bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deucravacitinib in Moderate Plaque Psoriasis: Efficacy in the Phase 3 POETYK PSO-1 and PSO-2 Trials
Authors: Blauvelt Andrew , Korman Neil J. , Merola Joseph F. , Gooderham Melinda , Balagula Eugene , Vanlandingham Rebecca , Treitel Michelle , Wittstock Keith , Hoyt Kim , Banerjee Subhashis , Desai Seemal R. 
Published: March 2024

Introduction: Deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, was efficacious and well tolerated in adults with moderate to severe plaque psoriasis in the global, 52-week, phase 3 POETYK PSO-1 (NCT03624127) and PSO-2 (NCT03611751) trials. We report clinical efficacy of deucravacitinib in the patient subgroup from these trials with baseline plaque psoriasis of moderate severity.
Methods: PSO-1 and PSO-2 randomized patients with moderate to severe plaque psoriasis (PASI ≥12, sPGA ≥3, BSA involvement ≥10% at baseline) 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. Placebo patients crossed over to deucravacitinib at Week 16 in both trials. In PSO-1, deucravacitinib-treated patients received continuous deucravacitinib through Week 52. In PSO-2, PASI 75 responders at Week 24 on deucravacitinib were rerandomized to placebo or deucravacitinib (1:1) through Week 52. In patients meeting criteria for plaque psoriasis of moderate severity, defined as sPGA 3 and BSA 10%-15% at baseline, in the pooled PSO-1/PSO-2 trials, PSO-1 alone, and the PSO-1 placebo crossover population, deucravacitinib efficacy vs placebo was evaluated by PASI 75, PASI 90, and sPGA 0/1 (clear/almost clear) responses (nonresponder imputation) and PASI change from baseline (mBOCF). The Clopper-Pearson method was used to calculate 95% CIs.
Results: PSO-1/PSO-2 moderate psoriasis subgroup PASI 75 response rates were higher with deucravacitinib vs placebo at Week 16 (49.1% [95% CI, 42.5%-55.7%] vs 11.7% [95% CI%, 5.9%-17.4%]) and continued to increase through Week 24 (63.8% [95% CI, 57.5%-70.1%]). PSO-1 PASI 75 response rates were higher with deucravacitinib vs placebo at Week 16 (54.1% [95% CI, 42.1%-65.7%] vs 12.0% [95% CI, 4.5%-24.3%]), Week 24, and were sustained until Week 52. Week 52 PASI 75 response rates for deucravacitinib and placebo crossover groups were comparable (74.3% [95% CI, 62.8%-83.8%] and 67.4% [95% CI, 51.5%-80.9%], respectively). PASI 90 and sPGA 0/1 response rates and change from baseline PASI followed similar patterns, with marked improvement vs placebo at Week 16; peak responses were observed at Week 24 and sustained through Week 52. Efficacy results were comparable to those previously reported for moderate to severe psoriasis.
Conclusion: Deucravacitinib efficacy was confirmed in moderate plaque psoriasis and was consistent with published data in the PSO-1 and PSO-2 overall study population with moderate to severe plaque psoriasis.
Deucravacitinib Long-Term Efficacy in Week 16 Placebo Crossovers: 3-year Results from the POETYK PSO Program
Authors: Lebwohl Mark , Warren Richard B. , Imafuku Shinichi , Bagel Jerry , Armstrong April W. , Passeron Thierry , Banerjee Subhashis , Kisa Renata M. , Vritzali Eleni , Colombo Matthew J. , Scharnitz Thomas , Hoyt Kim , Thaçi Diamant , Blauvelt Andrew 
Published: March 2024

Introduction: Deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, is approved in the US, EU, and other countries for treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy. Deucravacitinib was efficacious and well-tolerated in the global, 52-week, phase 3 POETYK PSO-1 (NCT03624127) and PSO-2 (NCT03611751) trials and through 2 additional years in the POETYK long-term extension (LTE) (NCT04036435) trial in patients treated with deucravacitinib from Day 1 of PSO-1/PSO-2. Here, long-term efficacy was assessed through 3 years in patients who crossed over from placebo to deucravacitinib at Week 16 in PSO-1 or PSO-2 and entered the LTE trial.
Methods: PSO-1 and PSO-2 randomized patients 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. At Week 16, patients randomized to placebo crossed over to deucravacitinib. At Week 52, patients could enroll in the LTE and receive open-label deucravacitinib. Efficacy was evaluated in patients who crossed over from placebo to deucravacitinib at Week 16 of the parent trial and received continuous deucravacitinib through 3 years (Week 148; cutoff June 15, 2022). Outcomes included ≥75%/≥90% reduction from baseline in Psoriasis Area and Severity Index (PASI 75/90) and static Physician Global Assessment score of 0 (clear) or 1 (almost clear) (sPGA 0/1). Efficacy is reported using modified nonresponder imputation (mNRI) in patients who reached the Week 148 assessment and those who discontinued before Week 148.
Results: Of 421 patients originally randomized to placebo, 348 crossed over to deucravacitinib at Week 16; of these, 298 completed the parent trials and entered the LTE, with 254 meeting mNRI criteria Efficacy response rates improved from Week 16 on placebo (PASI 75, 13.4%; PASI 90, 4.3%; sPGA 0/1, 11.0%) through Week 52 on deucravacitinib (PASI 75, 75.9%; PASI 90, 47.5%; sPGA 0/1, 59.4%), were generally maintained well through Week 112 (PASI 75, 78.4%; PASI 90, 52.0%; sPGA 0/1, 57.8%), with persistent responses overall observed through Week 148 (PASI 75, 74.4%; PASI 90, 48.1%; sPGA 0/1, 51.1%). Conclusion: These findings further confirm earlier results of once-daily oral deucravacitinib as an effective long-term treatment for patients with moderate to severe plaque psoriasis.
Gene Expression Differences Identified in Skin Samples of Mycosis Fungoides, Atopic Dermatitis, and Psoriasis
Authors: Farberg Aaron , Goldberg Matthew , Quick Ann , Bailey Christine , Zolochevska Olga , Wilkinson Jeff , Silverberg Jonathan , Lio Peter , Koo John , Weinberg Jeffrey , Lebwohl Mark 
Published: March 2024

Background: Recent advances in the understanding of the molecular mechanisms underlying atopic dermatitis (AD) and psoriasis (PSO) have led to the development of multiple targeted therapies. Yet, molecular heterogeneity contributes to inconsistent clinical presentation and therapeutic response. Further, systemic treatment of presumed AD or PSO can lead to delays in both diagnosis and proper treatment of patients with a true diagnosis of mycosis fungoides (MF) – a potentially dangerous clinical mimic of AD and PSO that requires a rigorous histologic and molecular workup to diagnose. Therefore, a non-invasive method to distinguish molecular profiles of MF from AD and PSO could inform accurate diagnoses and avoid inappropriate treatment of MF. We have previously shown transcriptomic differences in AD and PSO samples obtained by a non-invasive scraping technique. However, this technique has not been used to assess differences in gene expression profiles of MF samples.
Objectives: To identify gene expression differences based on diagnosis of MF, AD, or PSO and response to targeted systemic AD or PSO therapies.
Methods: Lesional baseline samples were assessed from 76 patients (AD, n=24; PSO, n=48; and MF, n=4) enrolled in one of two IRB-approved studies (IDENTITY or SIGNAL-MF). Lesional samples were collected by epidermal scraping and preserved in RNA buffer. Library preparation and next generation RNA sequencing was performed using the Ion AmpliSeq Transcriptome Human Gene Expression panel on the S5 Prime sequencer (ThermoFisher). Clinical responses for AD and PSO were further assessed over 3 months using the eczema and psoriasis area and severity index (EASI and PASI, respectively). Genes were considered differentially expressed if there was a log2fold change >|1.0| and padj <.05.
Results: Statistically significant differences in gene expression were observed between AD, PSO, and MF lesions. Further, genes were differentially expressed in baseline skin scrapings obtained from super-responders to dupilumab, which blocks both IL-4 and IL-13 signaling, and PSO therapies including the IL-23 inhibitor risankizumab relative to those who did not achieve ≥90% improvement.
Conclusion: A non-invasive molecular test could be developed to distinguish between AD, PSO, and MF, and further identify super-responders to targeted PSO and AD therapies.
Impact of Oral, Selective, Allosteric Tyrosine Kinase 2 Inhibitor, Deucravacitinib, on Psoriasis in Patients with Active Psoriatic Arthritis: Results from a Phase 2 Trial
Authors: Gottlieb Alice B. , Armstrong April W. , Merola Joseph F. , Napoli Andrew , Nowak Miroslawa , Banerjee Subhashis , Lehman Thomas , Mease Philip J. 
Published: March 2024

