JAKinhibs in Psoriatic Disease: Analysis of the Efficacy/Safety Profile in Daily Clinical Practice.

Psoriatic disease (PsD) affects multiple clinical domains and causes a significant inflammatory burden in patients, requiring comprehensive evaluation and treatment. In recent years, new molecules such as JAK inhibitors (JAKinhibs) have been developed. These have very clear advantages: they act quickly, have a beneficial effect on pain, are well tolerated and the administration route is oral. Despite all this, there is still little scientific evidence in daily clinical practice. This observational, retrospective, single-center study was carried out in patients diagnosed with PsA in the last two years, who started treatment with Tofacitinib or Upadacitinib due to failure of a DMARD. The data of 32 patients were analyzed, and the majority of them (75%) started treatment with Tofacitinib. Most had moderate arthritis activity and mild psoriasis involvement according to activity indices. Both Tofacitinib and Upadacitinib demonstrated significant efficacy, with rapid and statistically significant improvement in joint and skin activity indices, C-reactive protein reduction, and objective measures of disease activity such as the number of painful and inflamed joints. Although there was some difference in the baseline characteristics of the cohort, treatment responses were comparable or even superior to those in the pivotal clinical trials. In addition, there was a low frequency of mild adverse events leading to treatment discontinuation and no serious adverse events. These findings emphasize the strong efficacy and tolerability of JAKinhibs in daily clinical practice, supporting their role as effective therapeutic options for patients with PsD.

Optimising the Therapeutic Interval for Biologics in Patients with Psoriasis.

In our clinical experience, more than half of patients do not present a complete response to biologic drugs, or drug loses its efficacy over time. Plasma determinations of drug and anti-drug antibodies levels are an objective tool for optimisation in these patients; however, established therapeutic ranges are not suitable, so the objective of this study was to study these patients and optimise their healthcare. We have made a retrospective, observational study, using data of plasma levels of drugs and anti-drugs antibodies of infliximab, adalimumab or Etanercept, we summarise all data and make a study of sensitivity, specificity, positive and negative predictive value on current therapeutic ranges. We have found a statistically significant association between subtherapeutic levels and therapeutic failure in psoriasis treated with infliximab and adalimumab. New ranges were found with higher sensitivity than the established ones, we propose 2-10 µg/mL therapeutic range for infliximab, 3-11 µg/mL for adalimumab, and 1-7 µg/mL for etanercept. In conclusion, levels of drug and anti-drug antibodies are a decisive tool for predicting therapeutic response. The current therapeutic ranges may have minimum values that are excessively high, owing to which lowering them significantly increases the sensitivity of the test in all cases, and negative predictive value in the case of etanercept. Further prospective studies are needed to prove the usefulness of these new ranges.

Correction: Vidal et al. From Messengers to Receptors in Psoriasis: The Role of IL-17RA in Disease and Treatment. Int. J. Mol. Sci. 2021, 22, 6740.

In the original publication [...].

Study of the Visceral Adipose Tissue in a Cohort of Patients with Moderate-Severe Psoriasis Treated with Biological Therapy.

INTRODUCTION: Visceral adipose tissue (VAT) has a greater relationship with the genesis of the metabolic syndrome and the pathology associated with obesity. METHODS: A cross-sectional study of patients with moderate-severe psoriasis in the Psoriasis Unit of the San Cecilio University Hospital in Granada in the period July 1, 2020 - December 31, 2020, was performed. All the patients (n = 110) were receiving biological therapy to control the disease. The variables measured included age, sex, time since diagnosis, weight, height, body mass index (BMI), visceral and total fat, and severity parameters. The visceral fat index was evaluated using a bioimpedance scale, considering a cut-off point for a healthy level < 12. RESULTS: Our sample consisted of 110 patients with a mean age of 47.47 years, with a clear predominance of males (61.7% of patients). After testing for normality using the Kolmogorov-Smirnov test, the Mann-Whitney U test for nonparametric data for independent samples was used, which revealed significant differences between the number of previous treatments and visceral fat (U = -2.235, P = 0.025). No statistically significant differences were found when correlating total fat or visceral fat with BMI. CONCLUSIONS: The results presented lead us to consider if the levels of VAT could be a factor that contributes to some extent to therapeutic refractoriness. The determination of VAT using bioimpedance scales in patients with moderate-severe psoriasis is a valuable method to measure VAT.

