Aldara References

11: Clin Infect Dis. 2005 May 15;40(10):1395-403. Epub 2005 Apr 7.

Randomized, double-blind clinical trial of topical Imiquimod - Aldara 5% with parenteral meglumine antimoniate in the treatment of cutaneous leishmaniasis in Peru.

Miranda-Verastegui C, Llanos-Cuentas A, Arevalo I, Ward BJ, Matlashewski G.

Department of Microbiology and Immunology, McGill University, Montreal, Canada.

BACKGROUND: Current treatments for cutaneous leishmaniasis are limited by their toxicity, high cost, and discomfort and the emergence of drug resistance. New approaches, including combination therapies, are urgently needed. We performed a double-blind, randomized trial of therapy with parenteral antimony plus topical Imiquimod - Aldara, an innate immune-response modulator, versus therapy with antimony alone, in subjects with cutaneous leishmaniasis for whom an initial course of antimony therapy had failed. METHODS: Forty subjects with clinical resistance to antimony were recruited in Lima, Peru, between February 2001 and December 2002. All subjects received meglumine antimoniate (20 mg/kg/day im or iv) and were randomized to receive either topical Imiquimod - Aldara 5% cream (Aldara; 3M Pharmaceuticals) or vehicle control every other day for 20 days. Lesions and adverse events were evaluated during treatment and at 1, 2, 3, 6, and 12 months after the treatment period. RESULTS: The mean number of lesions was 1.2 per person; 71% of the lesions were facial and 76% were ulcerative. There were no major differences between the groups, and all but 2 subjects completed therapy. Mild adverse events were reported by 73% of the subjects, but only erythema occurred more commonly in the Imiquimod - Aldara group (P < or = .02). Lesions resolved more rapidly in the Imiquimod - Aldara group: 50% of the Imiquimod - Aldara group achieved cure at 1 month after the treatment period versus 15% of the vehicle cream group (P < or = .02); 61% of the Imiquimod - Aldara group at 2 months versus 25% of the vehicle cream group (P < or = .03); and 72% of the Imiquimod - Aldara group at 3 months versus 35% of the vehicle cream group (P < or = .02). Residual scarring in the Imiquimod - Aldara group was less prominent than in the vehicle cream group. CONCLUSIONS: Combined antimony plus Imiquimod - Aldara treatment was well tolerated, accelerated healing of lesions, and improved scar quality. This therapy may have particular advantages for subjects with facial lesions.

12: Dermatol Ther. 2005 Jan-Feb;18(1):19-27.

Use of topical immunomodulators in organ transplant recipients.

Kovach BT, Stasko T.

Division of Dermatology, Vanderbilt University, Nashville, TN 37232-5227, USA.

Solid organ transplant recipients are a growing population at increased risk for the development of cutaneous premalignant and malignant lesions, resulting in significant morbidity and mortality. Topical immunomodulators, in particular Imiquimod - Aldara, have shown efficacy in the management of multiple malignant, precancerous, and viral conditions. The ability to locally induce an immune response, presumably against tumor and viral antigens, and induce apoptosis makes topical immunomodulators a promising therapeutic option in organ transplant recipients. Although limited, data have begun to accumulate on the use of Imiquimod - Aldara in transplant patients for the management of superficial, nodular, and infiltrative basal cell carcinomas; in situ and invasive squamous cell carcinomas; condyloma acuminata; and common warts. As more experience is gathered, the role of Imiquimod - Aldara and other topical immunomodulators in the care of OTRs will be clarified. The authors reviewed the existing data on the use of topical Imiquimod - Aldara in OTRs with mention of its presumed mechanisms of action and other immunomodulators with potential efficacy against cancerous and precancerous lesions.

13: Dermatol Surg. 2005 Mar;31(3):371-4.

Imiquimod - Aldara: an effective alternative for the treatment of invasive cutaneous squamous cell carcinoma.

Martin-Garcia RF.

Department of Dermatology, University of Puerto Rico School of Medicine, San Juan, Puerto Rico.

