bluuebunny/crossref_metadata_2025 huggingface dataset:
Perawatan ulang saluran akar gigi molar kanan mandibula
Authors: Stefani Rosita , Steward
Published: November 2024

Background: An inadequate root canal treatment allows bacteria to thrive and survive, which is a major cause of endodontic failure. An appropriate treatment plan can be determined after a precise and accurate diagnosis has been made. Objective: The purpose of this case report is to demonstrate the root canal retreatment on a posterior mandibular tooth with periapical lesions. Case report: A 37-year-old female patient came with complaints of discomfort when chewing food with her lower right back tooth. The tooth had been treated ten years ago with a metal filling, which was replaced with a tooth-colored filling a year ago. Intra-oral examination of tooth 46 showed composite resin restoration on the distobuccal surface. Radiographic findings showed that there was restoration on the distal surface that reaches the floor of the pulp chamber and radiolucency in the furcation area. Root canal retreatment was performed based on the diagnosis of acute apical periodontitis et causa necrotic pulp. The treatment plan involved root canal retreatment with direct resin composite restoration. Root canal retreatment starts with the application of a rubber dam, followed by the removal of any existing restoration and caries, opening the cavity, root canal exploration, and root canal shaping. Biomechanical preparation was carried out with Protaper Hand Use with crown down technique, in conjunction with 2,5% NaOCl irrigation. The initial visit concludes with the disinfection of the root canal with calcium hydroxide. The following treatment involved a subjective and objective assessment, removal of the temporary filling, cleaning of calcium hydroxide, and final irrigation with 2,5% NaOCl, 17% EDTA, and 2% CHX. Obturation was accomplished utilizing the vertical condensation technique. The restoration was completed with composite resin. Conclusion: Root canal retreatment on teeth with acute apical periodontitis et causa necrotic pulp was successfully carried out.
Penerapan green dentistry dalam praktik kedokteran gigi
Authors: Hapsari Andayani Lia , Gani Soulisa Abdul
Published: November 2024

Environmental breakdown and global warming have become two of the important issues today. One of the factors contributing to those issues is improper waste management. Medical waste from dental practices significantly contributes to pollution and accumulated waste, causing environmental degradation. The concept of Green Dentistry was introduced in 2007 as a solution to preserve natural resources and reduce waste. Green Dentistry is a multi-sectoral approach based on the 4R principles: Reduce, Reuse, Recycle, and Rethink. Reduce means reducing the consumption of resources as well as becoming more energy efficient. Reuse involves encouraging the prolonged use of an item to prevent substantial waste production. Recycle refers to reprocessing an item into a new product so that it can be useful again. Rethink means redeveloping mindset as a strategy to change, as well as promoting effective alteration. Practices aligned with the concept of Green Dentistry need to be implemented to achieve environmental sustainability. Ideas of forming an eco-friendly dental practice must be supported with knowledge and feasible solutions to overcome the barriers.
Penatalaksanaan celah bibir
Authors: Putri Sekar Palupi Anggraeny
Published: November 2024

Cleft-lip is one of the congenital abnormalities that often occur in the orofacial area. Patients with orofacial cleft abnormalities need to be treated in the right way and at the right time in order to get functional and aesthetic results. Cleft lip management involves interdisciplinary collaboration from dentists, oral surgeons, orthodontists, prosthodontists, ear, nose, throat, speech specialists, and others
Kebebasan berbicara versus pertimbangan keamanan cyber menurut perspektif hukum dan HAM
Authors: Nurhayati Siti , Salsabila Lia , Hidayat Rizal
Published: November 2024

Freedom of speech is a human right and is also stated in the 1945 Constitution of the Republic of Indonesia Article 28 E Paragraph 3 concerning freedom of association, freedom to express opinions or be given freedom of speech, but this freedom also has other provisions regarding the use of this right. in the regulations regarding cyber security in Republic of Indonesia Law Number 3 of 2002 concerning Defense. The state states that national defense aims to maintain and protect the sovereignty of the country, the territorial integrity of the Unitary State of the Republic of Indonesia (NKRI) and the safety of the entire nation from all forms of threats, both military and non-military threats. Non-military threats, especially in cyber space, have caused the country's capabilities in the field of soft and smart power defense to be improved through strategies for deterring, taking action and restoring cyber defense in order to support the implementation of the national cyber security strategy driven by the Ministry of Communication and Information. Indonesian law also does not provide legal certainty in dealing with cyber attacks such as cyber espionage. Cyber security is not only the responsibility of the government, but also the responsibility of every individual. Awareness about the dangers of cyber espionage needs to be instilled in everyone. The National Police has a role in protecting society from cyber attacks.
A utilização da terapia cognitiva comportamental no tratamento da depressão em pacientes com doença de Parkinson: uma revisão integrativa
Authors: Vieira Bianca Araujo , Silva Alexandre Almeida da , Santos Júlio César Claudino dos
Published: November 2024

