Aldara (Imiquimod) Drug and Patient Profile

Drug Profile – Actinic Keratosis

Imiquimod applied 3 times a week to the head in one or two courses appears effective for the treatment of AK’s of the head. Complete clearance in 26.8% for 1 cycle and 53.7% for 2 cycles. One year follow up shows recurrence rates were 39% (Imiquimod) versus 57% (vehicle).

COMMENT: A series of short courses may be more acceptable to patients that one prolonged 16 week session.

J Jorizzo et.el. JAAD May 16 2007 ; 265-268

A repeated 4 week course of Imiquimod 5% cream for AK’s of the head is as safe and effective as one 16 week course. Repeat courses used o those who have failed to clear on the first 4 week course. This approach decreases drug exposure to the patient and decreases overall treatment time.

COMMENT. This approach is more acceptable to many patients who have to deal with the cosmetic consequences of therapy.

A Alomas et.al. Br J dermatol 2007 157,pp133-141

Comparison of 5% 5-Fluorouracil cream applied twice a day for 2-4 weeks and 5% Imiquimod cream twice weekly for 16 weeks in the managenment of Actinic Keratosis of the face and scalp. The total Ak count declined by 94% with %-FU compared with 66% with Imiquimod. The degree of erythema was significantly higher with 5-FU cream.

COMMENT. It is clear that 5FU in the short term clears more AK’s than Imiquimod when it is used in the approved way of twice a week for 16 weeks. Work from elsewhere suggests that the longer term clearance is indeed better with Imiquimod possibly due to it’s upregulatoin of the p53 tumour suppressor gene. The tolerability of 5-FU is certainly an issue for some patients

E Tanghetti J of drugs in Dermatology feb 2007 vol 6 issue 2 p144-147

Topical immunomodulation under systemic immunosuppression: results of a multicentre, randomised, placebo-controlled safety and efficacy study of Imiquimod 5% cream for the treatment of actinic keratosis in kidney, heart and liver transplant patients.

Ulrich C et al Br J Dematol 2007.157(suppl2) 25-31

Imiquimod: AK Course-of-Therapy (cycling) data

• 25 patients – 35 cosmetic units
• Twice/ week therapy on face and scalp for 1 month, then a break of 1 month followed by another cycle
• 1st cycle cleared 46%
• 2nd cycle cleared another 36%
• 3rd cycle – no additional patients cleared
• Total % clearance of AK lesions was 82%.

[Salache, et al. J Am Acad Dermatol. 2002; 47:571-7]

Imiquimod: AK Phase III Data

• 2 randomized, double-blind, vehicle-controlled, parallel-group trials
• 4 to 8 baseline AK lesions within a contiguous .25cm2 treated area on face or balding scalp
• Topical imiquimod 5% cream or vehicle .2 times/ week for 16 weeks
• Assessment at 8 weeks posttreatment
• Complete clearance (100%)
• Partial clearance (? 75%)

[Lebwohl M, et al. J Am Acad Dermatol. 2004; 50:714-21]

AK Phase III Data Conclusions

• Imiquimod 5% cream 2 times/ week for 16 weeks was effective in the clearance of AK lesions
• Significantly better than vehicle in complete clearance of AK lesions (P <.001)
• Median percent reduction in number of AKs from baseline was ~ 83%
• Cleared clinical and subclinical AK lesions
• Imiquimod was well tolerated
• Application site and local skin reactions were the predominant adverse events associated with therapy.
• Only 3% of patients discontinued due to adverse events.

[Lebwohl M, et al. J Am Acad Dermatol. 2004; 50:714-21]

Drug Profile – Bowen’s disease

BOWEN’S DISEASE OF THE PENIS TREATED WITH TOPICAL IMIQUIMOD 5% CREAM.
Taliaferro SJ, Cohen GF.
Veterans Affairs Medical Center, Washington, DC, USA.