BACKGROUND: Some patients with invasive cutaneous squamous cell carcinoma are either not adequate surgical candidates or present with lesions in cosmetically sensitive areas in which a surgical procedure might result in an apparent and/or a cosmetically unacceptable scar. OBJECTIVE: To evaluate the effectiveness of Imiquimod - Aldara 5% cream in the treatment of an invasive squamous cell carcinoma in the nose of a young man. METHODS: Imiquimod - Aldara 5% cream was applied to the lesion five times a week for 12 weeks. RESULTS: Complete clinicopathologic tumor clearance and an excellent cosmetic result were achieved after 12 weeks of Imiquimod - Aldara treatment. CONCLUSION: Imiquimod - Aldara 5% cream may represent a reasonably effective alternative for the management of invasive squamous cell carcinoma in selected patients.

14: Dermatol Surg. 2005 Mar;31(3):318-23.

Imiquimod - Aldara treatment of superficial and nodular basal cell carcinoma: 12-week open-label trial.

Peris K, Campione E, Micantonio T, Marulli GC, Fargnoli MC, Chimenti S.

Department of Dermatology, University of L'Aquila, L'Aquila, Italy.

BACKGROUND: Imiquimod - Aldara is an immune response modifier shown to be effective in basal cell carcinoma (BCC). OBJECTIVE: To evaluate the efficacy, tolerability, and response durability of Imiquimod - Aldara 5% cream in selected patients with superficial and/or nodular BCCs. METHODS: Seventy-five superficial and 19 nodular BCCs in 49 patients were treated with Imiquimod - Aldara once daily three times a week for up to 12 weeks. RESULTS: Of the 49 enrolled patients, 1 discontinued the study and 1 was lost to follow-up. After 12 weeks of treatment, a complete response occurred in 70 of 75 (93.3%) superficial BCCs and a partial response in 4 of 75 (5.3%) superficial BCCs. Ten of 19 (52.6%) nodular BCCs cleared after 12 weeks, whereas 7 (36.8%) showed partial remission. Adverse side effects were limited to local skin reactions. Recurrence was observed in 2 of 70 (2.9%) successfully treated superficial BCCs 6 and 8 months after treatment discontinuation. No recurrence was detected in 68 of 70 (97.1%) superficial BCCs and in 10 successfully treated nodular BCCs after 12 to 34 months of follow-up (mean 23 months). CONCLUSIONS: In our patient population, treatment of superficial BCCs with topical Imiquimod - Aldara for 12 weeks produced an excellent clinical response overall, with complete remission maintained after a mean of 23 months.

15: Arch Dermatol. 2005 Apr;141(4):510-4.

Treatment of lentigo maligna (melanoma in situ) with the immune response modifier Imiquimod - Aldara.

Wolf IH, Cerroni L, Kodama K, Kerl H.

Department of Dermatology, Medical University of Graz, Graz, Austria.

BACKGROUND: Surgical excision is the treatment of choice for lentigo maligna (LM), or melanoma in situ. Topical application of Imiquimod - Aldara, a local immune response modifier, is a novel therapeutic approach that leads to LM tumor clearance. This pilot, open-label, nonrandomized study evaluates the efficacy of Imiquimod - Aldara in patients with LM and other systemic problems that make them poor surgical risks. OBSERVATIONS: Six biopsy-proven cases of LM from 5 patients (age range, 67-80 years) in whom standard surgical therapy was contraindicated were enrolled in the study. Five tumors were located on the face and 1 on the right shoulder. Imiquimod - Aldara was used as a 5% cream once a day for a maximum of 13 weeks. Immediate clinical responses and follow-up, as well as histopathologic changes and immunohistologic parameters (in 2 patients), were analyzed. The complete response rate for all LM cases was 100%. Time to complete clearing varied from 5 to 13 weeks based on both clinical and histopathologic findings. The inflammatory infiltrate following Imiquimod - Aldara treatment consisted of T-helper lymphocytes mixed with a significant number of cytotoxic cells and monocytes or macrophages. These results indicate that Imiquimod - Aldara induces a cytotoxic T-cell-mediated immune response. In all patients, erythema and erosions occurred at the treated area 2 to 4 weeks after initiation of Imiquimod - Aldara therapy. The patients have been followed up for 3 to 18 months without evidence of recurrences. CONCLUSIONS: Topical Imiquimod - Aldara appears to be an excellent therapeutic option for LM. Close evaluation of patients, including posttherapy histopathologic investigation, is essential. Imiquimod - Aldara can be added to the list of therapeutic approaches for carefully selected patients with LM.