Introduction: Deucravacitinib (DEUC), an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in the US, EU, and other countries for treatment of adults with moderate-to-severe plaque psoriasis (PsO) who are candidates for systemic therapy. DEUC was superior to apremilast and placebo (PBO) in two phase 3 trials in patients with moderate to severe PsO. DEUC was efficacious on multiple measures of arthritis severity vs PBO in a phase 2 trial in patients with active psoriatic arthritis (PsA) who had ≥1 PsO lesion (≥2 cm). In patients with body surface area (BSA) involvement ≥3% at baseline (80% of patients in this trial), a greater proportion achieved PASI 75 with DEUC (6 mg QD: 42.4%, P=0.01; 12 mg QD: 59.6%, P<0.0001) vs PBO (20.4%) at Week 16. This analysis evaluated the impact of DEUC on PsO in patients with PsA in the phase 2 trial (NCT03881059).
Methods: The phase 2 double-blind PsA trial randomized patients (N=203) 1:1:1 to PBO, DEUC 6 mg once daily (QD), or DEUC 12 mg QD. After Week 16, patients could enroll in an optional, double-blind period until Week 52. DEUC-treated patients achieving minimal disease activity at Week 16 continued DEUC to Week 52. PsO disease activity measurements were assessed.
Results: Baseline PsO characteristics were comparable across groups. At Week 16, significant decreases from baseline in mean PASI were observed with DEUC vs PBO in patients with baseline BSA ≥3%-<10% or PASI ≤12 even with very low baseline PASI scores, and also in those with baseline BSA ≥10% and PASI >12. Significant decreases in PASI from baseline were observed with DEUC vs PBO in patients with background csDMARD use (DEUC 6 mg, -4.0 and 12 mg, -4.9 vs PBO, -2.3; both P<0.05) and those without csDMARD use (-3.7 and -4.0 vs -2.5, respectively; both P<0.001). At Week 16, greater proportions of DEUC vs PBO patients achieved PASI ≤1 with baseline BSA ≥3% (DEUC 6 mg: 32.2%; DEUC 12 mg: 44.2%; PBO: 18.5%) and in patients with baseline BSA ≥10% and PASI >12 (23.1%; 28.6%; 0.0%). In patients with baseline BSA ≥3%, decreases in mean PASI at Week 16 were maintained through Week 52 in patients continuing DEUC 6 mg (absolute PASI score, Week 16: 2.39, Week 52: 1.22) and 12 mg (Week 16: 0.64, Week 52: 0.24).
Conclusion: DEUC significantly improved PsO in patients with PsA, regardless of baseline PsO severity and background csDMARD use. Improvement was comparable to that observed in the phase 3 POETYK PSO-1 trial.
The 40-gene Expression Profile (40-GEP) Test Identifies Cutaneous Squamous Cell Carcinoma (cSCC) Patients at High Risk of Metastasis within Lower-Staged Tumors to Better Guide Treatment Decisions
Authors: Somani Ally-Khan , Ibrahim Sherrif , Fitzgerald Alison , Siegel Jennifer , Prasai Anesh , Goldberg Matthew , Farberg Aaron , Cañueto Javier , Arron Sarah 
Published: March 2024

