Oral antifungal medication for toenail onychomycosis

Sanne Kreijkamp‐Kaspers; Kate Hawke; Linda Guo; George Kerin; Sally EM Bell‐Syer; Parker Magin; Sophie V Bell‐Syer; Mieke L van Driel

doi:10.1002/14651858.CD010031.pub2

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Figure 1

Study flow diagram.

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Figure 2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

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Figure 3

Funnel plot of comparison: 3 Azole versus terbinafine, outcome: 3.1 Clinical cure.

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Figure 4

Funnel plot of comparison: 3 Azole versus terbinafine, outcome: 3.2 Mycological cure.

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Analysis 1.1

Comparison 1 Azole versus terbinafine, Outcome 1 Clinical cure.

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Analysis 1.2

Comparison 1 Azole versus terbinafine, Outcome 2 Mycological cure.

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Analysis 1.3

Comparison 1 Azole versus terbinafine, Outcome 3 Adverse events.

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Analysis 1.4

Comparison 1 Azole versus terbinafine, Outcome 4 Recurrence rate.

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Analysis 2.1

Comparison 2 Terbinafine versus placebo, Outcome 1 Clinical cure.

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Analysis 2.2

Comparison 2 Terbinafine versus placebo, Outcome 2 Mycological cure.

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Analysis 2.3

Comparison 2 Terbinafine versus placebo, Outcome 3 Adverse events.

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Analysis 2.4

Comparison 2 Terbinafine versus placebo, Outcome 4 Recurrence rate.

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Analysis 3.1

Comparison 3 Azole versus placebo, Outcome 1 Clinical cure.

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Analysis 3.2

Comparison 3 Azole versus placebo, Outcome 2 Mycological cure.

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Analysis 3.3

Comparison 3 Azole versus placebo, Outcome 3 Adverse events.

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Analysis 3.4

Comparison 3 Azole versus placebo, Outcome 4 Recurrence rate.

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Analysis 4.1

Comparison 4 Griseofulvin versus azole, Outcome 1 Clinical cure.

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Analysis 4.2

Comparison 4 Griseofulvin versus azole, Outcome 2 Mycological cure.

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Analysis 4.3

Comparison 4 Griseofulvin versus azole, Outcome 3 Adverse events.

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Analysis 4.4

Comparison 4 Griseofulvin versus azole, Outcome 4 Recurrence rate.

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Analysis 5.1

Comparison 5 Griseofulvin versus terbinafine, Outcome 1 Clinical cure.

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Analysis 5.2

Comparison 5 Griseofulvin versus terbinafine, Outcome 2 Mycological cure.

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Analysis 5.3

Comparison 5 Griseofulvin versus terbinafine, Outcome 3 Adverse events.

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Analysis 6.1

Comparison 6 Combination terbinafine plus azole versus terbinafine monotherapy, Outcome 1 Clinical cure.

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Analysis 6.2

Comparison 6 Combination terbinafine plus azole versus terbinafine monotherapy, Outcome 2 Mycological cure.

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Analysis 6.3

Comparison 6 Combination terbinafine plus azole versus terbinafine monotherapy, Outcome 3 Adverse events.

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Summary of findings for the main comparison. Azole compared to terbinafine for toenail onychomycosis

Azole compared to terbinafine for toenail onychomycosis
Patient or population: participants with confirmed toenail onychomycosis Setting: outpatients clinics Intervention: azole Comparison: terbinafine
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Quality of the evidence (GRADE)
	Risk with terbinafine	Risk with azole
Clinical cure	Study population		RR 0.82 (0.72 to 0.95)	2168 (15 RCTs)	⊕⊕⊕⊝ Moderate^a
	575 per 1000	471 per 1000 (414 to 546)
Mycological cure	Study population		RR 0.77 (0.68 to 0.88)	2544 (17 RCTs)	⊕⊕⊕⊝ Moderate^a
	682 per 1000	525 per 1000 (464 to 600)
Adverse events	Study population		RR 1.00 (0.86 to 1.17)	1762 (9 RCTs)	⊕⊕⊕⊝ Moderate^b
	346 per 1000	346 per 1000 (298 to 405)
Recurrence rate	Study population		RR 1.11 (0.68 to 1.79)	282 (5 RCTs)	⊕⊕⊝⊝ Low^c
	333 per 1000	370 per 1000 (227 to 597)
Quality of life	None of the studies addressed quality of life.
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio.
GRADE Working Group grades of evidence High quality: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low quality: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low quality: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.
^aDowngraded by one level for risk of bias because of large number of unblinded studies, lack of description of randomisation process and allocation concealment for most studies. ^bDowngraded by one level for risk of bias (large number of unblinded studies, lack of description of randomisation process and allocation concealment for most studies). ^cDowngraded by two levels for risk of bias (large number of unblinded studies, lack of description of randomisation process and allocation concealment for most studies) and imprecision (small numbers of participants in this comparison).

