Skip to main content
SpringerLink
Log in

Topical Imiquimod

A Review of its Use in the Management of Anogenital Warts, Actinic Keratoses, Basal Cell Carcinoma and Other Skin Lesions

  • Adis Drug Evaluation
  • Published:
Drugs Aims and scope Submit manuscript

Summary

Abstract

Topical imiquimod 5% cream (Aldara™) is an immune response modulator that is indicated for the treatment of external anogenital warts, superficial basal cell carcinoma and actinic keratoses. The cream is applied two to five times per week for varying periods, depending on the indication. Topical imiquimod cream has also been evaluated in the treatment of several other skin conditions.

Immunomodulatory therapy with topical imiquimod 5% is an effective option for the approved indications. The drug appears to be relatively well tolerated, with the option of breaks from treatment as required for local skin reactions (which are common). Systemic reactions have been reported. Treatment of human papillomavirus- and UV-associated skin lesions with topical imiquimod offers a noninvasive, tissue-sparing alternative to ablative treatment options. However, well designed trials of the sustained, long-term efficacy and tolerability of topical imiquimod versus those of common treatment approaches including surgery and other topical alternatives are required before the place of the drug in the management of these lesions can be finalised. Nonetheless, while other treatments for anogenital warts, superficial basal cell carcinoma or actinic keratoses are available, the advantages of self treatment linked with the demonstrated efficacy of topical imiquimod offer an attractive alternative for many patients.

Pharmacological Properties

The topical imidazoquinoline imiquimod stimulates both innate and cell-mediated immune responses to viruses and tumours via an array of molecular events initiated mainly by agonistic actions on toll-like receptor molecules 7 and 8. While most activity occurs at the site of administration, minimal systemic immunomodulation has also been recorded after topical administration. Topical imiquimod has no photosensitising effects and does not aggravate UV-induced damage.

Systemic absorption was minimal after application of imiquimod 5% daily for 7 days to healthy volunteers and for up to 16 weeks to patients with anogenital warts. The drug is retained in the skin for prolonged periods, resulting in an apparent elimination half-life of ≈1 day. Imiquimod and its active metabolites (S26704 and S27700) are excreted in urine and faeces.

Therapeutic Efficacy

Several randomised, double-blind trials have consistently demonstrated the short-term superiority of topical imiquimod 5% over placebo in immunocompetent patients with external anogenital warts. Complete clearance of the warts occurred in 40–70% of imiquimod recipients after three-times-weekly or daily administration for 8–16 weeks. Recurrence of anogenital warts occurred in up to 19% of those with complete clearance, over a period of 10–24 weeks of follow-up, resulting in sustained clearance rates of 29–70% with imiquimod. Short-term (≤16 weeks) clearance rates were similar in men with anogenital warts after treatment with topical imiquimod 5% or fluorouracil 1% three times weekly (58% and 36%) in a double-blind trial published as an abstract.

Superiority over placebo was also consistent in the treatment of immunocompetent patients with actinic keratoses in randomised, double-blind trials of topical imiquimod 5% two or three times weekly for 16 weeks, or for 4 weeks followed 4 weeks later by another course if necessary. Complete clearance occurred in 45–57% of imiquimod recipients. Recurrence rates of 8–43% over follow-up of up to 24 months have been reported after two- or three-times-weekly administration over 4–16 weeks.

Topical imiquimod 5% was also consistently superior to placebo in the treatment of immunocompetent patients with superficial basal cell carcinoma in randomised, double-blind trials. Complete clearance occurred in 79–87% of imiquimod recipients after five-times-weekly or daily administration for 6 or 12 weeks. Sustained clearance rates taking recurrence into account were not reported for these trials. Less robustly designed trials suggest sustained clearance rates of ≈80% at 4 years and 65% at 5 years after imiquimod treatment.

Experience with topical imiquimod 5% in the treatment of skin lesions in immunocompromised patients is less extensive. Imiquimod had at least a partial effect (reduction of >50%) on anogenital warts in about half of the HIV-seropositive patients (and was superior to placebo), and on actinic keratoses in about one-third of renal transplant recipients at high risk for skin cancer (similar to placebo), in well designed trials.

Tolerability

While local skin reactions are common, topical imiquimod 5% is also occasionally associated with systemic adverse events. Systemic events reported in clinical trials (all in ≤10% of recipients) include headache, fatigue, myalgia and nausea. Haemoglobin, white blood cell, absolute neutrophil and platelet counts may be reduced and severe remote skin reactions (erythema multiforme, Stevens-Johnson syndrome, cutaneous lupus erythematosus) have been reported. Underlying immunological disorders may be exacerbated.

Local skin reactions (e.g. erythema, excoriation/flaking, erosion, oedema, scabbing/crusting) are very common. Local pruritus in particular was reported in 23–62% of recipients in clinical trials.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Bernard HU. Established and potential strategies against papillomavirus infections. J Antimicrob Chemother 2004 Feb; 53(2): 137–9

    PubMed  CAS  Google Scholar 

  2. Koutsky LA, Galloway DA, Holmes KK. Epidemiology of genital human papillomavirus infection. Epidemiol Rev 1988; 10: 122–63

    PubMed  CAS  Google Scholar 

  3. Leung AKC, Kellner JD, Davies HD. Genital infection with human papillomavirus in adolescents. Adv Ther 2005 May; 22(3): 187–97

    PubMed  Google Scholar 

  4. American Cancer Society. Detailed guide: skin cancer — nonme-lanoma [online]. Available from URL: http://www.cancer.org [Accessed 2007 Mar 21]

  5. Bath-Hextall F, Perkins W, Bong J, et al. Interventions for basal cell carcinoma of the skin. Cochrane Database Syst Rev 2007; (1): CD003412