Introduction- The development of metastases has a profound impact on cSCC patient survival. Lower-stage tumors are those that lack factors that portend higher risk for disease progression and therefore not typically considered for increased surveillance or treatment. However, up to one-third of all metastatic events have been reported for patients originally staged as T1. The 40-GEP test is validated to accurately classify risk for regional and/or distant metastasis in patients with primary cSCC with at least one high-risk factor. The current study investigated whether the 40-GEP test could independently improve identification of lower-staged tumors at increased risk of metastasis.
Methods- In an IRB-approved, retrospective, multi-center study, primary tumor tissue and associated clinical data from patients with cSCC and one or more clinicopathologic risk factors (n=897) were collected. Within this overall cohort, lower Brigham and Women’s Hospital (BWH) T-staged samples (n=444 T1 and n=335 T2a) were evaluated by Kaplan-Meier survival analysis to determine metastasis-free survival (MFS) according to 40-GEP risk class (Class 1-low metastatic risk; Class 2A-higher risk; Class 2B-highest risk).
Results- There was a total of 118 metastatic events in the overall cohort, of which 25% (29/118) and 38% (45/118) occurred in BWH T1 and T2a, respectively. BWH T1 tumors had an overall event rate of 6.5% (29/444), with T1/Class 2B tumors having a 5.1-fold increased event rate of 33.3%. BWH T2a tumors had an overall event rate of 13.4% (45/335), with T2a/Class 2B tumors having a 2.7-fold increased event rate of 36.4%. Stratification by the 40-GEP test resulted in significantly different metastasis rates across all three 40-GEP classes within both the T1 and T2a subsets (log-rank tests, p<0.0001 each subset).
Conclusion- Within a cohort of cSCC patients considered lower risk by current staging alone, the 40-GEP identified patients with a substantial increase in metastatic risk. The observed rates of metastasis over 10% and 20% are clinically actionable for nodal staging or postoperative adjuvant radiation, respectively. Combining clinicopathologic risk assessment with individual biologic risk, as provided by the 40-GEP test, improves the accuracy of risk assessment used clinically as the basis of treatment decisions.
Real-World Evidence Confirms Risk Stratification of the 31-GEP and i31-GEP in Prospectively Tested Patients with Stage I-III Cutaneous Melanoma
Authors: Pariser David , Sussman Jeffrey , Martin Brian , Ackerman Lindsay , Kraffert Craig , Jarell Abel 
Published: March 2024

Introduction: Current American Joint Committee on Cancer (AJCC 8th edition) guidelines in patients with cutaneous melanoma (CM) separate them into risk categories based on the pathological tumor data of Breslow thickness, ulceration status, and sentinel lymph node status. The 31-gene expression profile was developed and prospectively validated to identify patients considered high or low risk by AJCC with low or high-risk tumor biology who may be over- or under-treated by current guidelines. To further advance personalized patient care, the 31-GEP result was integrated with clinical and pathological factors (i31-GEP for risk of recurrence, ROR) to provide a personalized, precise risk of tumor recurrence.

Methods: Patients with stage I-III CM enrolled in the CONNECTION study were prospectively tested with the 31-GEP between 2013 and 2017 (n=1,831). Kaplan-Meier analysis with the log-rank test was used to estimate survival differences between low (Class 1A), intermediate (Class 1B/2A), and high (Class 2) risk groups and the i31-GEP risk groups. The i31-GEP ROR combines Breslow thickness, ulceration, SLN status, mitotic rate, tumor location, age, and the 31-GEP result to provide a personalized estimate of recurrence-free survival (RFS). While guidelines have not established a ROR threshold for determining when to escalate or de-escalate care, the NCCN uses stage IIA versus IIB as the cut-point. This cut-point translates to a 5-year RFS rate of 69.8% and was used for the present analysis. Cox multivariable regression analysis was used to identify predictors of recurrence.

