An Oral Interleukin-23-Receptor Antagonist Peptide for Plaque Psoriasis.

BACKGROUND: The use of monoclonal antibodies has changed the treatment of several immune-mediated inflammatory diseases, including psoriasis. However, these large proteins must be administered by injection. JNJ-77242113 is a novel, orally administered interleukin-23-receptor antagonist peptide that selectively blocks interleukin-23 signaling and downstream cytokine production. METHODS: In this phase 2 dose-finding trial, we randomly assigned patients with moderate-to-severe plaque psoriasis to receive JNJ-77242113 at a dose of 25 mg once daily, 25 mg twice daily, 50 mg once daily, 100 mg once daily, or 100 mg twice daily or placebo for 16 weeks. The primary end point was a reduction from baseline of at least 75% in the Psoriasis Area and Severity Index (PASI) score (PASI 75 response; PASI scores range from 0 to 72, with higher scores indicating greater extent or severity of psoriasis) at week 16. RESULTS: A total of 255 patients underwent randomization. The mean PASI score at baseline was 19.1. The mean duration of psoriasis was 18.2 years, and 78% of the patients across all the trial groups had previously received systemic treatments. At week 16, the percentages of patients with a PASI 75 response were higher among those in the JNJ-77242113 groups (37%, 51%, 58%, 65%, and 79% in the 25-mg once-daily, 25-mg twice-daily, 50-mg once-daily, 100-mg once-daily, and 100-mg twice-daily groups, respectively) than among those in the placebo group (9%), a finding that showed a significant dose-response relationship (P<0.001). The most common adverse events included coronavirus disease 2019 (in 12% of the patients in the placebo group and in 11% of those across the JNJ-77242113 dose groups) and nasopharyngitis (in 5% and 7%, respectively). The percentages of patients who had at least one adverse event were similar in the combined JNJ-77242113 dose group (52%) and the placebo group (51%). There was no evidence of a dose-related increase in adverse events across the JNJ-77242113 dose groups. CONCLUSIONS: After 16 weeks of once- or twice-daily oral administration, treatment with the interleukin-23-receptor antagonist peptide JNJ-77242113 showed greater efficacy than placebo in patients with moderate-to-severe plaque psoriasis. (Funded by Janssen Research and Development; FRONTIER 1 ClinicalTrials.gov number, NCT05223868.).

Deucravacitinib, a selective, allosteric tyrosine kinase 2 inhibitor, in scalp psoriasis: A subset analysis of two phase 3 randomized trials in plaque psoriasis.

BACKGROUND: Scalp involvement in plaque psoriasis is challenging to treat. OBJECTIVE: To evaluate the efficacy and safety of deucravacitinib (DEUC) in scalp psoriasis. METHODS: POETYK PSO-1 and PSO-2 were global phase 3, 52-week, double-blinded trials in adults with moderate to severe psoriasis. Patients were randomized 1:2:1 to oral placebo, DEUC 6 mg once daily, or apremilast 30 mg twice daily. This pooled secondary analysis evaluated scalp-specific Physician Global Assessment score of 0 or 1 (0/1), ≥90% improvement from baseline in Psoriasis Scalp Severity Index, and change from baseline in Psoriasis Scalp Severity Index. Adverse events were evaluated through week 16. RESULTS: Overall, 1084 patients with moderate to severe scalp psoriasis at baseline were included. At week 16, response rates were greater with DEUC versus placebo or apremilast for scalp-specific Physician Global Assessment 0/1 (64.0% vs 17.3% vs 37.7%; P < .0001), ≥90% improvement from baseline in Psoriasis Scalp Severity Index (50.6% vs 10.5% vs 26.1%; P < .0001), and change from baseline in Psoriasis Scalp Severity Index. Responses were maintained through 52 weeks with continuous DEUC. Safety was consistent with the entire study population. LIMITATIONS: Lack of data in milder scalp psoriasis. CONCLUSION: DEUC was significantly more efficacious than placebo or apremilast in improving moderate to severe scalp psoriasis and was well tolerated.