  6. Schön M, Schön MP. The antitumoral mode of action of imiquimod and other imidazoquinolines. Curr Med Chem 2007; 14(6): 681–7

    PubMed  Google Scholar 

  7. Li VW, Li WW, Talcott KE, et al. Imiquimod as an antiangi-ogenic agent. J Drugs Dermatol 2005 Nov; 4(6): 708–17

    PubMed  Google Scholar 

  8. Perry CM, Lamb HM. Topical imiquimod: a review of its use in genital warts. Drugs 1999 Aug; 58(2): 375–90

    PubMed  CAS  Google Scholar 

  9. Pasmatzi ES, Chaidaroglou A, Sakkis T, et al. Short-term topical application of imiquimod induces systemic immunomodu-lation in healthy individuals [abstract]. J Immunother 2006 Nov; 29(6): 668

    Google Scholar 

  10. 3M Health Care Limited. Aldara prescribing information [online]. Available from URL: http://www.fda.gov [Accessed 2007 Jul 10]

  11. Tyring SK, Arany I, Stanley MA, et al. A randomized, controlled, molecular study of condylomata acuminata clearance during treatment with imiquimod. J Infect Dis 1998 Aug; 178(2): 551–5

    PubMed  CAS  Google Scholar 

  12. Jacobs S, Grussendorf-Conen E-I, Rösener I, et al. Molecular analysis of the effect of topical imiquimod treatment of HPV 2/ 27/57-induced common warts. Skin Pharmacol Physiol 2004 Sep; 17(5): 258–66

    PubMed  CAS  Google Scholar 

  13. Kreuter A, Brockmeyer NH, Weissenborn SJ, et al. 5% Imiquimod suppositories decrease the DNA load of intra-anal HPV types 6 and 11 in HIV-infected men after surgical ablation of condylomata acuminata [letter]. Arch Dermatol 2006 Feb; 142(2): 243–4

    PubMed  Google Scholar 

  14. Kawashima M, Uchida N, Nogita T. Evaluation of skin irritation of imiquimod 5% cream by patch test [in Japanese]. J Clin Ther Med 2007; 23(5): 357–61

    Google Scholar 

  15. Kawashima M, Uchida N, Nogita T. Evaluation of skin irritability and safety of imiquimod 5% cream in 7-day repeated application among healthy volunteers [in Japanese]. J Clin Ther Med 2007; 23(5): 363–9

    Google Scholar 

  16. Kaidbey K, Owens M, Liberda M, et al. Safety studies of topical imiquimod 5% cream on normal skin exposed to ultraviolet radiation. Toxicology 2002 Sep 2; 178(2): 175–82

    PubMed  CAS  Google Scholar 

  17. Thatcher TH, Luzina I, Fishelevich R, et al. Topical imiquimod treatment prevents UV-light induced loss of contact hypersen-sitivity and immune tolerance. J Invest Dermatol 2006 Apr; 126(4): 821–31

    PubMed  CAS  Google Scholar 

  18. Owens ML, Tygum KI, Senta TA, et al. Safety assessment of topical imiquimod [abstract no. 5151]. Australas J Dermatol 1997 Jun; 38 Suppl. 2: 269

    Google Scholar 

  19. Tygum KI, Smith SL, Myers JA, et al. Percutaneous penetration of [14C]imiquimod from a single application of cream [abstract no. PDD 7339]. Pharm Res 1995 Sep; 12 Suppl. 9: S277

    Google Scholar 

  20. Owens ML, Bridson WE, Smith SL, et al. Percutaneous penetration of Aldara™ cream, 5% during the topical treatment of genital and perianal warts. Prim Care Update Ob Gyns 1998 Jul 1; 5(4): 151

    Google Scholar 

  21. Harrison LI, Skinner SL, Marbury TC, et al. Pharmacokinetics and safety of imiquimod 5% cream in the treatment of actinic keratoses of the face, scalp, or hands and arms. Arch Dermatol Res 2004 Jun; 296(1): 6–11

    PubMed  CAS  Google Scholar 

  22. 3M Health Care Limited. Imiquimod: summary of product characteristics (Europe) [online]. Available from URL: www.emea.eu.int [Accessed 2007 Sep 6]

  23. Arican O, Guneri F, Bilgic K, et al. Topical imiquimod 5% cream in external anogenital warts: a randomized, double-blind, placebo-controlled study. J Dermatol 2004 Aug; 31(8): 627–31

    PubMed  CAS  Google Scholar 

  24. Beutner KR, Spruance SL, Hougham AJ, et al. Treatment of genital warts with an immune-response modifier (imiquimod). J Am Acad Dermatol 1998 Feb; 38(2 Pt 1): 230–9

    PubMed  CAS  Google Scholar 

  25. Beutner KR, Tyring SK, Trofatter Jr KF, et al. Imiquimod, a patient-applied immune-response modifier for treatment of external genital warts. Antimicrob Agents Chemother 1998 Apr; 42(4): 789–94

    PubMed  CAS  Google Scholar 

  26. Edwards L, Ferenczy A, Eron L, et al. Self-administered topical 5% imiquimod cream for external anogenital warts. Arch Dermatol 1998 Jan; 134(1): 25–30

    PubMed  CAS  Google Scholar 

  27. Nakagawa H. Randomized, double-blind, dose-response study of imiquimod cream in patients with external genital/perianal warts (condyloma acuminatum). Jpn J Sex Transm Dis 2007; 18(1): 134–44

    Google Scholar 

  28. Romero-Sanchez A, Castro-Castañeda B, Abad-Gastelum MA, et al. Comparative study using 5% imiquimod cream vs 1 % 5-fluorouracil cream for the treatment of genital warts in male patients [abstract no. L-894]. Abstracts of the 41st Interscience Conference on Antimicrobial Agents and Chemotherapy; 2001 Sep 22; Chicago (IL), 457