Introdução: A Doença de Parkinson (DP) é uma condição neurodegenerativa caracterizada pela degeneração da substância negra e está associada a complicações motoras e não motoras debilitantes. O surgimento de sintomas depressivos, por vezes, antecede os sintomas motores, podendo caracterizar-se como os primeiros indícios da DP. A aplicação da terapia farmacológica mediante o uso de antidepressivos em pacientes afetados pela depressão na DP é frequentemente adotada. Entretanto, as terapias não farmacológicas podem ser integradas ao protocolo terapêutico, logo, o objetivo do presente estudo é investigar a aplicabilidade e viabilidade da terapia cognitivo-comportamental, considerando tanto a modalidade presencial quanto às abordagens de telessaúde. Métodos: trata-se de uma revisão integrativa da literatura baseada no método de Whittemore e Knafl, no qual configura-se sendo um método de pesquisa que possibilita a síntese e análise do que existe de produção sobre a utilização da terapia cognitiva comportamental no tratamento da depressão em pacientes com Doença de Parkinson. Resultados: Neste estudo, realizamos uma revisão integrativa sobre a eficácia da terapia cognitivo-comportamental (TCC) no tratamento da depressão em pacientes com Doença de Parkinson (DP). Observamos que, embora alguns estudos sugiram benefícios adicionais quando a TCC é combinada com medicamentos, há interesse em investigar sua eficácia isolada. Diferentes escalas foram usadas para avaliar os sintomas depressivos, destacando-se a Escala de Avaliação de Depressão de Hamilton. Algumas intervenções incluíram estratégias de sono para melhorar o bem-estar geral. Notavelmente, a metodologia variou entre os estudos, com alguns optando por intervenções virtuais, o que mostrou uma menor taxa de abandono. Conclusão: Em suma, nossa revisão ressalta a eficácia da terapia cognitivo-comportamental (TCC) no tratamento da depressão em pacientes com Doença de Parkinson (DP). Embora a combinação com medicamentos pareça promissora, nossos resultados indicam que a TCC isolada também pode ser benéfica. Diante disso, sugerimos investigações adicionais focadas em intervenções virtuais, visando melhorar a acessibilidade e a adesão ao tratamento para essa população.
La reutilización del agua como servicio público (la experiencia de la Ley de Aguas de Canarias)
Authors:   Universidad de La Laguna (España), Villar Rojas Francisco José
Published: November 2024

European Regulation 2020/741 establishes a set of obligations on water reuse that raise the question of whether compliance requires the implementation of a new public service. Since 1990, the Canary Islands Water Law of 1990 declares the reuse of water a public service. This work analyzes the meaning of that legal declaration, the reasons behind and its effectiveness in the years since its approval. That reference allows identify the elements that are necessary so that water reuse could be configured as a public service.
Analysis Of Opportunities For Implementing The Amicus Curiae Concept As A Form Of Public Participation In The Judicial System In Indonesia
Authors: Thomas Jerry , Liman Vivaldi
Published: November 2024

This research uses the normative juridical method, and it aims to determine the amicus curiae mechanism in the Indonesian legal system. The research results show that the implementation of amicus curiae in the judicial system in Indonesia still needs a common perspective among judges, where there are still judges who accept or reject this concept or do not even consider it at all. The concept of amicus curiae in the Indonesian legal system has yet to be a significant consideration because no explicit regulations accommodate it. Still, it is often stated that the position of amicus curiae is embodied through Article 5 of Act Number 48 of 2009 on Judicial Power, which mandates judges to explore, follow, and understand legal values and a sense of justice that lives in society. In line with these provisions, the judge has the authority to provide space and open up the broadest possible information and opinions from various groups who pay special attention to a case being examined.  Judges using amicus curiae in their considerations, both from a philosophical, sociological, and juridical perspective, aim to prioritize legal certainty and provide justice with the participation of society. The research then provides a suggestion that the Supreme Court of the Republic of Indonesia can issue a Policy Circular or through a Decree of the Chief Justice of the Supreme Court regarding guidelines that judges can use to implement amicus curiae and how to assess the quality of information in amicus curiae.
Impactos do uso de telas na saúde ocular de universitários em Brasília-DF
Authors: Gonçalves Beatriz Moraes , Cunha Danielle Braz Amarilio da , Pinheiro João de Sousa Barbosa
Published: November 2024

Objetivo: O estudo avaliou a prevalência das manifestações clínicas da SVC e os fatores associados a essa condição em discentes universitários. Métodos: Foi realizada uma análise epidemiológica, quantitativa e retrospectiva de 3 formulários on-line. Ao todo, 158 questionários foram respondidos, porém apenas 85 foram selecionados para composição do estudo. Para a realização da análise estatística, as variáveis das respostas foram colocadas no software ®Microsoft Excel e no software estatístico R, nos quais foram feitos o teste de proporção e o teste qui-quadrado para comparação da frequência das respostas. Considerou-se nível de significância 0,05 e índice de confiança de 95%. Resultados: Evidenciou-se que o sintoma mais prevalente da SVC nesse estudo foi a dor de cabeça e/ou ombro. Tal achado, quando associado ao sexo, mostrou que o sexo feminino teve forte relação com a piora dos sintomas, mas não se sabe o principal motivo desse achado. Outrossim, percebeu-se que o tipo de iluminação interfere no aparecimento da SVC, sendo mais acentuado em um ambiente bem iluminado. Conclusão: A SVC pode impactar negativamente na qualidade de vida dos acadêmicos e, inclusive, potencializar o desenvolvimento de doenças oculares.
Concomitant Eruptive Squamous Atypia and Bullous Drug Eruption Associated with Pembrolizumab
Authors: Yang Kevin , Ho-Pham Hoang , Beam Jordan , Kole Lauren
Published: November 2024

This study involves the case of a rare eruptive squamous atypia (ESA) reaction and concurrent bullous eruption following pembrolizumab treatment for recurrent neck squamous cell carcinoma. This report aims to raise awareness to possible concurrent skin reactions related to PD-1 inhibitor treatment that has otherwise only been reported twice in melanoma patients.
The Non-Healing Wound: An Early Clue to Calciphylaxis
Authors: Reeves Carlie
Published: November 2024

Calciphylaxis, also known as calcific uremic arteriolopathy (CUA), is a rare disease that presents as painful, necrotic lesions. While calciphylaxis is most commonly associated with renal insufficiency, calciphylaxis can occur in those without renal impairment. A case of non-uremic calciphylaxis occurring at a below-knee amputation site presenting as a single non-healing wound is provided; this presentation stands in stark contrast to the multiple, exquisitely painful lesions that are typical of calciphylaxis.
Photosensitivity Dermatitis associated with the Moderna Booster Vaccination
Authors: Hudson Hadley , Shah Milaan
Published: November 2024

