Nail Fungus Clinical Trials: Efinaconazole
In our new ivory tower series, we review a dermatology article and summarize their findings. This month, we cover a clinical trial of Efinaconazole (Trade name: Jublia), a topical medication for nail fungus. This study1 was published on SkinTherapyLetter in December 2016, a peer reviewed publication indexed by the US National Library of Medicine.
Background: Why you should care
Nail fungus (technically called onychomycosis) is a very common infection of the nail that affects up to 10% of the population and accounts for up to 50% of all nail problems2. The problem becomes more common with age, and up to as much as 50% of people over the age of 70 may have nail fungus. Nail fungus damages and disfigures the nail, thickening the nail bed and causing it to have a yellowish appearance. The appearance of the affected nail can be unsightly, but it can also affect functionality as well. Nail fungus can cause difficulty with shoes, and even walking, and can even be painful. Finally, in people with diabetes or have a weakened immune system, nail fungus can also lead to other medical concerns and complications.
- Nail fungus is a challenge to treat. Cure rates (removal of fungus and restoration of nail appearance) are low (35-50%) and relapse rates are relatively high3.
- Topical medication has a low success rate as the nail is extremely hard to penetrate. Nail debridement was required with previous topical treatments.
- Oral medication has been much more effective, and is considered the gold standard treatment. The drawback is that oral medication comes with higher risks of drug to drug interactions and other adverse side-effects. For some patients with weakened immune systems, oral therapy is not an option for this reason.
- This is also the reason that the Internet is loaded with unfounded claims of miracle cures for nail fungus--it’s the perfect storm for a miracle cure ad4 : Popular but irritating condition, variable cure rate, high recurrence, often confused with other conditions.
Previous Trial Results:
Previously, two identical phase III clinical trials with patients applying efinaconazole for 48 weeks + 4 washout weeks following the trial showed a 17.8% and 15.2% complete cure rate (defined as negative fungal culture and negative KOH) and a 55.2% and 53.4% mycological cure rate (defined as negative fungal culture and negative KOH PLUS zero clinical involvement). What this means is that more than half of the patients have successfully removed the fungus, but less than 1 in 5 people have been completely cured, or has no visible signs of the fungus. That is, it takes time for the nail’s appearance to return to normal after the fungus has been cleared. In the previous trial, women did better (27.1% vs 15.8% complete cure), but this may be due to relative weight difference5.
Sample: 1655 patients (112 with diabetes) (352 with athlete’s foot)
Conditions: Mild to moderate nail fungus of the toenail
Methodology: Double-blind, vehicle controlled (Neither patient nor clinician is aware of whether they are receiving actual treatment with Efinaconazole or simply a vehicle6)
The study looked at 1655 patients, subdivided into several groups: Patients with concurrent tinea pedis (athlete’s foot), patients with diabetes, and by how long patients have had nail fungus (less than one year, less than 5 years, and more than 5 years), and by severity (mild or less than 25% nail involvement - and - moderate or more than 25% nail involvement).
The results of this study largely mirror the results of previous studies on efinaconazole, adding further weight to already established evidence. In all groups of patients, efinaconazole outperformed vehicle only, by significant margins for complete cure, mycological cure, almost complete cure, and treatment success. See article for more details.
- Efinaconazole shows evidence of efficacy for all patient groups (mild or moderate severity, patients with athlete’s foot, patients with diabetes, for patients who have had nail fungus for less than 1 year, less than 5 years, and more than 5 years).
- Efficacy was significantly higher in patients who have had nail fungus for less than 1 year, suggesting that early diagnosis and treatment are critical. Find out accurate information about nail fungus online and see a dermatologist if you suspect a nail fungus infection.
- The efficacy of efinaconazole was comparable between diabetic and non-diabetic patients. Given that traditionally, treatment was considered challenging for patients with diabetes and that ignoring the problem was also medically risky, this is a positive and important finding.
- As expected, patients who had milder involvement and earlier treatment performed better than those who did not.
This is not a promotion or endorsement of a drug but a summary of the key findings in a study, written for non-experts. We encourage readers to research the original source if they are interested in reviewing the detailed data and methodologies. The general conclusion is that Efinaconazole is much more effective than existing topical treatments, and is an appropriate treatment for patients with mild to moderate nail fungus or patients who cannot tolerate systemic treatments, but the treatment requires patience and a complete cure is not guaranteed.
Important caveats to remember:
- The length of the treatment in this clinical trial was 48 weeks, or close to a year, where efinaconazole is applied once a day. This is by no means a quick fix. Patients need to have realistic expectations, and be prepared for long-term treatment.
- Treatment success, defined as less than 10% involvement of the infected toenail is 65.7% for patients with mild involvement, and 40.7% for moderate involvement. This is a significant, but patients should understand that treatment success or complete cure (which came in at 25.8% and 15.9% respectively for mild and moderate involvement) is far from guaranteed. Efinaconazole is not a miracle cure. These results are, however, pleasing.
- Efinaconazole has been approved by Health Canada and the FDA as a prescription drug under the name Jublia. This drug is not an over the counter medication, and must be prescribed by a doctor. There are many nail and foot conditions that may mimic symptoms of nail fungus such as nail psoriasis, and it’s important that a doctor properly diagnose the condition. There are several treatment options available, and your doctor will prescribe an appropriate treatment based on your specific medical needs.
Dr. Thomas on Efinaconazole:
1Gupta, AK, Studholme, C. Update on Efinaconazole 10% Topical Solution for the Treatment of Onychomycosis. Skin Therapy Letter. 2016 Dec 21-6 http://www.skintherapyletter.com/2016/21.6/2.html
This number will likely seem much higher than you observe, but toenails are very often hidden from view, and those with nail fungus are much more inclined to hide them or not frequent public spaces where their toes are exposed (swimming pools, yoga, etc.)
2It’s a very common problem but it’s not always immediately evident if you have nail fungus. http://nailfungus.ca/what-is-nail-fungus/#/how-to-identify
3This is an unfortunate reality, but it’s very important not to have unrealistic expectations. http://www.skintherapyletter.com/2016/21.6/2.html
4Some problems attract more miracle cures than others, namely, the ones that are chronic and hard to fix. There are very few “home remedies” for strep throat because antibiotics are so effective and efficient at treating them. http://dermletter.com/skin-care-experts/complementary-alternative-medicine.html
5Mean weight 73.3kg vs 90.2kg. http://www.skintherapyletter.com/2016/21.6/2.html This can affect absorption of the drug.
6Vehicle can be thought of as “placebo” with a subtle difference. Vehicle enhances delivery of drug or actives, which may be relevant for patients.