  29. Sauder DN, Skinner RB, Fox TL, et al. Topical imiquimod 5% cream as an effective treatment for external genital and perianal warts in different patient populations. Sex Transm Dis 2003 Feb; 30(2): 124–8

    PubMed  CAS  Google Scholar 

  30. Schöfer H, Van Ophoven A, Henke U, et al. Randomized, comparative trial on the sustained efficacy of topical imiquimod 5% cream versus conventional ablative methods in external anogenital warts. Eur J Dermatol 2006 Nov; 16(6): 642–8

    PubMed  Google Scholar 

  31. Kaspari M, Gutzmer R, Kaspari T, et al. Application of imiquimod by suppositories (anal tampons) efficiently prevents recurrences after ablation of anal canal condyloma. Br J Dermatol 2002; 147: 757–9

    PubMed  CAS  Google Scholar 

  32. Fife KH, Ferenczy A, Douglas Jr JM, et al. Treatment of external genital warts in men using 5% imiquimod cream applied three times a week, once daily, twice daily, or three times a day. Sex Transm Dis 2001 Apr; 28(4): 226–31

    PubMed  CAS  Google Scholar 

  33. Trofatter Jr KF, Ferenczy A, Fife KH, et al. Increased frequency of dosing of imiquimod 5% cream in the treatment of external genital warts in women. Int J Gynaecol Obstet 2002 Feb; 76(2): 191–3

    PubMed  Google Scholar 

  34. Garland SM, Waddell R, Mindel A, et al. An open-label phase II pilot study investigating the optimal duration of imiquimod 5% cream for the treatment of external genital warts in women. Int J STD AIDS 2006 Jul; 17(7): 448–52

    PubMed  CAS  Google Scholar 

  35. Alam M, Stiller M. Direct medical costs for surgical and medical treatment of condylomata acuminata. Arch Dermatol 2001 Mar; 137(3): 337–41

    PubMed  CAS  Google Scholar 

  36. Langley PC, Tyring SK, Smith MH. The cost effectiveness of patient-applied versus provider-administered intervention strategies for the treatment of external genital warts. Am J Manag Care 1999 Jan; 5(1): 69–77

    PubMed  CAS  Google Scholar 

  37. Williams P, von Krogh G. The cost-effectiveness of patient-applied treatments for anogenital warts. Int J STD AIDS 2003 Apr; 14(4): 228–34

    PubMed  Google Scholar 

  38. Grussendorf-Conen E-I, Jacobs S, Rübben A, et al. Topical 5% imiquimod long-term treatment of cutaneous warts resistant to standard therapy modalities. Dermatology 2002; 205(2): 139–45

    PubMed  CAS  Google Scholar 

  39. Hengge UR, Esser S, Schultewolter T, et al. Self-administered topical 5% imiquimod for the treatment of common warts and molluscum contagiosum. Br J Dermatol 2000 Nov; 143(5): 1026–31

    PubMed  CAS  Google Scholar 

  40. Micali G, Dall’Oglio F, Nasca MR. An open label evaluation of the efficacy of imiquimod 5% cream in the treatment of recalcitrant subungual and periungual cutaneous warts. J Dermatolog Treat 2003 Dec; 14(4): 233–6

    PubMed  CAS  Google Scholar 

  41. Grussendorf-Conen E-I, Jacobs S. Efficacy of imiquimod 5% cream in the treatment of recalcitrant warts in children. Pediatr Dermatol 2002 May; 19(3): 263–6

    PubMed  Google Scholar 

  42. Theos AU, Cummins R, Silverberg NB, et al. Effectiveness of imiquimod cream 5% for treating childhood molluscum contagiosum in a double-blind, randomized pilot trial. Cutis 2004 Aug; 74(2): 134–8, 141–2

    PubMed  Google Scholar 

  43. Schacker TW, Conant M, Thoming C, et al. Imiquimod 5-percent cream does not alter the natural history of recurrent herpes genitalis: a phase II, randomized, double-blind, placebo-controlled study. Antimicrob Agents Chemother 2002 Oct; 46(10): 3243–8

    PubMed  CAS  Google Scholar 

  44. Mandekou-Lefaki I, Delli F, Teknetzis A, et al. Successful treatment of seborrheic keratosis with imiquimod 5% cream. Int J Immunother 2004; 20(1): 23–8

    CAS  Google Scholar 

  45. Berman B, Kaufman J. Pilot study of the effect of postoperative imiquimod 5% cream on the recurrence rate of excised keloids. J Am Acad Dermatol 2002 Oct; 47 Suppl. 4: S209–11

    PubMed  Google Scholar 

  46. Martín-García RF, Busquets AC. Postsurgical use of imiquimod 5% cream in the prevention of earlobe keloid recurrences: results of an open-label, pilot study. Dermatol Surg 2005 Nov; 31(11 Pt 1): 1394–8

    PubMed  Google Scholar 

  47. Redondo P, Del Olmo J, Idoate M. Angiolymphoid hyperplasia with eosinophilia successfully treated with imiquimod [letter]. Br J Dermatol 2004 Nov; 151(5): 1110–1

    PubMed  CAS  Google Scholar 

  48. Taverna JA, Stefanato CM, Wax FD, et al. Adult cutaneous Langerhans cell histiocytosis responsive to topical imiquimod [letter]. J Am Acad Dermatol 2006 May; 54(5): 911–3

    PubMed  Google Scholar 

  49. Crawford R, Holmes D, Meymandi S. Comparative study of the efficacy of combined imiquimod 5% cream and intralesional meglumine antimoniate versus imiquimod 5% cream and intralesional meglumine antimoniate alone for the treatment of cutaneous leishmaniasis [abstract no. P1706]. J Am Acad Dermatol 2005 Mar; 52(3): 118