Adverse reactions have been documented following administration of mRNA COVID vaccinations, including systemic and local cutaneous reactions. Cutaneous reactions have been reported more frequently and of greater severity when vaccinated with the Moderna vaccine compared to the Pfizer/BioNTech vaccine. While multiple studies have investigated cutaneous reactions following initial vaccinations, few have reported on the effects of booster vaccinations, specifically in individuals of darker skin color. Additionally, we have found no reported cases of photosensitive dermatitis following vaccination. Thus, we present a case of photosensitivity dermatitis likely secondary to a booster shot of the Moderna vaccination in a Fitzpatrick Type IV 81-year-old female patient.
Ixekizumab Improves Nail, Scalp, and Skin Response and Quality of Life Independent of Baseline Psoriasis Severity: Results From the Psoriasis in Special Areas (PSoSA) Study
Authors: Lipner Shari , Owen Cindy , Korman Neil , Malatestinic William , Feely McDonald Meghan , Murage Mwangi James , Sheikhi Mehrabadi Ali , Merola Joseph
Published: November 2024

Background: Ixekizumab has shown impressive efficacy among patients with nail, skin, and scalp psoriasis. Here, we present real-world data from the PSoSA study evaluating effectiveness of ixekizumab by cohorts of patients with mild and moderate/severe nail psoriasis.
Methods: PSoSA is an ongoing, prospective, multicenter, single-arm, observational study enrolling adult patients with confirmed diagnosis of moderate-to-severe psoriasis and nail involvement, with or without scalp involvement, initiating ixekizumab in a US dermatology clinic. Assessment of improvements in nail (by modified Nail Psoriasis Severity Index [mNAPSI], with scoring range 0–130), skin (by Psoriasis Area and Severity Index [PASI], with scoring range 0–72), and scalp (by Psoriasis Scalp Severity Index [PSSI], with scoring range 0–72) response and in quality of life (by Dermatology Life Quality Index [DLQI], with scoring range 0–30) were collected at weeks (W) 4, 12, 24, and 52. Percent change was calculated for patients with non-missing baseline values. Data were stratified by nail psoriasis severity at baseline; patients with mNAPSI scores <20 were categorized as mild while those with scores ≥20 were categorized as moderate/severe. In our second interim analysis, we will be reporting data to W24.
Results: Of 182 patients included in the analysis, 101 patients had baseline mNAPSI scores <20 and 81 had scores ≥20. Median percent changes from baseline in mNAPSI response at W4, W12, and W24 were −12.2, −33.3, and −71.9, respectively, for patients with baseline scores <20 and −6.1, −38.7, and −68.6, respectively, for patients with scores ≥20. Median percent changes from baseline in PASI response at W4, W12, and W24 were −60.0, −91.2, and −100.0, respectively, for patients with baseline mNAPSI scores <20 and −62.7, −91.4, and −96.7, respectively, for patients with scores ≥20. Median percent changes from baseline in PSSI response at W4, W12, and W24 were −79.3, −100.0, and −100.0, respectively, for patients with baseline mNAPSI scores <20 and −87.5, −100.0, and −100.0, respectively, for patients with scores ≥20. Median percent changes from baseline in DLQI response at W4, W12, and W24 were −66.7, −77.8, and −89.7, respectively for patients with baseline mNAPSI scores <20, and −57.1, −70.0, and −88.7, respectively, for patients with scores ≥20.
Conclusions: In a real-world setting, patients with moderate-to-severe psoriasis initiating ixekizumab saw major improvements in nail, skin, and scalp response as well as quality of life as early as 4 weeks and sustained through 24 weeks, independent of nail psoriasis severity at baseline.
Deucravacitinib in Plaque Psoriasis: Laboratory Parameters Through 4 Years of Treatment in the Phase 3 POETYK PSO-1, PSO-2, and LTE Trials
Authors: Korman Neil J. , Passeron Thierry , Okubo Yukari , Bagel Jerry , Warren Richard B. , Spelman Lynda , Winthrop Kevin , Hoyt Kim , Scharnitz Thomas , Banerjee Subhashis , Thaçi Diamant , Shahriari Mona , Stein Gold Linda
Published: November 2024

Introduction: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in multiple countries for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. Deucravacitinib was efficacious versus placebo and apremilast and was well tolerated in the global, 52-week, phase 3 POETYK PSO-1 (NCT03624127) and POETYK PSO-2 (NCT03611751) parent trials. At Week 52, patients could enroll in the ongoing POETYK long-term extension (LTE) (NCT04036435) trial and receive open-label deucravacitinib. Changes in blood laboratory parameters known to be associated with Janus kinase (JAK) 1,2,3 inhibitors were evaluated through 4 years of deucravacitinib treatment.
Methods: Changes from baseline in lipid (cholesterol, triglycerides), chemistry (alanine aminotransferase [ALT], aspartate aminotransferase [AST], creatinine, creatine phosphokinase [CPK]), and hematology (hemoglobin, lymphocytes, neutrophils, platelets) parameters in the blood known to be affected by JAK1,2,3 inhibitors in clinical trials were evaluated through Week 208 (4 years; data cutoff, November 1, 2023). Treatment discontinuations due to laboratory abnormalities were assessed.
Results: A total of 1519 patients received ≥1 deucravacitinib dose (total exposure, 4392.8 person-years); 1203 (79.2%) had ≥52 weeks and 542 (35.7%) had ≥208 weeks of continuous deucravacitinib exposure (median, 185 weeks). No trends or clinically meaningful mean changes from baseline were observed in any of the above laboratory parameters. In total, 3 patients discontinued treatment due to increased CPK, and 1 patient each discontinued due to lymphopenia, abnormal hepatic function, increased ALT, and increased AST. Discontinuations due to triglyceride elevations were not observed.
Conclusion: In PSO-1/PSO-2/LTE, no trends or clinically meaningful mean changes from baseline were observed in lipid, chemistry, or hematology parameters, in contrast to signature changes (eg, increased cholesterol, creatinine, serum transaminases, CPK, cytopenias) observed with JAK1,2,3 inhibitors. Discontinuations due to laboratory abnormalities noted above were rare (n=7 events) through 4 years of deucravacitinib treatment. Results suggest deucravacitinib treatment does not warrant routine laboratory testing for all patients, in contrast with the requirements for JAK1,2,3 inhibitors, reflecting its selectivity for TYK2.
Deucravacitinib, an Oral Selective Tyrosine Kinase 2 (TYK2) Inhibitor, in Patients with Moderate to Severe Scalp Psoriasis: Efficacy and Safety Results of a Phase 3b/4, Multicenter, Randomized, Double-blinded, Placebo-controlled Trial (PSORIATYK SCALP)
Authors: Duffin Kristina Callis , Griffiths Christopher E. M. , Hoffmann Matthias , Blauvelt Andrew , Balagula Eugene , Napoli Andrew , Jou Ying-Ming , Dyme Rachel , Hala Virginia , Pinter Andreas , Lebwohl Mark
Published: November 2024