Bowen’s disease of the penis is relatively uncommon, but the prevalence has increased in recent years. Risk factors for penile squamous cell cancer include smoking, infection with human papilloma virus (HPV), immunosuppression, and a history of conditions such as balanitis, phimosis, and lichen sclerosis et atrophicus. Bowen’s disease of the penis is often managed by local excision of the lesion. Less invasive methods are now employed more frequently and include laser ablation, electrodessication and curettage, cryosurgery, application of5-fluorouracil, and topical imiquimod 5% cream. This case report describes the successful treatment of Bowen’s disease of the penis with topical imiquimod 5% cream in a 42-year-old African American male with human immunodeficiency virus (HIV) disease.

J Drugs Dermatol. 2008 May;7(5):483-5.

Imiquimod: Squamous cell carcinoma in situ (Bowen’s disease) Phase III Data

• Bowen’s disease – (16 patients) daily applications for 16 weeks gave 93% biopsy proven clearance.
• [Mackenzie-Wood A. J Am Acad Dermatol. 2001; 44;462-70]
• Bowen’s and SCC in situ of the penis. All 5 patients cleared at 12-16 weeks.

[Arlette JP. Br J Dermatol. 2003; 149(suppl. 66):43-9]

Drug Profile – Genital Warts

OPTIMAL FREQUENCY OF IMIQUIMOD (ALDARA) 5% CREAM FOR THE TREATMENT OF EXTERNAL GENITAL WARTS IN IMMUNOCOMPETENT ADULTS: A META-ANALYSIS.
Gotovtseva EP, Kapadia AS, Smolensky MH, Lairson DR.
UT School of Public Health, Houston, Texas, USA.

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.

Sex Transm Dis. 2008 Apr;35(4):346-51.

COMPARISON OF CRYOTHERAPY TO IMIQUIMOD 5% IN THE TREATMENT OF ANOGENITAL WARTS.
Stefanaki C, Katzouranis I, Lagogianni E, Hadjivassiliou M, Nicolaidou E, Panagiotopoulos A, Anyfantakis V, Bethimoutis G, Rallis E, Antoniou C, Katsambas A.
Sexually Transmitted Infections Unit, Andreas Sygros Hospital, University of Athens, Athens, Greece.

The aim of this study was to compare the efficacy of crotherapy versus imiquimod 5% in the treatment of anogenital warts. Eighty HIV-negative males were included in the analysis; 35 of them were treated with imiquimod 5% three times a week for 6-10 hours and 45 of them with cryotherapy once in three weeks. Follow-up appointments were arranged every month for the first three months and then at six and 12 months, or in between whenever the patients noticed any signs of recurrence. Treatment for both groups was continued for a total of 12 weeks or until the warts cleared. At the end of three months, irrespective of the type of treatment, 78.8% of the patients demonstrated 100% improvement. Cryotherapy was more effective, as 86.7% of patients showed 100% improvement compared with 68.6% of patients in the imiquimod group. On the contrary, 17.1% of the imiquimod group did not show any signs of improvement, compared with 2.2% of the cryotherapy group (P = 0.017). However, patients treated with imiquimod tended to improve earlier than patients on cryotherapy (P = 0.012). No statistically significant difference was observed regarding the recurrence rate between the two groups (P = 0.138). Treatment with imiquimod was less painful than cryotherapy (P = 0.034). Cryotherapy was more effective than imiquimod 5% for the treatment of anogenital warts in males but was more inconvenient.

Int J STD AIDS. 2008 Jul;19(7):441-4.

EVALUATION OF IMIQUIMOD FOR THE THERAPY OF EXTERNAL GENITAL AND ANAL WARTS IN COMPARISON WITH DESTRUCTIVE THERAPIES.
Schöfer H.
Department of Dermatology and Venerology, University Hospital, J.W. Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt/M, Germany.

External genital and anal warts (acuminate condyloma) were the first medical indication the topical immune response modifier imiquimod was approved for in 1997. Since then, many placebo controlled randomized clinical trials have demonstrated the efficacy and safety of this synthetic imidazoquinoline derivate for the treatment of different human papillomavirus infections and tumours. Treatment modalities for genital warts (5% cream, three times weekly, minimum duration 4 weeks, control of side-effects) have been optimized and assured by further clinical trials and meta-analyses. For a few years clinical studies focussed on the long-term efficacy of the immunomodulatory therapy (sustained clearance from warts) and most recent studies compared the efficacy of ablative, destructive and imiquimod monotherapy as well as combination therapies.