    Google Scholar 

  50. Gul U, Gönül M, Çakmak SK, et al. A case of generalized discoid lupus erythematosus: successful treatment with imiquimod cream 5%. Adv Ther 2006 Sep; 23(5): 787–92

    PubMed  Google Scholar 

  51. Kelly SC, Purcell SM. Imiquimod therapy for elastosis perforans serpiginosa. Arch Dermatol 2006 Jul; 142(7): 829–30

    PubMed  Google Scholar 

  52. Chan CC, Thong HY, Chan YC, et al. Human papillomavirus type 5 infection in a patient with Hailey-Hailey disease successfully treated with imiquimod [letter]. Br J Dermatol 2007 Mar; 156(3): 579–81

    PubMed  CAS  Google Scholar 

  53. Kuwahara RT, Skinner Jr RB. Granuloma annulare resolved with topical application of imiquimod [letter]. Pediatr Dermatol 2002 Jul; 19(4): 368–9

    PubMed  Google Scholar 

  54. Martinez MI, Sanchez-Carpintero I, North PE, et al. Infantile hemangioma: clinical resolution with 5% imiquimod cream. Arch Dermatol 2002 Jul; 138(7): 881–4

    PubMed  Google Scholar 

  55. Welsh O, Olazaran Z, Gómez M, et al. Treatment of infantile hemangiomas with short-term application of imiquimod 5% cream. J Am Acad Dermatol 2004 Oct; 51(4): 639–42

    PubMed  Google Scholar 

  56. Hazen PG, Carney JF, Engstrom CW, et al. Proliferating hemangioma of infancy: successful treatment with topical 5% imiquimod cream. Pediatr Dermatol 2005; 22(3): 254–6

    PubMed  Google Scholar 

  57. Dytoc M, Ting PT, Man J, et al. First case series on the use of imiquimod for morphoea. Br J Dermatol 2005 Oct; 153(4): 815–20

    PubMed  CAS  Google Scholar 

  58. Urquhart JL, Weston WL. Treatment of multiple trichoepithe-liomas with topical imiquimod and tretinoin. Pediatr Dermatol 2005 Jan; 22(1): 67–70

    PubMed  Google Scholar 

  59. Goldenberg G, Krowchuk DP, Jorizzo JL. Successful treatment of a therapy-resistant pyogenic granuloma with topical imiquimod 5% cream. J Dermatolog Treat 2006; 17(2): 121–3

    PubMed  CAS  Google Scholar 

  60. Ezzell TI, Fromowitz JS, Ramos-Caro FA. Recurrent pyogenic granuloma treated with topical imiquimod [letter]. J Am Acad Dermatol 2006 May; 54 Suppl. 5: S244–5

    PubMed  Google Scholar 

  61. Baumann LS, Halem ML. Lip silicone granulomatous foreign body reaction treated with aldara (imiquimod 5%). Dermatol Surg 2003 Apr; 29(4): 429–32

    PubMed  Google Scholar 

  62. Stockfleth E, Röwert J, Arndt R, et al. Detection of human papillomavirus and response to topical 5% imiquimod in a case of stucco keratosis. Br J Dermatol 2000 Oct; 143(4): 846–50

    PubMed  CAS  Google Scholar 

  63. Bhaumik J. Vulvitis circumscripta plasmacellularis: success with a modified treatment regimen using imiquimod. J Obstet Gynaecol 2006 Jan; 26(1): 72

    PubMed  CAS  Google Scholar 

  64. Ee HL, Yosipovitch G, Chan R, et al. Resolution of vulvitis circumscripta plasmacellularis with topical imiquimod: two case reports. Br J Dermatol 2003 Sep; 149(3): 638–41

    PubMed  CAS  Google Scholar 

  65. Alomar A, Bichel J, McRae S. Vehicle-controlled, randomized, double-blind study to assess safety and efficacy of imiquimod 5% cream applied once daily 3 days per week in one or two courses of treatment of actinic keratoses on the head. Br J Dermatol 2007; 157(1): 133–41

    PubMed  CAS  Google Scholar 

  66. Jorizzo J, Dinehart S, Matheson R, et al. Vehicle-controlled, double-blind, randomized study of imiquimod 5% cream applied 3 days per week in one or two courses of treatment for actinic keratoses on the head. J Am Acad Dermatol 2007; 57(2): 265–8

    PubMed  Google Scholar 

  67. Korman N, Moy R, Ling M, et al. Dosing with 5% imiquimod cream 3 times per week for the treatment of actinic keratosis: results of two phase 3, randomized, double-blind, parallel-group, vehicle-controlled trials. Arch Dermatol 2005 Apr; 141(4): 467–73

    PubMed  CAS  Google Scholar 

  68. Lebwohl M, Dinehart S, Whiting D, et al. Imiquimod 5% cream for the treatment of actinic keratosis: results from two phase III, randomized, double-blind, parallel group, vehicle-controlled trials. J Am Acad Dermatol 2004 May; 50(5): 714–21

    PubMed  Google Scholar 

  69. Szeimies R-M, Gerritsen M-J, Gupta G, et al. Imiquimod 5% cream for the treatment of actinic keratosis: results from a phase III, randomized, double-blind, vehicle-controlled, clinical trial with histology. J Am Acad Dermatol 2004 Oct; 51(4): 547–55

    PubMed  Google Scholar 

  70. Tanghetti E, Werschler P. Comparison of 5% 5-fluorouracil cream and 5% imiquimod cream in the management of actinic keratoses on the face and scalp. J Drugs Dermatol 2007 Feb; 6(2): 144–7