Introduction: Deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, is approved in multiple countries for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. PSORIATYK SCALP, an ongoing, 52-week, phase 3b/4, multicenter, randomized, double-blinded, placebo-controlled trial, evaluated deucravacitinib efficacy/safety in patients with moderate to severe scalp psoriasis, including those with more limited overall psoriasis.
Methods: Adults with moderate to severe scalp psoriasis defined by more focused and objective inclusion criteria (ss-PGA ≥3, scalp surface area involvement ≥20%, and PSSI ≥12 at baseline) and BSA involvement ≥3% were randomized 1:2 to oral placebo or deucravacitinib 6 mg once daily through Week 16. The primary efficacy outcome was ss-PGA 0/1; key secondary outcomes were PSSI 90, change from baseline in scalp-specific itch numeric rating scale (NRS), and sPGA 0/1 at Week 16. Efficacy outcomes were evaluated at Week 16 for the overall population and the subpopulation with global sPGA ≥3. Nonresponder imputation and modified baseline observation carried forward were used for patients who discontinued or had missing data for binary and continuous outcomes, respectively.
Results: 154 patients were randomized (placebo, n=51; deucravacitinib, n=103). Baseline characteristics were similar in each group (placebo: mean BSA 10.0%, PASI 9.4, PSSI 32.2; deucravacitinib: mean BSA 10.5%, PASI 10.2, PSSI 33.5). In the overall population, a higher proportion of patients receiving deucravacitinib versus placebo achieved ss-PGA 0/1 at Week 16 (48.5% vs 13.7%; P<0.0001). Deucravacitinib was superior to placebo for PSSI 90 (38.8% vs 2.0%; P<0.0001) and mean change from baseline in scalp-specific itch NRS (−3.2 vs −0.7; P<0.0001). In the subpopulation (sPGA ≥3), a greater proportion achieved sPGA 0/1 with deucravacitinib versus placebo (51.0% vs 4.3%; P<0.0001). The most common adverse events (AEs) in the deucravacitinib group (≥5%) were nasopharyngitis (14.6%), upper respiratory tract infection (11.7%), acne (9.7%), headache (7.8%), COVID-19 (5.8%), and pustular acne (5.8%). Two serious AEs were reported (1/group); neither was considered treatment related or led to discontinuation.
Conclusion: Deucravacitinib was efficacious and well tolerated in patients with moderate to severe scalp psoriasis, including those with less extensive overall psoriasis (BSA ≥3%). The overall psoriasis response rate (sPGA 0/1) was consistent with POETYK trial results, despite including patients with more limited BSA involvement. Safety findings were consistent with the known deucravacitinib safety profile.
Real-World Achievement of Skin Clearance Targets and Improved Quality of Life With Risankizumab in Psoriasis Patients With Moderate Skin Involvement (BSA ≥ 3–10%)
Authors: Strober Bruce , Patel Manish , Kaldas Mark I , St John Greg , Garg Vishvas , Sima Adam P , Eckmann Thomas , Beeghly Alicia , Armstrong April
Published: November 2024

none
Treatments Used Among Patients with Psoriasis: A First Look at a New Patient-Centered Psoriasis Registry
Authors: Ogdie Alexis , Gelfand Joel , N’Dri Laetitia , Wu Ying , Scharnitz Thomas , Michaud Kaleb
Published: November 2024

Introduction: Psoriasis management in the US has changed substantially, with increasing treatment options including new topical, oral, and biologic medications. The objective of this study was to examine the demographics, disease characteristics, and treatment usage in the first patients enrolled in the new patient-centered psoriasis registry, the FORWARD Psoriasis Registry.
Methods: Adult patients with psoriasis were recruited from dermatology offices as part of a national practice group, through a patient support program for deucravacitinib, and online from the FORWARD registry website between August and December 2023. Patients were not required to be on therapy for psoriasis. We descriptively report demographics, disease characteristics, and current treatments at enrollment.
Results: A total of 702 patients met inclusion criteria and completed the full enrollment questionnaire. Mean age was 53 years and 66% were female; mean BMI was 30 (SD 7); 88% self-reported as White and 6% as Hispanic. A diagnosis of psoriatic arthritis was reported by 28%. Most (75%) had private insurance. Median psoriasis duration was 10 (IQR 3–23) years. 85% had plaque psoriasis, 19% guttate, 14% inverse, 6% generalized pustular, and 3% erythrodermic. Body surface area as assessed by the PREPI questionnaire was minimal (<1% BSA) in 21%, mild (1%–2%) in 39%, moderate (3%–10%) in 34%, and severe (>10%) in 6%. The most commonly used therapies included IL-23 inhibitors (11%), IL-17 inhibitors (8%), apremilast (7%), and TNF inhibitors (5%). Additionally, 14% of the cohort were using deucravacitinib; 62% reported using topicals, and 48% reported use of any systemic agent.Conclusion: The FORWARD psoriasis registry represents a new patient-centered approach and proof of concept for studies seeking to understand the natural history of the disease, treatment outcomes, and treatment needs relevant for individuals with psoriasis, and long-term outcomes related to comorbidities.
Zasocitinib (TAK-279), a Selective, Oral TYK2 Inhibitor, Reduces Body Surface Area Involvement in a Phase 2b Trial in Moderate-to-Severe Plaque Psoriasis
Authors: Laquer Vivian , Kircik Leon H. , Sadick Neil , Weisman Jamie , Blau Jessamyn , Zhang Wenwen , Uy Jonathan , Winkelman Warren , Gooderham Melinda
Published: November 2024