Br J Dermatol. 2007 Dec;157 Suppl 2:52-5.

TREATMENT OF VULVAR INTRAEPITHELIAL NEOPLASIA WITH TOPICAL IMIQUIMOD.
van Seters M, van Beurden M, ten Kate FJ, Beckmann I, Ewing PC, Eijkemans MJ, Kagie MJ, Meijer CJ, Aaronson NK, Kleinjan A, Heijmans-Antonissen C, Zijlstra FJ, Burger MP, Helmerhorst TJ.
Department of Gynecology, Erasmus University Medical Center, Rotterdam, The Netherlands.

BACKGROUND:
Alternatives to surgery are needed for the treatment of vulvar intraepithelial neoplasia. We investigated the effectiveness of imiquimod 5% cream, a topical immune-response modulator, for the treatment of this condition.

METHODS:
Fifty-two patients with grade 2 or 3 vulvar intraepithelial neoplasia were randomly assigned to receive either imiquimod or placebo, applied twice weekly for 16 weeks. The primary outcome was a reduction of more than 25% in lesion size at 20 weeks. Secondary outcomes were histologic regression, clearance of human papillomavirus (HPV) from the lesion, changes in immune cells in the epidermis and dermis of the vulva, relief of symptoms, improvement of quality of life, and durability of response. Reduction in lesion size was classified as complete response (elimination), strong partial response (76 to 99% reduction), weak partial response (26 to 75% reduction), or no response (< or =25% reduction). The follow-up period was 12 months.

RESULTS:
Lesion size was reduced by more than 25% at 20 weeks in 21 of the 26 patients (81%) treated with imiquimod and in none of those treated with placebo (P<0.001). Histologic regression was significantly greater in the imiquimod group than in the placebo group (P<0.001). At baseline, 50 patients (96%) tested positive for HPV DNA. HPV cleared from the lesion in 15 patients in the imiquimod group (58%), as compared with 2 in the placebo group (8%) (P<0.001). The number of immune epidermal cells increased significantly and the number of immune dermal cells decreased significantly with imiquimod as compared with placebo. Imiquimod reduced pruritus and pain at 20 weeks (P=0.008 and P=0.004, respectively) and at 12 months (P=0.04 and P=0.02, respectively). The lesion progressed to invasion (to a depth of <1 mm) in 3 of 49 patients (6%) followed for 12 months (2 in the placebo group and 1 in the imiquimod group). Nine patients, all treated with imiquimod, had a complete response at 20 weeks and remained free from disease at 12 months.

CONCLUSIONS:
Imiquimod is effective in the treatment of vulvar intraepithelial neoplasia. (Current Controlled Trials number, ISRCTN11290871 [controlled-trials.com].). Copyright 2008 Massachusetts Medical Society.

J Drugs Dermatol. 2008 Aug;7(8):801-7.

IMIQUIMOD LEADS TO A DECREASE OF HUMAN PAPILLOMAVIRUS DNA AND TO A SUSTAINED CLEARANCE OF ANAL INTRAEPITHELIAL NEOPLASIA IN HIV-INFECTED MEN.
Kreuter A, Potthoff A, Brockmeyer NH, Gambichler T, Stücker M, Altmeyer P, Swoboda J, Pfister H, Wieland U; German Competence Network HIV/AIDS. Collaborators (124)
Department of Dermatology, Ruhr-University Bochum, Bochum, Germany.

