Imiquimod: A Review of Off-Label Clinical Applications

November 2011 | Volume 10 | Issue 11 | Original Article | 1300 | Copyright © 2011

Consuelo V. David BA,a Hong Nguyen BS,b Gary Goldenberg MDc

aUniversity of Maryland, School of Medicine, Baltimore, MD bDavid Geffen School of Medicine at the University of California, Los Angeles, CA cMount Sinai School of Medicine, New York, NY


The immunomodulatory characteristics and topical application of imiquimod (IQ), a toll-like receptor 7 agonist, have lead to extensive off-label therapeutic trials. Off-label use is not uncommon in dermatology. However, clinicians must make informed decisions to ensure safe and effective implementation when standardized protocols are lacking. We present the highest level of clinical evidence for each off-label application of IQ, summarize management steps, treatment regimens, and results. We hope consolidation of this information will facilitate implementation of informed and evidence-based clinical decisions. Forty-six off-label applications were reported. Treatments were generally applied in the same manner, tailored to induce an inflammatory response and reduced with the development of adverse reactions. The efficacy of imiquimod ranged from promising to suboptimal compared to standard treatments and protocols. Clinicians who choose to use IQ off-label should have a firm understanding of the extent an application has been studied and how to manage adverse events.

J Drugs Dermatol. 2011;10(11):1300-1306.

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Toll-like receptors (TLRs) are located on antigen presenting cells of the innate immune system such as macrophages and dendritic cells.1 TLRs are links between the innate immune response and the adaptive immune response.2 The process begins when recognition of microbial pathogen-associated molecular patterns upregulates pro-inflammatory cytokines (e.g., interferon alpha, tumor necrosis factor alpha, interleukins 1, 2, 6 and 8) and co-stimulatory molecules.2,3 This maturation process enhances the ability of the antigen presenting cell to prime naïve T cells.2 Due to their immunomodulatory effects, TLRs have become an enticing target for therapeutic intervention. There is significant ongoing investigation of TLR agonists as vaccine adjuvants or immune response modifiers in the treatment of infectious diseases, allergic diseases, asthma, inflammatory disorders and neoplasms.4-8

Imiquimod (IQ) is a topical imidazoquinolone and primarily functions as a Toll-like receptor 7 agonist. IQ is distributed as a 5% cream. It is Food and Drug Administration (FDA) approved for the treatment of actinic keratoses, superficial basal cell carcinoma, and external genital warts. IQs efficacy in these conditions is likely mediated by cytokine induction in the skin. Induction triggers the host immune system to recognize the presence of viral infection or tumor and subsequently eliminates the presenting lesion.9 Within dermatology, the recognized immunomodulatory effects of IQ and its application as a topical cream have lead to a variety of off-label therapeutic attempts.

Approximately 21 percent of all prescribed medications are written for off-label applications. Among off-label uses, only 27 percent are supported by strong clinical evidence; the remaining 73 percent lack clinical efficacy.10,11 Once a medication is FDA approved for a specific use, physicians are free to prescribe it for non-FDA approved applications and at non-FDA approved doses based on their clinical judgment and experience. There are no known studies describing the percentage of IQ prescriptions used off-label. Informed consent is not required; however, discussion of risks and benefits of IQ with the patient is encouraged. Prior to prescribing IQ, it is imperative that the physician is aware of how well-studied and how effective IQ has been for this application.

Forty-six off-label applications of IQ were reported in the PubMed database at the time of our initial search in 2009. We summarize published clinical trials, case series, and case reports pertaining to each application. The strongest form of clinical evidence reported is presented in the text. If available, the total length of studies and follow-up periods are noted. Serologic and histopathologic studies are presented. Please keep in mind that suggestions made in this review are derived from our review of how IQ has been used in practice. While larger trials are necessary to develop standardized protocols, we hope this review will be a useful tool in guiding your clinical use of IQ should you choose to use IQ off-label.

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