Four years stability of type D personality in patients with moderate to severe psoriasis and its implications for psychological impairment

Abstract Background: Psoriasis is a systemic auto-inflammatory disease that is related to an increased risk of organic and psychological comorbidities. Type D is a stable personality trait in healthy subjects but there is no data regarding its stability in patients with moderate-severe psoriasis. Objectives: To assess the stability of type D personality in patients with moderate to severe psoriasis as well as assessing the influence of type D personality on anxiety and depression. Methods: Prospective cohort study. Forty psoriasis patients with type D personality and sixtysix patients with psoriasis without type D personality were included in the study. Participants completed the DS14 test and HADS at baseline and four years later. Results: At baseline, the prevalence of type D personality was 37.7% and at week 208 it was 27.3%. The stability of type D personality was higher in patients with an incomplete education level and in those who were separated/divorced or windowed. During follow-up, 15% of patients developed type D personality. Male sex, having topical treatment, the presence of previous depression, anxiety, and high levels of negative affectivity at baseline increase the risk of developing type D personality. Study limitations: Sample size, psoriasis severity restricted to moderate and severe and all patients being under treatment for psoriasis. Conclusion The presence of type D personality varies over time in psoriasis patients. Therefore, type D personality is possibly more a state than a trait phenomenon, modified by environmental factors. Type D personality is associated with a higher risk of anxiety.

From Messengers to Receptors in Psoriasis: The Role of IL-17RA in Disease and Treatment.

The paradigm of psoriasis as a Th17-driven disease has evolved in the last years towards a much deeper knowledge of the complex pathways, mechanisms, cells, and messengers involved, highlighting the crucial role played by the IL-17 family of cytokines. All IL-17 isoforms signal through IL-17R. Five subunits of IL-17R have been described to date, which couple to form a homo- or hetero-receptor complex. Characteristically, IL-17RA is a common subunit in all hetero-receptors. IL-17RA has unique structural-containing a SEFIR/TILL domain-and functional-requiring ACT-1 for signaling-properties, enabling Th17 cells to act as a bridge between innate and adaptive immune cells. In psoriasis, IL-17RA plays a key role in pathogenesis based on: (a) IL-17A, IL-17F, and other IL-17 isoforms are involved in disease development; and (b) IL-17RA is essential for signaling of all IL-17 cytokines but IL-17D, whose receptor has not been identified to date. This article reviews current evidence on the biology and role of the IL-17 family of cytokines and receptors, with focus on IL-17RA, in psoriasis and some related comorbidities, and puts them in context with current and upcoming treatments.

Four years stability of type D personality in patients with moderate to severe psoriasis and its implications for psychological impairment.

BACKGROUND: Psoriasis is a systemic auto-inflammatory disease that is related to an increased risk of organic and psychological comorbidities. Type D is a stable personality trait in healthy subjects but there is no data regarding its stability in patients with moderate-severe psoriasis. OBJECTIVES: To assess the stability of type D personality in patients with moderate to severe psoriasis as well as assessing the influence of type D personality on anxiety and depression. METHODS: Prospective cohort study. Forty psoriasis patients with type D personality and sixty-six patients with psoriasis without type D personality were included in the study. Participants completed the DS14 test and HADS at baseline and four years later. RESULTS: At baseline, the prevalence of type D personality was 37.7% and at week 208 it was 27.3%. The stability of type D personality was higher in patients with an incomplete education level and in those who were separated/divorced or windowed. During follow-up, 15% of patients developed type D personality. Male sex, having topical treatment, the presence of previous depression, anxiety, and high levels of negative affectivity at baseline increase the risk of developing type D personality. STUDY LIMITATIONS: Sample size, psoriasis severity restricted to moderate and severe and all patients being under treatment for psoriasis. CONCLUSIONS: The presence of type D personality varies over time in psoriasis patients. Therefore, type D personality is possibly more a state than a trait phenomenon, modified by environmental factors. Type D personality is associated with a higher risk of anxiety.