Anal intraepithelial neoplasia (AIN), a human papillomavirus (HPV)-associated precursor lesion of anal carcinoma, is highly prevalent in HIV-infected men having sex with men (MSM). This prospective follow-up study evaluated the long-term results of imiquimod treatment of AIN in 19 HIV-infected MSM. Standardized follow-up examinations included high-resolution anoscopy, anal cytology/histology, HPV typing, and DNA load determination for HPV types 16, 18, 31, and 33. Mean follow-up time was 30.3 months. A total of 74% (14/19) of the patients remained free of AIN at the previously treated site. Five patients (26%) had recurrent high-grade AIN after a mean time of 24.6 months. At the end of follow-up, the numbers of HPV types as well as high-risk HPV-DNA loads were significantly lower than before therapy. During follow-up, 58% of all patients (11/19) developed new anal cytological abnormalities in previously normal, untreated anal regions. 55% of these new AIN lesions were high-grade lesions and most of them were located intra-anally and associated with high-risk HPV types not detectable before therapy. These results demonstrate that imiquimod leads to a high rate of long-term clearance of AIN in HIV-positive men together with a prolonged decrease of high-risk HPV-DNA load. However, new AIN lesions associated with previously undetected HPV types frequently occur in untreated areas.

J Invest Dermatol. 2008 Aug;128(8):2078-83. Epub 2008 Feb 14.

HUMAN PAPILLOMAVIRUS-TYPE PREDICT THE CLINICAL OUTCOME OF IMIQUIMOD THERAPY FOR WOMEN WITH VULVAR CONDYLOMATA ACUMINATA.
Dede M, Kubar A, Yenen MC, Alanbay I, Guven S, Mesten Z, Baser I.
Department of Obstetrics and Gynecology, Gulhane Military Medicine Academy, Ankara, Turkey.

OBJECTIVE:
To investigate the effect of determination of human papillomavirus (HPV) subtype on the success of imiquimod therapy in women with vulvar condylomata acuminata.

METHODS:
A total of 132 women with biopsy-proven vulvar condylomata acuminata were enrolled in this prospective study. HPV DNA detection and determination of genotype were made through polymerase chain reaction (PCR) technique. The women were treated with imiquimod cream 5% in the area of the visible lesions, three times a week at night for 16 weeks.

RESULTS:
Twelve of the 132 women (9.1%) failed to detect any improvement with this therapy during the 16-week period. However, 80 women (60.6%) experienced total clearance of the lesions, and 20 women (15.2%) observed a partial response. The complete response rates were 76.2% for HPV-6, 66.7% for HPV-11, 35% for HPV-6 plus 11, and 6.3% for unclassified HPV subtypes (other HPV subtypes than HPV 6 and -11). CONCLUSIONS: Topical imiquimod 5% cream is an appropriate treatment modality for HPV-6 or -11 positive vulvar warts.

Acta Obstet Gynecol Scand. 2007;86(8):968-72.

THE ANTIVIRAL ACTIVITY OF TOLL-LIKE RECEPTOR 7 AND 7/8 AGONISTS.
Miller RL, Meng TC, Tomai MA.

Imiquimod 5% cream is approved for the topical treatment of external anogenital warts caused by human papillomavirus (HPV) and for the skin cancer conditions superficial basal cell carcinoma and actinic keratosis. This drug is the first approved topically active Toll-like receptor (TLR) 7 agonist. Imiquimod activates innate immune cells to produce interferon-a and other cytokines. The induced cytokine cascade, in combination with effects in enhancing antigen presentation, also promotes an antigen-specific T helper type 1 cell-mediated immune response. This immune-based mechanism provides activity against a number of viruses and other intracellular pathogens. Imiquimod was effective topically in clinical studies for HPV but caused mixed results for Molluscum contagiosum, and herpes simplex virus (HSV). Activity against several other viruses were reported in case reports or patient series involving “off-label” usage of imiquimod, while others were evaluated only in preclinical models. Resiquimod, a more potent investigational analogue of imiquimod with mixed TLR7/8 agonist activity, was evaluated in clinical studies topically for the treatment of HSV and systemically for hepatitis C virus also with mixed success. This review focuses on the mechanism of action and antiviral usage reported for the TLR7 agonist imiquimod, the TLR7/8 agonist resiquimod and related imidazoquinoline analogues. Copyright 2008 Prous Science, S.A.U. or its licensors. All rights reserved.

Drug News Perspect. 2008 Mar;21(2):69-87.