    PubMed  Google Scholar 

  71. Stockfleth E, Benninghoff B, Busch J-O, et al. Long-term clearance of multiple actinic keratoses after topical treatment with imiquimod (5%) [abstract no. P469]. J Am Acad Dermatol 2004 Mar; 50 Suppl. 3: P121. Plus poster presented at the 62nd annual meeting of the American Academy of Dermatology; 2004 Feb; Washington, DC

  72. European Medicines Agency. Aldara scientific discussion [online]. Available from URL: http://www.emea.europa.eu [Accessed 2007 Jul 11]

  73. Lee PK, Harwell WB, Loven KH, et al. Long-term clinical outcomes following treatment of actinic keratosis with imiquimod 5% cream. Dermatol Surg 2005 Jun; 31(6): 659–64

    PubMed  CAS  Google Scholar 

  74. Abbasakoor F, Boulos PB. Anal intraepithelial neoplasia. Br J Surg 2005 Mar; 92(3): 277–90

    PubMed  CAS  Google Scholar 

  75. Patel GK, Goodwin R, Chawla M, et al. Imiquimod 5% cream monotherapy for cutaneous squamous cell carcinoma in situ (Bowen’s disease): a randomized, double-blind, placebo-controlled trial. J Am Acad Dermatol 2006 Jun; 54(6): 1025–32

    PubMed  Google Scholar 

  76. Mackenzie-Wood A, Kossard S, de Launey J, et al. Imiquimod 5% cream in the treatment of Bowen’s disease. J Am Acad Dermatol 2001 Mar; 44(3): 462–70

    PubMed  CAS  Google Scholar 

  77. Le T, Menard C, Hicks-Boucher W, et al. Final results of a phase 2 study using continuous 5% Imiquimod cream application in the primary treatment of high-grade vulva intraepithelial neoplasia. Gynecol Oncol 2007; 106(3): 579–84

    PubMed  CAS  Google Scholar 

  78. Todd RW, Etherington IJ, Luesley DM. The effects of 5% imiquimod cream on high-grade vulval intraepithelial neoplasia. Gynecol Oncol 2002 Apr; 85(1): 67–70

    PubMed  CAS  Google Scholar 

  79. Wendling J, Saiag P, Berville-Levy S, et al. Treatment of undifferentiated vulvar intraepithelial neoplasia with 5% imiquimod cream: a prospective study of 12 cases. Arch Dermatol 2004 Oct; 140(10): 1220–4

    PubMed  CAS  Google Scholar 

  80. van Seters M, Fons G, van Beurden M. Imiquimod in the treatment of multifocal vulvar intraepithelial neoplasia 2/3: results of a pilot study. J Reprod Med 2002 Sep; 47(9): 701–5

    PubMed  Google Scholar 

  81. Marchitelli C, Secco G, Perrotta M, et al. Treatment of bowe-noid and basaloid vulvar intraepithelial neoplasia 2/3 with imiquimod 5% cream. J Reprod Med 2004 Nov; 49(11): 876–82

    PubMed  Google Scholar 

  82. Buck HW, Guth KJ. Treatment of vaginal intraepithelial neoplasia (primarily low grade) with imiquimod 5% cream. J Low Genit Tract Dis 2003 Oct; 7(3): 290–3

    PubMed  Google Scholar 

  83. Boonchai W. Treatment of precancerous and cancerous lesions of chronic arsenicism with 5% imiquimod cream [letter]. Arch Dermatol 2006 Apr; 142(4): 531–2

    PubMed  Google Scholar 

  84. Sachse MM, Zimmermann J, Bahmer FA. Efficiency of topical imiquimod 5% cream in the management of chronic radiation dermatitis with multiple neoplasias. Eur J Dermatol 2006; 16(1): 56–8

    PubMed  Google Scholar 

  85. Berthelot C, Dickerson MC, Rady P, et al. Treatment of a patient with epidermodysplasia verruciformis carrying a novel EVER2 mutation with imiquimod. J Am Acad Dermatol 2007; 56(5): 882–6

    PubMed  Google Scholar 

  86. Hughes PSH. Treatment of lymphomatoid papulosis with imiquimod 5% cream [letter]. J Am Acad Dermatol 2006 Mar; 54(3): 546–7

    PubMed  Google Scholar 

  87. Agarwal S, Berth-Jones J. Porokeratosis of Mibelli: successful treatment with 5% imiquimod cream [letter]. Br J Dermatol 2002 Feb; 146(2): 338–9

    PubMed  CAS  Google Scholar 

  88. Harrison S, Sinclair R. Porokeratosis of Mibelli: successful treatment with topical 5% imiquimod cream. Australas J Dermatol 2003 Nov; 44(4): 281–3

    PubMed  Google Scholar 

  89. Jain S. Successful treatment of porokeratosis of Mibelli with imiquimod 5% cream [letter]. Clin Exp Dermatol 2005 Mar; 31(2): 302–3

    Google Scholar 

  90. Montes-De-Oca-Sánchez G, Tirado-Sánchez A, García-Ramírez V. Porokeratosis of Mibelli of the axillae: treatment with topical imiquimod. J Dermatolog Treat 2006; 17(5): 319–20

    PubMed  Google Scholar 

  91. Weisberg NK, Varghese M. Therapeutic response of a brother and sister with xeroderma pigmentosum to imiquimod 5% cream. Dermatol Surg 2002 Jun; 28(6): 518–23

    PubMed  Google Scholar 

  92. Nijsten T, Lapière K, Lambert J. A patient with xeroderma pigmentosum treated with imiquimod 5% cream [letter]. J Am Acad Dermatol 2005 Jan; 52(1): 170–1

    PubMed  Google Scholar 

  93. Somani N, Martinka M, Crawford RI, et al. Treatment of atypical nevi with imiquimod 5% cream. Arch Dermatol 2007 Mar; 143(3): 379–85

