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.

Next:   Dosing

    More Presentations: