Meta-Analysis of 5% Imiquimod and 0.5% Podophyllotoxin in the Treatment of Condylomata Acuminata

Shandong University, Chi-nan-shih, Shandong Sheng, China
Dermatology (Impact Factor: 1.57). 02/2006; 213(3):218-23. DOI: 10.1159/000095039
Source: PubMed


Genital warts are a common sexually transmitted disease caused by human papillomaviruses. Podophyllotoxin 0.5%, approved for patient self-administration, has been used most extensively in the treatment of genital warts. Imiquimod, a novel immune response modifier capable of inducing interferon-alpha and a variety of cytokines, has been examined as a potential treatment for genital warts. But 0.5% podophyllotoxin and 5% imiquimod have not been compared in any extensive and formal studies, although they are the common topical agents for genital warts.
To evaluate the efficacy and safety of topical 5% imiquimod and 0.5% podophyllotoxin in the treatment of genital warts.
We searched Medline (1966 to June 2005), Embase (1974 to June 2005) and the Cochrane Controlled Trials Register (issue 3, 2005). Randomized controlled trials of 5% imiquimod or 0.5% podophyllotoxin in the treatment of genital warts were collected. Two reviewers extracted the data and independently assessed the quality of the included medical literature. Then, meta-analysis was conducted.
Twelve studies including 3 placebo-controlled trials of imiquimod and 9 placebo-controlled trials of podophyllotoxin were included. The clinical cure rates of imiquimod and podophyllotoxin were 50.34 and 56.41%, respectively, without statistically significant differences between the two (p > 0.05). A combined analysis of the 3 studies on imiquimod showed a statistically significant difference to the placebo group [pooled odds ratio (OR) 11.65, 95% confidence interval (CI) 6.05-22.44], as did a combined analysis of the 9 studies on podophyllotoxin (pooled OR 16.70, 95% CI 7.06-39.48). The most common adverse events of imiquimod were erythema, erosion, excoriation, itching and burning; those of podophyllotoxin were burning, pain, erosion, itching and inflammation.
Imiquimod and podophyllotoxin possess similar curative effects on condylomata acuminata but podophyllotoxin has more serious adverse effects.

