Double-Blind, Randomized, Placebo-Controlled Study of Topical 5% Acyclovir-1% Hydrocortisone Cream (ME-609) for Treatment of UV Radiation-Induced Herpes Labialis

Abstract

Immunopathology is recognized as an important component of infectious disease manifestations, and corticosteroids have been used as an adjunct to antimicrobial therapy for a variety of conditions. Antiviral therapy of herpes labialis has been shown to result in only a small reduction in the time to healing and the duration of pain. To determine if topical application of a combination product containing 5% acyclovir and 1% hydrocortisone (ME-609) could provide benefit to herpes labialis patients, 380 immunocompetent adults with a history of herpes labialis were exposed to experimental UV radiation (UVR) to induce a recurrence. On day 2, just before the appearance of the majority of lesions ("delayed" lesions), subjects were randomized to receive active medication or vehicle control six times per day for 5 days. Overall, 120 of 380 patients developed delayed classical lesions, of whom 50 of 190 (26%) had been treated with ME-609 and 70 of 190 (37%) had received placebo (a reduction of 29% [P ‫؍‬ 0.02]). Healing time, measured as the time to normal skin, was reduced by treatment with ME-609 (9.0 days for treated patients versus 10.1 days for the controls [P ‫؍‬ 0.04]). There was a trend toward a reduction in the maximum lesion size in the ME-609 recipients compared to that in the controls (43 versus 60 mm 2 , respectively [P ‫؍‬ 0.07]). The treatment had no effect on lesion pain, but ME-609 treatment reduced the number of patients with moderate or severe tenderness. Compared to treatment with a placebo, treatment with the combination antiviral-immunomodulatory cream provided benefit to patients with experimental UVR-induced herpes labialis, reducing classical lesion incidence, healing time, lesion size, and lesion tenderness. ME-609 is a novel product that merits further evaluation as a treatment for cold sores.Treatment of herpes simplex virus (HSV) infections with antiviral drugs has been a major challenge for investigators for more than 30 years. The benefits of treatment of recurrent HSV infection have been modest in contrast to the benefits of treatment of primary infection. The main clinical benefit in the treatment of recurrences has been the modest reduction in lesion healing time of approximately 10 to 15% (5, 10). Recurrent disease differs from the primary episode in that the virus is cleared much more rapidly, usually within 3 days or less. Although the immune response is quicker and more effective in controlling recurrent disease, it also may be responsible for most of the clinical symptoms, which persist for up to a week after the virus can no longer be isolated (6, 9). Thus, a combined modality of therapy aimed at both an antiviral effect and an immunomodulatory effect has been proposed in a number of studies (1, 9).The availability of a small-animal model for evaluation of the effects of treatment on the severity of recurrent lesions has been a limiting factor in evaluations of therapy. A novel animal model of recurrent HSV disease was recently developed by the use of zosteriform HSV infection in mic...

Efficacy of Topical 5% Acyclovir-1% Hydrocortisone Cream (ME-609) for Treatment of Herpes Labialis: a systematic review

“…A meta-analysis of these studies (Evans 2002, Hull 2011 showed that treatments with Topical 5% Acyclovir-1% Hydrocortisone Cream (ME-609) has a significant positive effect on developed ulcerative lesions compared with placebo patients. (RR 0.78, 95% CI 0.70-0.85; p<0.001) (Fig.…”

Novel Composite Efficacy Measure To Demonstrate the Rationale and Efficacy of Combination Antiviral–Anti-Inflammatory Treatment for Recurrent Herpes Simplex Labialis

“…This led to investigations into the use of antiviral-anti-inflammatory combinations, which have been shown to be more effective than antivirals alone (18,39,40,44). Because HSL therapy, especially combination treatments, can have multiple effects-prevention of lesion progression, reduced lesion area, shorter episode duration-composite endpoints may be the most appropriate measures of their total efficacy.…”

“…They showed that the combined durations of these stages was reduced by 43% (P Ͻ 0.001) by idoxuridine among patients with ulcerative recurrences, whereas total healing time was unaffected, thereby demonstrating that antiviral treatment can reduce the duration of the most bothersome stages of HSL lesions even if total healing time is unchanged. Similar endpoints have been utilized by Evans et al (40) and Crane et al (41). However, lesion stage duration endpoints do not capture the ability of an antiviral to prevent ulcerative lesions, which may be the most important goal of HSL therapy.…”

“…The combination AHC, which was approved by the U.S. FDA in 2009 for the early treatment of recurrent HSL to reduce the likelihood of ulcerative lesions and shorten lesion healing time in patients Ն12 years of age (47), has been shown to be safe and effective (18,40) without evidence of an increased risk of developing acyclovir resistance (18,48). In the 609-04 study, AHC was shown to prevent lesion progression (the proportion of nonulcerative lesions), shorten episode duration, and decrease maximum lesion area compared with 5% acyclovir cream (in the AHC vehicle, AC; significantly in some cases) and the vehicle (significantly in most cases) ( Table 1).…”

Early treatment of cold sores with topical ME-609 decreases the frequency of ulcerative lesions: A randomized, double-blind, placebo-controlled, patient-initiated clinical trial

“…This has consistently resulted in smaller lesions and an increase in the proportion of nonulcerative lesions, suggesting that a reduction of the inflammatory response may prevent some of the recurrences from developing into ulcerative lesions. 2,3,11 To further assess the value of combined topical steroid and antiviral therapy for HSL, the current phase III clinical trial was undertaken. We evaluated the efficacy and safety of topical ME-609, consisting of topical 5% acyclovir and 1% hydrocortisone in a proprietary cream formulation, for the treatment of recurrent HSL.…”