A second look at efficacy criteria for onychomycosis: clinical and mycological cure

Br J Dermatol. 2014 Jan;170(1):182-7. doi: 10.1111/bjd.12594.

Abstract

Background: Approval of topical onychomycosis drugs by regulatory agencies may be negatively impacted by an overly stringent definition of complete cure, which includes nail clearing plus mycological cure.

Objectives: In this position paper, we discuss interpretation of mycological outcome and clinical trial length.

Methods: We reviewed data from seven international onychomycosis trials that enrolled subjects with positive KOH and dermatophyte-positive culture at screening followed by 48 weeks of treatment. Further, we examined 94 KOH-positive/culture-negative week 52 follow-up samples for morphological hyphal damage.

Results: From 3054 samples collected at week 52 follow-up visits, 2360 were culture-negative. However, a significant percentage (78.7%) of these subungual samples (n = 1857) remained KOH-positive. From the subset of follow-up samples examined for morphological changes, we identified hyphal breakage or distortion in 56 direct smears (60%), which may indicate nonviability.

Conclusions: Reassessment of the definition of onychomycosis cure is critical. For clinical trials of topical agents, length of treatment should be re-examined. Further, in our experience, a high rate of subungual debris samples remained direct smear-positive while converting to negative culture. Evidence of morphological hyphal damage suggests that late-visit microscopic results may be false-positives. Therefore, the absence of clinical signs following an adequate washout period, coupled with a negative culture, with or without negative microscopy, should be considered the definition of onychomycosis cure.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Administration, Topical
  • Antifungal Agents / administration & dosage*
  • Female
  • Humans
  • Male
  • Multicenter Studies as Topic
  • Onychomycosis / drug therapy*
  • Randomized Controlled Trials as Topic
  • Treatment Outcome

Substances

  • Antifungal Agents