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.

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.

Network meta-analyses comparing the efficacy of biologic treatments for achieving complete resolution of nail psoriasis at 24-28 and 48-52 weeks.

BACKGROUND: Available 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. OBJECTIVE: We conducted two NMAs that update and extend results from a previous NMA comparing biologics for achieving complete resolution of NP. METHODS: Bayesian 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. RESULTS: For 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). CONCLUSION: Among 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.

Treatment of plaque psoriasis with deucravacitinib (POETYK PSO-2 study): a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of a paper published in a medical journal that describes the results of a study called POETYK PSO-2, which investigated a new treatment for plaque psoriasis. Plaque psoriasis appears on the body as dry, discolored, patches of skin that can be flaky and covered in scales. This can make the skin itch, crack or bleed and make it difficult for people with psoriasis to perform basic everyday tasks. Treatments are available, but some do not always reduce symptoms or may need to be injected or taken multiple times a day, which can be difficult to do, or can have undesirable side effects. Researchers are looking for new treatments for psoriasis. WHAT HAPPENED IN THE STUDY?: Deucravacitinib is a once-daily pill taken by mouth (orally) that was studied as a treatment for moderate to severe plaque psoriasis in two large studies conducted globally, PSO-1 and PSO-2. POETYK PSO-2 was a Phase 3 research study, which is a study that tests a treatment in a large group of participants, that looked at how well deucravacitinib worked in participants with moderate to severe plaque psoriasis compared to a placebo (an inactive pill that has no effect) and an approved psoriasis treatment called apremilast, which is a pill taken twice a day. These medications were tested in adults with moderate to severe plaque psoriasis, which is psoriasis involving 10% or more of their body (equal to 10 or more handprints). The aims of the POETYK PSO-2 study were to find out if treatment with deucravacitinib could improve psoriasis for the participants in the study and to see if there were any side effects. Side effects are events that happened during treatment that may or may not be caused by that treatment. The study also wanted to find out what would happen after stopping treatment with deucravacitinib in participants who had shown major improvements in their psoriasis. WHAT DO THE RESULTS OF THE POETYK PSO-2 STUDY SHOW?: After 4 months of treatment, more participants taking deucravacitinib had significantly greater improvements in psoriasis than those taking placebo or apremilast. The study also showed that participants continued to see these improvements after taking deucravacitinib for up to 1 year. Some participants maintained the improvements in their psoriasis with deucravacitinib after stopping treatment and switching to a placebo. Side effects for participants taking deucravacitinib were generally mild and occurred in similar numbers to those in participants taking placebo. The most common side effects in participants taking deucravacitinib were inflammation of the nose and throat (a common cold) which occurred at a similar rate in participants who took placebo. Clinical Trial Registration: NCT03611751 (POETYK PSO-2 study) (ClinicalTrials.gov).

Risankizumab in Patients with Moderate-to-Severe Atopic Dermatitis: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study.

INTRODUCTION: Atopic dermatitis (AD) is a heterogeneous disease, with involvement of the T-helper cell (Th) 2, Th22, and potentially Th17 pathways, supporting the use of interleukin (IL)-23 and IL-22 blockade in AD. METHODS: This phase 2, multicenter, randomized, double-blind, placebo-controlled trial (NCT03706040) evaluated the efficacy and safety of risankizumab, an IL-23 inhibitor, in patients (≥ 12 years old) with moderate-to-severe AD, defined by an Eczema Area and Severity Index (EASI) ≥ 16, affected body surface area ≥ 10%, and a Validated Investigator Global Assessment for AD (vIGA-AD) score ≥ 3. Patients were randomized 2:2:1 to 16-week treatment with risankizumab 150 mg, risankizumab 300 mg, or placebo in period A; patients receiving placebo were re-randomized 1:1 to risankizumab 150 mg or 300 mg and patients receiving risankizumab continued on their randomized dose in 36-week period B. Study drug was administered at baseline and weeks 4, 16, 28, and 40. The primary endpoint was the proportion of patients achieving a ≥ 75% reduction from baseline in EASI (EASI 75) at week 16. Safety was analyzed in all randomized patients who received study medication. RESULTS: Neither the risankizumab 150 mg (n = 69) nor the 300 mg dose group (n = 69) demonstrated a significantly higher proportion of patients achieving EASI 75 at week 16 compared with the placebo group (n = 34; treatment difference [95% CI] 13.0% [-1.7 to 27.7%; P = 0.084] and 10.0% [-4.6 to 24.6%; P = 0.179], respectively). Most adverse events were mild to moderate in severity; five patients receiving risankizumab reported serious adverse events, including two patients who reported cellulitis. CONCLUSIONS: Risankizumab was generally well tolerated, with no new safety concerns identified. The study's primary endpoint was not met, with no significant difference in the proportion of patients achieving an EASI 75 response at week 16 with risankizumab 150 mg or 300 mg versus placebo. TRIAL REGISTRATION: ClinicalTrials.gov NCT03706040.

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.

Efficacy and Safety of Ixekizumab Versus Adalimumab in Biologic-naïve Patients With Active Psoriatic Arthritis and Moderate-to-severe Psoriasis: 52-week Results From the Randomized SPIRIT-H2H Trial.

Introduction: The randomized, open-label, assessor-blinded, parallel-group SPIRIT-H2H trial (NCT03151551) demonstrated superiority of ixekizumab over adalimumab in simultaneously achieving improvement in joint symptoms (American College of Rheumatology [ACR]50) and skin clearance (Psoriasis Area and Severity Index [PASI]100) in biologic-naïve patients with active psoriatic arthritis (PsA) and plaque psoriasis (PsO) at Week (W) 24. Higher efficacy of ixekizumab versus adalimumab was maintained through W52. Objectives: This analysis investigated efficacy and safety of ixekizumab and adalimumab in the subgroup of patients with PsA and moderate-to-severe PsO through W52. Methods: Efficacy and safety outcomes were analyzed in patients with PsA and moderate-to-severe PsO (PASI ≥ 12, Body Surface Area ≥ 10%, static Physician Global Assessment ≥ 3) through W52. Categorical and continuous outcomes were analyzed using logistic regression models and mixed model for repeated measures, respectively. Results: More ixekizumab-versus adalimumab-treated patients simultaneously achieved PASI100 and ACR50 at W24 (40.8% versus 17.6%, P = 0.015) and W52 (38.8% versus 17.6%, P = 0.026). Likewise, more ixekizumab-versus adalimumab-treated patients achieved PASI100 (59.2% versus 25.5%, P = 0.001) and PASI90 (81.6% versus 60.8%, P = 0.028) through W52, and nail PsO clearance at W24. Joint symptom improvements were comparable between groups. No new safety findings were reported. Conclusions: Ixekizumab had higher efficacy than adalimumab in simultaneous achievement of ACR50 and PASI100 at W24 and W52 in patients with PsA and moderate-to-severe PsO. Ixekizumab-treated patients showed higher response rates for nail PsO clearance and for reporting minimal or no impact on quality of life at W24.

Efficacy of brodalumab in the treatment of scalp and nail psoriasis: results from three phase 3 trials.

INTRODUCTION: We evaluated the efficacy of brodalumab in patients with nail or scalp psoriasis in three phase 3 studies (AMAGINE-1/-2/-3). METHODS: 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. RESULTS: 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. CONCLUSIONS: Brodalumab was associated with clearance of scalp psoriasis through 12 weeks and improvements in nail psoriasis, including complete nail clearance, through 52 weeks.

Efficacy, tolerability, patient usability, and satisfaction with a 2 mL pre-filled syringe containing secukinumab 300 mg in patients with moderate to severe plaque psoriasis: results from the phase 3 randomized, double-blind, placebo-controlled ALLURE study.