Background: Zasocitinib (TAK-279) is an oral, allosteric, and highly selective inhibitor of tyrosine kinase 2 (TYK2). TYK2 mediates signaling from cytokines involved in the pathogenesis of psoriasis and other immune-mediated inflammatory diseases. In a phase 2b trial in patients with moderate-to-severe plaque psoriasis (NCT04999839), zasocitinib was well tolerated and demonstrated safety and efficacy, with a greater proportion of patients achieving skin clearance at doses ≥5 mg compared with placebo, with the two highest doses (15mg and 30mg) showing the strongest responses at Week 12. This analysis further evaluated the efficacy of the 15mg and 30mg doses of zasocitinib using body surface area (BSA) involvement.
Methods: In this randomized, multicenter, double-blind, placebo-controlled trial, patients with moderate-to-severe plaque psoriasis were randomized 1:1:1:1:1 to receive oral zasocitinib (2, 5, 15 or 30mg) or placebo, once daily for 12 weeks. BSA outcome measures assessed at Week 12 were mean change in BSA from baseline, mean percentage change in BSA from baseline and the proportion of patients achieving a BSA threshold of ≤1% by visit. Mean change in BSA from baseline was prespecified.
Results: Baseline mean (standard deviation [SD]) percentage BSA was generally consistent across the zasocitinib 15mg (n=53; 18.3 [10.3]), zasocitinib 30mg (n=52; 22.2 [14.3]) and placebo (n=52; 21.3 [13.6]) groups. Mean percentage BSA decreased as early as Week 2 and continued to decrease through to Week 12 in the zasocitinib groups, whereas scores slightly decreased in the placebo group. At Week 12, mean(SD) percentage BSA was 4.4 (5.3) (least-squares [LS] mean change: −14.7; LS mean percentage change: −72.9%) in the 15mg group, 6.5 (12.5) (LS mean change: −15.7; LS mean percentage change: −73.1%) in the 30mg group and 18.2 (13.6) (LS mean change: −4.0; LS mean percentage change: −19.3%) in the placebo group (p<0.001 for both doses versus placebo). From Week 8 onwards, higher proportions of patients achieved a BSA threshold of ≤1% in the zasocitinib 15mg and 30mg groups than in the placebo group (35.8% and 44.2% versus 0% at Week 12, respectively).
Conclusion: Patients with moderate-to-severe plaque psoriasis who received the two highest doses of zasocitinib (15mg and 30mg) in the phase 2b trial achieved greater reductions in BSA than those who received placebo over 12 weeks. Further investigation of the efficacy and safety of zasocitinib in phase 3 studies in psoriasis is ongoing (NCT06088043; NCT06108544).
Real-World Switch Rates of Risankizumab and Other Biologics in Psoriasis Patients With Psoriatic Arthritis
Authors: Armstrong April W. , Patel Manish , Babcock Zachary R. , Li Chao , Wu Jashin J.
Published: November 2024

Background: Psoriatic patients often experience issues with lack of therapeutic efficacy and intolerance, which may result in high levels of treatment switching. This study examined real-world, 12-month switch rates and patient characteristics associated with treatment switching in patients with both PsO and PsA treated with risankizumab and other biologics.
Methods: This analysis used the Merative MarketScan® Databases (2016–2024) to identify adults from the US who had ≥2 medical claims for PsO, 1 claim for PsA and did not have any other autoimmune condition in the 6 months pre- and post-index period. Patients must have initiated a PsO-approved biologic and have continuous insurance benefits for ≥6 months before and ≥12 months after the biologic initiation date. Switch rates were defined as the proportion of patients who switched to a new biologic or advanced oral in the 12-month follow-up after treatment initiation. Discontinuation and non-adherence were not included in the switch definition. Switch rates were compared between biologics with sufficient sample size (n 100). Univariate logistic regression analyses were conducted to compare switch rates for risankizumab versus other biologics. Multivariate logistic regression analyses were performed to examine the impact of baseline demographic and treatment characteristics on switch rates and determine predictors of switching.
Results: Among 3032 patients, mean age at baseline was 47.4 (SD 10.78) years and 55.4% were female. Overall treatment switch rate at 12-month follow-up was 24.9% (756/3032). Of those treatments with sufficient sample size, patients receiving risankizumab had the lowest switch rate (7.3%; 15/206) compared to all other biologics, including other IL-23 inhibitors (guselkumab 16.7%, P=0.0029), IL-17 inhibitors (ixekizumab 22.4%, P<0.0001; secukinumab 23.7%, P<0.0001), TNF inhibitors (adalimumab 28.3%, P<0.0001; etanercept 35.8%, P<0.0001), and IL-12/23 inhibitors (ustekinumab 22.4%, P<0.0001). Results were similar in multivariate logistic regression analyses after adjusting for variations in baseline characteristics. Predictors of switching at 12 months included female sex (adjusted odds ratio [aOR] [95% CI]: 1.63 [1.36, 1.94]; P<0.0001), baseline anxiety or depression (aOR [95% CI]: 1.47 [1.21, 1.80]; P=0.0001), baseline major adverse cardiovascular event (aOR [95% CI]: 1.47 [1.15, 1.88]; P=0.0023), and prior targeted immunomodulator (TIM) use (aOR [95% CI]: 1.45 [1.20, 1.74]; P=0.0001).
Conclusion: In a real-world setting, switching was common among psoriasis patients with PsA. Risankizumab showed the lowest rate of treatment switching at 12 months, compared with all other biologics. Sex, comorbidities, and prior TIM use were predictors of higher switch rates.
Long-Term Maintenance of Optimal Treatment Targets for Skin and Itch Outcomes With Upadacitinib in Moderate-to-Severe Atopic Dermatitis: 140-Week Results From the Phase 3 Measure Up 1 and 2 Studies
Authors: Issa Naiem T , Chovatiya Raj , Talia Jordan , Torres Tiago , Eyerich Kilian , Calimlim Brian M , Yang Yang , Pechonkina Alena , Moreira Alvaro , Grada Ayman , Bunick Christopher G
Published: November 2024

