Background Onychomycosis is a common nail infection, often resulting in nail plate damage and deformity. Topical lacquer treatments have negligible efficacy. Oral treatments, although more ...efficacious, are limited by drug interactions and potential hepatotoxicity. Objective We investigated the safety and efficacy of efinaconazole 10% solution (efinaconazole), the first triazole antifungal developed for distal lateral subungual onychomycosis. Methods Two identical, multicenter, randomized, double-blind, vehicle-controlled studies were conducted in patients with toenail distal lateral subungual onychomycosis (20%-50% clinical involvement study 1: N = 870, study 2: N = 785). Patients were randomized (3:1) to efinaconazole or vehicle, once daily for 48 weeks, with 4-week posttreatment follow-up. Debridement was not performed. The primary end point was complete cure rate (0% clinical involvement of target toenail, and both negative potassium hydroxide examination and fungal culture) at week 52. Results Mycologic cure rates were significantly greater with efinaconazole (study 1: 55.2%, study 2: 53.4%) compared with vehicle ( P < .001). The primary end point, complete cure, was also significantly greater for efinaconazole (study 1: 17.8% vs 3.3%, study 2: 15.2% vs 5.5%, P < .001). Treatment success (percent affected target toenail 0%-≤10%) for efinaconazole ranged from 21.3% to 44.8% in study 1 and from 17.9% to 40.2% in study 2, compared with 5.6% to 16.8% and 7.0% to 15.4%, respectively, with vehicle. Adverse events associated with efinaconazole were local site reactions (2%) and clinically similar to vehicle. Limitations A period of 52 weeks may be too brief to evaluate a clinical cure in onychomycosis. Conclusions Once daily topical efinaconazole appears to be a viable alternative to oral treatment options for onychomycosis.
Background Onychomycosis, a fungal nail infection, can impact quality of life. Objective We sought to evaluate the efficacy and safety of tavaborole topical solution, 5% for treatment of toenail ...onychomycosis. Methods In 2 phase-III trials, adults with distal subungual onychomycosis affecting 20% to 60% of a target great toenail were randomized 2:1 to tavaborole or vehicle once daily for 48 weeks. The primary end point was complete cure of the target great toenail (completely clear nail with negative mycology) at week 52. Secondary end points included completely or almost clear nail, negative mycology, completely or almost clear nail plus negative mycology, and safety. Results Rates of negative mycology (31.1%-35.9% vs 7.2%-12.2%) and complete cure (6.5% and 9.1% vs 0.5% and 1.5%) significantly favored tavaborole versus vehicle ( P ≤ .001). Completely or almost clear nail rates also significantly favored tavaborole versus vehicle (26.1%-27.5% vs 9.3%-14.6%; P < .001). Rates of completely or almost clear nail plus negative mycology (15.3%-17.9% vs 1.5%-3.9%) were significantly greater for tavaborole versus vehicle ( P < .001). Application-site reactions with tavaborole included exfoliation (2.7%), erythema (1.6%), and dermatitis (1.3%). Limitations Duration of follow-up is a limitation. Conclusion Tavaborole demonstrates a favorable benefit-risk profile in treatment of toenail onychomycosis.
We evaluated the efficacy of brodalumab in patients with nail or scalp psoriasis in three phase 3 studies (AMAGINE-1/-2/-3).
In AMAGINE-1, scalp clearance, measured by the psoriasis scalp severity ...index (PSSI), was reported for patients who received brodalumab 210 mg every 2 weeks (Q2W) or placebo through 12 weeks. In AMAGINE-2/-3, nail clearance, measured by the nail psoriasis severity index (NAPSI), was reported for patients receiving either brodalumab 210 mg Q2W or ustekinumab continuously through 52 weeks.
At week 12, significantly more patients receiving brodalumab achieved 75% and 100% improvement rates from baseline PSSI and had lower mean PSSI across 12 weeks compared with placebo, with significant improvement in PSSI evident with brodalumab 210 mg Q2W vs placebo by week 2. Across 52 weeks, patients receiving brodalumab achieved significantly greater complete clearance of nail psoriasis (NAPSI 0), lower mean NAPSI, and higher mean percent improvement rates from baseline NAPSI than patients receiving ustekinumab. At week 52, 63.8% of patients receiving brodalumab achieved NAPSI 0 vs 39.1% of patients receiving ustekinumab.
Brodalumab was associated with clearance of scalp psoriasis through 12 weeks and improvements in nail psoriasis, including complete nail clearance, through 52 weeks.
Approximately one-quarter of the global population have latent tuberculosis infection (LTBI), and tuberculosis (TB) is accountable for more than 1.5 million deaths annually. Methotrexate, ...cyclosporine, and tumor necrosis factor inhibitors may be associated with increased risk of TB and LTBI reactivation, although data are limited on the risks of TB with use of newer biologics.
To assess the association of secukinumab with reporting of active TB development, TB reactivation, and LTBI activation as an adverse event (AE) in patients with psoriasis, psoriatic arthritis, or ankylosing spondylitis.
