Safety and Efficacy of 5% Imiquimod Cream for the Treatment of Skin Dysplasia in High-Risk Renal Transplant Recipients

Brown, Victoria; Atkins, Catherine L.; Ghali, Lucy; Cerio, R.; Harwood, Catherine A.; Proby, Charlotte M.

doi:10.1001/archderm.141.8.985

Cited by 98 publications

(68 citation statements)

References 28 publications

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“…Transplant recipients might be unable to induce such local immune and inflammatory responses; immunosuppression may reduce the inflammatory response to imiquimod and thus could explain the lower frequency of adverse effects in transplant recipients. Brown et al [5] did not find a significant correlation between beneficial clinical response and the degree of inflammation in transplant recipients. Topical imiquimod 5% applied on anogenital warts in HIV-infected patients was also well tolerated [6].…”

Section: Discussionmentioning

confidence: 99%

5% Topical Imiquimod Tolerance in Transplant Recipients

M’barek

Mebazâa²,

Euvrard³

et al. 2007

Dermatology

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Background: Topical imiquimod is a new immunomodulator agent approved for genital warts, actinic keratosis (AK) or carcinoma, occurring in immunocompetent patients. Objectives: This study aimed to assess the safety and efficacy of imiquimod for the treatment of warts, AK and bowenoid papulosis (BP) in transplant patients. Methods: 24 transplant patients (18 kidney, 4 kidney-pancreas and 2 heart) were included in this retrospective study conducted between June 2000 and February 2003 at the department of dermatology of 3 hospitals. Imiquimod cream was applied 3 times a week over a median period of 9 weeks. Results: Graft function was not altered under therapy. Local tolerance was excellent. Complete responses were observed in 1 patient (1/12) with cutaneous warts and 1 (1/6) with AK. Two patients of 3 with BP had total clearance of their lesions. Partial responses were observed in 3 of the 6 AK-treated patients, 5 of 12 patients with cutaneous warts and 1 of 2 patients with anogenital warts. Conclusions: Imiquimod 5% cream is a promising, well-tolerated therapy for warts, AK and BP in transplant recipients.

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Section: Discussionmentioning

confidence: 99%

5% Topical Imiquimod Tolerance in Transplant Recipients

M’barek

Mebazâa²,

Euvrard³

et al. 2007

Dermatology

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“…Cutaneous tumors that have responded well to topical treatment with imiquimod include basal cell carcinomas (Sterry et al, 2002;BathHextall et al, 2004;Geisse et al, 2004;Gollnick et al, 2005;Schulze et al, 2005), keratoacanthomas (Dendorfer et al, 2003;Peris et al, 2003), actinic keratoses (Stockfleth et al, 2001(Stockfleth et al, , 2002Lebwohl et al, 2004;Szeimies et al, 2004;Korman et al, 2005) and Bowen's disease (the latter two entities represent epidermal carcinoma in situ) (Patel et al, 2006;Peris et al, 2006), cutaneous metastases of melanoma (Steinmann et al, 2000;Bong et al, 2002;Ugurel et al, 2002;Wolf et al, 2003;Zeitouni et al, 2005), some cases of primary melanoma in situ (Fleming et al, 2004;Kamin et al, 2005;Ray et al, 2005;Wolf et al, 2005;Lonsdale-Eccles et al, 2006) and cutaneous T-cell lymphomas (Suchin et al, 2002;Dummer et al, 2003b;Chong et al, 2004;Deeths et al, 2005). Clinical responses of cutaneous neoplasias to topical treatment with imiquimod have also been observed in difficult-to-treat patient populations, such as organ transplant patients under immunosuppressive therapy (Smith et al, 2001;Prinz et al, 2004;Brown et al, 2005) or Xeroderma pigmentosum patients suffering from rapid development of multiple UV-induced cutaneous malignancies (Giannotti et al, 2003;Roseeuw, 2003). A recent meta-analysis of five randomized, double blind clinical trials showed that approximately 50% of imiquimod...…”