Number of Affected Nails Is the Primary Determinant of Efinaconazole 10% Solution Usage for Onychomycosis.

Good adherence to treatment is necessary for the successful treatment of onychomycosis and requires that an appropriate amount of medication be prescribed. Most prescriptions for efinaconazole 10% solution, a topical azole antifungal, are for 4 mL per month but there are no data on patient factors or disease characteristics that impact how much medication is needed. Data from two phase 3 studies of efinaconazole 10% solution for the treatment of toenail onychomycosis were pooled and analyzed to determine monthly medication usage based on the number of affected toenails, percent involvement of the target toenail, body mass index (BMI), and sex. Participants with two or more affected nails required, on average, >4 mL of efinaconazole per month, with increasing amounts needed based on the number of nails with onychomycosis (mean: 4.39 mL for 2 nails; 6.36 mL for 6 nails). In contrast, usage was not greatly impacted by target toenail involvement, BMI, or sex. Together, these data indicate that the number of affected nails should be the major consideration when determining the monthly efinaconazole quantity to prescribe. J Drugs Dermatol. 2024;23(2):110-112.    doi:10.36849/JDD.7676.

Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: Efficacy and safety results from the 52-week, randomized, double-blinded, phase 3 Program fOr Evaluation of TYK2 inhibitor psoriasis second trial.

BACKGROUND: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, inhibits cytokine signaling in psoriasis pathogenesis. OBJECTIVE: The objective of this study was to demonstrate deucravacitinib superiority versus placebo and apremilast in moderate to severe plaque psoriasis based on ≥75% reduction from baseline in Psoriasis Area and Severity Index and a static Physician's Global Assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline at week 16. METHODS: POETYK psoriasis second trial (NCT03611751), a 52-week, double-blinded, phase 3 trial, randomized patients 2:1:1 to deucravacitinib 6 mg every day (n = 511), placebo (n = 255), or apremilast 30 mg twice a day (n = 254). RESULTS: At week 16, significantly more deucravacitinib-treated patients versus placebo and apremilast patients achieved ≥75% reduction from baseline in Psoriasis Area and Severity Index (53.0% vs 9.4% and 39.8%; P < .0001 vs placebo; P = .0004 vs apremilast) and static Physician's Global Assessment score of 0 or 1 (49.5% vs 8.6% and 33.9%; P < .0001 for both). Efficacy was maintained until week 52 with continuous deucravacitinib. The most frequent adverse event with deucravacitinib was nasopharyngitis. Serious adverse events and discontinuations due to adverse events were infrequent. No clinically meaningful changes were observed in laboratory parameters. LIMITATIONS: The study duration was 1 year. CONCLUSION: Deucravacitinib demonstrated superiority versus placebo and apremilast and was well tolerated in adults with moderate to severe plaque psoriasis.

Expert Consensus on Nail Procedures and Selection of CPT Codes.

BACKGROUND: Dermatologists specialize in treating conditions of the skin, hair, and nails; however, it is our experience that the field of nail diseases is the least discussed facet of dermatology. Even less acknowledged is the complexity of nail procedures and how best to accurately code for these procedures. OBJECTIVE: To convene a panel of experts in nail disease to reach consensus on the most accurate and appropriate Current Procedural Terminology (CPT) codes associated with the most commonly performed nail procedures. METHODS: A questionnaire including 9 of the most commonly performed nail procedures and potential CPT codes was sent to experts in the treatment of nail disease, defined as those clinicians running a nail subspecialty clinic and performing nail procedures with regularity. A conference call was convened to discuss survey results. RESULTS: Unanimous consensus was reached on the appropriate CPT codes associated with all discussed procedures. LIMITATIONS: Although this article details the most commonly performed nail procedures, many were excluded and billing for these procedures continues to be largely subjective. This article is meant to serve as a guide for clinicians but should not be impervious to interpretation in specific clinical situations. CONCLUSION: Billing of nail procedures remains a practice gap within our field. The authors hope that the expert consensus on the most appropriate CPT codes associated with commonly performed nail procedures will aid clinicians as they diagnose and treat disorders of the nail unit and encourage accurate and complete billing practices.

