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Conference summaries


Onychomycosis

Emerging treatments for onychomycosis

Presented by: Dr. Ditte Marie L. Saunte Department of Dermatology, Institute for Clinical Medicine, Zealand University Hospital, Roskilde, Denmark
  • Onychomycosis is commonly seen in clinical practice.
  • Topical antifungal treatment is often associated with treatment failure, and resistance to therapy remains a significant clinical issue.
  • Several interesting therapies are in the pipeline for onychomycosis.

Onychomycosis, or fungal infection of the nail unit, accounts for 50% of nail disorders seen in clinical practice. Population-based studies indicate that its prevalence varies depending on the geographic region, with around 4% in Europe and almost 19% in South America. [1] In most geographic areas, dermatophytes such as T. rubrum and T. interdigitale are responsible for the majority of cases of onychomycosis, although in some areas such as Africa and the Middle East yeasts like C. albicans and C. parapsilosis may be the causative agent. Non-D moulds such as Neoscytalidium, Aspergillus and Fusarium are responsible for only a minority of cases.

  • Treatment outcomes are related to a number of factors including the causative pathogen. [2]
  • Moreover, drug resistance, both primary (intrinsic) and secondary (acquired), after exposure to an antifungal agent is a problem of increasing concern.
  • Onychomycosis is a fungal infection of nails primarily caused by dermatophyte fungi, which are traditionally understood as existing in the environment as planktonic organisms; however, recent advancements in microbiology suggest that fungi can also form biofilms, which are complex sessile microbial communities irreversibly attached to epithelial surfaces by means of an extracellular matrix.
  • The extracellular matrix also acts as a protective barrier to the organisms within the biofilm.
  • With regards to treatment, a biofilm is surprisingly resistant to injury and may act as a persistent source of infection possibly accounting for antifungal resistance in onychomycosis.
  • The clinical factors associated with onychomycosis comprise percentage of nail involvement, lunula involvement, presence of yellow spikes, causative dermatophytoma and the presence of an air gap between the nail plate and nail bed.
  • A number of different therapies are used to treat onychomycosis.
  • While medical therapies with both topical and systemic antifungal agents are most commonly used, physical/chemical methods may also be of some benefit.
  • These include abrasion of the nail plate, etching the nail surface, mechanical debridement, microporation, use of keratolytic agents and penetration enhancers.
  • Device-based methods such as photodynamic therapy, lasers and iontophoresis are also utilised.
  • Cure may be considered as mycological or complete, and typically rates of the former are higher than the latter.
  • Thus, treatment failure typically occurs with antifungals in 20-25% of cases, with recurrence rates up to 50%.
  • Several clinical trials are underway with new oral drugs.
  • One such molecule is VT-1161, a tetrazole fungal CYP51 inhibitor that blocks the production of ergosterol.
  • VT-1161 has broad-spectrum activity against both dermatophytes and Candida species. [3]
  • In a phase IIb trial, complete cure was seen in 32-40% of cases, with mycological cure in 61-72% of cases, and low rates of adverse events.
  • Fosravuconazole L-lysine ethanol is a new triazole that is in phase III development.
  • This agent was associated with complete cure in almost 60% of patients with mycological cure in 82% after 48 weeks of treatment. [4]
  • With regards to formulations, several new chemical strategies are under investigation that incorporate chemical compounds into a topical formulation to enhance penetration of drugs through the nail.
  • So-called nano formulations, for example, should allow for deep nail penetration, greater stability of the active drug and extended drug delivery times.
  • One such formulation is MOB015B (topical formulation of terbinafine) that was investigated in an open, single centre phaseIIa pilot study in 25 patients. [5]
  • Highly encouraging results were seen, and phase III studies including approximately 750-800 patients are underway simultaneously in North America and Europe with results expected in 2020.
  • Laser treatment to provide selective photothermolysis of fungal chromophores is also being investigated.
  • A meta-analysis of controlled trials reported that mycological cure was seen in 70.4% of cases, but with complete cure in only 7.2%. [6]
  • Onychomycosis is associated with high rates of treatment failure.
  • The relative inefficacy of topical antifungal treatment is related to the difficulty in penetrating the nail.
  • Resistance to therapy remains a significant clinical issue.

Key messages/Clinical perspectives

  • Oral antifungal treatments are often associated with potential side effects and drug-drug interactions.
  • There is insufficient evidence for device-based treatment at present.


