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Gene profiling using a customized NanoString platform can be applied to routine mycosis fungoides (MF) samples, revealing their specific molecular features. This study shows that MF samples carry a signature derived from individual molecular features found in consecutive biopsies.

Background: Biologic treatments have been studied mainly in patients with a long-term history of psoriasis and previous treatment failures. Objectives: The purpose of this primary analysis of the STEPIn study is to determine whether early intervention with secukinumab in patients with new-onset moderate to severe plaque psoriasis is superior to standard of care treatment with narrow band ultraviolet B (nb-UVB) phototherapy. Methods: The STEPIn study is a randomized, open-label, multicentre study to investigate early intervention with 52 weeks of secukinumab 300 mg administered subcutaneously versus standard treatment with nb-UVB phototherapy in patients with new-onset (≤12 months) moderate to severe plaque psoriasis (NCT03020199). The primary and additional secondary endpoints were ≥90% improvement in Psoriasis Area and Severity Index (PASI 90) at Week 52 and Investigator's Global Assessment (IGA mod 2011) 0/1 response at Week 52, respectively. Results: In the secukinumab and nb-UVB study arms, 77/80 and 76/80 randomized patients received at least one dose of study treatment, respectively. The primary endpoint was achieved: 91.1% (70/77) of patients achieved a PASI 90 response at Week 52 in the secukinumab arm versus 42.3% (32/76) in the nb-UVB arm (p < 0.0001, odds ratio [OR] estimate [95% confidence intervals, CI] = 16.3 [5.6, 46.9]). The additional secondary endpoint was also achieved: 85.7% of patients achieved an IGA 0/1 response at Week 52 in the secukinumab arm versus 36.8% in the nb-UVB arm (p < 0.0001). The safety data were consistent with the safety profiles of secukinumab and nb-UVB with no new or unexpected safety signals. Conclusions: Secukinumab was superior to nb-UVB in treating patients with new-onset moderate to severe plaque psoriasis. The high and sustained skin clearance observed indicates that biologic treatment for psoriasis may be more effective if used early in the disease course.

Non-alcoholic fatty liver disease (NAFLD) is currently considered the most common cause of liver disease. Its prevalence is increasing in parallel with the obesity and type 2 diabetes mellitus (DM2) epidemics in developed countries. Several recent studies have suggested that NAFLD may be the hepatic manifestation of a systemic inflammatory metabolic disease that also affects other organs, such as intestine, lungs, skin and vascular endothelium. It appears that local and systemic proinflammatory/anti-inflammatory cytokine imbalance, together with insulin resistance and changes in the intestinal microbiota, are pathogenic mechanisms shared by NAFLD and other comorbidities. NAFLD is more common in patients with extrahepatic diseases such as inflammatory bowel disease (IBD), obstructive syndrome apnea (OSA) and psoriasis than in the general population. Furthermore, there is evidence that this association has a negative impact on the severity of liver lesions. Specific risk characteristics for NAFLD have been identified in populations with IBD (i.e. age, obesity, DM2, previous bowel surgery, IBD evolution time, methotrexate treatment), OSA (i.e. obesity, DM2, OSA severity, increased transaminases) and psoriasis (i.e. age, metabolic factors, severe psoriasis, arthropathy, elevated transaminases, methotrexate treatment). These specific phenotypes might be used by gastroenterologists, pneumologists and dermatologists to create screening algorithms for NAFLD. Such algorithms should include non-invasive markers of fibrosis used in NAFLD to select subjects for referral to the hepatologist. Prospective, controlled studies in NAFLD patients with extrahepatic comorbidities are required to demonstrate a causal relationship and also that appropriate multidisciplinary management improves these patients’ prognosis and survival.