Introduction: Despite undergoing prolonged systemic therapy, many patients with moderate-to-severe atopic dermatitis (AD) do not achieve optimal targets for skin and itch outcomes as defined by Aiming High in Eczema/AD (AHEAD) recommendations (eg, ≥90% improvement from baseline in Eczema Area and Severity Index [EASI 90] and Worst Pruritus Numerical Rating Scale [WP-NRS] score of 0/1 [no/minimal itch]). We evaluated long-term maintenance of optimal treatment targets with upadacitinib, an oral selective JAK inhibitor approved for moderate-to-severe AD in adolescents and adults.
Methods: This 140-week interim analysis included adolescents and adults with moderate-to-severe AD who were randomized at baseline to upadacitinib 15 mg (UPA15) or 30 mg (UPA30) in the ongoing, phase 3, double-blind Measure Up 1 and 2 studies. Assessments included the proportion of patients (at the population level) who maintained EASI 90, WP-NRS 0/1, or simultaneous achievement of EASI 90 + WP-NRS 0/1 responses from week 16 (end of the placebo-controlled period) onwards. Data are reported as observed cases with no imputation for missing data.
Results: Among patients who achieved EASI 90 at week 16 (UPA15, n=298; UPA30, n=384), EASI 90 was maintained by 79.8% (UPA15) and 83.7% (UPA30) at week 52, 76.7% (UPA15) and 83.0% (UPA30) at week 100, and 74.0% (UPA15) and 84.2% (UPA30) at week 140. Of patients achieving WP-NRS 0/1 at week 16 (UPA15, n=193; UPA30, n=281), WP-NRS 0/1 was maintained by 69.4% (UPA15) and 72.0% (UPA30) at week 52, 65.6% (UPA15) and 68.4% (UPA30) at week 100, and 62.3% (UPA15) and 66.0% (UPA30) at week 140. Of patients simultaneously achieving EASI 90 + WP-NRS 0/1 at week 16 (UPA15, n=156; UPA30, n=243), maintenance was achieved by 68.1% (UPA15) and 70.8% (UPA30) at week 52, 62.7% (UPA15) and 66.5% (UPA30) at week 100, and 58.7% (UPA15) and 64.4% (UPA30) at week 140. Among patients who did not maintain optimal outcomes, most still achieved clinically meaningful responses.
Conclusion: Most patients maintained optimal skin and itch outcomes through 140 weeks of upadacitinib treatment, demonstrating its potential to provide sustained long-term disease control in atopic dermatitis.
Switching from Dupilumab to Upadacitinib in Adults and Adolescents with Moderate-to-Severe Atopic Dermatitis and Inadequate Response to Dupilumab: Efficacy and Safety Results from the Phase 3b/4 LEVEL UP Study
Authors: Bunick Christopher , Magnolo Nina , Moore Angela , Xinghua Gao , Lynde Charles , Ibrahim Nadia , Grada Ayman , Levy Gweneth , Calimlim Brian , Wu Xiaoqiang , Armendariz Yolanda , Eyerich Kilian
Published: November 2024

Atopic dermatitis (AD) is a chronic skin disease characterized by intense itch and eczematous skin lesions. Upadacitinib (UPA), a selective oral Janus kinase (JAK) inhibitor, and dupilumab (DUPI), a monoclonal antibody targeting interleukin-4 and interleukin-13 signaling, are both approved treatments for moderate-to-severe AD. LEVEL UP is a phase 3b/4 efficacy assessor blinded monotherapy study comparing UPA to DUPI for treatment of moderate-to-severe AD in adults and adolescents over a 16-week period (Period 1). Patients not achieving ≥75% improvement in the Eczema Area and Severity Index (EASI 75) from baseline at Week 16 entered an additional 16-week extension phase (Period 2). In Period 2, patients either continued/escalated to UPA 30 mg (UPA/UPA 30) or switched from DUPI to UPA 15 mg (DUPI/UPA), with the potential to escalate to 30 mg based on clinical response. Efficacy for skin and itch outcomes in Period 2 were assessed using observed case analysis while on treatment, without statistical comparisons. Here we report efficacy and safety results for the DUPI/UPA switch group.
A total of 355 patients who did not achieve EASI 75 at Week 16 entered Period 2 of the study (DUPI/UPA, N=208). At Week 32, response rates in the DUPI/UPA group were: 79.6%, 58.7%, and 19.9% achieving EASI 75, EASI 90, and EASI 100, respectively; 60.2% achieving WP-NRS improvement ≥4 among those with baseline WP-NRS ≥4; 37.0% achieving WP-NRS 0/1 among those with baseline WP-NRS >1; and 26.8% simultaneously achieving EASI 90 and WP-NRS 0/1 by Week 32. Clinically meaningful outcomes were also observed at an earlier visit (Week 20). No new safety signals through Week 32 were identified compared to the established safety profile of UPA.
Most patients with an inadequate response to DUPI at Week 16 experienced clinically meaningful improvements in skin clearance and itch at 4 weeks post-switch to UPA, with additional patients achieving these outcomes by 16 weeks post-switch. These findings suggest that switching from DUPI to UPA is an effective treatment strategy for patients who do not meet moderate or optimal treatment targets with DUPI.
Achievement of No-to-minimal Itch and Sleep Improvement with Tapinarof Cream 1% Once Daily in Two Pivotal Phase 3 Trials in Adults and Children Down to 2 Years of Age with Atopic Dermatitis
Authors: Simpson Eric , Siri Dareen D. , Chovatiya Raj , Shahriari Mona , Burnette Autumn F. , Craiglow Brittany G. , Brown Philip M. , Tallman Anna
Published: November 2024