Risankizumab as a promising therapeutic approach in obese patients.

Obesity and increased waist circumference are associated with all the factors constituting the metabolic syndrome (type 2 diabetes, sleep apnea, hypertension, dyslipidaemia, acute myocardial infarction…) and also with an increased mortality. One of the main methods to determine the obesity is through the body mass index (BMI), which is calculated as weight in kilograms, divided by height in metres squared. Obesity is considered to be when the BMI is greater than 30 kg/m2 . The association with psoriasis has been revealed in different epidemiological studies and clinical trials and mainly affects patients who develop more severe forms of psoriasis. We report an obese patient under treatment with Risankizumab with successful and sustained response over 52 weeks, as a very promising therapeutic approach as an efficient treatment in this patients.

Type D personality is associated with poor quality of life, social performance, and psychological impairment in patients with moderate to severe psoriasis: A cross-sectional study of 130 patients.

BACKGROUND: Psoriasis is a systemic autoinflammatory disease that is related to an increased risk of organic and psychological comorbidities. Type D personality has been related to poor quality of life and worse physical and psychological outcomes in different diseases. AIMS: The aim of this study is to explore whether type D personality is associated with an increased risk of presenting physical and/or psychological comorbidities, their relationship with the capacity of social adaptation, and health-related quality of life (HRQOL) in patients with psoriasis. METHODS: This was a cross-sectional study. In all, 130 patients with moderate to severe psoriasis were included in this study. Participants completed the DS14 test and different validated questionnaires regarding quality of life and psychological morbidities. RESULTS: Type D personality was present in 38.4% (50/130) of the participants of the study. Patients with psoriasis and type D personality presented a higher risk of depression and anxiety. We observed that type D personality was associated with a lower educational level. These patients also presented a worse HRQOL in different dimensions of the Short Form Health Survey-36 questionnaire, more sleep problems, poor social adaptation, and a higher frequency of sexual disturbances. LIMITATIONS: Due to the cross-sectional design of the study, we could not confirm causality. Selection of sample was not random. Diagnoses of physical comorbidity were collected through clinical interview of patients under active treatment, which may imply a classification bias. CONCLUSION: Type D personality could represent a frequent personality profile in patients with psoriasis that could identify subjects with poor coping abilities to the disease with poorer levels of quality of life, increased psychological comorbidities, and inadequate social adaptation mechanisms.

Association Between Psoriasis and Sexual and Erectile Dysfunction in Epidemiologic Studies: A Systematic Review.

Importance: Sexual health is a major aspect of life. Increasing scientific evidence shows a potential association between psoriasis and sexual dysfunction (SD) and erectile dysfunction (ED). Objective: To evaluate the available scientific evidence regarding epidemiologic associations and treatment outcomes between psoriasis and SD and ED. Evidence Review: Information sources were MEDLINE and Embase databases, using the Scopus search engine. The search was performed on August 25, 2017. Search terms were psoriasis and sexual or sexual dysfunction, and the search was limited to epidemiologic studies published in English answering any of the 4 research questions. Quality was assessed according to the Centre for Evidence-Based Medicine. Findings: Twenty-eight studies representing 52 520 cases of psoriasis and 1 806 022 controls were included for review. Of the 28 studies, 19 were cross-sectional, 3 were clinical trials, 3 were quasi-experimental, 2 were population-based cohort, and 1 was population-based case-control. Prevalence of SD and ED ranged from 40.0% to 55.6% and 34.2% to 81.1%, respectively. Two of 2 studies observed an association between psoriasis and SD after adjusting for physical and psychological comorbidities. Five of 8 studies observed an independent association between ED and psoriasis. Among patients with psoriasis, the features that showed the strongest association with SD were anxiety and depression (5 of 5 studies), psoriatic arthritis (3 of 4 studies), and genital psoriasis (5 of 7 studies). Regarding ED, anxiety and depression (2 of 2 studies) and increasing age (3 of 3 studies) showed the strongest association. All 3 clinical trials using biologic drugs showed an improvement in SD compared with placebo. Conclusions and Relevance: Patients with psoriasis have physical and psychological comorbidities that have been associated with a higher risk of SD. In addition, psoriasis may play a role in its development. The presence of anxiety, depression, psoriatic arthritis, genital lesions, and increasing age should raise the awareness of SD. Biologic drugs have demonstrated the improvement of SD in patients with psoriasis.