This pooled cohort study pooled data from 28 clinical trials of secukinumab used in psoriasis (17 phase 3 or 3b and 2 phase 4 trials), psoriatic arthritis (5 phase 3 trials), and ankylosing spondylitis (4 phase 3 trials). A search of the Novartis Secukinumab Compound Pool Database was conducted for the 28 trials. All trial participants who had received at least 1 approved subcutaneous dose of secukinumab (150 mg or 300 mg) were included. Before randomization in these trials, patients underwent screening for TB. Patients with active TB were excluded, and patients with LTBI were treated according to local guidelines. Data were analyzed from the start of treatment in the individual studies through December 25, 2018.
Reporting of active TB or LTBI as an AE over a 5-year period using exposure-adjusted incidence rates (EAIR; incidence rates per 100 patient-years).
A total of 12 319 patients were included, of whom 8819 patients had psoriasis (71.6%; 5930 men 67.2%; mean SD age, of 44.9 13.5 years), 2523 had psoriatic arthritis (20.5%; 1323 women 52.4%; mean SD age, 48.8 12.1 years), and 977 had ankylosing spondylitis (7.3%; 658 men 67.3%; mean SD age, 42.3 11.9 years). In the total population, 684 patients (5.6%) had tested positive for LTBI at screening. Over 5 years, LTBI as an AE during secukinumab treatment was reported in 13 patients (0.1% of 12 319). Of these 13 patients, 6 had a prior positive LTBI test result, and 7 were newly diagnosed as having LTBI. Four of the 7 patients had psoriasis (EAIR, 0.03; 95% CI, 0.01-0.07), 1 had psoriatic arthritis (EAIR, 0.02; 95% CI, 0.00-0.11), and 2 had ankylosing spondylitis (EAIR, 0.08; 95% CI, 0.01-0.28). No cases of active TB were reported.
This study found that LTBI reported as an AE after secukinumab treatment was uncommon and appeared to support the use of secukinumab in chronic systemic inflammatory conditions.
Background In the phase III double-blind Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) 1 and 2, apremilast, an oral phosphodiesterase 4 inhibitor, demonstrated ...efficacy in moderate to severe psoriasis. Objective We sought to evaluate efficacy of apremilast in nail/scalp psoriasis in ESTEEM 1 and 2. Methods A total of 1255 patients were randomized (2:1) to apremilast 30 mg twice daily or placebo. At week 16, placebo patients switched to apremilast through week 32, followed by a randomized withdrawal phase to week 52. A priori efficacy analyses included patients with nail (target nail Nail Psoriasis Severity Index score ≥1) and moderate to very severe scalp (Scalp Physician Global Assessment score ≥3) psoriasis at baseline. Results At baseline, 66.1% and 64.7% of patients had nail psoriasis; 66.7% and 65.5% had moderate to very severe scalp psoriasis in ESTEEM 1 and 2. At week 16, apremilast produced greater improvements in Nail Psoriasis Severity Index score versus placebo; mean percent change: −22.5% versus +6.5% (ESTEEM 1; P < .0001) and −29.0% versus −7.1% (ESTEEM 2; P = .0052). At week 16, apremilast produced greater NAPSI-50 response (50% reduction from baseline in target nail Nail Psoriasis Severity Index score) versus placebo (both studies P < .0001) and ScPGA response (Scalp Physician Global Assessment score 0 or 1) versus placebo (both studies P < .0001). Improvements were generally maintained over 52 weeks in patients with Psoriasis Area and Severity Index response at week 32. Limitations Baseline randomization was not stratified for nail/scalp psoriasis. Conclusion Apremilast reduces the severity of nail/scalp psoriasis.
Previous clinical trials have not evaluated improvement in nail psoriasis as a primary end point.
This phase 3 trial evaluated the safety and efficacy of adalimumab in patients with ...moderate-to-severe fingernail psoriasis and moderate-to-severe plaque psoriasis.
Patients were randomized 1:1 to 40 mg adalimumab every other week or placebo. The primary efficacy end point was at least 75% improvement in total-fingernail modified Nail Psoriasis Severity Index (NAPSI75) response rate at week 26. Ranked secondary end point scores evaluated at week 26 were total-fingernail NAPSI and modified NAPSI, nail pain, Nail Psoriasis Physical Functioning Severity, Brigham Scalp Nail Inverse Palmo-Plantar Psoriasis Index, and Physician's Global Assessment (fingernail psoriasis).
Of the 217 randomized patients (108 received placebo and 109 received adalimumab), 188 (86.6%) completed 26 weeks of treatment (period A) or escaped early to the open-label period. The study met the primary end point (response rate of 3.4% with placebo vs 46.6% with adalimumab P < .001) and all ranked secondary end points. The serious adverse event rates (placebo vs adalimumab) in period A were 4.6% versus 7.3%; the serious infections rates were 1.9% versus 3.7%.