Therapeutic Recommendations for the Treatment of Toenail Onychomycosis in the US.

BACKGROUND: Onychomycosis affects around 14% of individuals in North America and Europe and is undertreated. Treatment is challenging as toenail growth can take 12–18 months, the nail plate may prevent drug penetration, and disease recurrence is common. National guidelines/consensus documents on onychomycosis diagnosis and treatment were last published more than 5 years ago and updated medical guidance is needed. METHODS: This document aims to provide recommendations for the diagnosis and pharmaceutical treatment of toenail onychomycosis following a roundtable discussion with a panel of dermatologists, podiatrists, and a microbiologist specializing in nail disease. RESULTS: There was a general consensus on several topics regarding onychomycosis diagnosis, confirmatory laboratory testing, and medications. Onychomycosis should be assessed clinically and confirmed with microscopy, histology, and/or culture. Terbinafine is the primary choice for oral treatment and efinaconazole 10% for topical treatment. Efinaconazole can also be considered for off-label use for maintenance to prevent recurrences. For optimal outcomes, patients should be counseled regarding treatment expectations as well as follow-up care and maintenance post-treatment. CONCLUSIONS: This article provides important updates to previous guidelines/consensus documents to assist dermatologists and podiatrists in the diagnosis and treatment of toenail onychomycosis. J Drugs Dermatol. 2021;20(10):1076-1084. doi:10.36849/JDD.6291.

Isolated nail lichen planus: An expert consensus on treatment of the classical form.

Lichen planus is a benign inflammatory disorder of unknown etiology that may affect the skin, mucosae, scalp, and nails. When the nails are affected, it may lead to permanent destruction with severe functional and psychosocial consequences. Therefore, prompt diagnosis and early treatment are essential, even in mild cases. There are currently no guidelines for the management of nail lichen planus and the published literature on treatment is limited. The aim of this review is to provide practical management recommendations for the classical form of nail lichen planus, especially when restricted to the nails. Topical treatment has poor short-term efficacy and may cause long-term side effects. Instead, intralesional and intramuscular triamcinolone acetonide should be considered first-line therapies. Oral retinoids are second-line choices, and immunosuppressive agents may also be considered.

Nail Psoriasis Does Not Affect Skin Response to Ixekizumab in Patients With Moderate-To-Severe Psoriasis.

Background: Presence of nail psoriasis in patients with plaque psoriasis may be an indicator of greater disease severity. Previously, patients with nail psoriasis have had delayed skin clearance after treatment compared to patients without nail psoriasis. Objective: This post-hoc analysis evaluated the efficacy of ixekizumab in clearance of plaque psoriasis in patients with and without nail psoriasis. Methods: Data were integrated from two phase 3 clinical trials (UNCOVER-2 and UNCOVER-3; N=2570) to assess skin response over 12 weeks of treatment with subcutaneous placebo, etanercept, or ixekizumab in patients with and without nail psoriasis. Nail response was assessed using Nail Psoriasis Severity Index (NAPSI) and skin response was assessed as the percentage of patients achieving 75%, 90%, or 100% improvement in Psoriasis Area and Severity Index (PASI 75, PASI 90, PASI 100) or a score of 0 or 1 on the static Physician Global Assessment (sPGA 0 or 0,1). Results: From baseline to week 12, progressive improvement in psoriasis occurred with ixekizumab and etanercept treatment; however, significantly more patients with nail psoriasis than without mild PASI 75 at weeks 8 and 12 and sPGA (0,1) at week 12 with ixekizumab. Significantly more patients with severe nail psoriasis than mild achieved PASI 75 at weeks 8 and 12 with ixekizumab. Conclusion: Patients with and without nail psoriasis responded well to ixekizumab. The presence of nail psoriasis did not negatively affect skin clearance in patients treated with ixekizumab. ClinicalTrials.gov: NCT01597245, NCT01646177 J Drugs Dermatol. 2020;19(8):741-746. doi:10.36849/JDD.2020.5116.

