Aldara
Imiquimod.

Richwald GA.

Sexually Transmitted Diseases Program, Los Angeles County Department of Health Services, Los Angeles, California, USA.

The imidazoquinoline, imiquimod, is a low molecular weight, synthetic immune response modifier that is used for the treatment of external genital and perianal warts. It is formulated in a 5% vanishing cream as Aldara. This self-applied therapy has shown good efficacy and safety in the treatment of external genital and perianal warts caused by human papillomavirus (HPV) infection. The antiviral mechanism of action of this compound is unlike any other approved antiviral therapy in that it induces the production of antiviral cytokines and cytokines that enhance cellular immunity believed to be necessary for the control or elimination of HPV infection. Imiquimod does not exert its antiviral effects directly on virus-infected cells. Treatment with imiquimod results in resolution of wart tissue and reduction of viral burden. Post-marketing trials using imiquimod demonstrated that patients who experience complete clearance of either new or recalcitrant warts tend to remain clear for longer periods as compared to other treatment modalities. Preclinical data demonstrate in vitro and in vivo that imiquimod directly induces antiviral and immunomodulating cytokines from monocytes, macrophages and dendritic cells. These immunomodulating cytokines have been shown to potentiate Th1 immunity. Self-application, good tolerability, a unique mechanism of action and a relatively high sustained clearance rate combine to make imiquimod a cost-effective first-line therapy for external genital warts and an appropriate second-line therapy when other treatments are unsuccessful. In small-scale studies requiring replication, imiquimod has also been shown to be effective in the treatment of non-HVP-related skin infections and some dermal neoplasias. (c) 1999 Prous Science. All rights reserved.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12973395&dopt=Abstract imiquimod Aldara



Aldara
Medical treatment of nasal squamous papilloma with imiquimod cream.

Caversaccio M, Aebi S.

Department of Oto-Rhino-Laryngology, Head and Neck Surgery, University Hospital, University of Bern, Switzerland. marco.caversaccio insel.ch

Warts are common lesions. The prevalence and incidence of squamous papilloma of the nasal vestibulum are not known, and it is not certain how often human papilloma viruses are involved. Numerous medical or surgical treatment modalities have been reported in the literature with variable, sometimes unsatisfactory results. Imiquimod cream is a topically applied immunomodulator. It is used for warts and other skin tumours on different locations of the body. We report results of six patients treated with imiquimod five per cent cream for nasal squamous papilloma.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14561362&dopt=Abstract imiquimod Aldara



Aldara
The immune response modifier imiquimod requires STAT-1 for induction of interferon, interferon-stimulated genes, and interleukin-6.

Bottrel RL, Yang YL, Levy DE, Tomai M, Reis LF.

Department of Microbiology, ICB, UFMG, Belo Horizonte, Brazil.

Imiquimod is an oral inducer of interferon (IFN) and several other proinflammatory cytokines and has been successfully used topically as an antiviral agent for the treatment of genital warts. We have investigated the molecular mechanisms by which imiquimod induces the expression of IFNs, IFN-stimulated genes (ISGs), and proinflammatory cytokines in vivo, using mice deficient in various components of the IFN signaling system. Mice deficient in the transcription factor interferon regulatory factor 1 (IRF-1) or in the serine/threonine protein kinase PKR responded normally to imiquimod, producing high levels of circulating IFN and induction of several ISGs. On the other hand, when mice deficient in STAT-1 were treated, a 32-fold reduction in the level of circulating IFN was observed, together with a lack of induction of 2-5 oligo adenylate synthetase (2-5 OAS) and IRF-1 genes. Interestingly, there was also a lack of induction of interleukin-6 (IL-6) gene expression, although tumor necrosis factor was induced and readily detected in serum. In mice deficient in the type I IFN receptor, imiquimod induced levels of IFN similar to those in control mice, but again, neither 2-5 OAS, IRF-1, nor IL-6 genes were induced in mutant mice. Our results suggest that STAT-1 plays a critical role in the mechanism of gene activation by imiquimod. Moreover, induction of IL-6 gene expression appears to be dependent on components of the IFN signaling cascade.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10103191&dopt=Abstract imiquimod Aldara



Aldara
Induction of apoptosis by Toll-like receptor-7 agonist in tissue cultures.