Introduction There is limited and conflicting evidence over the real-world drug survival of secukinumab (SEC) in patients with psoriasis, especially in the long term. Our objective was to analyze the short- and long-term survival of SEC (S-SEC) and its predictive factors for the treatment of psoriasis. Methods Patients clinically diagnosed with plaque psoriasis and under treatment with secukinumab (n = 384) in a daily practice setting were analyzed in a retrospective, multicenter study performed in a nationwide cohort and followed up for a period of 2 years. Kaplan-Meier curve was plotted to analyze drug survival time, and log-rank test was performed to compare several groups. Factors related to speed of treatment discontinuation were studied with a Cox regression model. Results The overall cumulative secukinumab drug survival rates observed at 6, 12, 18, and 24 months were 97.1%, 89.0%, 81.1%, and 74.3%, respectively. Obesity [hazard ratio (HR), 1.809, CI 95% 1.114-2.962; p = 0.004] and previous experience with biological therapies, particularly those who had been treated with >= 2 biologicals with different mechanisms of action (HR 3.476, CI 95% 1.875-6.444; p = 0.017) were associated with an early discontinuation, whereas psoriatic arthritis was associated with delayed discontinuation, (HR 0.493, CI 95% 0.265-0.917; p = 0.025). Conclusions In our study, we found that cumulative secukinumab drug survival for psoriasis patients for the period 6-18 months was in the range of real-world evidence studies. Additionally, we observed a relatively high long-term survival rate at 24 months (74.3%).

The aim of the study was to assess the long-term effectiveness and safety of secukinumab in Spanish patients with moderate-to-severe psoriasis in a daily practice setting. Nationwide multicenter, observational, retrospective, non-interventional, single-cohort study including patients who initiated treatment with secukinumab in daily clinical practice conditions. Subjects were followed for a minimum of 3 months and a maximum of 24 months. Psoriasis Area Severity Index (PASI), Body Surface Area and Physician's Global Assessments were collected at baseline and months 3, 6, 12, 18 and 24 during treatment. Adverse events and reasons for secukinumab withdrawal were collected and classified for analyses. A total of 384 patients were enrolled in the study. Median PASI declined rapidly from 14.3 at baseline to 2.7 at month 3, 2.1 at month 12, and remained low (2.8) at month 24. Within the group of patients with PASI >= 10 at baseline (n = 278), 58.3%, 60.4% and 56.5% achieved a PASI90 response at months 3, 12 and 24, respectively. As for absolute PASI, 86.5%, 69.5%, 42.7% and 37% achieved PASI

NAVIGATE clinical trial demonstrated a higher rate of Psoriasis Assesment Severity Index (PASI)90 response in patients treated with guselkumab when compared to ustekinumab and an improved response in those who switched from ustekinumab to guselkumab due to partial response. The objective of the study is to describe ustekinumab to guselkumab switching in clinical practice. Observational, multicentric, descriptive study including 54 psoriasis patients who switched to guselkumab after treatment with ustekinumab from March 2019 to February 2021. Mean basal PASI with ustekinumab (16.7) was higher than with guselkumab (7.2). Up to 49.01% of patients were able to reach PASI90 with ustekinumab and up to 21.56% had a less frequent dosage regime vs. summary of product characteristics. Main reason to start guselkumab was a loss of ustekinumab cutaneous or articular response (82.36%) but up to 17.64% were switched in order to increase dosage regime efficiency. Six months after starting guselkumab, the absolute PASI was lower than 2 in 72% of patients and 38.5% of them were treated with a reduced dosage regime. Guselkumab doses used by our cohort were 19.5% lower than the expected according to the summary of product characteristics. No adverse events reported. There is no real-world evidence regarding patients who switched from ustekinumab to guselkumab. A short paragraph in the article by Fougerousse et al, reported 63 patients with a mean basal PASI of 5.3 and similar efficacy rate at week 16 to NAVIGATE. Our study adds practical information regarding efficacy, safety and efficiency through dose optimization in a real-world cohort.

Psoriasis is a chronic dermatological disease with great impact on patients' quality of life (QoL). The main objective of this study was to assess the impact of secukinumab treatment on different patient-reported outcomes (PROs) during a long-term follow-up in Spanish patients with moderate-to-severe psoriasis under real-world conditions. Retrospective, observational, open-label, nationwide multicenter cohort study that included patients who initiated treatment with secukinumab in daily clinical practice conditions. PROs assessing disease impact and QoL included Dermatology Life Quality Index (DLQI), Patient's Global Psoriasis Assessment, Itch Numerical Rating Scale and EuroQoL Thermometer Visual Analogue Scale. Outcomes, including PROs and Psoriasis Area and Severity Index (PASI), were assessed at months 3, 6, 12, 18, and 24 during treatment. A total of 238 patients were enrolled in the study. Patients had a mean DLQI score of 14.9 at baseline; 78.3%, 73.7%, and 71.7% of them achieved a DLQI 0/1 response at months 6, 12, and 24, respectively. DLQI score was lower in the long term for naive patients. A sharp decrease in mean DLQI was observed during the first 3 months, reaching a plateau that was maintained until the end of follow-up. Similar findings were observed for the rest of QoL assessments. There was a close association between improvement in QoL and skin clearance (PASI), which progressively increased during follow-up. In this study, secukinumab sustainably improved patient's QoL during a 24-month follow-up, with strongest effects in patients naive to biological therapies and with a direct correlation with PASI improvement.

