Funding sources No external funding.
A second look at efficacy criteria for onychomycosis: clinical and mycological cure†
Article first published online: 13 JAN 2014
© 2013 British Association of Dermatologists
British Journal of Dermatology
Volume 170, Issue 1, pages 182–187, January 2014
How to Cite
Ghannoum, M., Isham, N. and Catalano, V. (2014), A second look at efficacy criteria for onychomycosis: clinical and mycological cure. British Journal of Dermatology, 170: 182–187. doi: 10.1111/bjd.12594
Conflicts of interest M.G. receives grants and acts as an adviser for Novartis Pharmaceuticals Corp., Celtic Pharma Development Services, Polichem SA, NexMed USA, Inc. and Anacor Pharmaceuticals, Inc.
Plain language summary available online
- Issue published online: 13 JAN 2014
- Article first published online: 13 JAN 2014
- Accepted manuscript online: 19 AUG 2013 10:27AM EST
- Manuscript Accepted: 12 AUG 2013
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.
In this position paper, we discuss interpretation of mycological outcome and clinical trial length.
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.
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.
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.