Aldara™ Cream, 5% (Imiquimod)

 

Aldara Cream, 5% (Imiquimod)

 

 

  Content:

DRUG AND PATIENT PROFILE

 

 

Drug Profile - Genital warts

  • Women and uncircumcised men have shown the best response for genital warts using imiquimod.
  • Warts on regular skin can be treated by destructive therapy combined with Aldara™. Occlusion of the warts, if possible, after application of the cream is likely to give better results but may also cause significantly more irritation.
  • The possibility of inducing a long-term immune memory against genital warts by using this cream makes a case for all warts (particularly stubborn ones) being treated with Aldara™, either alone or in combination.

Drug Profile - Actinic Keratosis

  • Extensive areas of actinic keratosis that are not easily treated by cryotherapy
  • An alternative to the use of 5FU cream or photodynamic therapy
  • In a trial of 24 patients with AKs, 21 cleared and 2 partially cleared when used 3 times/ week for 2 weeks and twice a week thereafter for 12 weeks or until cleared.

    [Stockfleth E, et al. Arch Dermatol. 2002; 138:1498-502]

  • The ideal frequency may vary by individual and site.
  • Also useful in treating actinic cheilitis.
  • [Smith KJ, et al. J Am Acad Dermatol. 2002; 47:497-501]

Imiquimod: AK Course-of-Therapy (cycling) data

  • 25 patients - 35 cosmetic units
  • Twice/ week therapy on face and scalp for 1 month, then a break of 1 month followed by another cycle
  • 1st cycle cleared 46%
  • 2nd cycle cleared another 36%
  • 3rd cycle - no additional patients cleared
  • Total % clearance of AK lesions was 82%.
  • [Salache, et al. J Am Acad Dermatol. 2002; 47:571-7]

Imiquimod: AK Phase III Data

  • 2 randomized, double-blind, vehicle-controlled, parallel-group trials
  • 4 to 8 baseline AK lesions within a contiguous .25cm2 treated area on face or balding scalp
  • Topical imiquimod 5% cream or vehicle .2 times/ week for 16 weeks
  • Assessment at 8 weeks posttreatment
  • Complete clearance (100%)
  • Partial clearance (? 75%)
  • [Lebwohl M, et al. J Am Acad Dermatol. 2004; 50:714-21]

AK Phase III Data Conclusions

  • Imiquimod 5% cream 2 times/ week for 16 weeks was effective in the clearance of AK lesions
  • Significantly better than vehicle in complete clearance of AK lesions (P <.001)
  • Median percent reduction in number of AKs from baseline was ~ 83%
  • Cleared clinical and subclinical AK lesions
  • Imiquimod was well tolerated
  • Application site and local skin reactions were the predominant adverse events associated with therapy.
  • Only 3% of patients discontinued due to adverse events.
  • [Lebwohl M, et al. J Am Acad Dermatol. 2004; 50:714-21]

Superficial BCC Phase III data

  • Aldara™ cleared after 12 weeks of therapy
  • 100% when used twice a day
  • 87% when used daily
  • 81% when used 5 times/ week
  • [Geisse JK, et al. J Am Acad Dermatol. 2002; 47:390-98]

  • Two prospective, double-blind, multicenter, vehicle-controlled studies
  • Imiquimod 5% cream 5 times/ week (n = 185) or placebo (n = 179) for 6 weeks
  • Primary, biopsy-confirmed sBCC
  • ~ 80% of target lesions were located on trunk or upper extremities
  • Complete response at 12 weeks posttreatment
  • Clinical and histologic clearance, or
  • Clinical suspicion but histologic evidence of no sBCC
  • [Geisse J, et al. J Am Acad Dermatol. 2004; 50:722-33.]

Superficial BCC Phase III data - Conclusions

  • Imiquimod 5% cream is safe and effective in the treatment of primary sBCC.
  • High efficacy was achieved at 5 times/ week for 6 weeks of treatment: pooled data showed that composite clearance rate for the imiquimod group was 75% and histological clearance rate was 82%.
  • Clinical observations were supported by histologic clearance of target tumour.
  • [Geisse J, et al. J Am Acad Dermatol. 2004; 50:722-33.]

