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.     

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.     

Optimal frequency of imiquimod (aldara) 5% cream for the treatment of external genital warts in immunocompetent adults: a meta-analysis

BACKGROUND: Postmarketing research has explored the optimal application schedule of imiquimod 5% cream for treatment of external anogenital warts. OBJECTIVES: We systemically reviewed the published literature on the efficacy and safety of the medication when applied either by a three times per week or once-daily regimen for 16 weeks. METHODS: MEDLINE (1966 to Feb 10, 2007), Scopus (1996 to Feb 10, 2007), and Cochrane Library (Issue 1, 2007) databases were searched for randomized trials on the medication. Primary efficacy outcome was the proportion of patients completely cleared of warts by end of treatment. Two primary safety outcomes were as follows: (a) proportion of patients who withdrew and (b) proportion of patients who required at least one rest period from treatment because of drug-related adverse events. RESULTS: Six studies were selected for subgroup analysis of circumcised men, uncircumcised men, and women. The once-daily compared to three times per week regimen did not improve treatment efficacy in any of the 3 subgroups (P <0.05), but resulted in greater incidence and severity of local skin reactions. There was no difference in medication-related withdrawals between the 2 regimens, although significantly more women and uncircumcised men required at least one rest period with the once-daily than the three times per week treatment schedule (P <0.05). CONCLUSIONS: The optimal application schedule of imiquimod 5% cream for external anogenital warts is three times per week.     

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.     

Imiquimod cream 5% for recalcitrant cutaneous warts in immunosuppressed individuals

BACKGROUND: Viral warts may cause significant morbidity in individuals unable to mount an adequate T-helper 1 cell-mediated immune response to human papillomavirus. Imiquimod is a potent inducer of antiviral cytokine activity which has shown significant efficacy in the treatment of genital warts. Similar efficacy in cutaneous warts is not yet established. OBJECTIVES: To assess the response of persistent cutaneous warts to 5% imiquimod cream in immunosuppressed individuals. METHODS: Fifteen immunosuppressed patients with warts on the hands and/or feet present for more than 18 months, which had failed to respond to a minimum of 12 weeks of topical salicylic acid and four cycles of cryotherapy, were recruited. Imiquimod 5% cream was applied in an open label, right vs. left comparison study for 24 weeks (three times weekly for 8 weeks, daily for 8 weeks, then daily with occlusion for 8 weeks). RESULTS: Twelve (80%) patients completed the study protocol. Benefit was seen in five patients [36% in the intent-to-treat analysis (14 patients)], including more than 30% clearance of warts in three patients and reduction in overall size of warts in two further cases. Local skin reactions occurred in four (29%) patients and were usually mild. A transient rise in creatinine (11-29% above baseline) was measured in three renal transplant recipients, but we did not consider that this was related to imiquimod exposure. CONCLUSIONS: This is the first controlled study to assess therapeutic efficacy of topical 5% imiquimod cream in persistent warts associated with immunosuppression. It provides preliminary evidence that topical imiquimod may benefit a subgroup of immunosuppressed patients with recalcitrant cutaneous warts.     

Complete remission of recalcitrant genital warts with a combination approach of surgical debulking and oral isotretinoin in a patient with systemic lupus erythematosus

Genital warts in immunocompromised patients can be extensive and recalcitrant to treatment. We report a case of recalcitrant genital warts in a female patient with systemic lupus erythematosus (SLE), who achieved complete remission with a combination approach of surgical debulking and oral isotretinoin at an initial dose of 20 mg/day with a gradual taper of dose over 8 months. She had previously been treated with a combination of topical imiquimod cream and regular fortnightly liquid nitrogen. Although there was partial response, there was no complete clearance. Her condition worsened after topical imiquimod cream was stopped because of her pregnancy. She underwent a combination approach of surgical debulking and oral isotretinoin after her delivery and achieved full clearance for more than 2 years duration. Oral isotretinoin, especially in the treatment of recalcitrant genital warts, is a valuable and feasible option when other more conventional treatment methods have failed or are not possible. It can be used alone or in combination with other local or physical treatment methods.     

