Recent Approval of Xerese in Canada: 5% Acyclovir and 1% Hydrocortisone Topical Cream in the Treatment of Herpes Labialis

Harrison P. Nguyen, BA; Kelly R. Stiegel, BS; Christopher Downing, MD; Stephen K. Tyring, MD, PhD, MBA

Disclosures

Skin Therapy Letter. 2014;19(3) 

In This Article

From Bench to Bedside: Duration and Efficacy

In order to obtain maximum clinical benefit from a topical antiviral medication, therapy should be initiated within 72 hours of onset of symptoms.[6] Patients with recurrent herpes labialis experience a rapid onset of disease and a short viral shedding period, both of which make it difficult to measure responses to therapy.

In an early basic science study conducted in 2003, researchers used mice that had undergone adaptive transfer of immunity and infected the skin on the mice's ear pinna with HSV-1.[7] After the mice developed a zosteriform infection, treatment groups received topical ACHC, 5% acyclovir (Zovirax®), 1% hydrocortisone, or no treatment at all. Medication was applied 3 times daily for 4 days. The treatment groups were analyzed based on ear thickness increase and zoster score. The zoster scores were adapted from a scale previously described in another study, and the scores used were: 0 for unchanged ear, 1 for isolated zosteriform lesions, and 2–4 for describing the ulceration of confluent zosteriform lesions from mild to severe.[8] ACHC outperformed both 5% acyclovir and 1% hydrocortisone creams, with an average increase in ear thickness of only 0.15 ± 0.03 mm compared to 0.48 ± 0.08 mm and 0.23 ± 0.03 mm, respectively. The average increase in ear thickness for ACHC was only 34% of that experienced by the mice in the control group, compared to 110% observed with acyclovir and 52% with hydrocortisone. The average zoster score for the ACHC group at day 9 was also the lowest of the four groups at 2.0 ± 0.2 (58% of control), compared to 2.4 ± 0.3 (70% of control) for acyclovir and 2.8 ± 0.2 (80% of control) for hydrocortisone.[7]

In a 2012 Phase 3 study, Strand et al instructed their human subjects to apply ACHC 5 times daily for 5 days at the onset of prodromal symptoms, preferably before the appearance of actual papules or vesicles. Of the 131 test subjects, 78 (59.5%) had nonulcerative recurrences, and 53 (40.5%) had ulcerative recurrences. At the follow-up visit, all 131 of the test subjects had returned to the stage of normal skin, 3 weeks after the last dose, with no signs or symptoms of herpes labialis recurrence. In the 40% of subjects who experienced ulcerative herpes lesions despite applying the ACHC cream, the mean maximum lesion area was 39 mm2, which was a 48% decrease from the mean lesion area size of 75 mm2 typically reported in immunocompetent adults.[9,10]

A similar study published in 2011, also using a dosing regimen of applying cream 5 times daily for 5 days, studied a much larger patient population in a randomized, double-blind, placebocontrolled trial.[11] The 2,437 volunteers were randomized to receive either ACHC, acyclovir in the ACHC vehicle, or placebo in the form of the ACHC vehicle. Of the 1,443 subjects who experienced a recurrence of herpes labialis during the trial and initiated treatment, 42% used ACHC, 42% acyclovir, and 16% placebo. The authors reported that 58% of the patients on ACHC developed an ulcerative lesion, vs. 65% in the acyclovir group and 74% in the placebo group. In patients who experienced an ulcerative lesion, the healing times were reduced in those who received ACHC or acyclovir, compared with placebo. The patients using ACHC also had a smaller cumulative lesion area (~50% less) than the placebo group (Table 1 and Table 2).

Finally, in a simulated 2002 trial, researchers tested the efficacy of ACHC in patients whose latent HSV-1 infection was intentionally reactivated using ultraviolet (UV) light.[12] Of the 380 subjects, 120 patients developed classical cold sores 2 days after UV light exposure, which was followed by initiation of treatment with either ACHC or placebo. Treatment with ACHC reduced lesion size, healing time, and lesion tenderness when compared with placebo. Healing time (defined as the time to restoration of normal skin) was reduced from 10.1 days in the placebo group to 9.0 days in the ACHC group (Table 2).

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