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

Hull, Christopher M.; Harmenberg, Johan; Arlander, Eva; Aoki, Fred Y.; Bring, Johan; Darpö, Börje; Levin, Myron J.; Tyring, Stephen K.; Spruance, Spotswood L.

doi:10.1016/j.jaad.2010.08.012

Cited by 21 publications

(30 citation statements)

References 20 publications

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“…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.…”

Section: Discussionmentioning

confidence: 99%

“…This may be due in part to the timing of viral replication and treatment initiation. Since viral replication is rapidly controlled (1 to 2 days) by host immune responses (8), if the antiviral drug is applied after viral replication reaches its maximum, there is little opportunity for the drug to have a significant effect, as demonstrated by the differences in efficacy observed when antivirals are initiated early (during the prodrome or erythema stages) versus late (during the vesicle or later stages) (14)(15)(16)(17)(18).…”

Section: Dual Disease Processes In Herpes Simplex Labialis Recurrencesmentioning

confidence: 99%

“…Recently, a new topical formulation of acyclovir with better dermal penetration showed improved antiviral efficacy in a randomized clinical trial (18). In addition, adding a corticosteroid to an antiviral may have additive or synergistic effects, including enhanced effective dermal concentration of the antiviral component via steroid-mediated vasoconstriction.…”

Section: Toward More Effective Treatments For Recurrent Herpes Simplementioning

confidence: 99%

“…Recently, the cumulative lesion area endpoint was used in a randomized, double-blind study to evaluate the efficacy of the combination 5% acyclovir-1% hydrocortisone cream (AHC) (Xerese; Valeant Pharmaceuticals North America LLC, Bridgewater, NJ) in patients with recurrent HSL (study 609-04; NCT00361881) (18). 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).…”

Section: Application Of Cumulative Lesion Area As a Measure Of Combinmentioning

confidence: 99%

“…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).…”

Section: Application Of Cumulative Lesion Area As a Measure Of Combinmentioning

confidence: 99%

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

Hull

Levin

Tyring³

et al. 2014

Antimicrob Agents Chemother

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c Historically, the primary target for research and treatment of recurrent herpes simplex labialis (HSL) has been limited to inhibiting herpes simplex virus (HSV) replication. Antiviral monotherapy, however, has proven only marginally effective in curtailing the duration and severity of recurrent lesions. Recently, the role of inflammation in the progression and resolution of recurrences has been identified as an additional target. This was evaluated in a randomized study comparing combination topical 5% acyclovir-1% hydrocortisone cream (AHC) with 5% acyclovir alone (AC; in the AHC vehicle) and the vehicle. The efficacy of each topical therapy was evaluated for cumulative lesion size-a novel composite efficacy endpoint incorporating episode duration, lesion area, and proportion of nonulcerative lesions. In that study, cumulative lesion area was significantly decreased with AHC compared with AC (25% decrease; P < 0.05) and the vehicle (50% decrease; P < 0.0001). As research continues in this arena, cumulative lesion area should be included as a measure of efficacy in clinical trials of recurrent HSL therapies.T he seroprevalence of herpes simplex virus 1 (HSV-1), the HSV type most often associated with herpes simplex labialis (HSL) or cold sores, is estimated to be 58% among immunocompetent Americans 14 to 49 years of age (1) and 31% among children 6 to 13 years of age (2). Approximately 15 to 40% of these seropositive individuals will experience a symptomatic HSL recurrence, the frequency of which depends on genetic susceptibility, immune status, age, site of infection, and viral subtype (HSV-1 versus HSV-2) (3, 4). In most cases, patients with recurrent HSL experience minimal discomfort, pain, and disfigurement, but frequent outbreaks (Ͼ5 episodes/year, experienced by approximately 35% of patients with recurrent HSL) are associated with significant impact on physical, emotional, and social well-being (5).Recurrences of HSL differ from the primary/initial infection with respect to the roles that viral replication and inflammation play in the course of a lesion. In primary infection, lesion development, progression, and resolution are closely correlated with viral replication. In recurrent disease, lesion development and progression depend primarily on the proinflammatory host response (6) (Fig. 1). The central role of inflammation in lesion progression in recurrent disease may explain the limited efficacy of current antiviral monotherapy and suggests a new approach for more effective treatment. The value of one such approach, antiviral-anti-inflammatory combination treatment, has been demonstrated via several endpoints, including cumulative lesion area, a new efficacy endpoint. DUAL DISEASE PROCESSES IN HERPES SIMPLEX LABIALIS RECURRENCESRecurrent lesion development: correlations with viral processes. In recurrent HSL, HSV periodically reactivates (by mechanisms that are not completely understood) and moves from the cell body of latently infected sensory neurons toward the epidermis, where the virus begins to r...

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Section: Discussionmentioning

confidence: 99%

Section: Dual Disease Processes In Herpes Simplex Labialis Recurrencesmentioning

confidence: 99%

Section: Toward More Effective Treatments For Recurrent Herpes Simplementioning

confidence: 99%

Section: Application Of Cumulative Lesion Area As a Measure Of Combinmentioning

confidence: 99%

Section: Application Of Cumulative Lesion Area As a Measure Of Combinmentioning

confidence: 99%

See 3 more Smart Citations

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

Hull

Levin

Tyring³

et al. 2014

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

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Herpes Simplex

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2014

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2019

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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

Cited by 21 publications

References 20 publications

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

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

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