Introduction: Itch frequently causes sleep disturbance in patients with atopic dermatitis (AD). The gold-standard Peak Pruritus Numerical Rating Scale (PP-NRS) improvement from baseline is 4 points; however, more stringent outcomes include achieving no-to-minimal itch (PP-NRS ≤1). Tapinarof cream 1% once daily (QD) demonstrated superior efficacy, including itch reduction, versus vehicle and was well tolerated in adults and children down to 2 years of age with AD in the ADORING 1 and 2 pivotal phase 3 trials. Here we present highly stringent itch outcomes and sleep improvement with tapinarof from these trials.
Methods: In ADORING 1 and 2, patients with a Validated Investigator Global Assessment for Atopic Dermatitis™ score ≥3 (moderate or severe), Eczema Area and Severity Index score ≥6, and body surface area involvement of 5–35% were randomized to tapinarof cream or vehicle QD for 8 weeks. Stringent PP-NRS assessments were analyzed post hoc and included achieving no‑to‑minimal itch (PP-NRS ≤1) or PP-NRS score <2. Mean weekly PP-NRS scores were assessed on an 11-point scale (0 indicates “no itch” and 10 is “worst imaginable itch”). The Patient Oriented Eczema Measure (POEM) question 2 evaluated sleep disturbance on a 5-point scale (0 indicates “no days” and 4 is “every day”); outcomes were pooled and stratified by age.
Results: 407 and 406 patients were randomized in ADORING 1 and 2. Mean baseline scores were similar across ADORING 1 and 2 treatment groups: PP-NRS, 6.7 and 6.8; pooled POEM sleep disturbance scores, 2.0 (aged ≥12 years) and 2.4 (<12 years), respectively. Statistically significant achievement of no-to-minimal itch (PP-NRS ≤1), PP-NRS <2, and improvement in sleep were achieved with tapinarof versus vehicle as early as Week 1, the first assessment, and continued through Week 8. Stringent itch outcomes were achieved with tapinarof versus vehicle at Week 8: no-to-minimal itch, 31.4% versus 17.4% (P=0.0072) and 33.0% versus 14.0% (P=0.0003); and PP-NRS <2, 48.1% versus 28.4% (P=0.0006) and 46.8% versus 19.6% (P<0.0001) in ADORING 1 and 2, respectively. Sleep scores improved with tapinarof versus vehicle at Week 8: –1.4 versus –0.8 (≥12 years); –1.7 versus –1.0 (<12 years; both P<0.0001).
Conclusion: Tapinarof cream 1% QD demonstrated early, significant, and meaningful achievement of no-to-minimal itch and improvement of sleep in adults and children down to 2 years of age with AD.
Efficacy of Ritlecitinib in Patients with Alopecia Areata by Extent of Hair Loss: Results from the Phase 2b/3 and Phase 3 ALLEGRO Clinical Trials
Authors: Mostaghimi Arash , Kindred Cheshana , Herranz Pinto Pedro , Mizuashi Masato , Wajsbrot Dalia , Adejumo Rahmat , Tran Helen , Takiya Liza
Published: November 2024

Introduction: Ritlecitinib, a dual JAK3/TEC family kinase inhibitor, demonstrated efficacy and safety in patients ≥12 years old with AA and ≥50% scalp hair loss in the phase 2b/3 ALLEGRO study. This post hoc, pooled analysis of the ALLEGRO-2b/3 and phase 3 ALLEGRO-LT studies evaluated the efficacy of ritlecitinib in patients with alopecia areata (AA) by extent of baseline scalp hair loss through Month 24.
Methods: Patients aged ≥12 years with AA and ≥50% scalp hair loss who received ritlecitinib 50 mg daily in ALLEGRO-2b/3 and rolled over to ALLEGRO-LT (continued to receive 50 mg) were included. Outcomes included the proportions of patients achieving response based on Severity of Alopecia Tool [SALT] score ≤20 (≤20% scalp hair loss), ≥2-grade improvement in eyebrow assessment [EBA] score (among patients with abnormal score at baseline), and ≥2-grade improvement in eyelash assessment [ELA] score (among patients with abnormal score at baseline). Patients were stratified by extent of scalp hair loss at baseline, defined as severe AA (SALT score 50-94) or very severe AA (SALT score 95-100), as per the Alopecia Areata Investigator Global Assessment (AA-IGA). Data as observed and imputed (last observation carried forward [LOCF]) are reported at the cutoff date (December 9, 2022).
Results: Of 191 patients included, 66 (34.6%) had severe AA and 125 (65.4%) had very severe AA at baseline. At Month 12, 64.4% and 34.3% (observed) and 60.6% and 29.6% (LOCF) of patients with severe AA and very severe AA, respectively, achieved SALT ≤20. At Month 24, these proportions increased to 70.2% and 54.8% (observed) and 63.6% and 36.8% (LOCF), respectively. EBA response was achieved in 54.6% and 46.9% (observed) and 52.8% and 42.4% (LOCF) of patients with severe AA and very severe AA, respectively, at Month 12; at Month 24, the proportions were 60.9% and 56.5% (observed) and 50.0% and 45.8% (LOCF). ELA response was achieved in 60.7% and 40.5% (observed) and 61.3% and 38.0% (LOCF) of patients with severe AA and very severe AA, respectively, at Month 12; at Month 24, the proportions were 70.0% and 45.3% (observed) and 61.3% and 38.0% (LOCF).
Conclusion: Ritlecitinib 50 mg daily achieves scalp, eyebrow, and eyelash hair regrowth in patients with severe and very severe AA.
Funding: This study was funded by Pfizer Inc
Race and Ethnicity Sub-Groups of Alopecia Areata Patients have Differing Clinical Characteristics: TARGET-DERM AA
Authors: Hordinsky Maria , Bristow Claire , Richter Sven , Soliman Ahmed , Knapp Keith , Munoz Breda , Crawford Julie , Paller Amy , Chapman Shane , Wine Lee Lara , Mesinkovska Natasha , Ungar Benjamin
Published: November 2024