Summary of findings for the main comparison. Azole compared to terbinafine for toenail onychomycosis

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Summary of findings 2. Terbinafine compared to placebo for toenail onychomycosis

Terbinafine compared to placebo for toenail onychomycosis
Patient or population: patients with confirmed toenail onychomycosis Setting: outpatient clinics Intervention: terbinafine Comparison: placebo
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Quality of the evidence (GRADE)
	Risk with placebo	Risk with terbinafine
Clinical cure	Study population		RR 6.00 (3.96 to 9.08)	1006 (8 RCTs)	⊕⊕⊕⊕ High^a
	62 per 1000	370 per 1000 (244 to 560)
Mycological cure	Study population		RR 4.53 (2.47 to 8.33)	1006 (8 RCTs)	⊕⊕⊕⊕ High^a
	167 per 1000	755 per 1000 (412 to 1000)
Adverse events	Study population		RR 1.13 (0.87 to 1.47)	399 (4 RCTs)	⊕⊕⊕⊝ Moderate^b
	429 per 1000	484 per 1000 (373 to 630)
Recurrence rate	667 per 1000	33 per 1000 (7 to 253)	RR 0.05 (0.01 to 0.38)	35 (1 RCT)	⊕⊕⊝⊝ Low^c
Quality of life	Not addressed by any of the trials
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio.
GRADE Working Group grades of evidence High quality: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low quality: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low quality: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.
^aLarge number of unblinded studies and studies with poor description of blinding and randomisation but large effect estimate; therefore, this outcome was not downgraded for risk of bias as the quality of evidence was considered to be high because of the large effect observed. ^bDowngraded by one level due to risk of bias (randomisation and blinding was poorly described in most studies). ^cDowngraded by two levels due to poor description of randomisation and blinding as well as due to selective follow‐up and only single study with small number of participants.

Summary of findings 2. Terbinafine compared to placebo for toenail onychomycosis

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Summary of findings 3. Azole compared to placebo for toenail onychomycosis

Azole compared to placebo for toenail onychomycosis
Patient or population: participants with confirmed toenail onychomycosis Setting: outpatient clinics Intervention: azole Comparison: placebo
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Quality of the evidence (GRADE)
	Risk with placebo	Risk with azole
Clinical cure	Study population		RR 22.18 (12.63 to 38.95)	3440 (9 studies)	⊕⊕⊕⊕ High^a
	14 per 1000	309 per 1000 (176 to 543)
Mycological cure	Study population		RR 5.86 (3.23 to 10.62)	3440 (9 RCTs)	⊕⊕⊕⊕ High^a
	74 per 1000	431 per 1000 (237 to 781)
Adverse events	Study population		RR 1.04 (0.97 to 1.12)	3441 (9 RCTs)	⊕⊕⊕⊝ Moderate^b
	537 per 1000	559 per 1000 (521 to 602)
Recurrence rate	Study population		RR 0.55 (0.29 to 1.07)	26 (1 RCT)	⊕⊕⊝⊝ Low^c
	1000 per 1000	550 per 1000 (290 to 1000)
Quality of life	None of the studies addressed quality of life.
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio.
GRADE Working Group grades of evidence High quality: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low quality: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low quality: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.
^aLarge number of unblinded studies and studies with poor description of blinding and randomisation, but large effect estimate; therefore, this outcome was not downgraded for risk of bias as the quality of evidence was considered to be high because of the large effect observed. ^bDowngraded by one level because of risk of bias (high number of unblinded studies and studies with poor description of blinding and randomisation). ^cDowngraded by two levels due to poor description of randomisation and blinding as well as selective follow‐up and only single study with small number of participants.

