The role of imiquimod 3.75% cream in the treatment of external genital warts

Imiquimod 3.75% cream has recently been approved by both the U.S. Federal Drug Administration and Health Canada for the treatment of external genital warts. Herein, we provide an overview of external genital warts, review the phase 3 clinical trials leading to the approval of imiquimod 3.75% cream, and compare its efficacy and clinical use with imiquimod 5% cream. Moreover, therapeutic options have further expanded with the relatively recent introduction of sinecatechins 15% ointment, an extract of green tea leaves.     

Topical imiquimod 5% cream as an effective treatment for external genital and perianal warts in different patient populations

BACKGROUND: Genital infection with human papillomavirus, the cause of genital warts, is one of the most common sexually transmitted diseases. GOAL: The aim of this analysis was to determine whether patients' demographic variables affect the efficacy of imiquimod 5% cream versus vehicle cream for the treatment of external genital and perianal warts. STUDY DESIGN: Male and female immunocompetent patients applied imiquimod 5% cream topically to external genital warts 3 times a week until wart clearance or for up to 16 weeks. RESULTS: As previously published, the intent-to-treat (ITT) clearance rate was 50% (54/109) in the imiquimod-treated group and 11% (11/100) in the vehicle-treated group ( P< 0.0001). The ITT clearance rate in the imiquimod-treated group was higher in females (72%) than in males (33%). We have examined the clearance rates for subgroups based on variables of gender, baseline wart area, duration of current outbreak of warts, previous wart treatment, and tobacco use. For each of these subgroups, imiquimod was statistically more effective than vehicle in eradicating external genital and perianal warts. CONCLUSION: Imiquimod 5% cream is an effective treatment for external genital and perianal warts and provides a significant benefit in comparison with vehicle cream, independent of gender, initial wart size, duration of current outbreak of warts, previous wart treatment, or tobacco use.     

Successful treatment of perianal warts in a child with 5% imiquimod cream

Treatment of anogenital warts in children is difficult. Commonly used therapeutic regimes can be painful, variably effective and recurrence rates are high. Imiquimod is a recently developed imidazoquinolin heterocyclic amine that is an immune response modifier. Topical imiquimod has been used successfully to treat anogenital warts in adults. This case documents the effective use of topical imiquimod in the treatment of perianal warts in children.     

Topical imiquimod 5% cream in external anogenital warts: a randomized, double-blind, placebo-controlled study

The complete treatment of anogenital warts has not been obtained with any combination of methods; therefore, new methods are still under investigation. In this study the activity and side effects of imiquimod 5% cream were investigated. The study group consisted of 23 male and 11 female volunteers and the control group of 9 male and 2 female volunteers. Patients applied the cream three times a week, every other day in the evenings for a period of 12 weeks. After the treatment, patients were regularly monitored for six months for recurrences. At the end of the study, 23 (69.7%) patients (all of females and 54.5% of males) in the study group displayed a complete clearance, 9 patients displayed 50-90% clearance and 1 patient displayed less than 50% clearance. In the control group, only 1 patient displayed a complete clearance, 1 patient displayed 50-90% clearance, and the other 8 patients showed no alteration in the lesions. These results were statistically significantly different (p<0.01). In 15 patients in the study group, no side effects were reported; the most frequently seen side effects were erythema and erosion. In six patients that were observed for a period of six months, recurrences occurred. Imiquimod 5% cream is a topically applied medicament that should be considered as an effective and reliable medical option in the treatment of anogenital warts.     

Efficacy of imiquimod 5% cream in the treatment of recalcitrant warts in children

Long-lasting cutaneous warts are a therapeutic challenge, especially widespread or symptomatic recalcitrant warts in children. It can be speculated that natural immunity to these human papillomavirus (HPV)- induced lesions is extremely poor. Therefore ideally treatment should focus on increasing local immune response. Recently imiquimod, a topical immune modifier, has been successfully used in the treatment of external genital warts. Our purpose is to report on our experiences with imiquimod 5% cream applied to therapy-resistant, long-lasting (duration 2-7 years) common warts in children. In 18 children, imiquimod cream was self-applied by the patients or by their parents to the warts twice a day. Assessment for response and occurrence of adverse effects was performed every 4 weeks until clinical cure. Follow-ups could be arranged in 14 of the 18 patients 1-2 years after total clearance. Sixteen of 18 patients experienced total clearance of their warts; 2 showed partial improvement but were lost to follow-up. The mean duration of treatment was 5.8 months. Two of the 14 patients in whom a follow-up was performed showed a small number of new warts after a period of at least 1 year without recurrence. Our data demonstrate that the topical application of imiquimod 5% cream is an effective treatment for long-lasting cutaneous warts in children.     