BACKGROUND: Evidence shows good tolerability in patients for subcutaneous injection volumes up to 3 mL. OBJECTIVES: We investigated efficacy, pharmacokinetics, and tolerability of secukinumab 300 mg/2 mL pre-filled syringe (PFS) in patients with moderate to severe plaque psoriasis. METHODS: ALLURE was a 52-week, multicenter, randomized (1:1:1), double-blind, placebo-controlled, parallel-group study. Co-primary endpoints were secukinumab Psoriasis Area Severity Index (PASI) 75 and Investigator's Global Assessment modified 2011 0/1 (IGA mod 2011 0 or 1) responses at week 12 versus placebo. Other endpoints included the Self-Injection Assessment Questionnaire (SIAQ), and the ability to follow the instructions for use (IFU). RESULTS: Overall, 214 patients were randomized. The secukinumab 300 mg/2 mL PFS showed superiority over placebo for both PASI 75 (88.9% versus 1.7%; p<.0001) and IGA mod 2011 0 or 1 (76.4% versus 1.4%; p<.0001) responses at week 12. All secondary efficacy endpoints were met. The SIAQ scores were similar across groups and improved similarly over 12 weeks. All patients completed critical steps in the IFU at week 1. CONCLUSIONS: The secukinumab 300 mg/2 mL PFS groups showed superiority versus placebo, and it was a safe, effective, and convenient option for patients with psoriasis. NCT02748863.

Network meta-analysis comparing the efficacy of biologic treatments for achieving complete resolution of nail psoriasis.

BACKGROUND: 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. OBJECTIVE: To evaluate the comparative efficacy of approved biologics in achieving complete resolution of NP at week 24‒26. METHODS: 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). RESULTS: 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%). CONCLUSION: 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.

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.

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.

Nail Tumors.

This article describes nail tumors and their clinical features, biologic behavior, and treatment. Tumors included are onychopapilloma, onychomatricoma, periungual fibromas/fibrokeratomas, glomus tumors, subungual exostosis, myxoid cysts, and squamous cell carcinoma.

Nail Psoriasis: Diagnosis, Assessment, Treatment Options, and Unmet Clinical Needs.

OBJECTIVE: An estimated 40-50% of patients with psoriasis (PsO) have psoriatic nail disease, which is associated with and directly contributes to a greater clinical burden and worse quality of life in these patients. In this review, we examine how recent advances in the use of new diagnostic techniques have led to improved understanding of the link between nail and musculoskeletal manifestations of psoriatic disease (PsD; e.g., enthesitis, arthritis) and we review targeted therapies for nail PsO (NP). METHODS: We performed a literature search to identify which systemic therapies approved for the treatment of PsO and/or psoriatic arthritis (PsA) have been evaluated for the treatment of NP, either as a primary or secondary outcome. A total of 1546 articles were identified on February18, 2019, and evaluated for relevance. RESULTS: We included findings from 66 articles on systemic therapies for the treatment of NP in PsD. With several scoring systems available for the evaluation of psoriatic nail disease, including varied subtypes and application of the Nail Psoriasis Area Severity Index, there was a high level of methodological heterogeneity across studies. CONCLUSION: NP is an important predictor of enthesitis, which is associated with the early stages of PsA; therefore, it is important for rheumatologists and dermatologists to accurately diagnose and treat NP to prevent nail damage and potentially delay the onset and progression of joint disease. Further research is needed to address the lack of both standardized NP scoring systems and well-defined treatment guidelines to improve management of PsD.

Deferring Nail Mycological Sampling during the COVID-19 Pandemic: Recommendations from a Multidisciplinary Panel of Nail Specialists.

Onychomycosis is the most common nail condition seen in clinical practice, with significant impact on quality of life. Clinical examination alone is insufficient for accurate diagnosis, but mycological confirmation can be challenging during the COVID-19 pandemic. In this letter, a multidisciplinary panel of dermatologists, a podiatrist, dermatopathologists, and a mycologist, discuss considerations for mycological sampling during the pandemic.

Association of Secukinumab Treatment With Tuberculosis Reactivation in Patients With Psoriasis, Psoriatic Arthritis, or Ankylosing Spondylitis.

Importance: 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. Objective: 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. Design, Setting, and Participants: 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. Main Outcomes and Measures: 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). Results: 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. Conclusions and Relevance: 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.

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.

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.

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.