HUMAN PAPILLOMAVIRUS (HPV) VIRAL LOAD AND HPV TYPE IN THE CLINICAL OUTCOME OF HIV-POSITIVE PATIENTS TREATED WITH IMIQUIMOD FOR ANOGENITAL WARTS AND ANAL INTRAEPITHELIAL NEOPLASIA.
Sanclemente G, Herrera S, Tyring SK, Rady PL, Zuleta JJ, Correa LA, He Q, Wolff JC.
Dermatology Section, Department of Internal Medicine, University of Antioquia, Medellín, Colombia.

OBJECTIVE:
To evaluate the efficacy of 5% imiquimod in HIV-positive male patients with anogenital warts or anal intraepithelial neoplasia (AIN), and to elucidate whether human papillomavirus (HPV) type and viral load were important for clinical outcome and recurrences.

METHODS:
Thirty-seven patients with histologically proven anogenital warts or AIN were enrolled. Topical 5% imiquimod was applied three times per week for more than 8 h overnight for 16 weeks, although patients were allowed to continue therapy for 4 more weeks if they did not have complete clearance of lesions. RESULTS: Mean age was 34 years. The perianal area was the main lesion location. Thirty-three patients had CD4 counts of < 500 cells/mm(3). Eighteen patients had a histopathological diagnosis of AIN-1. Main HPV types detected corresponded to low-risk HPV types. At 20 weeks of therapy, 46% patients achieved total clearance whereas 14 patients had > 50% clearance. Recurrence was observed in 5 of 17 patients who cleared. Clearance was not influenced by patients’ CD4 counts, wart location, HIV viral load or HPV viral load.

CONCLUSIONS:
The assumption that visible perianal warts are benign lesions in HIV-positive patients has to be reevaluated since an important number of such lesions could correspond to low-grade anal disease, which in turn could progress to high-grade anal disease or cancer. In addition, our results in this preliminary study indicate that imiquimod appears to be effective in treating AIN in HIV-positive patients. Further studies are needed to document its utility to prevent high-grade dysplasia and/or anal cancer.

J Eur Acad Dermatol Venereol. 2007 Sep;21(8):1054-60.

Drug Profile – Basal Cell Carcinoma

IMIQUIMOD: A REVIEW OF BASAL CELL CARCINOMA TREATMENTS.
Karve SJ, Feldman SR, Yentzer BA, Pearce DJ, Balkrishnan R.
Department of Pharmacy Practice and Administration, The Ohio State University College of Pharmacy, Columbus, OH 43210, USA.

Basal cell carcinoma (BCC) is regarded as the most prevalent malignant skin tumor in whites. A variety of surgical and nonsurgical interventions are available to treat BCC. In recent years, an immune response modifier drug, imiquimod, has been approved in treating superficial BCC (sBCC). The objective of the authors was to review the published literature to evaluate outcomes such as efficacy, safety, and quality of life associated with imiquimod treatment among patients with sBCC. A MEDLINE search of the literature was performed to identify studies published between January 1, 1995 and March 31, 2008 that evaluated imiquimod efficacy, safety, and quality of life in treating BCC. Overall, imiquimod 5% cream was associated with increased clinical and histologic clearance among patients with sBCC as compared to placebo. The findings from short-term cost effectiveness studies suggest that use of imiquimod 5% cream can be more cost-effective than surgical interventions such as excision surgery among patients with superficial BCC. Future studies evaluating long term cost effectiveness of imiquimod treatment are warranted.

J Drugs Dermatol. 2008 Nov;7(11):1044-51

RECURRENCE RATE OF SUPERFICIAL BASAL CELL CARCINOMA FOLLOWING TREATMENT WITH IMIQUIMOD 5% CREAM: CONCLUSION OF A 5-YEAR LONG-TERM FOLLOW-UP STUDY IN EUROPE.
Gollnick H, Barona CG, Frank RG, Ruzicka T, Megahed M, Maus J, Munzel U.
Clinic for Dermatology and Venereology, Otto von Guericke University of Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany.