Summary of findings 3. Azole compared to placebo for toenail onychomycosis

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Summary of findings 4. Griseofulvin compared to azole for toenail onychomycosis

Griseofulvin compared to azole for toenail onychomycosis
Patient or population: participants with confirmed toenail onychomycosis Setting: outpatient clinics Intervention: griseofulvin Comparison: azole
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Quality of the evidence (GRADE)
	Risk with azole	Risk with griseofulvin
Clinical cure	Study population		RR 0.94 (0.45 to 1.96)	222 (5 RCTs)	⊕⊕⊕⊝ Moderate^a
	144 per 1000	136 per 1000 (65 to 283)
Mycological cure	Study population		RR 0.87 (0.50 to 1.51)	222 (5 RCTs)	⊕⊕⊕⊝ Moderate^a
	186 per 1000	161 per 1000 (93 to 280)
Adverse events	Study population		RR 2.41 (1.56 to 3.73)	143 (2 RCTs)	⊕⊕⊕⊝ Moderate^b
	276 per 1000	665 per 1000 (430 to 1000)
Recurrence rate	Study population		RR 4.00 (0.26 to 61.76)	7 (1 RCT)	⊕⊝⊝⊝ Very low^c
	0 per 1000	0 per 1000 (0 to 0)
Quality of life	None of the studies addressed quality of life.
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio.
GRADE Working Group grades of evidence High quality: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low quality: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low quality: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.
^aDowngraded by one level due to risk of bias (about half of the studies were not blinded). ^bDowngraded by one level due to risk of bias (two unblinded studies; neither participants nor outcome assessors were blinded). ^cDowngraded by three levels due to risk of bias (single study; neither participants nor outcome assessors were blinded) and imprecision (two levels due to single study, low number of participants and wide confidence intervals).

Summary of findings 4. Griseofulvin compared to azole for toenail onychomycosis

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Summary of findings 5. Griseofulvin compared to terbinafine for toenail onychomycosis

Griseofulvin compared to terbinafine for toenail onychomycosis
Patient or population: participants with confirmed toenail onychomycosis Setting: outpatient clinics Intervention: griseofulvin Comparison: terbinafine
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Quality of the evidence (GRADE)
	Risk with terbinafine	Risk with Griseofulvin
Clinical cure	Study population		RR 0.32 (0.14 to 0.72)	270 (4 RCTs)	⊕⊕⊝⊝ Low^a
	561 per 1000	179 per 1000 (78 to 404)
Mycological cure	Study population		RR 0.64 (0.46 to 0.90)	465 (5 RCTs)	⊕⊕⊝⊝ Low^a
	716 per 1000	458 per 1000 (329 to 645)
Adverse events	Study population		RR 2.09 (1.15 to 3.82)	100 (2 RCTs)	⊕⊕⊝⊝ Low^b
	160 per 1000	334 per 1000 (184 to 611)
Recurrence rate	No studies addressed recurrence rate.
Quality of life	No studies addressed quality of life.
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio.
GRADE Working Group grades of evidence High quality: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low quality: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low quality: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.
^aDowngraded by two levels due to risk of bias (two studies not blinded; other studies at unclear risk for blinding of participant and outcome assessor). ^bDowngraded by two levels due to risk of bias (two levels: one unblinded study; one study at unclear risk of bias for blinding or participants and outcome assessor).