Recommendations for the definition, evaluation, and treatment of nail psoriasis in adult patients with no or mild skin psoriasis: A dermatologist and nail expert group consensus.

Nail involvement in psoriasis is common, and the severity of it does not always parallel the intensity of cutaneous disease. We created a consensus group, of which the aim was to provide practical recommendations for the treatment of nail psoriasis in patients without skin psoriasis or with mild skin lesions with no indication for a systemic treatment. This collaborative process was conducted by an international panel of dermatologists with special expertise in nail disorders, using formal consensus methods. During this process, the panel strived to establish an agreement regarding the definition of nail psoriasis, the severity of nail psoriasis, and treatment response. Treatment recommendations are provided regarding nail psoriasis severity and matrix or bed involvement. Few-nail disease was considered as nail psoriasis affecting ≤3 nails. In the case of matrix involvement only, intralesional steroid injections were considered the treatment of choice. Topical steroids alone or in combination with topical vitamin D analogues were suggested for nail psoriasis limited to the nail bed. For the systemic treatment of nail psoriasis acitretin, methotrexate, cyclosporine, small molecules, and biologics may be employed.

Immunohistochemical characterization of benign activation of junctional melanocytes and melanoma in situ of the nail unit.

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.

A Randomized, Vehicle-Controlled Phase 3 Study of Aminolevulinic Acid Photodynamic Therapy for the Treatment of Actinic Keratoses on the Upper Extremities.

BACKGROUND: Blue-light aminolevulinic acid photodynamic therapy (ALA-PDT) after broad-area application and 3-hour incubation is efficacious for actinic keratosis (AK) lesion clearance on upper extremities, with use of occlusive dressing significantly increasing efficacy. OBJECTIVE: To prove the safety and efficacy of ALA-PDT versus vehicle (VEH-PDT) in the spot treatment of multiple AKs on upper extremities. METHODS: Aminolevulinic acid or VEH was spot applied only to lesions on one upper extremity 3 hours before blue-light exposure. Treated extremity was covered with occlusive dressing during incubation. Identical treatment was repeated at Week 8 if AK lesions were present in the treated area. RESULTS: Thirty-one percent (42/135) of subjects treated with ALA-PDT had complete clearance at Week 12, compared with 13% (17/134) of the subjects treated with VEH-PDT (p = .0001). The mean AK lesion clearance rate for ALA-treated subjects at Weeks 8 and 12 was 53% and 69%, respectively, compared with 26% and 30% for the VEH-treated group (p < .0001, linear mixed model). Safety profile observed in this study is consistent with previous studies/reports in the literature, and the therapy was well tolerated overall. CONCLUSION: Aminolevulinic acid-PDT spot treatment using a 3-hour occluded incubation was superior to VEH-PDT for AK lesion clearance of the upper extremity.

Tavaborole 5% Topical Solution for the Treatment of Toenail Onychomycosis in Pediatric Patients: Results from a Phase 4 Open-Label Study

Background: This study was designed to evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of tavaborole in pediatric patients. Study Design: In this open-label, single-arm study, pediatric patients (aged 6 to <17 years) with distal subungual onychomycosis affecting ≥20% of the target great toenail applied tavaborole once daily to all affected toenails (2 drops/great toenail, 1 drop/other toenail) for 48 weeks. In addition, a maximal-use subgroup (aged 12 to <17 years) applied tavaborole to all 10 toenails and ≤2 mm of surrounding skin for the first 28 days. Results: Treatment-emergent adverse events (TEAEs) were reported by 55.6% of patients; the most frequently reported (≥5% of patients) were nasopharyngitis, contusion, sinusitis, and vomiting. Most TEAEs and local treatment reactions (LTRs) were mild or moderate and considered unrelated to treatment. There was 1 serious AE (severe appendicitis, considered unrelated to treatment) and there were no deaths, discontinuations because of AEs, or dose adjustments because of AEs. The most frequently reported LTRs were erythema and scaling. The incidence of LTRs diminished over time. Tavaborole was absorbed systemically, and plasma concentrations were measurable. The PK parameters determined in this study under maximal-use conditions indicate that steady state was achieved within the study period. For efficacy, 8.5% of patients achieved complete cure (clear nail and negative mycology [negative fungal culture and negative potassium hydroxide wet mount]) at week 52, and 14.9% achieved complete/almost complete cure at week 52 (clear or almost clear nail [≤5% dystrophic or discolored distal toenail plate] and negative mycology). Conclusion: Tavaborole was well tolerated in this pediatric population, and safety, PK, and efficacy profiles were comparable with those in adults. Trial registration: ClinicalTrials.gov identifier: NCT03405818 J Drugs Dermatol. 2019;18(2):190-195.