Imiquimod 5% cream in the treatment of superficial basal cell carcinoma: results of a multicenter 6-week dose-response trial

BACKGROUND: Superficial basal cell carcinoma (sBCC) is an increasingly common tumor in fair-skinned populations throughout the world. Imiquimod, an immune response modifier that induces cytokines including interferons, has been shown in preliminary studies to have an effect when applied topically to BCC. OBJECTIVE: We conducted a multicenter, randomized, open-label dose-response trial of imiquimod 5% cream in the treatment of primary sBCC assessing efficacy and safety of different dose regimens. METHODS: Ninety-nine patients were randomized to 6 weeks' application of imiquimod in 1 of 4 treatment regimens: twice every day, once every day, twice daily 3 times/week, once daily 3 times/week. The treatment site was excised and examined histologically 6 weeks after cessation of imiquimod. RESULTS: Intention-to-treat analysis revealed 100% (3/3) histologic clearance in the twice-daily regimen, 87.9% (29/33) clearance in the once every day regimen, 73.3% (22/30) clearance in the twice-daily 3 times/week regimen, and 69.7% (23/33) clearance in the once-daily 3 times/week regimen. Dose-related inflammatory skin reactions at the site of application were common. The majority were well tolerated and only 1 patient withdrew from the trial as a result of a medication-related skin reaction. CONCLUSION: Imiquimod 5% cream appears to have potential as a patient-administered treatment option in sBCC.     

Open-label study to assess the safety and efficacy of imiquimod 5% cream applied once daily three times per week in cycles for treatment of actinic keratoses on the head

BACKGROUND: Local skin reactions are common during imiquimod treatment of actinic keratosis (AK). Cyclical application of imiquimod may improve tolerability while maintaining efficacy. OBJECTIVE: To assess the tolerability of imiquimod and clearance rate of AK lesions after imiquimod application. METHODS: Imiquimod 5% cream was administered three times per week for 4 weeks followed by 4 weeks of rest (cycle 1) to AK lesions on the head. If AK lesions remained visible at the end of cycle 1, a second treatment cycle was instituted. RESULTS: Fifty percent (30 of 60) of patients experienced complete clearance of AK lesions, and 75% (30 of 40) of patients experienced partial clearance of AK lesions after imiquimod treatment at the end of cycle 2. Moreover, 77% of patients who achieved complete clearance had no visible AK lesions 12 weeks post-treatment. Imiquimod was well tolerated. CONCLUSION: Imiquimod cycle therapy may be a safe and effective treatment option for AK lesions.     

Imiquimod 5% cream for external genital or perianal warts in human immunodeficiency virus-positive patients treated with highly active antiretroviral therapy: an open-label, noncomparative study

Background  Human immunodeficiency virus (HIV)+ patients have an increased risk of anogenital warts. High-risk (HR) human papillomaviruses (HPVs), especially types 16 and 18, are major risk factors for precancerous and cancerous lesions of the anogenital tract, while low-risk (LR) HPVs are associated with benign lesions. Cure of genital warts with ablative techniques, surgical excision, podophyllotoxin or trichloroacetic acid is frequently difficult. Treatment with imiquimod cream showed a total clearance of external genital or perianal warts in about 50% of immunocompetent subjects. However, total clearance was reduced in HIV+ subjects not treated with highly active antiretroviral therapy (HAART).
Objectives  To assess clinically and by monitoring HPV content the efficacy of 5% topical imiquimod to treat anogenital warts in HIV+ subjects with at least partially restored immune functions.
Methods  Fifty HIV+ patients successfully treated with HAART (total CD4+ cells ≥ 200 cells mm⁻³ and plasma HIV RNA load < 10⁴ copies mL⁻¹) with anogenital warts were included. Imiquimod 5% cream was applied on external genital or perianal warts three times weekly for up to 16 weeks. Warts were tested at entry and after treatment for human LR- and HR-HPV DNA.
Results  Total wart clearance was observed in 16 of 50 (32%) patients at week 16. At enrolment, HPV DNA was present in more than 90% of lesions with a majority of lesions co-infected by HR- and LR-HPV. At study end, the HPV load decreased or became undetectable in 40% of cases studied.
Conclusions  Imiquimod 5% cream did not show safety concerns and is suitable for use in HIV+ subjects with anogenital warts and successful HAART treatment.     