Treatment of non-genital warts with topical imiquimod 5% cream

Common warts (verrucae vulgaris) are associated with human papillomavirus infection and are routinely treated by ablative procedures such as cryotherapy, electrodessiccation and salicylic acid. We report 10 cases of recurrent warts treated with a potential new topical therapy, imiquimod 5% cream. Nine of the 10 patients were successfully treated with imiquimod 5% cream applied, under occlusion, once daily for 4 weeks. No recurrences were reported during 3 months of follow up.     

5％咪喹莫特乳膏治疗外生殖器/肛周疣随机对照研究

目的评价5％咪喹莫特乳膏（艾达乐）治疗外生殖器／肛周疣的有效性和安全性。方法采用随机、双盲、平行对照、七个中心临床研究。患者随机入组，一组患者先接受咪喹莫特治疗16周或至所有基线疣消失，然后给予赋形剂4周。另一组患者先接受赋形剂治疗4周，然后再接受咪喹莫特治疗16周或至所有基线疣消失。每周外用乳膏3次（晚上应用，至少保留8h），每4周评估一次临床疗效。结果共144例患者人选。在研究结束时（20周），综合两个治疗组合并显示，基线疣计数减少≥50％的患者为75．0％（意向性治疗分析，ITT）和83．5％（符合方案完成试验集分析，PP），疣完全清除率分别为79．9％（ITT分析）和89．8％（PP分析）。在第4周时，咪喹莫特组基线疣计数减少≥50％的患者为48．6％，赋形剂组为19．4％，P=0．0004；咪喹莫特组疣完全清除率为22．2％，赋形剂组为6．9％，P=0．009。最常见的不良事件发生是用药部位的皮肤反应（38．9％），无严重不良事件发生。结论咪喹莫特乳膏治疗外生殖器／肛周疣疗效明显优于赋形剂，每周3次，疗程16周，安全有效，使用方便。     

5％咪喹莫特乳膏治疗尖锐湿疣Meta分析

目的以循证医学的方法对5％咪喹莫特乳膏治疗尖锐湿疣的疗效与安全性进行系统评价。方法检索PubMed、Ovid、Web of Seience、UMI、Elsevier以及Cochrane图书馆、中文科技期刊数据库（CNKI）、中国生物医学文献数据库（CBMDisc），纳入比较5％咪喹莫特乳膏与安慰剂或氟尿嘧啶乳膏的随机对照试验，南两名评价者独立提取资料并进行方法学质量评估。试验数据的统计分析采用Cochrane协作网提供的RevMan4．2培软件进行。结果最终纳入8个临床随机对照试验，对5％咪喹莫特乳膏治疗尖锐湿疣进行了Meta分析，与安慰剂组相比，差异具有统计学意义；与氟尿嘧啶乳膏组相比．疗效差异无统计学意义，没有报道与5％咪喹莫特乳膏临床应用相关的严重系统性不良反应。结论现有临床证据表明，5％咪喹莫特乳膏治疗尖锐湿疣有确切的疗效与较好的安全性。     

Vagarious successful treatment of recalcitrant warts in combination with CO2 laser and imiquimod 5% cream

Abstract

Background. Imiquimod 5% cream is widely regarded as a safe and effective option when treating recalcitrant warts, owing to the ointment's negligible side effects. However, our observations highlighted case of a patient incurring severe adverse reactions due to application of the cream, although the treatment proved successful in curing recalcitrant warts which had developed on the external auditory canal and external ear. Methods. All lesions were entirely removed with short-pulsed CO₂ laser. As soon as the wound-healing process was completed, imiquimod 5% cream was self-applied on the healing wounds once daily for 5 days per week in a total of 2 weeks. Results. The patient appeared normal after the CO₂ laser treatment and experienced severe redness, itching, exudation, and incrustation after a 2-week imiquimod 5% cream therapy. All lesions showed no recurrence during the 12-month followed-up process. Conclusions. We concluded that a feasible treatment modality to cure recalcitrant cutaneous warts is in combination of CO₂ laser and imiquimod. Immunoenhancement plays an important role in the treatment of recalcitrant warts.     