Adalimumab for nail psoriasis: Efficacy and safety from the first 26 weeks of a phase 3, randomized, placebo-controlled trial.

BACKGROUND: Previous clinical trials have not evaluated improvement in nail psoriasis as a primary end point. OBJECTIVE: 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. METHODS: 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). RESULTS: 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%. LIMITATIONS: Patients with less than 5% BSA involvement were not eligible for enrollment. CONCLUSIONS: 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.

Once-Daily Oral Sarecycline 1.5 mg/kg/day Is Effective for Moderate to Severe Acne Vulgaris: Results from Two Identically Designed, Phase 3, Randomized, Double-Blind Clinical Trials.

BACKGROUND: Side effects may limit the use of current tetracycline-class antibiotics for acne. OBJECTIVE: Evaluate the efficacy and safety of once-daily sarecycline, a novel, narrow-spectrum tetracycline-class antibiotic, in moderate to severe acne. METHODS: Patients 9-45 years with moderate to severe facial acne (Investigator's Global Assessment [IGA] score ≥ 3, 20-50 inflammatory and ≤ 100 noninflammatory lesions, and ≤ 2 nodules) were randomized 1:1 to sarecycline 1.5 mg/kg/day or placebo for 12 weeks in identically designed phase 3 studies (SC1401 and SC1402). RESULTS: In SC1401 (sarecycline n=483, placebo n=485) and SC1402 (sarecycline n=519, placebo n=515), at week 12, IGA success (≥ 2-grade improvement and score 0 [clear] or 1 [almost clear]) rates were 21.9% and 22.6% (sarecycline), respectively, versus 10.5% and 15.3% (placebo; P less than 0.0001 and P equals 0.0038). Onset of efficacy in inflammatory lesions occurred by the first visit (week 3), with mean percentage reduction in inflammatory lesions at week 12 in SC1401 and SC1402 of -51.8% and -49.9% (sarecycline), respectively, versus -35.1% and -35.4% (placebo; P less than 0.0001). Onset of efficacy for absolute reduction of noninflammatory lesion count occurred at week 6 in SC1401 (P less than 0.05) and week 9 in SC1402 (P less than 0.01). In SC1401, the most common TEAEs (in ≥ 2% of either sarecycline or placebo group) were nausea (4.6% [sarecycline]; 2.5% [placebo]), nasopharyngitis (3.1%; 1.7%), headache (2.7%; 2.7%), and vomiting (2.1%; 1.4%) and, in SC1402, nasopharyngitis (2.5%; 2.9%) and headache (2.9%; 4.9%). Most were not considered treatment-related. Vestibular (dizziness, tinnitus, vertigo) and phototoxic (sunburn, photosensitivity) TEAEs both occurred in ≤ 1% of sarecycline patients. Gastrointestinal TEAE rates for sarecycline were low. Among females, vulvovaginal candidiasis (SC1401: 1.1% [sarecycline] and 0 [placebo]; SC1402: 0.3% and 0) and mycotic infection (0.7% and 0; 1.0% and 0) rates were low. CONCLUSION: The narrow-spectrum antibiotic sarecycline was safe, well tolerated, and effective for moderate to severe acne, with low rates of side effects common with tetracycline antibiotics. J Drugs Dermatol. 2018;17(9):987-996.

Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with difficult-to-treat nail and scalp psoriasis: Results of 2 phase III randomized, controlled trials (ESTEEM 1 and ESTEEM 2).