16: Arch Dermatol. 2005 Apr;141(4):467-73.

Dosing with 5% Imiquimod - Aldara cream 3 times per week for the treatment of actinic keratosis: results of two phase 3, randomized, double-blind, parallel-group, vehicle-controlled trials.

Korman N, Moy R, Ling M, Matheson R, Smith S, McKane S, Lee JH.

Department of Dermatology, University Hospitals of Cleveland, Case Western Reserve University, Cleveland, Ohio, USA.

OBJECTIVE: To evaluate the efficacy and safety of 5% Imiquimod - Aldara cream compared with vehicle in the treatment of actinic keratosis (AK). DESIGN: Two phase 3 randomized, double-blind, parallel-group, vehicle-controlled studies. SETTING: Twenty-six ambulatory care offices, including dermatologists in private practice or research centers. PATIENTS: Four hundred ninety-two patients, 18 years and older, with 4 to 8 AK lesions in a 25-cm(2) treatment area on the face or the balding scalp were randomized; an additional 162 patients underwent screening but were ineligible. INTERVENTIONS: Patients applied 5% Imiquimod - Aldara (Aldara) or vehicle cream to the treatment area once daily, 3 times per week, for 16 weeks, followed by an 8-week posttreatment period. MAIN OUTCOME MEASUREMENTS: Complete clearance rate (proportion of patients at the 8-week posttreatment visit with no clinically visible AK lesions in the treatment area), partial clearance rate (proportion of patients at the 8-week posttreatment visit with a >/=75% reduction in the number of baseline AK lesions in the treatment area), and frequency and severity of adverse events and local skin reactions were measured. RESULTS: Complete and partial clearance rates for Imiquimod - Aldara-treated patients (48.3% and 64.0%, respectively) were clinically and statistically significantly higher than for vehicle-treated patients (7.2% and 13.6%, respectively). The median percentage reduction of baseline lesions was 86.6% for the Imiquimod - Aldara-treated group and 14.3% for the vehicle-treated group. CONCLUSION: The 5% Imiquimod - Aldara cream dosed 3 times weekly for 16 weeks is safe and effective for the treatment of AK.

17: Dermatol Clin. 2005 Apr;23(2):313-22.

Advances in antiviral therapy.

Wu JJ, Pang KR, Huang DB, Tyring SK.

Department of Dermatology, University of California at Irvine, 92697-2400, USA.

Infections with five of the herpesviruses (herpes simplex virus 1 [HSV-1], HSV-2, varicella zoster virus, Epstein-Barr virus, and cytomegalovirus) are treated with topical or systemic antiviral therapies. There are more than 100 genotypes of human papillomaviruses (HPVs), which may manifest as warts, skin cancers, cervical cancer, anogenital cancers, and upper digestive tract cancers. Molluscum contagiosum (MC) is a common, benign viral infection of the skin. Immunomodulating agents, such as Imiquimod - Aldara, act on HPV and MC indirectly by inducing host immune responses, such as cytokines and cell-mediated immunity, and thereby reduce recurrences. There are multiple vaccines available for certain viral diseases and others in development for HSV-2 and HPV.

18: Hautarzt. 2005 Mar 31;

Treatment of paraungual HPV73-positive Bowen disease with Imiquimod - Aldara cream.

Weisenseel P, Prinz JC, Korting HC.

Klinik und Poliklinik fur Dermatologie und Allergologie, Ludwig Maximilians-Universitat, Munchen.