Results: Patients with a Class 1A result had higher 5-year RFS than those with a Class 1B/2A or Class 2B result (94.4% vs. 78.6% vs. 65.5%, p<0.001). The following were significant predictors of recurrence in multivariable analysis: Class 1B/2A (HR=2.07, p<0.001), Class 2B (HR=2.40, p<0.001), positive SLN (HR=4.54, p<0.001), Breslow thickness (HR=1.09, p=0.028), presence of ulceration (HR=1.57, p=0.005), mitotic rate >2/mm2 (HR=1.47, p=0.016), and age (HR=1.02, p<0.001). Patients with a low-risk i31-GEP result had significantly higher 5-year RFS than those considered high risk by the i31-GEP (92.4% vs. 49.7%, p<0.001).

Conclusions: The i31-GEP is validated in a real-world group of prospectively tested patients. The independent i31-GEP ROR test result improves identification of patients whose management should be escalated or de-escalated within current guidelines.
Early Acne Improvements With Fixed-Dose Clindamycin Phosphate 1.2%/ Adapalene 0.15%/Benzoyl Peroxide 3.1% Gel: What to Expect in the First 4 Weeks of Treatment
Authors: Harper Julie , Kircik Leon , Gold Michael , Hebert Adelaide , Sugarman Jeffrey , Green Lawrence , Stein Gold Linda , Baldwin Hilary , Del Rosso James , Guenin Eric 
Published: March 2024

Background: Treatments with fast and substantial acne clearance are highly desirable. While a three-pronged approach may increase treatment efficacy versus monotherapy or dual-combination therapy, it is unknown if triple-combination provides more rapid improvement. CAB gel—clindamycin phosphate (clin) 1.2%/adapalene 0.15%/benzoyl peroxide (BPO) 3.1%—is the first fixed-dose, triple-combination acne topical. Since rapid/substantial acne improvements and fewer side effects can increase adherence, the efficacy and safety of CAB in the first 4 weeks of treatment was evaluated.
Methods: In a phase 2 (N=741; NCT03170388) and two phase 3 (N=183; N=180; NCT04214639; NCT04214652), double-blind, 12-week studies, participants aged ≥9 years with moderate-to-severe acne were randomized to once-daily CAB or vehicle gel; the phase 2 study included 3 additional dyad arms: BPO/adapalene; clin/BPO; and clin/adapalene. Efficacy assessments included least-squares mean percent change from baseline in inflammatory and noninflammatory lesions. Cutaneous safety/ tolerability assessments were graded from 0=none to 3=severe. Post hoc analyses included percentages of participants with one-third and one-half acne lesion reductions.
Results: At week 4, CAB led to ~55% reductions from baseline in inflammatory acne lesions in the ph2 and pooled ph3 studies, significantly greater than vehicle (~40%) and its 3 dyads (ph2 range: 44.2-47.6%; P<0.05, all). The percentages of participants with one-third and one-half reductions of inflammatory lesions were significantly greater with CAB than vehicle and dyads (P<0.05, all). Similar trends were observed for noninflammatory lesions, though reductions were less pronounced. As expected for retinoids, transient increases from baseline to week 2 in scaling, erythema, itching, burning, and stinging were observed for CAB, BPO/adapalene, and clin/adapalene, with mean scores ≤0.6 (1=mild); no trends in dyspigmentation were observed. Mean scores for all cutaneous assessments were highest for BPO/adapalene, indicating that adding a third product in the fixed-dose CAB gel formulation did not worsen tolerability.
Conclusions: Acne lesion reductions were significantly greater with clin 1.2%/ adapalene 0.15%/BPO 3.1% gel versus its dyads and vehicle gel as early as week 4. More rapid efficacy with this first fixed-dose triple-combination acne product—coupled with its optimized formulation, once-daily dosing, and tolerability—may positively impact treatment adherence.
Funding: Ortho Dermatologics.
Clinical Efficacy and Patient Reported Impacts of Roflumilast Foam 0.3% in Seborrheic Dermatitis: An Analysis of STRATUM Data for Patients Unresponsive or Intolerant to Topical Corticosteroids
Authors: Chu David , Stephenson Brett , Lee Jeff , Bannister Breyanne , Hickey Conor , Westley Tracy , Zirwas Matthew 
Published: March 2024