References

References


  1. Sigurgeirsson B, Baran R. The prevalence of onychomycosis in the global population: a literature study. J Eur Acad Dermatol Venereol. 2014 Nov;28(11):1480-91.
  2. Gupta AK, Mays RR, Versteeg SG, et al. Global perspectives for the management of onychomycosis. Int J Dermatol. 2019 Oct;58(10):1118-29.
  3. Elewski et al. Efficacy and Safety of VT-1161 in a Randomized, Double-Blinded, Placebo-Controlled Phase 2 Study of Four Oral Dosing Regimens in the Treatment of Patients with Moderate-to-Severe Distal-Lateral Subungual Onychomycosis (DLSO). 4th International Summit for Nail Diseases; 2017.
  4. Watanabe S, Tsubouchi I, Okubo A, et al. Efficacy and safety of fosravuconazole L-lysine ethanolate, a novel oral triazole antifungal agent, for the treatment of onychomycosis: A multicenter, double-blind, randomized phase III study. J Dermatol. 2018 Oct;45(10):1151-9.
  5. Faergemann J, et al. An open, single-center pilot study of efficacy and safety of topical MOBO15B in the treatment of distal subungual onychomycosis (DSO). AAD 2015, eP 963.
  6. Yeung K, Ortner VK, Martinussen T, et al. Efficacy of laser treatment for onychomycotic nails: a systematic review and meta-analysis of prospective clinical trials. Lasers Med Sci. 2019 Oct;34(8):1513-25.

Presenter disclosure information: DML Saunte: Abbvie, Astellas, Bayer, Destitin, Galderma, Jannsen, LeoPharma, Novartis, Pfizer, Sanofi, Schering-Plough.

Medical writer: Patrick Moore, PhD

Reviewer: Martina Lambertini, MD

Local reviewers: Martina Lambertini, MD (Italian); Alain Brassard, MD (French); Jorge Moreno González, MD (Spanish); Swen Malte John, MD, PhD (German); Marcelo Arnone, MD (Portuguese)

Scientific Editor: Prof. Brigitte Dréno, MD


CLINICAL TRIALS

PSORIASIS

Efficacy and safety of ixekizumab in a phase 3, randomized, double-blind, placebo-controlled study in paediatric patients with moderate-to-severe plaque psoriasis

Presented by: Prof. Kim A. Papp, Department of Medicine, Division of Dermatology, University of Toronto, Toronto, Canada

ATOPIC DERMATITIS

Efficacy and safety of baricitinib in combination with topical corticosteroids in moderate to severe atopic dermatitis: results of a phase 3 randomized, double-blind, placebo-controlled 16-week trial (BREEZE-AD7)

Presented by: Prof. Kristian Reich, Translational Research in Inflammatory Skin Diseases, Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf, and Skinflammation® Center, Hamburg, Germany

PRURIGO NODULARIS

Phase 2b study of nemolizumab in patients with moderate to severe prurigo nodularis and associated severe pruritus

Presented by: Prof. Sonja Ständer, Department of Dermatology and Center for Chronic Pruritus (KCP), University Hospital Münster, Germany

VITILIGO

Efficacy and safety of a 52-week, randomized, double-blind trial of ruxolitinib cream for the treatment of vitiligo

Presented by: Dr. Amit G. Pandya, University of Texas Southwestern Medical Center, Dallas, TX, USA
 

EMERGING TERAPIES

PSORIASIS

Emerging therapies for psoriasis

Presented by: Prof. Michel Gilliet, Department of Dermatology, Lausanne CHUV, Switzerland

ATOPIC DERMATITIS

New and emerging therapies in atopic dermatitis

Presented by: Prof. Dagmar Simon, Department of Dermatology, Inselspital, Bern University Hospital, Bern, Switzerland

ONYCHOMYCOSIS

Emerging treatments for onychomycosis

Presented by: Dr. Ditte Marie L. Saunte, Department of Dermatology, Institute for Clinical Medicine, Zealand University Hospital, Roskilde, Denmark
 

REVIEW & UPDATES

ACNE & ROSACEA

Isotretinoin for acne and rosacea

Presented by: Dr. Pedro Mendes-Bastos, Dermatology Centre, Hospital CUF Descobertas, Lisbon, Portugal

ALOPECIA AREATA

New drugs for alopecia areata

Presented by: Prof. Spyridon Gkalpakiotis, Department of Dermatovenereology, Third Faculty of Medicine and University Hospital of Kralovske Vinohrady, Prague, Czech Republic.

DERMATOSURGERY

Update in dermatosurgery

Presented by: Prof. Eduardo Nagore, Department of Dermatology, Instituto Valenciano de Oncología, Valencia, Spain

EPIDERMOLYSIS BULLOSA

New start of gene therapy in epidermolysis bullosa

Presented by: Prof. Leena K. Bruckner-Tuderman, University Medical Center, Albert-Ludwigs-University of Freiburg, Germany

MELANOMA

Treatment resistance in metastatic melanoma

Presented by: Prof. Martin Röcken, Department of Dermatology, Eberhard-Karls-University Tübingen, Germany

SCAR TREATMENT

Future of medical scar treatment

Presented by: Prof. Gabriella Fabbrocini, Department of Dermatology, University of Naples Federico II, Naples, Italy
 

EDUCATION FORUM

NON-MELANOMA SKIN CANCER

Systemic treatments of non-melanoma skin cancer

Presented by: Prof. Henrik F. Lorentzen, Department of Dermatology, Aarhus University Hospital, Denmark
 

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