Long-term etanercept survival in patients with psoriatic arthritis: a multicenter retrospective analysis in daily clinical practice in Spain.

Although several randomized clinical trials and observational studies have evaluated the effectiveness, safety and drug survival of etanercept (ETN) in the treatment of psoriatic arthritis (PsA), long-term data regarding these aspects are currently scarce. For this reason, we sought to investigate the long-term survival and safety of ETN in PsA patients in 4 tertiary care Spanish hospitals over a 13-year observation period (from 2004 to 2017). The records of 85 PsA patients were reviewed. ETN showed an excellent survival profile, with rates of treatment discontinuation at 1, 3, 5 and 10 years of 15, 37, 46 and 59%, respectively. In our cohort, a trend toward longer drug survival in patients with shorter disease duration and those who were treated with ETN as their first biologic agent was observed. On the other hand, combination therapy with conventional disease-modifying antirheumatic drugs did not provide greater improvement on the long-term drug survival. Only 12% of the patients reported adverse events (AEs) during therapy, being most of them of mild to moderate intensity, and in only 7% AEs led to drug discontinuation. To the best of our knowledge, the present study shows the largest follow-up period of ETN-treated population analyzed in a real-life setting, and these results demonstrate the positive safety profile and long-term effectiveness of this biologic agent in the management of PsA patients.

La inhibición del TNF-alpha puede disminuir los biomarcadores de disfunción endotelial en pacientes con psoriasis de moderada-grave: un estudio cuasiexperimental eco doppler a 52 semanas / TNF-alpha inhibition could reduce biomarkers of endothelial dysfunction in patients with moderate to severe psoriasis: A 52-week echo-Doppler based quasi-experimental study

Objetivos: La psoriasis se asocia a la disfunción endotelial, lo cual provoca un deterioro del funcionamiento vascular. Los inhibidores del TNF-alpha han mostrado la capacidad de mejorar el funcionamiento vascular en la psoriasis. El índice de resistencia de los vasos ungueales (IRVU) evalúa el funcionamiento microvascular en la uña. El objetivo del estudio fue evaluar el efecto de la inhibición del TNF-alpha con adalimumab en el IRVU. Material y métodos: Estudio cuasiexperimental. Quince pacientes con psoriasis moderada-grave recibieron adalimumab 40mg sc según ficha técnica. Se valoró a los participantes al inicio y a las 12, 24 y 52 semanas tras la intervención del estudio. Resultados: En la semana 52 se observó una reducción del IRVU de −0,09±0,02 (p<0,01) y de −11,2±2,41ng/ml (p<0,001) en la E-selectina. Conclusiones: Adalimumab podría producir una reducción progresiva y sostenida de la resistencia de los vasos ungueales y marcadores de disfunción endotelial

Objectives: Psoriasis is associated to endothelial dysfunction, which causes impaired vascular functioning. TNF-alpha blockers have shown the ability to improve vascular functioning in psoriasis. The nailfold vessel resistance index (NVRI) assesses microvascular functioning at nailfold. The objectives of the study is to assess the effect of the TNF-alpha inhibition with adalimumab on NVRI. Material and methods: Quasi-experimental study. Fifteen patients with moderate-severe psoriasis received adalimumab 40mg sc according to label information. Participants were assessed at baseline and at 12, 24 and 52 weeks after study intervention. Results: A reduction of −0.09±0.02 (P<.01) in NVRI and a −11.2±2,41ng/ml (P<.001) in E-selectin was observed at week 52. Conclusions: Adalimumab could produce a progressive and sustained reduction of vessel resistance at nailfold and E-selectin in patients with psoriasis

TNF-alpha inhibition could reduce biomarkers of endothelial dysfunction in patients with moderate to severe psoriasis: A 52-week echo-Doppler based quasi-experimental study. / La inhibición del TNF-α puede disminuir los biomarcadores de disfunción endotelial en pacientes con psoriasis de moderada-grave: un estudio cuasiexperimental eco doppler a 52 semanas.