Psoriatic arthritis is a common type of inflammatory arthritis found in up to 40% of patients with psoriasis. Because skin involvement usually precedes joint involvement, dermatologists play a key role in early detection. Early diagnosis is important for reducing the risk of irreversible structural damage, attenuating the deterioration of physical function, and improving patients' quality of life. This consensus statement was drafted by a group of 9 dermatologists and 1 rheumatologist to provide simple recommendations to help dermatologists screen for psoriatic arthritis in patients with psoriasis. The experts offer consensus-based guidelines that draw on a review of available scientific evidence and on experience acquired in routine clinical practice.

Background and objective The 4-item Psoriatic Arthritis Uncluttered Screening Evaluation (PURE-4) questionnaire is a useful tool for identifying patients with suspected psoriatic arthritis before referring them to a rheumatology department for confirmation. The original English version has good discriminant validity (sensitivity, 85.7%; specificity 83.6%). We aimed to produce an adapted Spanish version of the PURE-4 for validation and use in Spain. Material and method We applied the method recommended by the International Society for Pharmacoeconomic and Outcome Research for the cultural adaptation of patient-centered measurement tools. The phases in the processes involved forward translation, reconciliation, back translation review, harmonization, cognitive debriefing and review, and proofreading. Results We obtained the permission of the author of the original questionnaire. Two native-speaking translators translated the questionnaire into Spanish. Small changes, mainly in the way the items were expressed, were then made in order to reconcile the 2 translations. The questionnaire was then back translated to English and revised to achieve a version equivalent to the original. A Spanish translation derived from the revision was tested for understandability in 7 patients, and the final Spanish version was then produced. During the translation phases, the project manager and a scientific committee made up of a dermatologist and a rheumatologist reviewed the different versions. Team members exchanged information throughout the process, providing for harmonization and the quality control that guaranteed conceptual equivalence. Conclusions This adaptation of the PURE-4 questionnaire for use in Spain has been the first step toward using it in routine clinical practice. The standardized method we used ensures that the Spanish and the original versions are equivalent.

Resumen Antecedentes y objetivo El cuestionario 4-item Psoriatic arthritis UnclutteRed screening Evaluation (PURE-4) puede considerarse una herramienta util para identificar pacientes con posible artritis psoriasica y derivarlos al servicio de reumatologia para confirmar el diagnostico. La version original en ingles presenta alta validez discriminatoria (85,7% de sensibilidad, 83,6% de especificidad). El objetivo de este trabajo es adaptarlo para poblacion espanola como paso previo a su validacion. Material y metodo Se aplico la metodologia recomendada por la International Society Pharmacoeconomic and Outcome Research (ISPOR) para adaptaciones culturales de medidas centradas en el paciente. Fases: preparacion, traduccion, reconciliacion, retrotraduccion/revision, armonizacion, test de comprension/revision, correccion de pruebas. Resultados En la preparacion se obtuvo el permiso del autor del cuestionario original. Dos traductores nativos realizaron la traduccion del cuestionario original al espanol. En la reconciliacion se realizaron pequenas modificaciones, principalmente en el enunciado de los items. Se realizo retrotraduccion al ingles, logrando una version equivalente al cuestionario original. La version espanola derivada se administro en el test de comprension a 7 pacientes, obteniendose la version final en espanol. Durante las traducciones, el responsable del proyecto y un comite cientifico formado por un dermatologo y un reumatologo revisaron las diferentes versiones. Los intercambios de informacion entre el equipo durante todo el proceso integraron la fase de armonizacion, siendo un control de calidad continuo que garantizo la equivalencia conceptual de las traducciones. Conclusiones La adaptacion del cuestionario PURE-4 para poblacion espanola constituye la primera etapa para su uso en practica clinica habitual. La metodologia estandarizada garantiza la equivalencia entre la version espanola y la original.

