow‐up period for patients with complete clearance. Results About 53% of patients treated with Polyphenon^® E 15% ointment showed complete clearance of all baseline and new anogenital warts, 51% for Polyphenon^® E 10% ointment, and 37% for vehicle (P = 0·01 and P = 0·03, respectively; two‐sided Fisher’s exact test; intent‐to‐treat population, last observation carried forward analysis). Women responded better than men, with about 60% of women and 45% of men in both active groups achieving complete clearance of all warts. Time to complete clearance was comparable for both strengths of Polyphenon^® E ointment. About 78% of all patients treated with either Polyphenon^® E 15% or 10% ointment showed wart clearance rates of 50% or better. Less than 6% and 4% of patients in the Polyphenon^® E 15% and 10% ointment groups experienced wart recurrence during follow‐up. Polyphenon^® E ointments demonstrated a good safety profile with the majority of all adverse events being local application site reactions assessed as mild or moderate. Local reactions declined during continued treatment. Conclusions The results indicate that Polyphenon^® E ointment is an efficacious and safe patient‐applied topical treatment for external genital and perianal warts. Its use in intra‐anal, intravaginal and cervical condylomas and other intraepithelial lesions warrants further clinical investigation.     

Efficacy,safety and tolerability of green tea catechins in the treatment of external anogenital warts: a systematic review and meta‐analysis

Background External anogenital warts (EGWs) are non‐malignant skin tumours caused by human papillomavirus. They are one of the fastest growing sexually transmitted diseases. Current treatments are unsatisfactory. Green tea sinecatechin Polyphenon E ointment is a botanical extract from green tea leaves exhibiting anti‐oxidant, anti‐viral and anti‐tumour properties. Objective The aim of this study was to integrate valid information and provide basis for rational decision making regarding efficacy and safety of green tea extracts in the treatment of EGWs. Methods A systematic search in electronic databases was conducted using specific key terms. Main search was performed independently by two reviewers. The accumulated relevant literature was subsequently systematically reviewed and a meta‐analysis was conducted. Results Three randomized, double‐blind, placebo‐controlled studies evaluating efficacy and safety of Polyphenon E 15% and 10% in the treatment of warts were included in the systematic review and meta‐analysis. A total of 660 men and 587 women were enrolled. Regarding primary outcome, both Polyphenon E 15% and 10% demonstrated significantly higher likelihood of complete clearance of baseline and baseline and new warts compared with controls. No significant heterogeneity was detected. Recurrence rates were very low. Commonest local skin sign was erythema and local skin symptom was itching. Conclusions Efficacy of Polyphenon 15% and 10%, at least for the primary endpoint, is clearly indicated. Polyphenon E treatment exhibits very low recurrence rates and appears to have a rather favourable safety and tolerability profile. Recommendations for future studies should include evaluation of the efficacy of green tea catechins in the treatment of internal anogenital warts and direct comparison with its principal comparator, imiquimod.     

Topical treatment for human papillomavirus-associated genital warts in humans with the novel tellurium immunomodulator AS101: assessment of its safety and efficacy

Background  Various methods are currently used for the treatment of anogenital warts. However, a complete cure is unlikely, and the rate of recurrence is high.
Objectives  The purpose of this open-label, multicentre trial was to evaluate the safety and clinical efficacy of a new treatment using the immunomodulator ammonium trichloro (dioxoethylene- O , O ') tellurate (AS101; Biomas Ltd, Kefar Saba, Israel) 15% w/w cream to clear vulval/perianal condylomata acuminata.
Methods  Study participants comprised 48 women and 26 men, age range 18–62 years. Of the 48 woman, 44 were diagnosed with vulval condylomata and four with perianal condylomata. All 26 men were diagnosed with perianal condylomata. All the patients in the study received AS101 15% w/w cream twice a day. Maximal treatment duration was 16 weeks. To evaluate the safety and clinical efficacy, patients were examined and lesional areas photographed on a biweekly basis.
Results  By the end of the treatment, 56 of 74 (76%) patients were considered completely cleared. Complete cure was achieved in 35 of 44 (80%) patients with vulval condylomata and in 21 of 30 (70%) patients with perianal condylomata. No scarring of treated areas was observed. Complete cure was achieved within a time range of 10–109 days. The most frequent side-effects observed were mild-to-moderate itching, soreness, burning and erythema. In post-treatment follow up of up to 6 months, disease recurrence was observed in two patients (4%), at 105 and 144 days following completion of treatment.
Conclusions  AS101 15% w/w cream is an effective and safe, self-administered therapy used for the treatment of external vulval and perianal warts. The cream is applied topically twice daily for up to 16 weeks. A very low recurrence rate was reported.     

Dermoscopic monitoring of efficacy of ingenol mebutate in the treatment of pigmented and non‐pigmented basal cell carcinomas

Basal cell carcinoma is the most common non‐melanoma skin cancer, and its incidence continues to raise. Although surgery can be considered the mainstay of therapy, new current pharmacological options are available and focus on tumor eradication, maximizing cosmetic results, and functional capacity. Several studies have recently reported on safety and efficacy of topical ingenol mebutate gel, a derivative of the plant Euphorbia Peplus, used to treat actinic keratosis and superficial basal cell carcinoma. In our knowledge, we report for the first time the dermoscopic evaluation of outcome and monitoring of superficial pigmented and non‐pigmented basal cell carcinomas in four patients treated by this novel non‐ablative agent. Ingenol mebutate gel therapy has showed to be effective and without important side‐effects for pigmented and non‐pigmented superficial basal cell carcinomas. We emphasize the usefulness of dermoscopy in supporting the clinical diagnosis and excluding the presence of tumor residue or recurrence. In a future scenario, we hope it will be soon possible to follow‐up the lesions, after treatment, avoiding post‐control biopsy punch.     

A comparison of a 5% potassium hydroxide solution with a 5‐fluorouracil and salicylic acid combination in the treatment of patients with anogenital warts: a randomized,open‐label clinical trial

Anogenital warts are caused by human papillomavirus (HPV), over 30 types of which are infectious for the anogenital tract. Without treatment, warts may regress spontaneously, remain unchanged, or increase in number and size. This study compared the efficacy of a topical 5% potassium hydroxide (KOH) solution with that of a topical 0.5% 5‐fluorouracil (5‐FU) and 10% salicylic acid (SA) combination in the treatment of anogenital warts. Sixty patients were randomly assigned to receive topical KOH or 5‐FU + SA. Both groups demonstrated a significant decrease in numbers of lesions (P < 0.05), but this difference was not significant at week 12 (P > 0.05). The mean number of lesions decreased from baseline to week 12 from 17.03 ± 12.64 to 3.73 ± 7.30 and from 16.13 ± 12.97 to 3.10 ± 4.90 in the KOH and 5‐FU + SA groups, respectively (P < 0.001). Excellent clearance was achieved by 70.0 and 76.7% of patients in the KOH and 5‐FU + SA groups, respectively. Marked improvement was seen in 13.3 and 20.0% of patients in the KOH and 5‐FU + SA groups, respectively. At week 16, relapse was observed in two patients in the KOH group and three in the 5‐FU + SA group (P > 0.05). No serious adverse events were reported. Neither treatment was more efficacious. Safety and ease of application are important goals in treatments for anogenital warts. A 5% KOH solution is a promising alternative treatment because it is effective and inexpensive and causes minimal side effects.