Section: Antitumoral Efficacy Of Tlr7/8 Agonists In Clinical Trialsmentioning

confidence: 99%

TLR7 and TLR8 as targets in cancer therapy

2008

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Small-molecule agonists at Toll-like receptor 7 (TLR7) and TLR8 have sparked a vivid interest in cancer research owing to their profound antitumoral activity. The lead compound of the imidazoquinoline family, imiquimod, is marketed as a topical formulation. It is efficacious against many primary skin tumors and cutaneous metastases. Using different imidazoquinoline species, distinct functions of TLR7 and TLR8 have been discovered. The predominant antitumoral mode of action of these agents is TLR7/ 8-mediated activation of the central transcription factor nuclear factor-jB, which leads to induction of proinflammatory cytokines and other mediators. Cutaneous dendritic cells are the primary responsive cell type and initiate a strong Th1-weighted antitumoral cellular immune response. Recent research has shown that dendritic cells themselves acquire direct antitumoral activity upon stimulation by imiquimod. In addition, there are a number of secondary effects on the molecular and cellular level that can be explained through the activation of TLR7/8. The proinflammatory activity of imiquimod, but not resiquimod, appears to be augmented by suppression of a regulatory mechanism, which normally limits inflammatory responses. This is achieved independently of TLR7/8 through interference with adenosine receptor signaling pathways. Finally, at higher concentrations imiquimod exerts Bcl-2-and caspase-dependent proapoptotic activity against tumor cells.

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“…In a randomized, doubleblind, placebo-controlled study evaluating the safety and efficacy of 5% imiquimod for the treatment of skin dysplasia in high risk renal transplant recipients (46), mean serum creatinine levels were compared with mean values 12 months before the study and during the 8 months after treatment. A 20 to 60 em' skin area was treated 3 times per week for 16 …”

Section: Safety Ofthe Treatmentmentioning

confidence: 99%

“…In a first study (51) reporting the use of imiquimod two to three times weekly for 12 to 16 weeks on multiple AK in 6 OTR patients, total clearance for five out of six patients was demonstrated histologically. In the first randomized, double-blinded and placebo controlled study on high risk renal transplant recipients, the safety and efficacy of 5% imiquimod in skin dysplasia was examined after a 16-week application, three times weekly of either imiqimod 5% cream or matching placebo cream 250 mg (l sachet) (46). Of the 14 patients using the active cream, 7 (50%) demonstrated a reduction in skin atypia and viral warts in the treatment area compared with I (17%) of the 6 patients who received placebo.…”

Section: Actinic Keratosis Bowenoid Papulosis and Skin Dysplasiamentioning

confidence: 99%

Efforts to Counteract Locally the Effects of Systemic Immunosupression: A Review on the Use of Imiquimod, a Topical Immunostimulator in Organ Transplant Recipients

Trakatelli

Katsanos

Ulrich

et al. 2010

Int J Immunopathol Pharmacol

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The potent systemic immunosuppression therapy necessary to sustain a life-saving solid organ transplant is associated with an increased incidence of various infections including human papillomavirus infection and skin cancers in organ transplant recipients. Imiquimod, a topical agent that functions through local induction of a specific anti-viral or anti-tumor immune response, appears to be a promising therapeutic option that could potentially counteract in situ the effects of systemic immunosupression in this vulnerable group. Up-to-date studies using this local immune-response modifier in transplanted patients have yielded reassuring and encouraging results regarding its safety and efficacy in this population. However, in order to establish the use of imiquimod as a standard treatment option for organ transplant recipients, additional research and clinical trials are required.The past decades have seen unprecedented progress in the development of solid organ transplantation as a therapeutic choice for endstage organ disease. Organ Transplant Recipients (OTR) live longer, have a good quality of life and represent a rapidly growing population of people with specific medical needs. As the number of solid organ transplants continues to rise, so too does the number of various infections including human papillomavirus (HPV) infections and skin cancers in OTR. Consequently, physicians will be called upon to manage these diseases in the sensitive OTR population and to develop novel therapeutic and preventive strategies to better deal with them.The clinical efficacy of imiquimod 5% cream (a topical therapy approved for genital warts, actinic keratoses and superficial basal cell carcinoma) stems from stimulation ofinnate and cell-mediated immune responses, resulting in antiviral, antiproliferative and antitumor activity. Because of these properties, imiquimod and other members of this family of immune response modifiers are potential agents for treatment of conditions where the immune system can affect the regression of the disease (1). In light of the role of systemic immunosupression in the development of cutaneous infections and neoplasms in OTR, the use of imiquimod to locally stimulate immune responses against cancerous, pre-cancerous

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Safety and Efficacy of 5% Imiquimod Cream for the Treatment of Skin Dysplasia in High-Risk Renal Transplant Recipients

Cited by 98 publications

References 28 publications

5% Topical Imiquimod Tolerance in Transplant Recipients

5% Topical Imiquimod Tolerance in Transplant Recipients

TLR7 and TLR8 as targets in cancer therapy

Efforts to Counteract Locally the Effects of Systemic Immunosupression: A Review on the Use of Imiquimod, a Topical Immunostimulator in Organ Transplant Recipients

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