Objective. Roflumilast foam 0.3% has demonstrated efficacy and tolerability in a Phase 3 clinical trial of moderate-to-severe seborrheic dermatitis (SD) patients (STRATUM). The aim of this subgroup analysis is to assess the efficacy and patient-reported quality of life (QOL) effects of roflumilast vs vehicle in patients with an inadequate response, intolerance, or contraindication to topical corticosteroids (TCS).
Methods: Patients 9 years or older with at least moderate seborrheic dermatitis (Investigator Global Assessment [IGA] ≥ 3) were randomized 2:1 to roflumilast or vehicle for 8 weeks. Patients reporting a history of inadequate response, intolerance, or contraindication to topical corticosteroids (TCS) were included in this subgroup analysis. The primary efficacy endpoint was IGA success (Clear or Almost Clear with at least a 2-grade improvement) at Week 8. QOL was assessed using the Dermatology Life Quality Index (DLQI) for patients aged ≥17 years. QOL endpoints included percentage change from baseline in DLQI score, achievement of a minimal important difference (MID; defined as at least a 4-point reduction in DLQI score), and patients achieving a DLQI score of 0 or 1 by treatment group at weeks 2, 4, and 8. Differences in change from baseline DLQI scores were assessed using the Kruskal-Wallis rank sum test. The Cochran–Mantel–Haenzel test was used to assess differences in the proportion of patients achieving binary endpoints between treatments.
Results: 189 patients (129 roflumilast, 60 vehicle) were included in the subgroup analysis. At Week 8, 78.8% of roflumilast patients achieved IGA success vs. 48.3% of vehicle patients (odds ratio [OR] 3.45; 95% confidence interval [CI]: 1.62, 7.36; p<0.001). At each time point, percentage change from baseline in DLQI score was significantly larger for roflumilast-treated patients relative to vehicle (p≤0.001). Treatment with roflumilast significantly increased the odds of achieving an MID in DLQI across all time points (OR: 6.97; 95% confidence interval [CI]: 3.97, 12.24; p<0.001) and achieving a DLQI score of 0 or 1 (OR: 2.46; 95% CI: 1.58, 3.81; p<0.001).
Conclusions: Roflumilast foam 0.3% provided significant and meaningful efficacy with improved QOL in patients with moderate-to-severe SD who had a prior history of an inadequate response, intolerance, or contraindication to TCS. Clinical improvement aligned with patient-reported outcomes at all key assessment periods.
Developing EFL Critical Reading Aids: Project-Based Learning Activities for Electrical Industrial Engineering Students
Authors: Khulaifiyah Khulaifiyah , Milawati Milawati , Suparti Suparti 
Published: March 2024

The Independent Learning and Independent Campus (MBKM) curriculum for vocational education provided learning experiences for students. However, the reading material conducted had not reached the curriculum target. Thus, this study aimed to develop critical reading material and worksheets based on the MBKM curriculum. The development procedure was designed in three stages: defining, designing, and developing for 3-D aids. The research resources employed were validation sheets for critical reading aids and semi-observation sheets to provide student activity during PjBL field trial. The results of this study were project-based learning (PjBL) used to construct English language learning aids for the syllabus and coursework units, including worksheets for critical reading. Hence, this learning aid could slightly enhance students' reading competence, which could lead them to have soft and hard skills as well as meet the MBKM curriculum target.