INTRODUCTION
Despite a number of discussions on the topic, there remains no agreement on practical criteria defining resolution of onychomycosis.1,2 Many of the clinical data reported in the literature use a combination of mycologic cure (negative fungal culture and negative potassium hydroxide [KOH]), clinical cure (with 80%-100% clearing of the nail plate), or complete cure (a combination of mycologic and clinical cure, usually comprising a completely normal-appearing nail plate) as the primary and secondary end points for defining success of therapeutic intervention.
The definition of complete cure differs slightly between regulatory agencies; with the US Food and Drug Administration (FDA) requiring a completely clear nail and the EU authorities requiring only a 90% clearing of the nail plate.2 In addition, regulatory guidelines and clinical studies base complete cure on the progress of a single affected target toenail (the great toenail). However, in clinical practice it is common for a number of toenails to be affected, with patients and physicians evaluating the potentially different responses of all toenails. This point is illustrated by a recent study with terbinafine where significant, but expected due to nail length, differences were found in clinical improvement between the great toenail and all other
toenails, suggesting efficacy should be based on all involved onychomycotic toenails.3
Complete cure data from clinical trials may be misleading in that it is highly unlikely to see complete nail clearance in the majority of patients immediately after completion of therapy. Efficacy assessments are often based on final evaluations at 48 (end of therapy) to 52 (4-week follow-up) weeks, but a toenail may not grow fully for up to 78 weeks.4,5 For some patients this timeframe may be longer; toenail growth can be influenced by age, gender and comorbidities. The rate of linear nail growth decreases by 50% during a normal life span,5 while concomitant conditions and certain medications may also cause either an increase or decrease in nail growth.1,6 As a result, the demographics of patients achieving complete cure in clinical trials may not reflect that seen in clinical practice if either longer treatment courses or longer follow-up were possible. In addition, it is important for both clinician and patient to realize that cure may not result in a normal looking nail. While it is the patient’s expectation to get the nail back looking like it once did, it is the physician’s expectation of eradicating the mycological burden; as a result, endpoints could be different.