Topical imiquimod for recalcitrant facial flat warts

Imiquimod is a unique topical therapeutic agent useful in the treatment of external genital and perianal warts (condyloma acuminata) in adults. The authors report a case of a 21-year-old woman who experienced complete clearance of recalcitrant facial flat warts after 3 weeks of therapy with topical imiquimod 5% cream.     

Management of Female Genital Warts with an Analog of Imiquimod 2% in Cream: A Randomized,Double-Blind,Placebo-Controlled Study

The purpose of this randomized, double-blind, placebo-controlled study was to determine the clinical efficacy and tolerability of an analog of imiquimod (2%) in cream to cure genital warts in women. Sixty preselected women, ranging between 18 and 45 years of age (mean 24.3) and having 411 lesions (mean 6.8) with clinical, histopathological and polymerase chain reaction (PCR) confirmed diagnosis of human papilloma virus (HPV) infection were randomized to two parallel groups. Each patient received a precoded 40-g tube and instructions on how to apply the trial medication to their lesions at home two times daily for five consecutive days per week. The active treatment period was six weeks. Patients were evaluated on a weekly basis. A clinically and PCR established total clearance of target warts was recorded as a cure. By the end of the treatment, 43.3% of patients and 42.8% of warts were cured. Code disclosure revealed that imiquimod cream had cured 83.3% of the treated patients and 84.3% of the treated warts, while the placebo healed one subject and four warts (p<0.0001). Eight patients (13.3%) in the imiquimod group experienced mild to moderate, non-objective, drug-induced symptoms with no dropouts. Among the 26 cured patients, five had a relapse after 11 months. In conclusion, the data presented demonstrate that 2% imiquimod in cream with mild to moderate subjective side effects is significantly more effective than placebo in eliminating genital warts in women.     

Extensive condyloma acuminata treated with imiquimod 5% cream: a case report

Genital warts are one of the most common sexually transmitted infections, and are caused by human papillomavirus (HPV) types 6 and 11. Standard treatments for genital warts include cryotherapy, laser therapy, trichloroacetic acid and podophyllotoxin. We report the case of a 21-year-old female with extensive genital warts. A patient-applied, non-destructive therapy was considered to be the most appropriate treatment in this case, due to the extent of the disease and the resulting psychological distress experienced by the patient. She applied imiquimod 5% cream three times per week for a period of 5 weeks, which resulted in complete clearance of all the warts. Minor inflammatory changes were observed during treatment; however, no significant pain was by reported the patient. No recurrences were reported during 2 years of follow-up.     

国产5％咪喹莫特乳膏治疗生殖器疣荟萃分析

目的：以循证医学的方法对国产5％咪喹莫特乳膏治疗生殖器疣的疗效、安全性以及预防生殖器疣复发的效果进行系统性评价。方法：检索中文科技期刊数据库（CNKI）、中国生物医学文献数据库（CBMDisc），由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Co-chrane协作网提供的RevMan4．2．8软件进行。结果：咪喹莫特乳膏单疗组，最终纳入8个临床随机对照试验，Meta分析结果显示，与安慰剂比较，疗效差异有统计学意义；与2．5％氟尿嘧啶软膏比较，疗效差异没有统计学意义。没有严重系统性不良反应的报道。咪喹莫特乳膏联合物理治疗组，最终纳入12个临床随机对照试验，Meta分析结果显示，以观察3个月或6个月没有在原位复发作为痊愈标准，与安慰剂组比较，疗效差异有统计学意义。结论：现有临床证据表明，国产5％咪喹莫特乳膏治疗生殖器疣有确切的疗效和较好的安全性，对预防生殖器疣复发也有确切的疗效。     

