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Topical and oral treatments for foot fungal infections

Systematic reviews
Results for topical azoles
Results for topical allylamines
Results for topical undecanoates
Results for oral treatments [2]
Comment and costs

Fungal infections of the foot are remarkably common, affecting about 15% of people in the UK. Topical fungicides, some available without prescription from chemists, are the first treatment option. When they fail, oral fungicides can be tried. Two systematic reviews tell us how effective these are.

Systematic reviews

Both systematic reviews [1,2] had a wide search strategy for randomised trials. As well as at least 10 electronic databases, several journals were hand searched and companies and schools of podiatry in the UK were asked for unpublished trials. For skin infections, only trials that used microscopy and culture were included. The outcome was cure rate at follow up from the reported mycological results, with negative results on microscopy and no growth on culture.

Results for topical azoles

Twelve trials with more than 10 patients in both treatment groups compared azoles with placebo (Figure 1). Usually treatment was for four to six weeks, and follow up for four to 10 weeks.

Figure 1: Topical azoles versus placebo


With azole, 407/480 (85%) patients were cured compared with 173/438 (39%) with placebo. The relative benefit was 2.1 (95% confidence interval 1.9 to 2.4). The number needed to treat to affect one cure compared with placebo was 2.2 (2.0 to 2.5).

Six trials had more than 50 patients, with 74% of the patients. The proportions cured with azole and placebo were 83% and 37% respectively. The NNT was 2.2 (1.9 to 2.6).

Results for topical allylamines

Ten trials with more than 10 patients in both treatment groups compared allylamines with placebo (Figure 2). Usually treatment was for one to four weeks, and follow up for six to eight weeks.

Figure 2: Topical allylamines versus placebo



With allylamine, 519/706 (74%) patients were cured compared with 139/687 (20%) with placebo. The relative benefit was 3.6 (95% confidence interval 3.1 to 4.2). The number needed to treat to affect one cure compared with placebo was 1.9 (1.7 to 2.1).

Nine trials had more than 50 patients, with 97% of the patients. For these the proportions cured with allylamine and placebo were 73% and 20% respectively. The NNT was 2.2 1.9 (1.7 to 2.0).

Results for topical undecanoates

Four trials with more than 10 patients in both treatment groupscompared undecanoates with placebo. Usually treatment was for four to six weeks, and follow up for six to eight weeks.

With undecanoates, 83/123 (67%) patients were cured compared with 21/81 (26%) with placebo. The relative benefit was 2.7 (95% confidence interval 1.8 to 3.9). The number needed to treat to affect one cure compared with placebo was 2.4 (1.9 to 3.5). All trials had more than 50 patients.

For azoles, allylamines, and undecanoates there was much more variability for the cure rate with placebo in small trials (Figure 3). Including the smallest trials, with only six patients per treatment group, the cure rate varied between 0% and 100%. Overall the rate with topical placebo was 28%.

Figure 3: Response with topical placebo



Results for oral treatments [2]

There were 12 randomised trials, all described as double blind, which evaluated a number of treatments, few of which compared the same treatments. The results as percentage of patients cured for all 24 treatment arms are shown in Figure 4. Higher cure rates were seen for fluconazole and ketaconazole, ahead of terbinafine, itraconazole and griseofulvin.

Figure 4: Oral treatments for fungal foot infections (daily doses)



Two trials, with only 71 patients in total, evaluated terbinafine 250 mg versus griseofulvin 500 mg. Cure rates were 92% and 39% respectively, with a NNT of 1.9 (1.4 to 2.9) for terbinafine compared with griseofulvin.

Four trials, with 339 patients in total, evaluated terbinafine 250 mg versus itraconazole 100 mg. Cure rates were 80% and 65% respectively, with a NNT of 7 (4.2 to 20) for terbinafine compared with itraconazole.

Comment and costs

An immediate reflection on these trials is, that for a common complaint, how small was the total number of patients treated, and how small were many of the trials. Admittedly, for topical treatments there were other active-controlled trials, but trials with more than 20 patients per treatment group were the exception.

Both the reviews have a brief discussion about cost effectiveness, based on acquisition costs of medicines and effectiveness from trials. For a number of possible treatments any estimate of the size of the treatment effect is little more than a guess because the numbers are so small.

The best evidence was for topical azoles and allylamines, with 480 and 706 patients. For all others there was information on fewer than 200 patients, and for oral griseofulvin only 33 (Table 1). It is impossible to do useful cost effectiveness work when the limits on knowledge of effectiveness are so profound.

Some of these treatments cost more than others, and some work better than others. Maybe we should ask whether we should use treatments for which there is little information, especially when the evidence we have says they are less effective. Treatments that are more effective will probably cost less in the end, especially when it means patients do not have to come back so often.

In a health service where lack of capacity is the big issue, interventions that relieve the strain on capacity should have a premium to balance against acquisition costs. The second review begins to address this argument for the economic comparison of oral griseofulvin versus oral terbinafine. Even though griseofulvin has a lower aquisition cost, the implication from the trial results is that terbinafine is actually cheaper when a consultation costs more than £25. Given that in some areas of the UK general practitioners are thin on the ground, the traditional cost of a GP visit of about £16 may need revision.

References:

  1. R Hart et al. Systematic review of topical treatments for fungal infections of the skin and nails of the feet. BMJ 1999 319: 79-82.
  2. SEM Bell-Sayer et al. A systematic review of oral treatments for fungal infections of the skin of the feet. Journal of Dermatological Treatments 2001 12: 69-74.
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