Aldara References

31: Int J Dermatol. 2005 Jan;44(1):14-9.

Imiquimod - Aldara is a strong inhibitor of tumor cell-induced angiogenesis.

Majewski S, Marczak M, Mlynarczyk B, Benninghoff B, Jablonska S.

Department of Dermatology and Venereology, Warsaw School of Medicine, Warsaw, Poland.

BACKGROUND: Imiquimod - Aldara, a potent immunomodulator, not having a direct antiproliferative activity, was found to be effective in genital and cutaneous premalignancies and malignancies. As tumor development depends on blood vessel supply, the inhibition of angiogenesis could be responsible for the antitumor activity. OBJECTIVE: To find in a murine model whether Imiquimod - Aldara has antiangiogenic activity and whether this activity is mediated by locally induced cytokines. METHODS: The study was performed in two cell lines: Skv human keratinocytes containing multiple integrated copies of HPV16 derived from bowenoid papulosis, and murine L1 lung sarcoma cells of Balb/c mice. The murine model of cutaneous angiogenesis was used to assess and count the new blood vessel formation. The mice were immunosuppressed by a total body X-ray irradiation and treated with 5% or 2.5% Imiquimod - Aldara cream before or after induction of angiogenesis with intradermally injected tumor cell suspension. In some experiments the mice were, in addition, treated intraperitoneally with monoclonal antibodies against murine IFNalpha, TNFgamma or IL-18. RESULTS: Topical application of Imiquimod - Aldara on the murine skin resulted in reduction of angiogenesis (P < 0.001) induced by intradermal injection of both human and mouse tumor cells, more pronounced when 5% cream was applied on three consecutive days. Antibodies against murine IFNgamma, TNFalpha and IL-18 completely abolished the inhibitory effect of Imiquimod - Aldara on angiogenesis induced by murine L1 sacroma cells. When human Skv cells were used in angiogenesis assay, the effect of Imiquimod - Aldara was abolished by antibodies against IL-18 but not against TNFalpha, which may be due to overproduction of TNFalpha by Skv cells. CONCLUSIONS: Antiangiogenic effect of Imiquimod - Aldara was found to be mediated by IL-18, probably through promoting production of INFgamma, the most important inhibitor of angiogenesis.

32: Am J Clin Dermatol. 2004;5(6):453-8.

Role of Imiquimod - Aldara in skin cancer treatment.

Urosevic M, Dummer R.

Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.

Cancer of the skin is by far the most common form of all cancers. Given the increasing incidence of skin cancer worldwide, it seems feasible to reconsider the treatment options available for dealing with this growing problem. Despite the lower costs associated with classical methods such as surgery and radiotherapy, immune response modifiers such as Imiquimod - Aldara appear to be good candidates for the future given their good cosmetic effects, the possibility of treating large areas, and the simpleness of patient-applied treatment with a cream formulation. This article reviews current literature on the use of Imiquimod - Aldara in the treatment of nonmelanoma and melanoma skin cancer.

33: J Immunol. 2005 Feb 1;174(3):1259-68.

Synthetic TLR agonists reveal functional differences between human TLR7 and TLR8.

Gorden KB, Gorski KS, Gibson SJ, Kedl RM, Kieper WC, Qiu X, Tomai MA, Alkan SS, Vasilakos JP.

3M Pharmaceuticals, St. Paul, MN 55144, USA.

Although TLR7 and TLR8 are phylogenetically and structurally related, their relative functions are largely unknown. The role of TLR7 has been established using TLR7-deficient mice and small molecule TLR7 agonists. The absence of TLR8-selective agonists has hampered our understanding of the role of TLR8. In this study TLR agonists selective for TLR7 or TLR8 were used to determine the repertoire of human innate immune cells that are activated through these TLRs. We found that TLR7 agonists directly activated purified plasmacytoid dendritic cells and, to a lesser extent, monocytes. Conversely, TLR8 agonists directly activated purified myeloid dendritic cells, monocytes, and monocyte-derived dendritic cells (GM-CSF/IL-4/TGF-beta). Accordingly, TLR7-selective agonists were more effective than TLR8-selective agonists at inducing IFN-alpha- and IFN-regulated chemokines such as IFN-inducible protein and IFN-inducible T cell alpha chemoattractant from human PBMC. In contrast, TLR8 agonists were more effective than TLR7 agonists at inducing proinflammatory cytokines and chemokines, such as TNF-alpha, IL-12, and MIP-1alpha. Thus, this study demonstrated that TLR7 and TLR8 agonists differ in their target cell selectivity and cytokine induction profile.

34: Pediatr Dermatol. 2005 Jan-Feb;22(1):67-70.

Treatment of multiple trichoepitheliomas with topical Imiquimod - Aldara and tretinoin.

Urquhart JL, Weston WL.

Department of Dermatology, University of Colorado Health Sciences Center, Aurora, CO 80010, USA.

An 11-year-old white girl presented multiple flesh-colored dome-shaped papules on the forehead, nose, scalp, and posterior neck. The lesions had been present for 2 years and were asymptomatic. Family history was negative for skin diseases. A skin biopsy specimen revealed histopathology consistent with trichoepitheliomas. Treatment of multiple trichoepitheliomas is usually difficult. Methods reported in the literature include laser treatment, surgery, cryotherapy, electrodessication, and radiation. The parents were concerned about the risk of scarring and wanted to pursue a nonscarring treatment. The patient was initially treated with topical Imiquimod - Aldara three times a week. She progressively increased the frequency of application to twice daily and added topical tretinoin gel once daily to her regimen for more resistant lesions. After 3 years of treatment, the patient experienced approximately 80% clearing of lesions without scarring. The advantage of using this nonsurgical treatment is no scarring, painless, and no need for other invasive procedures such as injection of local anesthetic.

35: Br J Dermatol. 2005 Jan;152(1):122-9.

Imiquimod - Aldara cream 5% for recalcitrant cutaneous warts in immunosuppressed individuals.

Harwood CA, Perrett CM, Brown VL, Leigh IM, McGregor JM, Proby CM.

Centre for Cutaneous Research, Barts and the London School of Medicine and Dentistry, Queen Mary College, University of London, 2 Newark Street, London, E1 2AT, UK.

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 - Aldara 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 - Aldara 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 - Aldara 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 - Aldara exposure. CONCLUSIONS: This is the first controlled study to assess therapeutic efficacy of topical 5% Imiquimod - Aldara cream in persistent warts associated with immunosuppression. It provides preliminary evidence that topical Imiquimod - Aldara may benefit a subgroup of immunosuppressed patients with recalcitrant cutaneous warts.

36: J Cutan Med Surg. 2004 Dec;8 Suppl 3:3-12.

Mechanism of action and emerging role of immune response modifier therapy in dermatologic conditions.

Sauder DN.

Department of Dermatology, Johns Hopkins University, Baltimore, Maryland, USA.

Immune response modifiers (IRMs) are agents that target the body's immune system (i.e., cytokines, receptors, and inflammatory cells) to combat disease. Topical IRM therapies, which encompass both proinflammatory and immunosuppressive therapeutics, have been used to successfully treat a number of dermatologic conditions. Proinflammatory treatments include Toll-like receptor agonists (e.g., Imiquimod - Aldara 5% cream) and interferon (e.g., interferon-alpha) therapies, which have been used in the treatment of external genital warts, basal cell carcinoma, and other dermatologic diseases. Immunosuppressive therapies include topical and intralesional corticosteroids, anti-tumor necrosis factor agents (e.g., infliximab and etanercept), and anti-CD4(+) T-cell agents, including calcineurin inhibitors and mycophenolate. These agents have been used to treat a number of conditions, including atopic and seborrheic dermatitis and psoriasis. This article reviews the mechanism of action of IRMs and the application of IRMs in several dermatologic diseases.

37: J Cutan Med Surg. 2004 Dec;8 Suppl 3:13-21.

Current and novel treatment options for actinic keratosis.

Jorizzo JL.

Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.

Actinic keratosis (AK), located on sun-exposed areas of the skin, is an increasing global health burden. Multiple ablative and topical treatment options are available to manage this disease; however, topical treatment options are receiving significant interest because AK is commonly associated with areas of substantial photodamage, and destructive modalities cannot effectively treat subclinical AK. Several topical therapies, including 0.5% and other 5-fluorouracil concentrations, photodynamic therapy, 3% diclofenac sodium gel, and Imiquimod - Aldara 5% cream, are indicated in the treatment of AK. This article will review key data on the efficacy and safety of several topical therapies in the treatment and management of AK. The review includes discussions of Imiquimod - Aldara 5% cream, approved in 2004 in the treatment of AK of the face or scalp. Whether administered as monotherapy or adjunctive therapy, topical therapies provide the opportunity to effectively manage AK and will likely emerge as an important tool for healthcare providers.

38: J Cutan Med Surg. 2004 Dec;8 Suppl 3:22-31.

Role of topical therapies in the management of cutaneous disease.

Skinner R.

Department of Medicine, Division of Dermatology, University of Tennessee Health Science Center, Memphis, Tennessee, USA.

Within the last decade, healthcare providers have had a larger selection of effective novel topical immunomodulatory agents to treat many dermatologic conditions. Novel mechanisms of action of newer topical agents have facilitated differentiation from well-established topical agents such as corticosteroids and 5-fluorouracil. Further, because of a growing understanding of the immune mechanisms within the skin, the opportunity has arisen to use the body's immune system to effectively treat many dermatologic conditions, such as condyloma acuminata, actinic keratosis, basal cell carcinoma, and atopic dermatitis, while maintaining a favorable safety profile. Imiquimod - Aldara 5% cream, an immune response modifier, is safe and effective in the treatment of condyloma acuminata, actinic keratosis, and primary superficial basal cell carcinoma (sBCC). Pimecrolimus cream 1% and tacrolimus ointment (0.1% and 0.03%) are safe and effective in the treatment of atopic dermatitis. This review highlights newer data on approved and investigational indications for these topical immunomodulatory agents.

39: J Cutan Med Surg. 2004 Dec;8 Suppl 3:32-6.

Novel opportunities in the treatment and prevention of scarring.

Berman B, Villa AM, Ramirez CC.

Department of Dermatology and Cutaneous Surgery, University of Miami School of Medicine, Miami, Florida, USA.

Numerous treatments have been described for the treatment and prevention of scars, but the optimal management strategy is yet to be defined. In this article we present and evaluate new opportunities for the treatment and prevention of hypertrophic scars, keloids, and atrophic scars. Clinical, animal, and in vitro studies reporting novel techniques for the treatment and prevention of scarring were identified primarily from the MEDLINE/PubMed database. We found that a variety of new treatments exist with potential effectiveness for the treatment of hypertrophic scars and keloids, including interferon, Imiquimod - Aldara 5% cream, tacrolimus, botulinum toxin, 5-fluorouracil, bleomycin, and verapamil. For atrophic scars, different types of lasers represent modern treatment modalities with satisfactory results. Several agents have been reported to be effective in reducing scarring in vitro and in animal studies, representing potential opportunities for scarring management. We conclude that several novel modalities may be potential therapies for scarring.