Background Experience in the use of apremilast in clinical practice complements the information available from pivotal clinical trials. Materials and methods Following a review of the literature, a panel of dermatologists with expertise in the management of psoriasis considered 5 scenarios in which the evidence supporting the use of apremilast to treat moderate psoriasis is insufficient or controversial. These scenarios were then assessed using a Delphi questionnaire. Results Consensus was reached on 96 (67%) of the 143 items (positive in 85 and negative in 11). The therapeutic goal for apremilast should be based on 4 outcomes: clinical response, symptoms, quality of life, and patient satisfaction. The scenario in which the use of apremilast was considered to have the greatest possibility of success was in patients with stable moderate psoriasis. Most of the clinicians considered apremilast to be an appropriate treatment when conventional therapies fail or are contraindicated, preferably before the prescription of biologic therapy. Consensus was reached that apremilast is an appropriate treatment for psoriasis in difficult locations, such as the scalp or the palms and soles. It was also agreed that apremilast requires less prescreening and monitoring than other conventional and biologic systemic therapies. Conclusions Apremilast could be a treatment option for patients with a different profile to that of clinical trial participants. The limitations of this proposal are the absence of consensus on the definition of moderate psoriasis, the lack of real-world evidence on the use of apremilast, and certain aspects related to tolerability.

Resumen Antecedentes El manejo de apremilast en la practica clinica complementa la informacion procedente de los ensayos clinicos pivotales. Material y metodo Tras una revision de la literatura se consideraron, por parte de un panel de dermatologos expertos en el manejo de la psoriasis, 5 areas donde la evidencia sobre el uso de apremilast en la psoriasis moderada era insuficiente o controvertida, que fueron evaluadas a traves de un cuestionario disenado segun la metodologia Delphi. Resultados Se alcanzo consenso en 96 de los 143 items planteados (67%) (85 en el acuerdo y 11 en el desacuerdo). El objetivo terapeutico con apremilast deberia ponderarse entre la respuesta clinica, la sintomatologia asociada, la calidad de vida y la satisfaccion del paciente. El perfil en el que el uso de apremilast se considera con mayores posibilidades de exito seria el de un paciente con psoriasis moderada estable. La mayoria de los clinicos consideraron que apremilast es adecuado para pacientes en los que hayan fracasado o esten contraindicados los tratamientos convencionales, preferentemente de forma previa a la indicacion de terapia biologica. Hubo consenso en reconocer apremilast como una opcion terapeutica adecuada para el tratamiento en localizaciones dificiles, como la psoriasis palmoplantar y del cuero cabelludo. La necesidad de cribado, asi como de su monitorizacion durante el seguimiento, se considero menor que la de otros tratamientos sistemicos, convencionales y biologicos. Conclusiones Apremilast podria representar una opcion terapeutica en un perfil de pacientes distinto al presentado en los ensayos clinicos. La ausencia de un consenso sobre la definicion de psoriasis moderada, la escasa evidencia acerca del farmaco en la vida real, asi como algunos aspectos relacionados con la tolerabilidad representan limitaciones a estas propuestas.

The augmented moduli space $$\widehat{\mathcal M}_n$$ is a compactification of moduli space $$\mathcal M_n$$ obtained by adding stable hyperbolic surfaces. The different topological types of the added stable surfaces produce a stratification of $$\partial \widehat{\mathcal M}_n$$ . Let $$\mathcal {P}_n\subset {\mathcal M}_n$$ be the pyramidal locus in moduli space, i.e., the set of hyperbolic surfaces of genus n such that the topological action of its preserving-orientation isometry group is the pyramidal action of the dihedral group $$D_n$$ . The purpose of this paper is to state the complete list of strata in the boundary of $$\mathcal {P}_n$$ .