    PubMed  CAS  Google Scholar 

  94. Dusza SW, Delgado R, Busam KJ, et al. Treatment of dysplastic nevi with 5% imiquimod cream, a pilot study. J Drugs Dermatol 2006 Jan; 5(1): 56–62

    PubMed  Google Scholar 

  95. Geisse JK, Rich P, Pandya A, et al. Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: a double-blind, randomized, vehicle-controlled study. J Am Acad Dermatol 2002 Sep; 47(3): 390–8

    PubMed  Google Scholar 

  96. Geisse J, Caro I, Lindholm J, et al. Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: results from two phase III, randomized, vehicle-controlled studies. J Am Acad Dermatol 2004 May; 50(5): 722–33

    PubMed  Google Scholar 

  97. Schulze HJ, Cribier B, Requena L, et al. Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: results from a randomized vehicle-controlled phase III study in Europe. Br J Dermatol 2005 May; 152(5): 939–47

    PubMed  CAS  Google Scholar 

  98. Shumack S, Robinson J, Kossard S, et al. Efficacy of topical 5% imiquimod cream for the treatment of nodular basal cell carcinoma: comparison of dosing regimens. Arch Dermatol 2002 Sep; 138(9): 1165–71

    PubMed  CAS  Google Scholar 

  99. Eigentler TK, Kamin A, Weide BM, et al. A phase III, randomized, open label study to evaluate the safety and efficacy of imiquimod 5% cream applied thrice weekly for8 and 12 weeks in the treatment of low-risk nodular basal cell carcinoma (in ENG]. J Am Acad Dermato 2007; 57(4): 616–21

    Google Scholar 

  100. Gollnick H, Barona CG, Frank RG, et al. Recurrence rate of superficial basal cell carcinoma following successful treatment with imiquimod 5% cream: interim 2-year results from an ongoing 5-year follow-up study in Europe. Eur J Dermatol 2005 Sep; 15(5): 374–81

    PubMed  CAS  Google Scholar 

  101. Quirk C, Gebauer K, Owens M, et al. Two-year interim results from a 5-year study evaluating clinical recurrence of superficial basal cell carcinoma after treatment with imiquimod 5% cream daily for 6 weeks. Australas J Dermatol 2006 Nov; 47(4): 258–65

    PubMed  Google Scholar 

  102. Vidal D, Matías-Guiu X, Alomar A. Fifty-five basal cell carcinomas treated with topical imiquimod: outcome at 5-year follow-up [letter]. Arch Dermatol 2007 Feb; 143(2): 266–8

    PubMed  Google Scholar 

  103. Spencer JM. Pilot study of imiquimod 5% cream as adjunctive therapy to curettage and electrodesiccation for nodular basal cell carcinoma. Dermatol Surg 2006 Jan; 32(1): 63–9

    PubMed  CAS  Google Scholar 

  104. Rigel D, Torres A, Ely H. Effectiveness of curettage and 5% imiquimod cream in the treatment of basal cell carcinoma: clinical and cosmetic evaluation [abstract no. P2420]. J Am Acad Dermatol 2006 Mar; 54 (3 Suppl. 1): AB174

    Google Scholar 

  105. De Cock E, Nuijten MJ, Hollestein A, et al. Cost-effectiveness model of Aldara™ (imiquimod) cream, 5% in superficial basal cell carcinoma in The Netherlands [abstract no. PSN4]. Value Health 2005 Nov; 8(6): A144. Plus poster presented at the ISPOR Eighth Annual European Congress; 2005 Nov 6; Florence

    Google Scholar 

  106. Sverre JM, Kristensen FKO, Hamel-Gariépy L, et al. Cost-effectiveness analysis: aldara™ (imiquimod) cream, 5% in the treatment of superficial basal cell carcinoma in Norway [abstract no. PSN2]. Value Health 2005 Nov; 8(6): A143. Plus poster presented at the ISPOR Eighth Annual European Congress; 2005 Nov 6; Florence

    Google Scholar 

  107. Green DS, Bodman-Smith MD, Dalgleish AG, et al. Phase I/II study of topical imiquimod and intralesional interleukin-2 in the treatment of accessible metastases in malignant melanoma. Br J Dermatol 2007 Feb; 156(2): 337–45

    PubMed  CAS  Google Scholar 

  108. Fisher GH, Lang PG. Treatment of melanoma in situ on sun-damaged skin with topical 5% imiquimod cream complicated by the development of invasive disease [letter]. Arch Dermatol 2003 Jul; 139(7): 945–7

    PubMed  Google Scholar 

  109. Fleming CJ, Bryden AM, Evans A, et al. A pilot study of treatment of lentigo maligna with 5% imiquimod cream. Br J Dermatol 2004; 151(2): 485–8

    PubMed  CAS  Google Scholar 

  110. Haque R. Topical imiquimod as an efficacious treatment for lentigo maligna [abstract no. P3]. 61st Annual Meeting of the American Academy of Dermatology poster abstracts; 2003 Mar 21; San Francisco (CA), 2

  111. Naylor MF, Crowson N, Kuwahara R, et al. Treatment of lentigo maligna with topical imiquimod. Br J Dermatol 2003 Nov; 149 Suppl. 66: 66–70

    Google Scholar 

  112. Powell AM, Russell-Jones R, Barlow RJ. Topical imiquimod immunotherapy in the management of lentigo maligna. Clin Exp Dermatol 2004 Jan; 29(1): 15–21

    PubMed  CAS  Google Scholar 

  113. Wolf IH, Cerroni L, Kodama K, et al. Treatment of lentigo maligna (melanoma in situ) with the immune response modifier imiquimod. Arch Dermatol 2005 Apr; 141(4): 510–4