Imiquimod 5% cream is an immune response modifier approved for the treatment of superficial basal cell carcinoma (sBCC) once daily, 5 x per week for 6 weeks. This report reveals the final results of a 5-year follow-up study to evaluate the recurrence rate of sBCCs treated with imiquimod. As previously reported, 182 patients were enrolled in the study and 163 (89.6%) had no clinical evidence of their target sBCC at the 12-week post-treatment assessment; these 163 were followed for up to 5 years. During the follow-up period, 18 clinical recurrences occurred at the target tumour site, 8 and 10 of which occurred during the first 6 and 12 months of follow-up, respectively. The 5-year Kaplan-Meier and life-table estimates for sustained clinical clearance of those patients initially cleared were 84.5% and 86.9%, respectively, and 90.3% considering histology. The estimate of overall treatment success for all treated patients at the end of follow-up was 77.9% (80.9% considering histology). The data support clinical assessment of initial response as predictive of long-term outcome. Most of the recurrences occurred early, indicating that careful follow-up is important during the first year after treatment.

Eur J Dermatol. 2008 Nov-Dec;18(6):677-82. Epub 2008 Oct 27.

CONFIRMATION OF HISTOLOGICAL CLEARANCE OF SUPERFICIAL BASAL CELL CARCINOMA WITH MULTIPLE SERIAL SECTIONING AND MOHS’ MICROGRAPHIC SURGERY FOLLOWING TREATMENT WITH IMIQUIMOD 5% CREAM.
Ezughah FI, Affleck AG, Evans A, Ibbotson SH, Fleming CJ.
Department of Dermatology, Ninewells Hospital and Medical School, Dundee, UK.

BACKGROUND:
Although the effectiveness of daily dosing regimens of 5% imiquimod cream for the treatment of superficial basal cell carcinomas (sBCC) has been documented by recent studies, concerns about long-term outcome remain. The majority of efficacy data is based on clinical clearance and limited histological examination which may not identify tumour presence at the periphery.

OBJECTIVE:
To assess the efficacy of 5% imiquimod cream for sBCC using detailed histological assessment 1 year after completion of treatment.

METHODS:
Nine individuals with biopsy-proven sBCC treated with 5% imiquimod cream 1 year previously and who remained clinically clear were recruited. Paraffin-embedded excision specimens from the original tumour site were extensively examined by a dermatopathologist. Examination and analysis of frozen sections of the original tumour perimeter using Mohs’ micrographic surgery (MMS) were then performed.

RESULTS:
Eight of nine individuals, 89% (95% CI 56% to 97%) were histologically clear of sBCC at 52 weeks. One individual had a single focus of sBCC at one lateral margin.

CONCLUSION:
The results show agreement between the clinical and histological assessment of tumour clearance. However, the persistence of disease in one patient, although limited, indicates the need for cautious long-term follow-up studies on the use of 5% imiquimod cream for sBCC.

J Dermatolog Treat. 2008;19(3):156-8.

CLEARANCE OF BASAL CELL AND SUPERFICIAL SQUAMOUS CELL CARCINOMAS AFTER IMIQUIMOD THERAPY.
Warshauer E, Warshauer BL. Center for Pediatric, Adolescent, and Adult Dermatology, Point Pleasant, NJ, USA.

The short-term and long-term outcomes of 108 patients with 122 nodular basal cell carcinomas (BCCs), morpheaform BCCs, or low-risk squamous cell carcinomas (SCCs) treated with imiquimod 5% cream at a community-based dermatology practice were retrospectively reviewed. The overall initial tumor clinical cure rate was 93.4% (114/122), with an initial clinical cure rate of 90% (72/80) for BCCs combined, and 100% (42/42) for SCCs combined. During a median follow-up time of 18 months, there was only 1 recurrence in the 114 tumors considered initially clinically cured. Imiquimod may be an appropriate initial treatment for these tumors in patients with good posttreatment follow-up.

J Drugs Dermatol. 2008 May;7(5):447-51.