OBJECTIVES: Psoriasis is associated to endothelial dysfunction, which causes impaired vascular functioning. TNF-α blockers have shown the ability to improve vascular functioning in psoriasis. The nailfold vessel resistance index (NVRI) assesses microvascular functioning at nailfold. The objectives of the study is to assess the effect of the TNF-α inhibition with adalimumab on NVRI. MATERIAL AND METHODS: Quasi-experimental study. Fifteen patients with moderate-severe psoriasis received adalimumab 40mg sc according to label information. Participants were assessed at baseline and at 12, 24 and 52 weeks after study intervention. RESULTS: A reduction of -0.09±0.02 (P<.01) in NVRI and a -11.2±2,41ng/ml (P<.001) in E-selectin was observed at week 52. CONCLUSIONS: Adalimumab could produce a progressive and sustained reduction of vessel resistance at nailfold and E-selectin in patients with psoriasis.

Modelos de atención multidisciplinar en pacientes con artritis psoriásica en España / Multidisciplinary care models for patients with psoriatic arthritis

Objetivo. Describir la estructura y procesos de distintos modelos de atención multidisciplinar de pacientes con artritis psoriásica (APs) en España, así como las barreras y facilitadores en su implantación. Métodos. Se realizó un estudio cualitativo mediante entrevistas estructuradas a 24 profesionales (12 reumatólogos y 12 dermatólogos que realizan atención multidisciplinar en pacientes con APs). Se recogieron datos relacionados con el centro, servicio, población atendida y sobre el modelo de atención multidisciplinar (tipo, recursos materiales y humanos, requerimientos de los profesionales, objetivos, criterios de entrada y salida, agendas, protocolos de actuación, responsabilidades, toma de decisiones, actividad investigadora y docente, sesiones clínicas conjuntas, creación/inicio, planificación, ventajas/desventajas del modelo y barreras/facilitadores en la implantación del modelo. Se describen sus características. Resultados. Analizamos 12 modelos de atención multidisciplinar en APs, implantados desde hace al menos 1-2 años, que globalmente pueden resumirse en 3 subtipos diferentes: presencial conjunto, presencial paralelo y circuito preferencial. La implantación de uno u otro modelo es consecuencia de la adaptación a las circunstancias del centro y profesionales. Una correcta planificación de la implantación es fundamental. La implicación y buena sintonía entre profesionales así como un acceso y criterios de derivación bien definidos son facilitadores muy importantes en la implantación de un modelo. La gestión de las agendas y la recogida de datos para medir resultados de salud de estos modelos son las principales barreras. Conclusiones. Existen distintos modelos de atención multidisciplinar implantados que tienen como objetivo intentar mejorar la atención del paciente con APs, la eficiencia del sistema y la colaboración entre especialistas (AU)

Objetive. To describe (structure, processes) of the multidisciplinary care models in psoriatic arthritis (PsA) in Spain, as well as barriers and facilitators of their implementation. Methods. A qualitative study was performed following structured interviews with 24 professionals (12 rheumatologists, 12 dermatologists who provide multidisciplinary care for patients with PsA). We collected data related to the hospital, department, population and multidisciplinary care model (type, physical and human resources, professional requirements, objectives, referral criteria, agendas, protocols, responsibilities, decision- making, research and education, clinical sessions, development and planning of the model, advantages and disadvantages of the model, barriers and facilitators in the implementation of the model. The models characteristics are described. Results. We analyzed 12 multidisciplinary care models in PsA, with at least 1-2 years of experience, and 3 subtypes of models, face-to-face, parallel, and preferential circuit. All are adapted to the hospital and professionals characteristics. A proper implementation planning is essential. The involvement and empathy between professionals and an access and well-defined referral criteria are important facilitators in the implementation of a model. The management of agendas and data collection to measure the multidisciplinary care models health outcomes are the main barriers. Conclusions. There are different multidisciplinary care models in PsA that can improve patient outcomes, system efficiency and collaboration between specialists (AU)