Summary of findings 5. Griseofulvin compared to terbinafine for toenail onychomycosis

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Summary of findings 6. Combination terbinafine plus azole compared to terbinafine monotherapy for toenail onychomycosis

Combination terbinafine plus azole compared to terbinafine monotherapy for toenail onychomycosis
Patient or population: participants with confirmed toenail onychomycosis Setting: outpatient clinics Intervention: combination terbinafine plus azole Comparison: terbinafine monotherapy
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Quality of the evidence (GRADE)
	Risk with terbinafine monotherapy	Risk with combination terbinafine plus azole
Clinical cure	Study population		RR 1.41 (1.01 to 1.97)	176 (1 RCT)	⊕⊝⊝⊝ Very low^a
	368 per 1000	519 per 1000 (732 to 726)
Mycological cure	Study population		RR 1.41 (1.08 to 1.83)	176 (1 RCT)	⊕⊝⊝⊝ Very low^a
	474 per 1000	668 per 1000 (512 to 867)
Adverse events	Study population		RR 0.64 (0.34 to 1.21)	176 (1 RCT)	⊕⊕⊝⊝ Low^b
	232 per 1000	148 per 1000 (79 to 280)
Recurrence rate	No studies addressed recurrence rate.
Quality of life	No studies addressed quality of life.
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio.
GRADE Working Group grades of evidence High quality: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low quality: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low quality: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.
^aDowngraded by three levels due to risk of bias (two levels: single non‐blinded study) and imprecision (single study). ^bDowngraded by two levels due to risk of bias (single non‐blinded study) and imprecision (single study)

Summary of findings 6. Combination terbinafine plus azole compared to terbinafine monotherapy for toenail onychomycosis

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Comparison 1. Azole versus terbinafine

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinical cure Show forest plot	15	2168	Risk Ratio (M‐H, Random, 95% CI)	0.82 [0.72, 0.95]

1.1 Short‐term follow‐up (≤ 52 weeks)	6	911	Risk Ratio (M‐H, Random, 95% CI)	0.86 [0.77, 0.96]
1.2 Long‐term follow‐up (> 52 weeks)	9	1257	Risk Ratio (M‐H, Random, 95% CI)	0.80 [0.63, 1.00]
2 Mycological cure Show forest plot	17	2544	Risk Ratio (M‐H, Random, 95% CI)	0.77 [0.68, 0.88]

2.1 Short‐term follow‐up (≤ 52 weeks)	8	1287	Risk Ratio (M‐H, Random, 95% CI)	0.77 [0.64, 0.93]
2.2 Long‐term follow‐up (> 52 weeks)	9	1257	Risk Ratio (M‐H, Random, 95% CI)	0.78 [0.64, 0.95]
3 Adverse events Show forest plot	9	1762	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.86, 1.17]

4 Recurrence rate Show forest plot	5	282	Risk Ratio (M‐H, Random, 95% CI)	1.11 [0.68, 1.79]

Comparison 1. Azole versus terbinafine

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Comparison 2. Terbinafine versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinical cure Show forest plot	8	1006	Risk Ratio (M‐H, Random, 95% CI)	6.00 [3.96, 9.08]

1.1 Short‐term follow‐up (≤ 52 weeks)	6	800	Risk Ratio (M‐H, Random, 95% CI)	5.60 [3.66, 8.55]
1.2 Long‐term follow‐up (> 52 weeks)	2	206	Risk Ratio (M‐H, Random, 95% CI)	26.01 [3.69, 183.44]
2 Mycological cure Show forest plot	8	1006	Risk Ratio (M‐H, Random, 95% CI)	4.53 [2.47, 8.33]

2.1 Short‐term follow‐up (≤ 52 weeks)	6	800	Risk Ratio (M‐H, Random, 95% CI)	4.60 [2.26, 9.36]
2.2 Long‐term follow‐up (> 52 weeks)	2	206	Risk Ratio (M‐H, Random, 95% CI)	7.79 [0.42, 144.44]
3 Adverse events Show forest plot	4	399	Risk Ratio (M‐H, Random, 95% CI)	1.13 [0.87, 1.47]

4 Recurrence rate Show forest plot	1	35	Risk Ratio (M‐H, Random, 95% CI)	0.05 [0.01, 0.38]

Comparison 2. Terbinafine versus placebo

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Comparison 3. Azole versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinical cure Show forest plot	9	3440	Risk Ratio (M‐H, Random, 95% CI)	22.18 [12.63, 38.95]

