Three phase III randomized controlled trials of topical resiquimod 0.01-percent gel to reduce anogenital herpes recurrences.
Resiquimod, a Toll-like receptor 7 and 8 agonist, stimulates production of cytokines that promote an antigen-specific T helper type 1 acquired immune response. Animal and phase II human trials showed posttreatment efficacy in reducing recurrent herpes lesion days and/or time to first recurrence. Three phase III randomized, double-blind, vehicle-controlled trials of topical resiquimod to reduce anogenital herpes recurrences were conducted in healthy adults with ≥4 recurrences within the prior year. Participants applied resiquimod 0.01% gel or vehicle gel 2 times per week for 3 weeks to each recurrence for 12 months. Trials 1 and 2 had 2:1 resiquimod-vehicle randomization. Trial 3 had 1:1:1 randomization for resiquimod and 500 mg valacyclovir orally twice daily for 5 days (RESI-VAL), resiquimod and oral placebo (RESI-PLA), and vehicle and oral placebo (VEH-PLA). The median time to first recurrence was similar for resiquimod and vehicle (trial 1, 60 and 56 days, P=0.7; trial 2, 54 and 48 days, P=0.47; trial 3, 51 [RESI-VAL], 55 [RESI-PLA], and 44 [VEH-PLA] days, P=not significant [NS]). The median time to healing of initial treated recurrence was longer for resiquimod (trial 1, 18 compared to 10 days, P<0.001; trial 2, 19 compared to 13 days, P=0.16; trial 3, 14 [RESI-VAL], 16 [RESI-PLA], and 8 [VEH-PLA] days, P<0.001). In trials 1 and 2, moderate to severe erythema and erosion/ulceration at the application site were more common in resiquimod recipients. In conclusion, no posttreatment efficacy of resiquimod 0.01% gel was observed. Increased application site reactions and initial recurrence healing time are consistent with resiquimod-induced cytokine effects.
Department of Medicine, University of Washington, Seattle, Washington, USA Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA Karen.Mark@cdph.ca.gov.
Karen E
KE
Mark
Department of Medicine, University of Utah, Salt Lake City, Utah, USA.
Spotswood
S
Spruance
Department of Genitourinary Medicine, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom.
George R
GR
Kinghorn
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Stephen L
SL
Sacks
Medical and Scientific Affairs, 3M Pharmaceuticals, St. Paul, Minnesota, USA.
Herbert B
HB
Slade
Medical and Scientific Affairs, 3M Pharmaceuticals, St. Paul, Minnesota, USA.
Tze-Chiang
TC
Meng
Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA.
Stacy
S
Selke
Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA.
Amalia
A
Magaret
Department of Medicine, University of Washington, Seattle, Washington, USA Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA Department of Epidemiology, University of Washington, Seattle, Washington, USA.
Anna
A
Wald
D000212:Acyclovir / Q000008:administration & dosage / Q000031:analogs & derivatives; D000293:Adolescent; D000328:Adult; D000368:Aged; D016207:Cytokines / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D005782:Gels / Q000008:administration & dosage*; D006561:Herpes Simplex / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D018139:Simplexvirus / Q000187:drug effects*; D000077483:Valacyclovir; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives; D014945:Wound Healing / Q000187:drug effects; D055815:Young Adult
D016207:Cytokines; D005782:Gels; D007093:Imidazoles; D014633:Valine; D000077483:Valacyclovir; C402365:resiquimod; D000212:Acyclovir