Combination Therapy of Oral Valacyclovir and Topical Clobetasol Is the Most Effective in Herpes Labialis Management

This study is a systematic review and network meta-analysis that evaluated the efficacy and safety of antiviral agents in the prevention and management of herpes labialis. The use of a network meta-analysis allowed the authors to simultaneously compare many different antiviral agents tested in clinical trials. A traditional meta-analysis allows for the evaluation of trials that have no more than two interventions for the same disease. The study protocol was registered in the PROSPERO database of systematic reviews with full reporting based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. There is a complete outline of the data source and the search strategy following the Population, Intervention, Comparison, Outcome, Studies framework. The participants in the selected trials had to be healthy and immunocompetent adults with a history of herpes labialis (new or recurrent) subjected to antiviral interventions. The comparisons were between placebo and any intervention with antiviral properties. Outcomes of the trials included time to healing (TTH), primary prevention outcomes (no evidence of recurrent lesions), duration of the episodes, pain, etc. Information on how the data were extracted was based on three main categories: study characteristics, interventions, and outcomes. The risk of bias of the selected studies was analyzed based on deviations of intended interventions, missing outcomes, measurement methods and selection of the reported results, and one overall bias domain. The statistics evaluated the study results based on the principle of intention to treat. Several aspects of the selected trials were considered, such as the direct and indirect evidence, random effects, network inconsistency assumption, and the evaluation and ranking of the antiviral agents as well as the surface area under the cumulative ranking (SUCRA) scores.

The study was done well and followed all the current guidelines required for a systematic review and meta-analysis. The network meta-analysis allowed for the evaluation of many available antiviral agents and over-the-counter or alternative methods. A total of 52 studies were included in the final analysis involving 19,669 randomized patients. Of these patients, 6769 were excluded owing to incomplete data, leaving 12,900 patients for the post analysis. Selected studies were international, including studies performed in 14 countries. The most commonly used antiviral was acyclovir. Treatment protocols used both topical and systemic combinations, some including corticosteroids combined with antiviral therapy. There were studies that used natural and herbal formulations like olive leaf extract, kanuka, honey, propolis, tea leaves, and many other agents. Most of the studies evaluating TTH showed a range of 3 to 14 days or until the lesion healed. The prophylactic trials followed patients for up to 9 months. TTH was reported in 37 studies, with 21 showing statistical significance in the improvement of the lesions. There were studies showing pain reduction, reduction in the episodic duration of lesions, improvement in the total symptom scores, complete epithelialization, and itchiness decrement as well as assessing bleeding tendency and change in mucosal color. Using the SUCRA method, the results favored the combination of topical clobetasol and systemic valacyclovir in the management of recurrent episodes of herpes labialis. The second-best protocol was the use of topical vidarabine monophosphate. In the prevention analysis, inosine pranobex demonstrated the best results, followed by acyclovir, valacyclovir, and the combination of topical acyclovir and hydrocortisone. However, none of these interventions were superior to placebo. It is important to point out that the authors only studied the antiviral effects on herpes labialis. Similar results may not be applied to genital herpes prevention and recurrence, where oral acyclovir, valacyclovir, and famciclovir have been shown to be very effective.

Take-home messages from the study

• The study shows that a large number of interventions using antivirals are available for the prevention and recurrence of herpes labialis.
• Some of the interventions for prevention performed below the placebo effect.
• Although some antiviral interventions may have efficacy in the treatment of herpes labialis, it was shown that the addition of corticosteroids to the treatment protocol improves the efficacy. This is the case for both topical therapy and/or the combination of topical steroids and systemic antivirals. Therefore, the regimen of choice to treat herpes labialis would be topical clobetasol and systemic valacyclovir.
• Other combinations using systemic acyclovir and topical steroids may also be effective in decreasing the TTH.
• The results addressing the side effects showed them to be not significant. Specific trials focusing on adverse events associated with antiviral therapy are warranted. Most of the current protocols have been proven to be safe.
• The supplemental material of the study confirms the robustness of the project.

My experience as a clinician

• Treatment regimens for herpes labialis differ between primary infection and recurrent herpes. In both cases, prompt diagnosis and initiation of therapy will produce better outcomes with a quicker healing time.
• Managing herpes labialis in immunocompetent patients is different from managing it in immunocompromised individuals. Clinical manifestations are diverse, and the diagnosis and treatment may be challenging.
• In primary infection, valacyclovir hydrochloride 1000 mg twice daily for 7 days and famciclovir 500 mg twice daily for 7 days are the accepted regimens that promote a quicker healing time and alleviation of pain.
• In recurrent herpes labialis, topical penciclovir 1% cream every 2 hours for 4 days and acyclovir 5% cream five times daily for 4 days are the accepted regimens.
• In severe cases, the addition of a topical corticosteroid may decrease the healing time and pain.
• Counseling patients on how to prevent the contamination of others is of great importance.