Superficial BCC Phase III data

• Aldara™ cleared after 12 weeks of therapy
• 100% when used twice a day
• 87% when used daily
• 81% when used 5 times/ week

[Geisse JK, et al. J Am Acad Dermatol. 2002; 47:390-98]

• Two prospective, double-blind, multicenter, vehicle-controlled studies
• Imiquimod 5% cream 5 times/ week (n = 185) or placebo (n = 179) for 6 weeks
• Primary, biopsy-confirmed sBCC
• ~ 80% of target lesions were located on trunk or upper extremities
• Complete response at 12 weeks posttreatment
• Clinical and histologic clearance, or
• Clinical suspicion but histologic evidence of no sBCC

[Geisse J, et al. J Am Acad Dermatol. 2004; 50:722-33.]

Superficial BCC Phase III data – Conclusions

• Imiquimod 5% cream is safe and effective in the treatment of primary sBCC.
• High efficacy was achieved at 5 times/ week for 6 weeks of treatment: pooled data showed that composite clearance rate for the imiquimod group was 75% and histological clearance rate was 82%.
• Clinical observations were supported by histologic clearance of target tumour.

[Geisse J, et al. J Am Acad Dermatol. 2004; 50:722-33.]

Drug Profile – Common warts

• Warts on the trunk, hands and face respond the best. Significant reduction in size or clearance was seen in 56% of patients.

[Hengge UR, et al. Br J Dermatol. 2000; 143:1026-31]

• Aldara™ should be used in combination with other therapy as penetration into the keratinized warts is difficult; occlusion of the wart area should also be considered.

Drug Profile – Keloids

• Recurrences of excised keloids on the earlobe were significantly reduced by daily application of Aldara™ 5% to the suture line for 2 months. At 24 weeks, the recurrence rate was lower than recurrence rates previously reported in the literature.[Berman B, et al. J Am Acad Derm. 2002; 47(4 Suppl):s209-11]
• Anecdotally, plastic surgeons have been using this cream post-surgery to minimize the risk of hypertrophic scars – formal studies need to be done.

Drug Profile – Lentigo maligna

Imiquimod pilot study data

• 93% (26/28 patients) cleared (biopsy-confirmed)
• Aldara™ daily for 12 weeks
• Erythema not seen in 2 patients that did not clear
• May be useful as an adjunctive therapy to excision, as recurrence can be high after surgery because of ill-defined margins.

[Naylor M, et al. Br J Dermatol. 2003; 149(suppl. 66):66-70]

Profile – Molluscum Contagiosum

Patient Profile

• Children, sexually active adults, and especially the HIV+ are prone.

Drug Profile

• Studies and case reports show efficacy.
• Useful, non-painful procedure; usually an inflammatory reaction is present, which is desirable.
• One study showed no recurrence in HIV patients after 3 months.
• The frequency of application and treatment duration have not as yet been optimized.

Topical Imiquimod in Nodular BCC

Dose-Response Studies

• 6-week, randomized, open-label study
• Once a day 3 times/wk
• Twice a day 3 times/wk
• Once a day 7 times/wk
• 12-week, randomized, vehicle-controlled study
• Once a day 3 times/wk
• Once a day 5 times/wk
• Once a day 7 times/wk
• Histologic assessment 6 weeks posttreatment

[Shumack S, et al. Arch Dermatol. 2002;138:1165-71].

Imiquimod in the Treatment of Nodular BCC

• Imiquimod 5% cream is safe and effective in the treatment of nBCC.
• Dosing once daily for 7 days/ week resulted in the highest clearance rate, with 71% of patients showing clearance of their tumour after 6 weeks of treatment
• 7 times/week treatment for 6 weeks may be a clinically useful dosing regimen.
• Clearance was lower than that observed in sBCC clinical studies, potentially because of pathophysiologic attributes of nBCC versus sBCC.
• Imiquimod may be useful as adjunctive therapy to surgery or when surgical options are contraindicated or undesirable.

[Shumack S, et al. Arch Dermatol. 2002; 138:1165-71]

Overall Conclusions: AK and BCC

• Topical imiquimod 5% cream is a nonablative topical agent in the treatment of AK and BCC.
• Its novel mechanism of action stimulates the body’s own natural defenses to target diseased tissue.
• Stimulation of both innate and cell-mediated immunity
• It has favorable efficacy and safety profiles for the treatment of AK and primary sBCC.
• In clinical practice, topical imiquimod 5% cream may frequently be used in combination with other treatment modalities.