    PubMed  CAS  Google Scholar 

  114. Naylor MF, Chen WR, Teague TK, et al. In situ photoimmunotherapy: a tumour-directed treatment for melanoma. Br J Dermatol 2006 Dec; 155(6): 1287–92

    PubMed  CAS  Google Scholar 

  115. Konstantopoulou M, Lord MG, Macfarlane AW. Treatment of invasive squamous cell carcinoma with 5-percent imiquimod cream. Dermatol Online J 2006; 12(3): 10

    PubMed  CAS  Google Scholar 

  116. Martín-García RF. Imiquimod: an effective alternative for the treatment of invasive cutaneous squamous cell carcinoma. Dermatol Surg 2005 Mar; 31(3): 371–4

    PubMed  Google Scholar 

  117. Oster-Schmidt C, Eul A. Successful treatment of a squamous cell carcinoma on the back of the hand with imiquimod 5% cream [abstract no. P2128]. Ann Dermatol Venereol 2002 Jul; 129 Suppl.: 1S787

    Google Scholar 

  118. Li VW, Ball RA, Vasan N, et al. Antiangiogenic therapy for squamous cell carcinoma using combinatorial agents [abstract no. 3032]. J Clin Oncol 2005 Jun 1; 23 (16 Pt I Suppl.): 199

    Google Scholar 

  119. Chong A, Loo WJ, Banney L, et al. Imiquimod 5% cream in the treatment of mycosis fungoides: a pilot study [letter]. J Dermatolog Treat 2004 Feb; 15(2): 118–9

    PubMed  CAS  Google Scholar 

  120. Born AK, Schreiber K, Lukowsky A, et al. Imiquimod for the treatment of cutaneous T cell lymphoma [abstract no. 272]. J Invest Dermatol 2002 Sep; 119(3): 758

    Google Scholar 

  121. Dendorfer M, Oppel T, Wollenberg A, et al. Topical treatment with imiquimod may induce regression of facial keratoa-canthoma. Eur J Dermatol 2003; 13(1): 80–2

    PubMed  Google Scholar 

  122. Scott DR. Apparent response of cutaneous Merkel cell tumor to topical imiquimod [letter]. Cutis 2006 Feb; 77(2): 109–10

    PubMed  Google Scholar 

  123. Jo J-H, Ko H-C, Jang H-S, et al. Infiltrative trichilemmal carcinoma treated with 5% imiquimod cream. Dermatol Surg 2005 Aug; 31(8 Pt 1): 973–6

    PubMed  CAS  Google Scholar 

  124. Brown VL, Atkins CL, Ghali L, et al. Safety and efficacy of 5% imiquimod cream for the treatment of skin dysplasia in high-risk renal transplant recipients: randomized, double-blind, placebo-controlled trial. Arch Dermatol 2005 Aug; 141(8): 985–93

    PubMed  CAS  Google Scholar 

  125. Gilson RJC, Shupack JL, Friedman-Kien AE, et al. A randomized, controlled, safety study using imiquimod for the topical treatment of anogenital warts in HIV-infected patients. AIDS 1999 Dec 3; 13(17): 2397–404

    PubMed  CAS  Google Scholar 

  126. Cusini M, Salmaso F, Zerboni R, et al. 5% Imiquimod cream for external anogenital warts in HIV-infected patients under HAART therapy. Int J STD AIDS 2004 Jan; 15(1): 17–20

    PubMed  CAS  Google Scholar 

  127. Harwood CA, Perrett CM, Brown VL, et al. Imiquimod cream 5% for recalcitrant cutaneous warts in immunosuppressed individuals. Br J Dermatol 2005 Jan; 152(1): 122–9

    PubMed  CAS  Google Scholar 

  128. Wieland U, Brockmeyer NH, Weissenborn SJ, et al. Imiquimod treatment of anal intraepithelial neoplasia in HIV-positive men. Arch Dermatol 2006 Nov; 142(11): 1438–44

    PubMed  CAS  Google Scholar 

  129. Brown Jr CW, O’Donoghue M, Moore J, et al. Recalcitrant molluscum contagiosum in an HIV-afflicted male treated successfully with topical imiquimod. Cutis 2000 Jun; 65(3): 363–6

    PubMed  Google Scholar 

  130. Buckley R, Smith K. Topical imiquimod therapy for chronic giant molluscum contagiosum in a patient with advanced human immunodeficiency virus 1 disease. Arch Dermatol 1999 Oct; 135(10): 1167–9

    PubMed  CAS  Google Scholar 

  131. Liota E, Smith KJ, Buckley R, et al. Imiquimod therapy for molluscum contagiosum. J Cutan Med Surg 2000 Apr; 4(2): 76–82

    PubMed  CAS  Google Scholar 

  132. Strauss RM, Doyle EL, Mohsen AH, et al. Successful treatment of molluscum contagiosum with topical imiquimod in a severely immunocompromised HIV-positive patient. Int J STD AIDS 2001 Apr; 12(4): 264–6

    PubMed  CAS  Google Scholar 

  133. Ulrich C, Busch JO, Meyer T, et al. Successful treatment of multiple actinic keratoses in organ transplant patients with topical 5% imiquimod: a report of six cases. Br J Dermatol 2006 Aug; 155(2): 451–4

    PubMed  CAS  Google Scholar 

  134. Vidal D, Alomar A. Efficacy of imiquimod 5% cream for basal cell carcinoma in transplant patients. Clin Exp Dermatol 2004 May; 29(3): 237–9

    PubMed  CAS  Google Scholar 

  135. Eklind J, Tartler U, Maschke J, et al. Imiquimod to treat different cancers of the epidermis. Dermatol Surg 2003 Aug; 29(8): 890–6; discussion 896