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.

Ixekizumab Is Effective in Subjects With Moderate to Severe Plaque Psoriasis With Significant Nail Involvement: Results From UNCOVER 3.

BACKGROUND: Ixekizumab, a monoclonal antibody that selectively targets interleukin-17A, has been established as safe and effective in 3 Phase 3 trials for the treatment of moderate to severe plaque psoriasis. The lifetime incidence of psoriatic nail disease is 80%-90% of patients, and approximately 50% of patients with psoriasis have nail involvement.
MATERIALS AND METHODS: The design of UNCOVER-3, a Phase 3, multicenter, double-blind, placebo- and active-controlled trial that evaluated the efficacy and safety of ixekizumab for moderate to severe psoriasis, has been published previously. Patients were randomized to receive blinded placebo, etanercept (50 mg twice weekly) or 80 mg ixekizumab every 2 weeks (IXEQ2W) or every 4 weeks (IXEQ4W) for 12 weeks. At week 12, all patients were assigned to open-label ixekizumab 80 mg every 4 weeks through week 60. In this 60-week post hoc subset analysis, we evaluated only those patients with significant baseline nail involvement, defined as fingernail NAPSI ≥16 and at least 4 fingernails involved.
RESULTS: Ixekizumab Q2W or Q4W resulted in greater improvement in nail psoriasis than placebo or etanercept by week 12 of administration, as measured by percent NAPSI reduction (IXEQ2W 39% improvement, IXEQ4W 40%, etanercept 28%, placebo -4.7%). At week 24, significantly more patients receiving ixekizumab exhibited no signs of nail involvement (IXEQ2W/Q4W 34%, IXEQ4W/Q4W 30%). Similar gains were observed at 60 weeks in all treatment groups.
CONCLUSION: Ixekizumab led to improvement in fingernail psoriasis by week 12 compared with placebo. Continued improvement in fingernail psoriasis with ixekizumab was observed, with >50% of patients achieving complete fingernail psoriasis resolution (NAPSI=0) at week 60.

J Drugs Dermatol. 2016;15(8):958-961.

Nail psoriasis.

Nail psoriasis affects nearly 80% of patients with plaque psoriasis and is even more prevalent in patients with psoriatic arthritis. Nail psoriasis is not simply a cosmetic problem but one that effects the structure and function of the nail, resulting in negative psychological effects. The first level in management of nail psoriasis is patient education. The hierarchy of nail psoriasis therapy begins with topical medication followed by devices, intralesional injections, and small molecules. For nail psoriasis patients unresponsive to these treatments, and especially in patients with severe plaque psoriasis, biologics are safe and effective options.

Efficacy and safety of tavaborole topical solution, 5%, a novel boron-based antifungal agent, for the treatment of toenail onychomycosis: Results from 2 randomized phase-III studies.

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.

Efinaconazole topical solution, 10%: the benefits of treating onychomycosis early.

OBJECTIVE: To evaluate efficacy of efinaconazole topical solution, 10% in onychomycosis patients with early and long-standing disease. METHODS: An analysis of 1655 patients, aged 18-70 years, randomized to receive efinaconazole topical solution, 10% or vehicle from two identical multicenter, double-blind, vehicle-controlled 48-week studies evaluating safety and efficacy. 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. Three groups were compared: those with early disease (<1year), patients with a baseline disease of 1-5 years, and those with long-standing onychomycosis (>5years). RESULTS: The majority of patients had long-standing disease; were older, male and white. While nail involvement of the target toenail did not differ noticeably amongst the three groups, the number of nails involved did increase progressively with disease duration. Differences were seen in terms of infecting pathogens in early disease that might have important treatment implications. Efinaconazole was more effective in treating early disease, however more than 40% of patients with long-standing disease were considered treatment successes. LIMITATIONS: A period of 52 weeks may be too brief to evaluate a clinical cure in onychomycosis. CONCLUSIONS: Treatment of onychomycosis early to avoid disease progression to other toenails is important. Once daily efinaconazole topical solution, 10% is particularly effective in these patients.