Ingenol Mebutate Gel 0.05% in the Treatment of Anogenital Warts: A Prospective Controlled Trial Comparing It With Topical Podophyllin Solution 25%

Abstract

Background Anogenital warts (AGWs) are a common therapeutic challenge. All therapies are associated with burning, pain, and frustrating high rate of recurrence. The search for a new alternative continues. Recently, a diterpene ester extracted from the Euphorbia peplus plant (ingenol mebutate [IM]) has been shown to possess activity against AGWs. Objective This study aimed to compare and evaluate the therapeutic efficacy and safety of topical 0.05% ingenol gel with another herbal extract medication (topical 25% podophyllin solution) in treatment of AGWs. Methods This was a comparative single blinded nonrandomized, 2-arm trial of ingenol 0.05% gel versus podophyllin solution 25% administered up to 6 times to patients with AGWs. To evaluate the therapeutic efficacy, the complete clearance rate and recurrence rate were assessed 1 and 12 weeks after last treatment, respectively. Safety was assessed by occurrence and severity of pain and local skin reaction (LSR). Results Of 31 and 36 patients in the IM group and podophyllin group who completed the study, initial complete resolution was observed in 20 (64.5%) and 14 (38.9%) patients, respectively (P = 0.03). The initial clearance was faster in the IM group (2.00 ± 0.91 weeks) compared with the podophyllin group (4.21 ± 1.05 weeks, P = 0.00). After 3 months, recurrence was seen in 13 (65.0%) of 20 patients in the IM group and 6 (42.8%) of 14 in the podophyllin group (P = 0.20). The number of patients with complete resolution after 3 months was not different between the 2 groups (7/31 in the IM group and 8/36 in the podophyllin group, P = 0.97). The mean ± SD severity scores for LSR and pain in the IM group were 6.65 ± 1.76 and 6.13 ± 2.57, respectively, which was significantly higher than their scores (3.39 ± 1.57 and 2.58 ± 1.38) in the podophyllin group (P = 0.00). Conclusion Ingenol mebutate 0.05% gel is effective as podophyllin 25% solution in treating AGWs, with further benefit of being much more rapid. However, high recurrence rate, sever pain, and LSR limit its use.

Effectiveness and safety of topical application of diphenylcyclopropenone versus podophyllin in treatment of genital warts

“…27 Previous studies with podophyllin treated patients showed low clearance rates of 37%-63% and high rates of recurrence (42%-60%). 26,28,29 Our work supports the earlier findings and demonstrates that 9 of 28 (32.1%) patients treated with podophyllin had a complete response, and the recurrence rate was detected in seven patients (77.8%).…”

“…24 Genital warts are commonly treated with podophyllin, a cytotoxic substance obtained from Podophyllum peltatum and Podophyllum hexandrum. 25 Human skin keratinocytes infected with the human papillomavirus are prevented from proliferating by podophyllin, 26 which inhibits mitotic activity in rapidly dividing cells by preventing the positioning of chromosomes on the spindle during metaphase of mitosis due to a mixture of antimitotic chemicals, of which podophyllotoxin is the primary component. 27 Previous studies with podophyllin treated patients showed low clearance rates of 37%-63% and high rates of recurrence (42%-60%).…”

A comparative study of intralesional bleomycin versus cryotherapy in the treatment of condyloma accuminata

“…1 Currently, for the treatment of anogenital warts (AGW), a wide variety of modalities are available, including imiquimod, podophyllin, podophyllotoxin, cryotherapy, carbon dioxide laser, and surgical removal. 2 Other medical treatments such as Ingenol mebutate 3,4 and nitrizinc 5 have been recently reported to be effective in several studies, but no approach has been shown to be universally successful, and failure of treatment and recurrence after the initial clearance are seen after performing any form of treatment. So, the treatment of AGW has always been a challenge for investigators.…”

Immunothrombotic Mechanisms Induced by Ingenol Mebutate Lead to Rapid Necrosis and Clearance of Anogenital Warts

“…AGW are benign epithelial tumors caused by an infection with certain types of human papillomavirus (HPV) [ 4 ]. Many individual case reports, smaller case series, and initial pilot studies have shown, that IM gel application effectively and quickly removes AGW [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. In most cases, a single application of the gel was sufficient to ablate the warts within 24 h. After 8 h, the treated warts showed clinical signs of necrosis and peeled off within the next 24 h. Some patients felt severe pain at the treatment site, which peaked after 8 h and quickly ameliorated over the next half day.…”