Drug Profile - Common warts

  • Warts on the trunk, hands and face respond the best. Significant reduction in size or clearance was seen in 56% of patients.
  • [Hengge UR, et al. Br J Dermatol. 2000; 143:1026-31]

  • Aldara™ should be used in combination with other therapy as penetration into the keratinized warts is difficult; occlusion of the wart area should also be considered.

Drug Profile - Keloids

  • Recurrences of excised keloids on the earlobe were significantly reduced by daily application of Aldara™ 5% to the suture line for 2 months. At 24 weeks, the recurrence rate was lower than recurrence rates previously reported in the literature.

    [Berman B, et al. J Am Acad Derm. 2002; 47(4 Suppl):s209-11]

  • Anecdotally, plastic surgeons have been using this cream post-surgery to minimize the risk of hypertrophic scars - formal studies need to be done.

Drug Profile - Lentigo maligna

Imiquimod pilot study data

  • 93% (26/28 patients) cleared (biopsy-confirmed)
  • Aldara™ daily for 12 weeks
  • Erythema not seen in 2 patients that did not clear
  • May be useful as an adjunctive therapy to excision, as recurrence can be high after surgery because of ill-defined margins.
  • [Naylor M, et al. Br J Dermatol. 2003; 149(suppl. 66):66-70]

Profile - Molluscum Contagiosum

Patient Profile

  • Children, sexually active adults, and especially the HIV+ are prone.

Drug Profile

  • Studies and case reports show efficacy.
  • Useful, non-painful procedure; usually an inflammatory reaction is present, which is desirable.
  • One study showed no recurrence in HIV patients after 3 months.
  • The frequency of application and treatment duration have not as yet been optimized.

Topical Imiquimod in Nodular BCC

Dose-Response Studies

  • 6-week, randomized, open-label study
  • Once a day 3 times/wk
  • Twice a day 3 times/wk
  • Once a day 7 times/wk
  • 12-week, randomized, vehicle-controlled study
  • Once a day 3 times/wk
  • Once a day 5 times/wk
  • Once a day 7 times/wk
  • Histologic assessment 6 weeks posttreatment
  • [Shumack S, et al. Arch Dermatol. 2002;138:1165-71].

Imiquimod in the Treatment of Nodular BCC

  • Imiquimod 5% cream is safe and effective in the treatment of nBCC.
  • Dosing once daily for 7 days/ week resulted in the highest clearance rate, with 71% of patients showing clearance of their tumour after 6 weeks of treatment
  • 7 times/week treatment for 6 weeks may be a clinically useful dosing regimen.
  • Clearance was lower than that observed in sBCC clinical studies, potentially because of pathophysiologic attributes of nBCC versus sBCC.
  • Imiquimod may be useful as adjunctive therapy to surgery or when surgical options are contraindicated or undesirable.
  • [Shumack S, et al. Arch Dermatol. 2002; 138:1165-71]

Imiquimod: Squamous cell carcinoma in situ (Bowen’s disease) Phase III Data

  • Bowen’s disease – (16 patients) daily applications for 16 weeks gave 93% biopsy proven clearance.
  • [Mackenzie-Wood A. J Am Acad Dermatol. 2001; 44;462-70]
  • Bowen’s and SCC in situ of the penis. All 5 patients cleared at 12-16 weeks.
  • [Arlette JP. Br J Dermatol. 2003; 149(suppl. 66):43-9]

Overall Conclusions: AK and BCC

  • Topical imiquimod 5% cream is a nonablative topical agent in the treatment of AK and BCC.
  • Its novel mechanism of action stimulates the body’s own natural defenses to target diseased tissue.
  • Stimulation of both innate and cell-mediated immunity
  • It has favorable efficacy and safety profiles for the treatment of AK and primary sBCC.
  • In clinical practice, topical imiquimod 5% cream may frequently be used in combination with other treatment modalities.

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