Monotherapy for Toenail Onychomycosis

A Systematic Review and Network Meta-analysis

A.K. Gupta; K.A. Foley; R.R. Mays; N.H. Shear; V. Piguet


The British Journal of Dermatology. 2020;182(2):287-299. 

In This Article

Abstract and Introduction


Background: Onychomycosis is a fungal infection of the nail caused by dermatophytes, yeasts and nondermatophyte moulds that accounts for approximately 50% of all nail-related disease.

Objectives: This study aims to assess the effectiveness and safety of monotherapy and combination treatments for toenail onychomycosis using a network meta-analysis (NMA).

Methods: Quality of evidence was assessed using Cochrane-compliant rules and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Efficacy and safety outcomes were compared using a random-effects NMA to estimate pooled odds ratios (ORs) of direct and indirect comparisons among oral and topical treatments (PROSPERO 2015: CRD42018086912). There were not enough eligible combination and device-based therapy trials to include in the NMA.

Results: Of 77 randomized controlled trials, 26 were included in the ORs (8136 patients). There were no significant inconsistencies between the direct and indirect evidence. Relative effects show that the odds of mycological cure with continuous terbinafine 250 mg or continuous itraconazole 200 mg are significantly greater than topical treatments. Fluconazole, pulse regimens of terbinafine and itraconazole, and topical treatments did not differ significantly in the odds of achieving mycological cure. The ORs of adverse events occurring with oral or topical treatments were not significantly different from each other. For mycological cure, evidence was of moderate or high quality while evidence ranged from very low to high quality for adverse events.

Conclusions: Our review suggests that oral and topical treatments for toenail onychomycosis are safe and effective in producing mycological cure.


Onychomycosis, or tinea unguium, is a fungal infection of the nail[1] caused by dermatophytes, yeasts and nondermatophyte moulds that accounts for approximately 50% of all nail-related disease.[2–4] It is characterized by onycholysis, hyperkeratosis, and splitting, roughening and/or discoloration of the nail.[4,5] It has a prevalence of 4·3% in Europe and North America and it is more commonly found in toenails rather than fingernails.[6] Prevalence is higher in certain patient populations such as the elderly, diabetic and immunocompromised.[7] Other risk factors that increase susceptibility to onychomycosis include sex (male), genetics, occlusive footwear and nail trauma. Generally onychomycosis is seen as a simple cosmetic issue; however, patients are concerned with a decreased quality of life (QoL).[8,9]

Onychomycosis is a chronic infection that can be notoriously difficult to treat. The goal of treatment is to eradicate the infecting organism while returning the nail to a normal 'cosmetically clear' appearance. Topical treatments traditionally have lower success rates than oral treatments. Oral treatments have the advantage of shorter treatment durations, but also present challenges in cases of polypharmacy or immunosuppression. Recently, device-based therapies have been explored and emerging topical treatments are using advanced technology that may improve clinical outcomes. To effectively treat onychomycosis clinicians need reliable evidence of comparative benefits to make informed clinical decisions regarding the use of these treatments.

In order to visualize and interpret a broader picture of the evidence produced by these multiple interventions, a network meta-analysis (NMA; or multiple treatment comparison meta-analysis or mixed treatment meta-analysis) can be conducted.[10] NMA is a method that compares multiple interventions concurrently by combining studies making different comparisons into the same analysis.[11] An NMA gathers data from indirect evidence to gain confidence about all treatment comparisons and allows for estimation of comparative effects that have not been investigated head-to-head in randomized clinical trials.[12] For these reasons, the NMA is swiftly attaining popularity among clinicians, guideline developers and health technology agencies. It can be useful when new evidence on novel interventions continues to be published and needs to be appraised in the context of all available data.[13]

Our review builds on a previous NMA for oral and topical treatments for toenail onychomycosis.[14] In addition to the phase III trials that the previous analysis included, we include all randomized controlled trials (RCTs) of oral, topical, combination and device-based treatments; we also expand the number of clinical outcomes. Finally, the quality of the evidence is assessed to assist those requiring evidence-based recommendations for treatment.