    PubMed  Google Scholar 

  136. Smith KJ, Germain M, Skelton H. Squamous cell carcinoma in situ (Bowen’s disease) in renal transplant patients treated with 5% imiquimod and 5% 5-fluorouracil therapy. Dermatol Surg 2001 Jun; 27(6): 561–4

    PubMed  CAS  Google Scholar 

  137. Gardner LS, Ormond PJ. Treatment of multiple giant molluscum contagiosum in a renal transplant patient with imiquimod 5% cream [letter]. Clin Exp Dermatol 2006 May; 31(3): 452–3

    PubMed  CAS  Google Scholar 

  138. Smith KJ, Germain M, Skelton H. Bowen’s disease (squamous cell carcinoma in situ) in immunosuppressed patients treated with imiquimod 5% cream and a cox inhibitor, sulindac: potential applications for this combination of immunotherapy. Dermatol Surg 2001 Feb; 27(2): 143–6

    PubMed  CAS  Google Scholar 

  139. Hanger C, Dalrymple J, Hepburn D. Systemic side effects from topical imiquimod. NZ Med J 2005 Oct 7; 118(1223): U1682

    Google Scholar 

  140. Benson E. Imiquimod: potential risk of an immunostimulant. Australas J Dermatol 2004 May; 45(2): 123–4

    PubMed  Google Scholar 

  141. Rajan N, Langtry JAA. Generalized exacerbation of psoriasis associated with imiquimod cream treatment of superficial basal cell carcinomas [letter]. Clin Exp Dermatol 2005 Jan; 31(1): 140–1

    Google Scholar 

  142. Taylor CL, Maslen M, Kapembwa M. A case of severe eczema following use of imiquimod 5% cream. Sex Transm Infect 2006 Jun; 82(3): 227–8

    PubMed  CAS  Google Scholar 

  143. Wu JK, Siller G, Strutton G. Psoriasis induced by topical imiquimod. Australas J Dermatol 2004 Feb; 45(1): 47–50

    PubMed  Google Scholar 

  144. Barton JC. Angioedema associated with imiquimod [letter]. J Am Acad Dermatol 2004 Sep; 51(3): 477–8

    PubMed  Google Scholar 

  145. Chakrabarty AK, Mraz S, Geisse JK, et al. Aphthous ulcers associated with imiquimod and the treatment of actinic cheilitis. J Am Acad Dermatol 2005 Feb; 52 (2 Suppl. 1): S35–7

    Google Scholar 

  146. Zalaudek I, Petrillo G, Argenziano G. Aphthous ulcers and imiquimod [letter]. J Am Acad Dermatol 2005 Aug; 53(2): 360–1

    PubMed  Google Scholar 

  147. McQuillan O, Higgins SP. Acute urinary retention following self treatment of genital warts with imiquimod 5% cream [letter]. Sex Transm Infect 2004 Oct; 80(5): 419–20

    PubMed  CAS  Google Scholar 

  148. Lin R, Ladd Jr DJ, Powell DJ, et al. Localized pemphigus foliaceus induced by topical imiquimod treatment [letter]. Arch Dermatol 2004 Jul; 140(7): 889–90

    PubMed  Google Scholar 

  149. Trevino J, Prieto VG, Hearne R, et al. Atypical lymphocytic reaction with epidermotropism and lymphocytic vasculopathic reaction (lymphocytic vasculitis) after treatment with imiquimod [letter]. J Am Acad Dermatol 2006 Nov; 55 Suppl. 5: S123–5

    PubMed  Google Scholar 

  150. Yan J, Chen S-L, Wang H-N, et al. Meta-analysis of 5% imiquimod and 0.5% podophyllotoxin in the treatment of condylomata acuminata. Dermatology 2006; 213(3): 218–23

    PubMed  CAS  Google Scholar 

  151. Centers for Disease Control and Prevention — Federal Government Agency (US). HPV infection and genital warts: sexually transmitted diseases treatment guidelines 2006 [online]. Available from URL: http://www.guidelines.gov [Accessed 2007 May 31]

  152. von Krogh G, Lacey CJN, Gross G, et al. European course on HPV associated pathology: guidelines for primary care physicians for the diagnosis and management of anogenital warts. Sex Transm Infect 2000 Jun; 76(3): 162–8

    Google Scholar 

  153. Berman B, Bienstock L, Kuritzky L, et al. Actinic keratoses: sequelae and treatments. Recommendations from a consensus panel. J Fam Pract 2006 May; 55 Suppl. 5: 1–8

    Google Scholar 

  154. National Institute for Health and Clinical Excellence. Guidance on cancer services: improving outcomes for people with skin tumours including melanoma [online]. Available from URL: http://www.nice.org.uk [Accessed 2007 Jun 5]

  155. Hadley G, Derry S, Moore RA. Imiquimod for actinic keratosis: systematic review and meta-analysis. J Invest Dermatol 2006 Jun; 126(6): 1251–5

    PubMed  CAS  Google Scholar 

  156. Falagas ME, Angelousi AG, Peppas G. Imiquimod for the treatment of actinic keratosis: A meta-analysis of randomized controlled trials [letter]. J Am Acad Dermatol 2006 Sep; 55(3): 537–8

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Wolters Kluwer Health ¦ Adis, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore 0754, Auckland, New Zealand

    Antona J. Wagstaff & Caroline M. Perry

  2. Wolters Kluwer Health, Conshohocken, Pennsylvania, USA

    Antona J. Wagstaff & Caroline M. Perry

Authors
  1. Antona J. Wagstaff
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Caroline M. Perry
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Antona J. Wagstaff.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wagstaff, A.J., Perry, C.M. Topical Imiquimod. Drugs 67, 2187–2210 (2007). https://doi.org/10.2165/00003495-200767150-00006

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-200767150-00006

Keywords

Search

Navigation