Resumen Objetivo 1) Analizar la implementacion de los modelos de atencion multidisciplinar en pacientes con artritis psoriasica (APs), y 2) definir estandares de calidad de minimos y de excelencia. Metodos Se envio una encuesta a profesionales que ya realizan atencion multidisciplinar o estan en vias preguntando por: 1) tipo de modelo de abordaje multidisciplinar, y 2) grado, prioridad y facilidad de la implementacion de los estandares de calidad de estructura, proceso y resultado. En 6 reuniones regionales se presentaron y discutieron los resultados de la encuesta, tanto a nivel nacional como regional, y se definio la prioridad definitiva de los estandares de calidad. En una reunion de grupo nominal, 11 expertos (reumatologos y dermatologos) analizaron los resultados de la encuesta y las reuniones regionales. Con ello definieron que estandares de calidad son actualmente de minimos y cuales de excelencia. Resultados Los modelos de atencion multidisciplinar conjunto y paralelo son los mas implementados, y los de los estandares de calidad es muy variable: en los de estructura varia del 22 al 74%, en los de proceso del 17 al 54% y en los de resultado del 2 al 28%. De los 25 estandares de calidad originales, 9 se consideran solo de minimos, 4 de excelencia y 12 tienen definidos unos criterios para ser de minimos y otros para la excelencia. Conclusiones La definicion de estandares de calidad de minimos y de excelencia ayudara en la consecucion del objetivo de la atencion multidisciplinar para pacientes con APs, que es la mejor asistencia sanitaria posible.

Resumen {0>El debut de la psoriasis en la edad pediatrica, aunque generalmente leve, puede requerir tratamiento sistemico en las formas moderadas o graves de la enfermedad. Childhood-onset psoriasis generally follows an indolent course but patients with moderate or severe disease may require systemic treatment. El objetivo de este trabajo es analizar la frecuencia relativa, las caracteristicas de los pacientes, el tratamiento empleado y los eventos adversos (EA) observados a partir del registro BIOBADADERM en ninos y jovenes con psoriasis moderada-grave. The aim of this study was to determine the relative proportion of children and young people aged up to 21 years with moderate to severe psoriasis in the BIOBADADERM registry and to analyze the characteristics of these patients, treatments used, and adverse events. Del total de 3946 pacientes del registro, se incluyen 24 pacientes menores de 21 anos, con una edad media al inicio del tratamiento en BIOBADADERM de 16,1 anos y un PASI medio de 9,4. Of the 3946 patients in the registry, 24 were aged 21 years or younger.They had mean age of 16.1 years on starting treatment. When the registry was started, they had a Psoriasis Area and Severity Index of 9.4 El 67% de los pacientes estaba en tratamiento sistemico clasico al inicio del registro. and 67% were being treated with a conventional systemic drug. Treatment was discontinued in 14 patients ({0>14 pacientes (58%) suspendieron el tratamiento por perdida o falta de eficacia o por EA. 58%) due to adverse events or a loss or lack of effectiveness. En conclusion, los datos del registro BIOBADADERM muestran que los menores representan un grupo muy pequeno dentro de los pacientes con psoriasis que reciben tratamiento sistemico y son manejados mas frecuentemente con tratamientos clasicos. In conclusion, the BIOBADADERM registry shows that young people account for a small proportion of psoriasis patients receiving systemic treatment, and they are more likely to be treated using conventional systemic drugs.

Convenient administration is an important factor for treatment adherence in patients with psoriasis. MATURE study reports the efficacy, safety, tolerability, and pharmacokinetics (PKs) of secukinumab 300 mg 2 ml autoinjector (AI) from MATURE trial (NCT03589885). Eligible patients were randomized to secukinumab 300 mg 2 ml AI or 2x 1 ml prefilled syringe (PFS) or placebo. The co-primary endpoints were psoriasis area and severity index (PASI) 75 and investigator's global assessment (IGA) 0/1 response rates at Week 12 versus placebo. Other endpoints included PASI90/100 response, dermatology life quality index (DLQI) 0/1, PKs, 2 ml AI usability rated using self-injection assessment questionnaire (SIAQ), and safety. The study met both co-primary and secondary endpoints (p < 0.0001). Secukinumab 300 mg 2 ml AI and 2x 1 ml PFS treatments led to superior PASI75/90/100 (2 ml AI: 95.1%/75.6%/43.9%; 2x 1 mL PFS: 83.2%/62.6%/37.5% and placebo: 10%/5.0%/0.0%, respectively), IGA, and DLQI 0/1 responses compared with placebo, and efficacy was sustained through 52 weeks. SIAQ results showed high usability of self-injection with 2 mL AI device. No new safety signals were observed. Study design may bias the interpretation of safety profile after Week 12, due to different exposure of secukinumab versus placebo. Secukinumab 300 mg administered with the 2 mL AI demonstrated superior efficacy over placebo, good tolerability, and convenient administration.