Treatment of facial verrucae with topical imiquimod cream in a patient with human immunodeficiency virus

Imiquimod is a recently developed imidazoquinolin heterocyclic amine that is an immune response modifier. Treatment with topical 5% imiquimod cream has shown promising results in the treatment of genital warts in immunocompetent individuals. We report here the first case of successful treatment with topical 5% imiquimod cream of facial verrucae in an individual with human immunodeficiency virus.     

A randomized,double-blind,vehicle-controlled study to assess 5% imiquimod cream for the treatment of multiple actinic keratoses

BACKGROUND: Actinic keratoses (AKs) are precancerous epidermal lesions found most frequently on areas of the skin exposed to the sun. Several case studies published recently have indicated that 5% imiquimod cream, currently licensed for the treatment of genital warts, may be an effective treatment for AK. OBJECTIVE: To assess the efficacy and safety of imiquimod for the treatment of AK. DESIGN: Patients in this randomized, double-blind, vehicle-controlled study applied 5% imiquimod cream or vehicle to AK lesions 3 times per week for a maximum of 12 weeks or until lesions had resolved. In the event of an adverse reaction, application of imiquimod was reduced to 1 or 2 times per week. Rest periods were also allowed if necessary. SETTING: A specialized outpatient dermatology clinic within a state-funded hospital in Germany. PATIENTS: The study population was aged 45 to 85 years. Of 52 patients screened, 36 men and women with AK confirmed by histological diagnosis were enrolled. Patients were excluded from the study if they did not have a histological diagnosis for AK, if they were older than 85 years, or if they did not comply with the protocol. All patients had responded to a notice asking for volunteers. MAIN OUTCOME MEASURES: The number and appearance of lesions were evaluated before, during, and after treatment. All adverse effects were recorded. RESULTS: Lesions treated with 5% imiquimod cream were clinically cleared in 21 (84%) of 25 patients and partially cleared in 2 (8%). Clearance was histologically confirmed 2 weeks after the last application of imiquimod in all patients clinically diagnosed as lesion free. Only 10% of patients treated with imiquimod were clinically diagnosed with recurrence 1 year after treatment. No reduction in the size or number of AK lesions was observed in vehicle-treated patients. Adverse effects reported by patients treated with imiquimod included erythema, edema, induration, vesicles, erosion, ulceration, excoriation, and scabbing. However, imiquimod was well tolerated since all patients completed the 12-week treatment. Only a few, mild adverse reactions to the vehicle cream were reported. CONCLUSION: Application of 5% imiquimod cream for 12 weeks is an effective and well-tolerated treatment for AK.     

5%咪喹莫特乳膏治疗尖锐湿疣多中心、随机、双盲研究

目的观察5%咪喹莫特乳膏治疗肛周和外生殖器尖锐湿疣的临床疗效和安全性。方法采用随机、双盲、平行对照的临床研究方法,受试者每周3次局部外搽研究药物,用药后6￣8h用清水清洗,疗程8周。疣体完全消退者继续随访1个月以观察复发率。结果共有231例肛周及外生殖器尖锐湿疣患者参加本次研究,其中5%咪喹莫特乳膏治疗组116例,安慰剂对照组115例。治疗后2、4、6、8周的痊愈率在治疗组分别为8.41%、30.84%、49.53%及61.68%,对照组分别为2.68%、7.14%、16.07%及24.11%,两组间差异有统计学意义(P<0.001);疗后2、4、6、8周的有效率在治疗组分别为34.58%、60.75%、68.22%及74.77%,对照组分别为10.72%、18.75%、28.57%及32.14%,两组间差异有统计学意义(P<0.001)。治疗组痊愈患者随访1个月后的复发率为10.61%,与对照组相比差异无统计学意义。治疗组无系统不良反应,仅有给药部位的局部不良反应,以轻度和中度红斑为多见,发生率为34.55%。结论5%咪喹莫特乳膏治疗肛周和外生殖器尖锐湿疣疗效好,安全性好,使用方便。     