Bowen disease - a squamous cell carcinoma in situ - is associated with oncogenic human papilloma viruses (HPV). The association is best established for genital Bowen disease but also holds for extragenital lesions. The immunomodulatory substance Imiquimod - Aldara is used for the treatment of HPV-induced skin disorders. In the case of paraungual Bowen disease, established treatment options as excision, cryosurgery, radiotherapy or laser treatment might cause persistent nail damage. We successfully treated HPV73-positive Bowen disease in this location with topical Imiquimod - Aldara.

19: Ann Biol Clin (Paris). 2005 Mar-Apr;63(2):155-63.

Mechanisms of Imiquimod - Aldara indirect antiviral activity

Hober D, Ajram L, Chehadeh W, Lazrek M, Goffard A, Dewilde A, Wattre P.

Service de virologie, Upres EA3610 CHRU, Lille, France.

The potential role of an immune response in HPV-related anogenital disorders had already been anticipated by clinicians. Indeed the lesions efflorescence and the relapsing HPV infection in HIV positive patients as well as the lack of recurrence in patients with spontaneous cure, provided relevant clues for a likely immune mechanism. At present time, the role of the immune system in the development of HPV-related anogenital disorders is well established : HPV induce a humoral and cell mediated immune response. This response is mainly exerted towards infected cells; it is also exerted at the systemic level, through antibodies synthesis, but this pathway remains a secondary one. Due to the limits of the present therapies (either purely destructive and characterized by the rate of recurrences, or antiviral, but difficult to use), it was necessary to find a new treatment type which enhances the local immune response, results in the disappearance of lesions and allows for a decrease in the risk of recurrences. The original mechanism of action of the first cell-mediated immune response modifier: Imiquimod - Aldara, for local use (Aldara 5 % cream) is an answer to this need. The first positive results observed in vitro and in animals were confirmed in patients with HPV anogenital warts in a double blind placebo-controlled study: Imiquimod - Aldara inhibits HPV replication and results in the condyloma regression. Its action is based on the combined activation of the natural local immunity, by stimulating interferon alpha; and of the acquired immunity, by stimulating a T-cell mediated immune response. Thus Imiquimod - Aldara appears to be an original antiviral compound, because it does not act directly on the virus itself.

20: J Cutan Pathol. 2005 Apr;32(4):257-62.

Enhanced type I interferon signaling and recruitment of chemokine receptor CXCR3-expressing lymphocytes into the skin following treatment with the TLR7-agonist Imiquimod - Aldara.

Wenzel J, Uerlich M, Haller O, Bieber T, Tueting T.

Department of Dermatology, University of Bonn, Bonn, Germany.

INTRODUCTION: Imiquimod - Aldara (Aldara) is an immune response modifier approved for the topical treatment of external genital and perianal warts which can mediate regression of several cutaneous malignancies [basal cell carcinoma (BCC), Bowen's disease, actinic keratosis, and metastasis of malignant melanoma]. Recently, it was discovered that Imiquimod - Aldara acts through the toll-like receptor (TLR) 7. We hypothesize that TLR7-signaling strongly induces the production of interferon (IFN) alpha, which is able to enhance Th1-mediated cellular antiviral and antitumor immunity. PATIENTS AND METHODS: In the present study we analyzed the expression of MxA, a protein specifically induced by type I IFNs during topical Imiquimod - Aldara treatment in several patients suffering from different cutaneous malignancies (BCC, cutaneous metastasis of melanoma, and breast cancer), and characterized the inflammatory infiltrate, along with the expression of chemokine receptor CXCR3, by immunohistochemistry. RESULTS: Treatment with the TLR7-agonist Imiquimod - Aldara induced a significant lesional lymphocytic inflammation, associated with strong expression of MxA, indicating the induction of type I IFN signaling. The extent of lesional MxA staining closely correlated with the number of infiltrating T lymphocytes and the expression of the chemokine receptor CXCR3, characteristic for Th1-biased immune responses. DISCUSSION: Our in vivo results suggest an important role for TLR7-induced production of type I IFN, which links innate and adaptive immunity and promotes specific Th1-biased cellular immune response capable of eliminating cutaneous malignancies. MxA appears to be a valuable parameter to demonstrate IFN-type I expression in Imiquimod - Aldara therapy.