Patients with less than 5% BSA involvement were not eligible for enrollment.
After 26 weeks of adalimumab treatment, significant improvements were seen in the primary and all ranked secondary end points and in signs and symptoms of moderate-to-severe nail psoriasis versus with placebo and no new safety risks were identified.
The Nail Psoriasis Severity Index (NAPSI) is a numeric, reproducible, objective, simple tool for evaluation of nail psoriasis. This scale is used to evaluate the severity of nail bed psoriasis and ...nail matrix psoriasis by area of involvement in the nail unit. The NAPSI will be useful during clinical trials for evaluating response to treatment of psoriatic nails. The scale is reproducible, and because there are few data points, statistical analysis is simplified.
Nail psoriasis (NP) is common and of high importance in patients with psoriasis. Complete resolution of NP at week 24‒26 is an unambiguous nail outcome accessible for indirect treatment comparison of ...biologics.
To evaluate the comparative efficacy of approved biologics in achieving complete resolution of NP at week 24‒26.
A network meta-analysis (NMA) was conducted to indirectly compare the efficacy of six biologics in achieving complete resolution of NP at week 24‒26 in patients with moderate-to-severe psoriasis and concomitant NP. Complete resolution of NP was defined as a score of zero on the Nail Psoriasis Severity Index (NAPSI), modified NAPSI (mNAPSI) or Physician's Global Assessment of Fingernails (PGA-F).
The probability of achieving complete resolution of NP was highest for ixekizumab (46.5%; 95% credibility interval CrI 35.1‒58.0; Surface Under the Cumulative RAnking curve SUCRA 97%), followed by brodalumab (37.0%; 17.0‒61.0; 79%), adalimumab (28.3%; 24.4‒32.4; 62%), guselkumab (27.7%; 21.1‒35.1; 58%), ustekinumab (20.8%; 10.2‒35.2; 37%), and infliximab (0.8%; 0.0‒8.9; 17%).
In patients with moderate-to-severe psoriasis and concomitant NP, ixekizumab has the greatest likelihood among approved biologics of achieving complete resolution of NP at week 24‒26. Findings should be interpreted carefully because of inherent study limitations.
BACKGROUNDAvailable network meta-analyses (NMAs) comparing the efficacy of biologics in nail psoriasis (NP) have not included recently approved biologics such as bimekizumab nor have they provided ...comparisons up to 1 year. OBJECTIVEWe conducted two NMAs that update and extend results from a previous NMA comparing biologics for achieving complete resolution of NP. METHODSBayesian NMAs were performed using a generalized linear model with a logit link to model the binary outcome of nail clearance at weeks 24-28 and 48-52. RESULTSFor the NMA at weeks 24-28, which included seven biologics and placebo, the absolute probability of achieving complete resolution of NP was highest for ixekizumab (46.4%; 95% credibility interval CrI 35.2-58.0), followed by brodalumab (37.1%; 95% CrI 17.1-62.2) and bimekizumab (30.3%; 95% CrI 12.7-53.9). For the NMA at weeks 48-52, which included six biologics, the absolute probability was highest for ixekizumab (77.2%; 95% CrI 51.1-93.4), followed by adalimumab (75.6%; 95% CrI 61.5-87.3) and brodalumab (71.9%; 95% CrI 38.4-93.2). CONCLUSIONAmong biologics included in these two NMAs, ixekizumab has the highest absolute probability of achieving complete resolution of NP. Results may help to inform treatment decisions for patients with NP.
Background
Immunohistochemical (IHC) stains that distinguish benign, pigmented nail lesions from malignancy are needed. Candidate markers of malignant transformation include p16, HMB45, and Ki‐67, ...with p16 being of particular interest. There is limited knowledge about the spectrum of p16 expression in pigmented lesions, especially junctional melanocytic proliferations of the nail. The objective of this study was to determine if any of these markers demonstrate diagnostic utility in distinguishing between benign activation of junctional melanocytes (BAM) and melanoma in situ (MIS) of the nail unit.
Methods
In this retrospective study, ten cases of BAM and eight cases of MIS were identified. Archival slides available for review included H&E (hematoxylin and eosin), Fontana‐Masson, and MelanA (Mart1) IHC slides. IHC studies for p16, HMB45, and dual‐color Ki‐67/MelanA (Mart1) were then performed.
Results
None of the tested IHC stains distinguished BAM from MIS. p16 IHC expression was uniformly negative with the exception of two cases of MIS. HMB45 was positive in all BAM and MIS cases. Ki‐67/MelanA showed positive Ki‐67 staining of MelanA‐positive melanocytes in two cases of MIS, and all other cases of MIS and BAM were negative for Ki‐67. The two positive p16 and two positive Ki‐67/MelanA cases were non‐overlapping.
Conclusion
p16, HMB45, and Ki‐67/MelanA IHC studies show no apparent utility in distinguishing BAM from MIS in the nail unit.
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