Treatment of Human Papilloma Virus in a 6-Month-Old Infant with Imiquimod 5% Cream

A healthy female infant was diagnosed with genital warts at six months of age. She was the product of an uncomplicated vaginal delivery to a mother who was diagnosed with genital warts during the pregnancy, but did not undergo any treatment. The infant's warts were clinically resolved following a three week course of 5% imiquimod cream, an immunomodulating agent that has been demonstrated to be a potent inducer of several cytokines promoting an antiviral cell-mediated immune response.     

Successful treatment of actinic keratosis with imiquimod cream 5%: a report of six cases

BACKGROUND: Actinic keratoses (AK) are premalignant lesions, which are routinely treated by destructive procedures such as cryotherapy, electrodessication or topical 5-fluorouracil. OBJECTIVES: The aim of this study is to report six cases of AK treated with a potential new topical therapy, imiquimod. METHODS: Subjects included in this study had suffered with recurrent AK for between 5 and 16 years. All six men were treated with imiquimod 5% cream three times a week for 6-8 weeks. In the event of a local skin reaction treatment was modified to two times per week. RESULTS: All the AK lesions were successfully cleared after treatment with imiquimod cream 5% for 6-8 weeks. Histologically, no apparent signs of persisting AK could be detected, and no recurrences were reported during follow up. CONCLUSIONS: This study suggests that imiquimod may be useful as a new therapy for the treatment of actinic keratoses.     

Genital vitiligo following use of imiquimod 5% cream

Imiquimod is a small molecule with adjuvant pro-inflammatory effects that can be topically delivered as a cream for treating external genital and perianal warts. In our report, two Chinese males at the ages of 25 and 22 years were treated with imiquimod 5% cream for recurrent condyloma accuminatum, three times per week for 18 and 12. weeks, respectively. Depigmentation were noted and gradually enlarged in the treated areas after the two patients discontinued imiquimod. Therefore, clinicians should be made aware of the possible pigmentary changes associated with application of this cream.     

Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: results from two phase III, randomized, vehicle-controlled studies

BACKGROUND: Imiquimod is an immune response modifier that is a Toll-like receptor 7 agonist that induces interferon and other cytokines through the innate immune system and stimulates cell-mediated immunity through T cells. Imiquimod has been shown to be efficacious as a topical treatment for basal cell carcinoma (BCC). OBJECTIVE: We sought to evaluate the efficacy and safety of imiquimod 5% cream compared with vehicle for treating superficial BCC (sBCC). METHODS: Two identical studies were conducted. Subjects with one sBCC were dosed with imiquimod or vehicle cream once daily 5 or 7x/week for 6 weeks in these 2 randomized, double-blind, vehicle-controlled Phase III studies. The lesion site was clinically examined 12 weeks posttreatment and then excised for histological evaluation. RESULTS: Data from both studies were pooled. Composite clearance rates (combined clinical and histological assessments) for the 5 and 7x/week imiquimod groups were 75% and 73%, respectively. Histological clearance rates for the 5 and 7x/week imiquimod groups were 82% and 79%, respectively. Increasing severity of erythema, erosion, and scabbing/crusting was associated with higher clearance rates. CONCLUSION: Imiquimod appears to be safe and effective for the treatment of sBCC when compared with vehicle cream. The difference in clearance rates between the two imiquimod dosing groups was not significant. The 5x/week regimen is recommended.