RCT mejor tratamiento onicomicosis.

Toenail onychomycosis – it's no fungi to have
around: treatment analysis to the rescue!
DOI: 10.1111/bjd.18378
Linked Article: Gupta et al. Br J Dermatol 2020; 182:287–299.
Toenail onychomycosis is notoriously difficult to treat with
multiple potential outcomes/end points for patients in addi-
tion to concerns about possible adverse effects of systemic
therapy. Historically, guidelines produced by the National
Institute for Health and Care Excellence and the Cochrane Col-
laboration usually include direct evidence from randomized
controlled trials (RCTs) and conventional meta-analyses to
indirect evidence. Recently the World Health Organization has
begun using network meta-analyses (NMA)
1
to more usefully
inform relevant clinical guidelines, particularly where multiple
interventions and combinations are possible.
The NMA method enables the comparison of multiple inter-
ventions simultaneously by combining studies making different
comparisons into the same analysis to provide us with a clinically
useful therapeutic ranking. This NMA methodology lends itself
well to the analysis of monotherapy efficacy and safety for toe-
nail onychomycosis, and is elegantly presented by Gupta et al.
2
They analyse toenail onychomycosis treatments including all
RCTs of oral, topical, combination and device-based treatments
for toenail onychomycosis. Twenty-six RCTs were included in
this NMA, representing 8136 patients. There were no significant
inconsistencies between the direct and indirect evidence.
So, what is the most effective treatment for toenail ony-
chomycosis? Well, it is no real surprise that this current analy-
sis shows that continuous oral therapy for 3–4 months with
terbinafine 250 mg once daily (OD) is the most effective with
continuous itraconazole 200 mg OD coming a close second.
Interestingly fluconazole, pulsed therapy with terbinafine 500
mg OD/itraconazole 400 mg OD and 9 months of topical
treatment did not differ significantly in the odds of achieving
a mycological cure. Additionally, the odds were of equal
efficacy for the topical treatments analysed (efinaconazole,
tavaborole and ciclopirox).
When considering what treatment to recommend an indi-
vidual patient we need also to take into consideration drug
interactions, hepatotoxicity and cardiac events (with itracona-
zole). In my experience many patients choose topical therapy
as they prefer the decreased potential efficacy over the possi-
bility of adverse events with systemics. From the analysis,
adverse events with continuous terbinafine 250 mg were twice
as likely than with pulsed itraconazole 400 mg. The odds
ratios of having adverse events with any other oral or topical
treatments were equal.
To put that into perspective, oral therapy with terbinafine is
associated with elevations in serum aminotransferases in less
than 1% of patients and the elevations are generally asymp-
tomatic and resolve without stopping therapy.
The estimated probability of developing elevated serum aminotransferase
levels requiring stopping treatment is about 031% for 2–6
weeks of treatment and 044% for treatment longer than 8
weeks.
Clinically apparent liver injury from terbinafine occurs
rarely (1 in 50 000–120 000 prescriptions).
So, it is gener-ally felt that there is an over-reporting bias giving us the false
impression that terbinafine is markedly hepatotoxic when the
evidence suggests adverse liver events are actually quite rare.
R. Morris-Jones iD
Department of Dermatology, Guys and St Thomas' NHS Foundation Trust,
London, U.K.
E-mail: Rachael.morris-jones1@gstt.nhs.uk