1.1 Short‐term follow‐up (≤ 52 weeks)	7	2695	Risk Ratio (M‐H, Random, 95% CI)	23.89 [11.99, 47.64]
1.2 Long‐term follow‐up (> 52 weeks)	2	745	Risk Ratio (M‐H, Random, 95% CI)	19.11 [7.21, 50.65]
2 Mycological cure Show forest plot	9	3440	Risk Ratio (M‐H, Random, 95% CI)	5.86 [3.23, 10.62]

2.1 Short‐term follow‐up (≤ 52 weeks)	7	2695	Risk Ratio (M‐H, Random, 95% CI)	7.05 [2.91, 17.07]
2.2 Long‐term follow‐up (> 52 weeks)	2	745	Risk Ratio (M‐H, Random, 95% CI)	4.22 [2.34, 7.59]
3 Adverse events Show forest plot	9	3441	Risk Ratio (M‐H, Random, 95% CI)	1.04 [0.97, 1.12]

4 Recurrence rate Show forest plot	1	26	Risk Ratio (M‐H, Random, 95% CI)	0.55 [0.29, 1.07]

Comparison 3. Azole versus placebo

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Comparison 4. Griseofulvin versus azole

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinical cure Show forest plot	5	222	Risk Ratio (M‐H, Random, 95% CI)	0.94 [0.45, 1.96]

1.1 Short‐term follow‐up (≤ 52 weeks)	2	60	Risk Ratio (M‐H, Random, 95% CI)	0.89 [0.32, 2.45]
1.2 Long‐term follow‐up (> 52 weeks)	3	162	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.34, 2.93]
2 Mycological cure Show forest plot	5	222	Risk Ratio (M‐H, Random, 95% CI)	0.87 [0.50, 1.51]

2.1 Short‐term follow‐up (≤ 52 weeks)	2	60	Risk Ratio (M‐H, Random, 95% CI)	0.96 [0.52, 1.76]
2.2 Long‐term follow‐up (> 52 weeks)	3	162	Risk Ratio (M‐H, Random, 95% CI)	0.58 [0.16, 2.10]
3 Adverse events Show forest plot	2	143	Risk Ratio (M‐H, Random, 95% CI)	2.41 [1.56, 3.73]

4 Recurrence rate Show forest plot	1	7	Risk Ratio (M‐H, Random, 95% CI)	4.0 [0.26, 61.76]

Comparison 4. Griseofulvin versus azole

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Comparison 5. Griseofulvin versus terbinafine

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinical cure Show forest plot	4	270	Risk Ratio (M‐H, Random, 95% CI)	0.32 [0.14, 0.72]

1.1 Short‐term follow‐up (≤ 52 weeks)	1	89	Risk Ratio (M‐H, Random, 95% CI)	0.05 [0.01, 0.39]
1.2 Long‐term follow‐up (> 52 weeks)	3	181	Risk Ratio (M‐H, Random, 95% CI)	0.51 [0.36, 0.71]
2 Mycological cure Show forest plot	5	465	Risk Ratio (M‐H, Random, 95% CI)	0.64 [0.46, 0.90]

2.1 Short‐term follow‐up (≤ 52 weeks)	2	284	Risk Ratio (M‐H, Random, 95% CI)	0.70 [0.40, 1.20]
2.2 Long‐term follow‐up (> 52 weeks)	3	181	Risk Ratio (M‐H, Random, 95% CI)	0.48 [0.21, 1.09]
3 Adverse events Show forest plot	2	100	Risk Ratio (M‐H, Random, 95% CI)	2.09 [1.15, 3.82]

Comparison 5. Griseofulvin versus terbinafine

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Comparison 6. Combination terbinafine plus azole versus terbinafine monotherapy

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinical cure Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

1.1 Short‐term follow‐up (≤ 52 weeks)	1		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
1.2 Long‐term follow‐up (> 52 weeks)	0		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2 Mycological cure Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

2.1 Short‐term follow‐up (≤ 52 weeks)	0		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2.2 Long‐term follow‐up (> 52 weeks)	1		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
3 Adverse events Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

Comparison 6. Combination terbinafine plus azole versus terbinafine monotherapy

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