Genital Warts: Podofilox vs. Aldara

Clinical Question: In a patient with genital warts from HPV, does treatment with podophyllotoxin (podofilox or condylox) vs imiquimod (aldara) provide greater clinical efficacy and safety?

Background:
--genital warts caused by HPV the most common viral STD in U.S.
--treatments ablative (cryotherapy, electrocautery, laser, surgical excision) or cytotoxic (podophyllotoxin, imiquimod, 5-FU, trichloroacetic acid, interferon alpha)
--due to convenience the most prevalent cytotoxic therapies are podophyllotoxin and imiquimod
--podophyllotoxin is anti-mitotic, arrests cells in metaphase
--imiquimod is a positive immune response modifier, induces local cytokines
--in general, all therapies lead to recurrence rates 30-70% in 6 mo
--20-30% genital warts show spontaneous regression w/in 3 months

Data:
--no head to head trials comparing podophyllotoxin and imiquimod

Study: Meta-analysis of 5% imiquimod and 0.5% podophyllotoxin in the treatment of condylomata acuminata. 2006 study from China.

--Inclusion: RCT of 5% imiquimod and 0.5% podophyllotoxin to treat genital warts. Patients had clinically visible genital warts determined by h&p. Dose of imiquimod was 3x/week until warts cleared or x 16 wks. Dose of podophyllotoxin was 2-3 topical applications/day x 3 days followed by 4 day tx-free period until warts cleared or max 4 wks
--Exclusion: studies with combination therapies, patients with immune defects
--Outcome measures: primary outcome = curative effect measured as clearance rate by # of patients. secondary outcome = adverse events measured as instances of moderate or severe degree events
--Searched Medline (1996-2005), Embase (19808-2005), and Cochrane (issue 3, 2005) for all published and unpublished RCTs in all languages

--Results:
--12 studies: 3 RCT of imiquimod and 9 RCT of podophyllotoxin
--Imiquimod studies: clinical cure rate 50.34 %, recurrence rate 13-19%, total pooled patients were 194 experimental and 168 control
--Podophyllotoxin studies: clinical cure rate 56.41 %, recurrence rate 2-90%, total pooled patients were 479 experiemental and 294 control
--combined analysis of the 3 studies for imiquimod and the 9 studies for podophyllotoxin showed stastically significant difference to placebo
--however clinical cure rates of imiquimod vs podophyllotoxin show no statistically significant difference
--most common SE imiquimod: redness, erosion, excoriation, itching, burning
--most common SE podophyllotoxin: burning, erosion, pain, erosion, inflammation
--podophyllotoxin group had higher percentage rate of SE and of more serious degree

Bottom Line:
No significant difference between clinical efficacy of podophyllotoxin and imiquimod. Podophyllotoxin may have more serious side effects.

References:
--“Meta-analysis of 5% imiquimod and 0.5% podophyllotoxin in the treatment of condylomata acuminata.” Yan J, Che SL, Wang HN, Wu TX. Dermatology. 2006; 213 (3): 218-23.
--UpToDate: Treatment and Prevention of HPV Infections