Meyer T, Nindl I, Schmook T, Ulrich C, Sterry W, Stockfleth E.

Institute of Immunology, Clinical Pathology and Molecular Medicine, Lademannbogen 61, 22339 Hamburg, Germany. meyer labor-arndt-partner.de

Toll-like receptor (TLR)-7 agonists represent a new group of immune response modifiers, which include imiquimod and resiquimod (R-848). Topically applied imiquimod is used for the treatment of both external and perianal genital warts, and benign and malignant epithelial lesions. Based on the induction of interferons and other cytokines in vitro and in vivo, regression of epithelial lesions probably depends on induction of both innate and cellular immune responses. As clinical remission is not always associated with inflammation, other mechanisms may also be involved. Using two different assays for detection of apoptosis (TUNEL test and gel analysis of DNA fragmentation), we observed induction of apoptosis by imiquimod in human epithelial cell lines (HeLa S3) and keratinocytes (HaCaT, A431 cells), as well as in mouse fibroblasts (McCoy cells). These findings suggest that the mode of action of imiquimod to eliminate virus-infected, dysplastic or neoplastic epithelial cells may also include the induction of apoptotic processes.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14616338&dopt=Abstract imiquimod Aldara



Aldara
Experience in treating molluscum contagiosum in children with imiquimod 5% cream.

Bayerl C, Feller G, Goerdt S.

Department of Dermatology, Venerology and Allergology, Mannheim University Clinic, Theodor Kutzer Ufer 1-3, 68135 Mannheim, Germany. christiane.bayerl haut.ma.uni-heidelberg.de

There is a wide variety of topical or surgical treatment options for molluscum contagiosum (MC). However, treatment in young or anxious children is difficult, time-consuming and often painful. We studied the topical efficacy and tolerance of imiquimod, a topical immune-response modifier, which stimulates the production of interferon-alpha and other cytokines in children with MC. In an open-label, follow-up trial, imiquimod 5% cream was applied three times a week for 16 weeks to 15 children aged 4-11 years with multiple MC. Nine of 13 children (69%) who completed treatment responded. Two patients (15%) showed a complete remission, and seven (54%) had a partial response, with a remarkable reduction of the MC lesions. Four children (31%) showed stable or progressive disease. In three children (23%) with partial remission, the number of mollusca were considerably reduced, thus avoiding surgical treatment. In general, the treatment was well-tolerated, without systemic side-effects. Local side-effects included erythema (85%), itching (75%), burning sensations (23%) and pain (11%). Three children (23%) discontinued treatment because of local side-effects. The results of this study suggest that imiquimod 5% cream is a useful new treatment option for MC in children, especially in severe cases. The dosing schedule and length of treatment requires further evaluation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14616342&dopt=Abstract imiquimod Aldara



Aldara
An audit of patients who have received imiquimod cream 5% for the treatment of anogenital warts.

Maitland JE, Maw R.

Department of Genitourinary Medicine, Royal Victoria Hospital, Belfast, UK.

With the licensing of the new drug Imiquimod cream 5% (Aldara 3M Health Care) for the treatment of anogenital warts and its inclusion into clinic guidelines, a case note review audit was performed of its use. The treatment of 52 patients was audited. Results showed that clinic guidelines were being followed and that patient outcomes in terms of clearance were at least as good as the quoted rates in the literature. Significant issues included firstly patient education-especially for those who had previously received ablative therapy. Secondly the length of time that therapy would be continued before a patient was deemed to be a non-responder to Imiquimod cream 5%, and if this was the case should the frequency of application be amended from the manufacturer's recommended regime of 3 times a week.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10772094&dopt=Abstract imiquimod Aldara