Introduction Alopecia areata (AA) is a chronic, autoimmune disease that disproportionately impacts particular subgroups.1
Methods United States and Canadian clinics enrolled participants in the TARGET-DERM AA registry (December 2021 - June 2024, data collection ongoing). Those who completed a baseline patient questionnaire [self-reported race / ethnicity, Patient Global Impression of Severity (PGIS-AA)] and clinician-reported outcome measures [Severity of Alopecia Tool (SALT), ClinRO Measure for Eyebrow / Eyelash Hair Loss] were summarized.
Results Of the 267 AA patients, 61.4% were female; 53.2% were adults, 28.5% identified as Hispanic, 52.1% Non-Hispanic (NH)-White, 8.6% NH Black and 6.4% as NH Asian. 47.1% of NH Asian patients had severe disease (SALT>50) and represented the group with the highest proportion of SALT>50, followed by 34.8% of NH Black, 31.7% NH White, and 19.7% Hispanic AA patients. 47.1% of NH Asian patients reported PGIS-AA ‘severe/very severe’ disease, 41.9% of NH White, 39.1% of NH Black and 27.6% of Hispanic AA patients. Eyebrow involvement was highest in NH Whites (44.6%), followed by NH Asian (41.2%), NH Black (34.8%), and Hispanic AA patients (26.3%). Eyelash involvement was highest in NH Black patients, followed by NH White, NH Asian, and Hispanic patients (39.1%, 34.7%, 35.3%, and 17.1%, respectively).
Discussion In this large real-world cohort, there are differences in clinician reported measures by race/ethnicity subgroups. NH-Asian patients represented the largest proportion of patients with patient and clinician-reported severe disease, and clinician-reported eyebrow / eyelash involvement was most prevalent in NH White patients. Hispanic patients had the smallest proportion with severe SALT, eyebrow and eyelash involvement. Additional research is required to better characterize AA and health-related quality of life burden in non-White AA patients.
Bimekizumab impact on patient-reported outcomes in patients with moderate to severe hidradenitis suppurativa: Pooled Week 48 results from BE HEARD I&II
Authors: Szepietowski Jacek C , Lev-Tov Hadar , Shi Vivian Y. , Schneider-Burrus Sylke , Costanzo Antonio , Hayama Koremasa , Lambert Jérémy , Vaux Tom , Lukowski Bartosz , Rolleri Robert , Gottlieb Alice B
Published: November 2024

Introduction: Hidradenitis suppurativa (HS) has substantial negative effects on patients’ lives,1 with debilitating symptoms, such as intense pain/fatigue/draining and odor, which lead to overall low quality of life (QoL).1,2 Bimekizumab (BKZ) is a humanized IgG1 monoclonal antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A; clinical efficacy was previously shown in the phase 3 BE HEARD I&II trials.3 Here, the impact of BKZ on patient-reported outcomes (PROs) in patients with moderate to severe HS in BE HEARD I&II is reported.
Procedure/Study: Pooled data included an initial (Weeks [Wks]0–16) and maintenance (Wks16–48) treatment period. Patients were randomized 2:2:2:1 (initial/maintenance) to BKZ 320 mg every 2 wks (Q2W)/Q2W, BKZ Q2W/ Q4W, BKZ Q4W/Q4W or placebo (PBO)/BKZ Q2W. HS Symptom Questionnaire (HSSQ; each symptom item scored 0–10) mean values are reported to Wk48 for skin pain, itch, smell/odor, and drainage/oozing. Proportions of patients achieving minimal clinically important difference (MCID) for Dermatology Life Quality Index (DLQI; scored 0–30; improvement from baseline score ≥4) were reported at Wk16 and Wk48. Data are reported as observed case.
Results: Overall, 1,014 patients were randomized to BKZ Q2W/Q2W (N=288), BKZ Q2W/Q4W (N=292), BKZ Q4W/Q4W (N=288), PBO/BKZ Q2W (N=146). Within each HSSQ item, similar baseline scores were observed across treatment groups. At Wk16, for skin pain, itch, smell/odor and draining/oozing, greater improvements (i.e. score reduction) from baseline were seen in BKZ- vs PBO-treated patients. HSSQ item scores were substantially reduced from Wk16 to Wk48 in Wk16 PBO/BKZ switchers, further decreases were observed in those continually treated with BKZ. At Wk16, a greater proportion of BKZ- vs PBO-treated patients achieved MCID in DLQI: BKZ Q2W/Q2W, 64.6%; BKZ Q2W/Q4W, 54.9%; BKZ Q4W/Q4W, 63.5% vs PBO, 49.1%. At Wk48, a greater proportion of patients continually treated with BKZ achieved MCID in DLQI vs at Wk16; Wk16 PBO/BKZ switchers attained similar proportions (BKZ Q2W/Q2W: 73.4%; BKZ Q2W/Q4W: 63.5%; BKZ Q4W/Q4W: 74.5%; PBO/BKZ Q2W: 76.5%).
Conclusion: At Wk16, BKZ-treated patients achieved a reduction from baseline of HS symptoms: skin pain, itch, smell/odor, and drainage/oozing. Clinically meaningful health-related QoL improvements from baseline were observed and maintained/slightly improved through Wk48. PBO/BKZ switchers experienced improvements in PRO responses from Wk16 to Wk48 and achieved comparable outcomes at Wk48 to patients continually treated with BKZ.