Volume 50, Issue 1 , Pages 151-152, January 2004
Fungus-free versus disease-free nails
Article Outline
To the Editor:
In the October 2000 journal supplement devoted to ciclopirox nail lacquer (J Am Acad Dermatol 2000;43:S55-102), guest editor Aditya Gupta and coauthors Drs Baran and Fleckman1 attempt to make the case that ciclopirox lacquer is an effective treatment for toenail onychomycosis. What is their evidence?
It depends on the end point that is chosen. In their article, “Ciclopirox nail lacquer topical solution 8% in the treatment of toenail onychomycosis,”1 the results provided in their summary refer to mycologic cure rates. However, patients desire a normal-appearing nail. The combination of a normal-appearing nail that is mycologically negative (negative potassium hydroxide examination plus negative fungal culture) has been termed a “disease-free nail” (DFN)2 to avoid such ambiguous terms as “clinical cure,” “total cure,” or “clinical response.”
In the body of their article can be found the figures as to how often 48 weeks of daily treatment with ciclopirox lacquer produces a DFN that they term “treatment cure.” They describe the results of 2 identical studies, one involving 110 and the other 118 patients treated with ciclopirox lacquer. Among these 228 patients, 16–that is, only 7%–achieved the DFN criteria of a normal-appearing nail and negative mycology. There is more bad news. Three months after completing the 48-week course of treatment, 12 of the patients achieving a DFN were re-examined. Of the 12, 5–that is, 40%–had their disease reappear. Consequently, 3 months after completing almost a year of daily treatment, only 4% of patients had achieved a DFN.
In the same article, the authors summarize 13 studies of ciclopirox lacquer in the treatment of onychomycosis. Although their table presents both mycologic and morphologic results (the morphologic results as clinical cure and clinical response), the mycologic and morphologic results were not combined and, therefore, it is impossible to determine how often a normal nail with negative mycology was achieved.
Dr Gupta's study, “Pharmacoeconomic analysis of ciclopirox nail lacquer solution 8% and the new oral antifungal agents used to treat dermatophyte toe onychomycosis in the United States,”3 contains some interesting numeric juggling. In comparing the treatment results achieved by ciclopirox lacquer versus the newer systemic antifungals, he does not compare how often these achieved a DFN but, rather, uses mycologic cure rates and clinical response rates obtained from meta-analyses of multiple studies. Because the rates of mycologic cure and clinical response with ciclopirox nail lacquer (52.6% and 52.4%) are similar to those achieved by terbinafine (77.2% and 75.3%), his cost calculations are on the basis of ciclopirox being about two thirds as effective as oral terbinafine. This is nonsense. Terbinafine produces a DFN in an approximate range of 40% to 60% of patients.2, 4, 5 Dr Gupta's own figures show, at best, a 7% DFN rate for ciclopirox lacquer. In terms of DFN rates, Dr Gupta's figures for the relative cost of treatment with ciclopirox versus terbinafine should be multiplied by a factor of at least 6!
In an apparent oversight in calculating the cost of ciclopirox treatment, Dr Gupta does not allow for the cost of the follow up visits recommended by the manufacturer: “removal of the unattached affected nail as frequently as monthly by a health care professional is needed with use of this medication.” In his Table 5, only 3 return visits are allowed for ciclopirox treatment. No mention is made of the cost of the patient's time lost for these monthly visits. Ciclopirox lacquer is expensive, wholesaling for about $60 for a vial containing 3.3 mL. Patients will undoubtedly be frugal in their applications, but Dr Gupta may be optimistic in assuming that 2.5 vials will suffice for 48 weeks of daily treatment. That works out to 0.027 mL, or half a drop per day.
Evidence-based medicine depends on realistic end points. A DFN is the only logical end point because patients desire a normal-appearing nail, and clinicians recognize that mycologic clearing is necessary to prevent prompt reappearance of disease. In terms of the DFN, ciclopirox is a failure. Are we, as clinicians, fulfilling our obligation to our patients if we recommend an expensive medication that requires daily application and monthly visits to health professionals for nearly a year, and then produces a DFN in only 7% of cases—with disease reappearing in 40% of those “cured” within 3 months? Have the authors fulfilled their obligation to present the clinically relevant data in a straightforward and readily comprehensible manner?
References
- . Ciclopirox nail lacquer topical solution 8% in the treatment of toenail onychomycosis. J Am Acad Dermatol. 2000;43:S70–80
- . How often does oral treatment of toenail onychomycosis produce a disease-free nail?. Arch Dermatol. 1998;134:1551–1554
- . Pharmacoeconomic analysis of ciclopirox nail lacquer solution 8% and the new oral antifungal agents used to treat dermatophyte toe onychomycosis in the United States. J Am Acad Dermatol. 2000;43:S81–95
- LION study (efficacy and tolerability of continuous terbinafine (Lamisil) compared to intermittent itraconazole in the treatment of toenail onychomycosis). Br J Dermatol. 1999;141:5–14
- A double-blind, randomized study to compare the efficacy and safety of terbinafine (Lamisil) with fluconazole (Diflucan) in the treatment of onychomycosis. Br J Dermatol. 2000;142:97–102
PII: S0190-9622(03)00339-6
doi:10.1016/S0190-9622(03)00339-6
© 2004 American Academy of Dermatology, Inc. Published by Elsevier Inc All rights reserved.
Volume 50, Issue 1 , Pages 151-152, January 2004