Imiquimod 5% cream is an acceptable treatment option for external anogenital warts in uncircumcised males

OBJECTIVES: To determine the safety and efficacy of imiquimod (Aldara) 5% cream in the treatment of prepuce-associated warts in uncircumcised males. METHODS: An open-label study in six UK medical centres with 35 uncircumcised males with prepuce-associated warts treated with imiquimod 5% cream three times per week for up to 16 weeks. Other anogenital warts were also treated. RESULTS: Three times weekly application of imiquimod was found to be safe, with erythema as the most commonly reported local skin reaction. Forty per cent of patients had complete clearance of anogenital warts within 16 weeks. CONCLUSIONS: Imiquimod cream at a dosing regimen of three times per week, is effective and has an acceptable safety profile in the treatment of prepuce associated warts and other external anogenital warts in uncircumcised males.     

Treatment of external genital warts in men using 5% imiquimod cream applied three times a week, once daily, twice daily, or three times a day

BACKGROUND: Medical therapy for genital warts remains suboptimal. The topical interferon and cytokine inducer, imiquimod, has been proved effective for the treatment of external genital and perianal warts, but there is a substantial difference in the response rates between men and women. When 5% imiquimod cream is applied three times a week up to 16 weeks, approximately two thirds of women treated with imiquimod achieve complete clearance of genital warts, whereas only about one third of men clear completely. GOAL: This study was undertaken to determine whether more frequent application of topical imiquimod cream would improve the rate of genital wart clearance in men. STUDY DESIGN: A randomized treatment trial involving adult men with biopsy-proven genital warts was conducted at nine centers in the United States and Canada using four different application frequencies. RESULTS: Complete clearance rates during the 16-week treatment period were as follows for the different imiquimod treatment frequencies: three times a week (35 %), once daily (28 %), twice daily (24%), and three times a day (27%)(P = 0.88). The four treatment groups all showed comparable reductions in the total lesion area, with a median of more than a 90% reduction in the lesion area by the end of treatment. There was a significant increase in the incidence and severity of local skin reactions including erythema, vesicle formation, ulceration, and excoriation as the dosing frequency increased from three times a week to three times a day. CONCLUSIONS: In this study, the optimal dosage regimen was the approved three times a week regimen. More frequent application (up to three times a day) did not improve clearance and was associated with an increase in local adverse events.     

Successful treatment of multiple filiform facial warts with imiquimod 5% cream in a patient infected by human immunodeficiency virus

Imiquimod, an imidazoquinoline amine, is approved for the topical treatment of external anogenital warts induced by human papilloma virus. Several clinical trials have shown imiquimod to be an effective and safe drug for treatment of anogenital warts. Consequently, it was considered that imiquimod might be effective on warts caused by the same aetiological agent located on other skin areas. We describe the favourable outcome of a case of multiple facial verrucae in a human immunodeficiency virus (HIV)-infected patient treated with imiquimod 5% cream. This is a promising finding which supports those of two previous reports. We feel that imiquimod could be used in HIV-infected patients with multiple facial warts in whom conventional therapies are ineffective or produce significant side-effects.     

Randomized, comparative trial on the sustained efficacy of topical imiquimod 5% cream versus conventional ablative methods in external anogenital warts

Conventional ablative treatments for external anogenital warts are affected by high recurrence rates. This study compared sustained clearance after ablation vs. treatment with imiquimod 5% cream vs. the combination of both methods. This was a 3-arm, open-label, randomized clinical study comparing ablation alone (Group A), imiquimod 5% cream monotherapy (Group B), or combined ablation followed by topical imiquimod (Group C). Subjects whose anogenital warts were completely cleared entered a 6-month follow-up to evaluate sustained clearance.After 3 months follow-up, 83.9% (73/87), 93.8% (90/96) and 91.7% (66/72) of subjects in Groups A, B, C, respectively, remained free of recurrent anogenital warts. After 6-months follow-up, 73.6% (64/87), 93.7% (89/95) and 91.5% (65/71) of subjects presented free of recurrence (Group A vs. B & C p-values each p < 0.004 in favour of the imiquimod-treated groups).Imiquimod 5% cream, as monotherapy or in combination with ablation, was superior to ablation alone in reducing the recurrence of successfully treated anogenital warts.