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    • "As a new and experimental treatment for targeting BLT, there are no large series available let alone randomized trials. The majority of available data comes from other case reports and small case series concerning CA [17] [18] [19] [20]. We present a rare case and provide a literature overview on the treatment options for a BLT, with emphasis on interferon therapy. "
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    ABSTRACT: Giant condyloma acuminatum or Buschke-Lowenstein tumour is a very rare disease which usually is located in the genital, anorectal, and perianal regions. It is regarded as a type of verrucous carcinoma occurring on anogenital mucosal surfaces where it is locally invasive but displays a benign cytology. We describe a case of a 24-year-old woman with persisting condyloma acuminata progressing to a large intra-abdominal Buschke-Lowenstein tumour. To our knowledge such an advanced stage has only been reported once before. The severity and extent of the tumour both determine the treatment and patient outcome. Treatment was impeded by cachexia, an immunosuppressive state after kidney transplantation and difficulties in establishing a reliable diagnose. Interferon treatment was started which initially led to tumour reduction but was complicated by an interferon-induced pancreatitis, pneumonia, and fasciitis necroticans resulting in death. We present a literature overview on the treatment options for a Buschke-Lowenstein tumour, with emphasis on interferon therapy, with all the advantages and disadvantages.
    09/2013; 2013(9):187682. DOI:10.1155/2013/187682
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    ABSTRACT: Imiquimod is a topically active immunomodulatory agent that is formulated as a 5% cream for application by the patient. It is the first agent of its class, the immune response modifiers, to be used in the treatment of genital warts. In immunocompetent patients with genital warts, imiquimod stimulates the production of interferon-α and various other cytokines, and has indirect antiviral activity. In randomised, double-blind, vehicle-controlled clinical trials, complete clearance of warts occurred in 37 to 50% of immunocompetent patients with genital warts treated with imiquimod 5% cream 3 times a week for up to 16 weeks; partial clearance of warts (defined as a reduction in wart area of ≥50%) was observed in 76% of recipients of imiquimod 5% cream. Rates of complete orpartial clearance of warts were significantly higher in patients who applied imiquimod 5% cream 3 times a week than in recipients of imiquimod 1% or vehicle cream, each applied 3 times a week. A between-gender difference in clinical response to imiquimod 5% cream has been reported, with female patients experiencing higher rates of complete clearance of warts than males. Recurrence(s) of ≥1 wart occurred in 13 to 19% of immunocompetent patients in whom complete clearance of warts had been achieved with imiquimod 5% cream. Imiquimod 5% cream also shows some clearance of warts in immunosup-pressed HIV-infected patients with genital warts. Preliminary results of a vehicle-controlled study showed that the rate of partial clearance of warts (defined as a reduction in baseline wart area of >50%) [38%] was significantly higher with imiquimod 5% cream than with vehicle cream; however, the rate of complete clearance was not significantly higher than with vehicle cream. Imiquimod 5% cream is generally well tolerated by immunocompetent and HIV-infected patients. Local skin reactions (mainly mild or moderate), including erythema, itching and burning, are the most commonly reported adverse events, occurring in ≤67% of patients applying imiquimod 5% cream 3 times a week. The incidence of adverse events is lower in patients applying the cream 3 times a week than with daily application. The incidence of systemic adverse events with imiquimod 5% cream (applied daily or 3 times a week) is similar to that of vehicle cream. The tolerability profile of imiquimod cream appears favourable compared with that of podophyllotoxin. Conclusion: Imiquimod 5% cream is a new therapeutic option for patients with genital warts. It produces clearance rates broadly similar to those of other treatment approaches and rates of wart recurrence compare favourably with those reported for established treatments. In contrast to most alternative treatment strategies, which are administered in the physician’s office, imiquimod cream is a self-administered therapy for outpatient use. Overview of Pharmacological Properties Imiquimod, an imidazoquinoline, is a new type of treatment for genital warts. Its antiviral activity is mediated in part by its ability to stimulate the production of interferon-α and other cytokines. It is formulated as a 5% cream for application to genital warts by the patient. In patients with genital warts receiving treatment with imiquimod 5% cream 3 times a week, a strong correlation between wart regression and increases in levels of mRNA for interferon-α, interferon-β, interferon-γ and tumour necrosis factor-α (TNF-α) in wart tissue has been observed. Increases in levels of mRNAs for interleukin (IL)-2 and 2′,5′-oligoadenylate synthetase (an effector protein induced by interferon) have also been reported. Interferon-α, IL-6 and TNF-α production is stimulated by topical, oral or parenteral imiquimod in various animal models. The drug stimulates natural killer cell activity in mice and T cell activity in guinea pigs and mice. Exposure to imiquimod also leads to the proliferation and differentiation of B lymphocytes in vivo. Imiquimod stimulates the production of some cytokines in human and animal monocyte/macrophage cells and in human keratinocytes in vitro. In human peripheral blood mononuclear cells (PBMCs), imiquimod induces the production of interferon-α, IL-1, IL-6, IL-8, IL-10, IL-12, TNF-α, granulocyte colony stimulating factor and granulocyte/macrophage colony-stimulating factor in vitro. Imiquimod increases expression of mRNAs for IL-6 and IL-8 but not mRNA for IL-1α in vitro in human keratinocytes and epidermal carcinoma cells. Levels of IL-8 have been shown to increase in human keratinocytes and fibroblast cultures exposed to imiquimod. In patients with genital warts, imiquimod 5% cream applied 3 times a week significantly decreased levels of human papillomavirus (HPV) DNA and mRNA for the L1 HP gene in wart tissue, compared with baseline. Levels of HPV DNA and mRNA for the L1 HPV gene significantly correlated with wart regression. Little information is available on the pharmacokinetics of imiquimod after application to the skin. In healthy volunteers, the drug shows minimal evidence of percutaneous absorption after topical application of a single 5mg dose. Therapeutic Efficacy The therapeutic efficacy of imiquimod cream (1 and 5% strengths) has been evaluated in 3 randomised, double-blind, vehicle-controlled trials that included 698 immunocompetent adults with genital warts. In these trials, imiquimod 5% cream was significantly more effective than imiquimod 1% cream or vehicle cream in achieving complete clearance of genital warts. Application of imiquimod 5% cream either daily or 3 times a week produced complete clearance of warts in 37 to 52% of patients (intention-to-treat data) in median times of 7 to 12 weeks; clearance rates were higher in the 2 trials of 16 weeks’ duration than in the trial of 8 weeks’ duration. Complete response rates in patients treated with imiquimod 1% cream were 14 and 21% and with vehicle cream ranged from 0 to 11%. Rates of complete clearance were higher in female than in male patients: 72 versus 33% in a trial of imiquimod applied 3 times a week and 64 versus 42% in another trial in which the cream was applied daily (intention-to-treat data). Partial clearance of warts (defined as a reduction in baseline wart area of ≥50%) was documented after application of imiquimod 5% cream 3 times a week or daily for 16 weeks in 76 and 93% of patients. Within a 12-week follow-up period, recurrence(s) of ≥1 wart(s) occurred in 13 to 19% of patients who had complete clearance with imiquimod 5% cream applied 3 times a week or daily. With 1% imiquimod cream applied 3 times a week or daily, recurrence rates were 17 and 0%. Imiquimod 5% cream is also a beneficial treatment for some HIV-infected patients with genital warts, although response rates are lower than in immunocompetentindividuals. Preliminary results of a randomised, double-blind trial showed that complete clearance of warts occurred in 11 % of HIV-infected patients who applied imiquimod 5% cream 3 times a week for up to 16 weeks, compared with 6% of patients who applied the vehicle cream. Partial clearance of warts (defined as a reduction in wart area of >50%) occurred in significantly more recipients of imiquimod 5% cream than vehicle cream (38 vs 14%; p = 0.013). Tolerability Imiquimod 5% cream is generally well tolerated. Local skin reactions, including erythema, itching and burning, are the most common adverse events. These events are more common with daily application of imiquimod cream than with application 3 times a week. Local reactions occurred in significantly more recipients of imiquimod than vehicle cream (p < 0.05). Local erythema developed in 67% (71) patients who used imiquimod 5% cream; of these, 27.4, 34.0 and 5.7% had mild, moderate or severe symptoms. Rates of discontinuation of treatment because of adverse events ranged from 1 to 14% in clinical trials of imiquimod cream. The incidence of systemic adverse events, including headache and flu-like symptoms, with imiquimod 1 or 5% cream is similar to that with vehicle cream alone. Dosage and Administration Imiquimod is available as a 5% cream in single-use sachets. It is recommended that the cream is applied to cleaned and dried affected areas and washed off with soap and water 6 to 10 hours later. Imiquimod 5% cream should be applied 3 times a week either until the warts have cleared or for a maximum of 16 weeks.
    Drugs 01/2007; 67(15). DOI:10.2165/00003495-200767150-00006 · 4.34 Impact Factor
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