Treatment of psoriasis with biologic and non-biologic targeted therapies in patients with latent tuberculosis infection or at risk for tuberculosis disease progression: Recommendations from a SPIN-FRT expert consensus.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a significant global health problem. In immunocompetent individuals, the microorganism can remain in a latent, non-contagious form, however, it may become active under conditions of immunosuppression. Tumour necrosis factor (TNF) inhibitors, which are frequently used for the management of immune-mediated disorders like psoriasis, have been associated with a significantly increased risk of reactivating latent TB. Consequently, international guidelines recommend TB screening and preventive treatment before starting anti-TNF therapy. These recommendations have extended to IL-12/23, IL-17, IL-23 and TYK2 inhibitors under a caution principle, despite their different mechanisms of action. However, current evidence suggests that some of these agents are arguably not associated with an increased risk of TB reactivation or development of TB disease after infection, which calls for a critical reassessment of these guidelines. We have conducted a literature search evaluating the risk of TB reactivation associated with these innovative therapies, integrating findings from both randomized clinical trials and real-world evidence. The identified evidence is limited but the low number of identified cases of reactivation with IL-17 and IL-23 inhibitors prompts reconsidering the need for preventive treatment for latent TB in all cases, regardless of biologic class or individual patient's risk of TB reactivation or drug toxicity. This review, along with the clinical insight of a panel of experts on behalf of the SPIN-FRT, led to the development of these consensus recommendations for managing psoriasis treatment in patients with latent TB infection or at risk of TB infection, who are receiving or are intended to receive biologic and non-biologic targeted therapies. These recommendations highlight the need for updates to the existing guidelines, aiming to provide a more differentiated approach that reflects the evolving landscape of psoriasis treatment and its implications for TB management.

Comparative Treatment of Mucocutaneous Lesions in Hereditary Haemorrhagic Telangiectasia Patients With Dual Sequential Pulsed Dye Laser and Neodymium: Yttrium-Aluminium-Garnet Versus Neodymium: Yttrium-Aluminium-Garnet Laser Alone: A Double-Blind Randomized Controlled Study With Quality-of-Life Evaluation. / [Artículo traducido] Tratamiento comparativo de lesiones mucocutáneas en pacientes con telangiectasia hemorrágica hereditaria con láser dual secuencial de colorante pulsado y neodimio: itrio-aluminio-granate versus neodimio: itrio-aluminio-granate solo: un estudio controlado aleatorizado doble ciego con evaluación de la calidad de vida.

BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) is characterized by the presence of telangiectases and larger arteriovenous malformations in different organs. Mucocutaneous telangiectases can bleed and become an aesthetic concern, impairing quality of life (QoL). However, the best treatment approach has not been defined yet. OBJECTIVE: To evaluate the efficacy and safety of dual wavelength sequential 595/1064nm laser (DWSL) compared to 1064nm laser (Nd:YAG) alone. Secondarily, to evaluate QoL impairment in HHT patients, and its improvement with laser therapy. METHODS: A comparative randomized split-body double-blinded prospective study (DWSL vs Nd:YAG). Demographic, clinical and treatment characteristics were recorded. The severity and degree of improvement were evaluated by three blinded examiners who scored pre-treatment and post-treatment pictures on a 5-point scale. Patients fulfilled Skindex-29 and FACE-Q® tests and assessed procedure-associated pain and patient satisfaction. RESULTS: 111 treatment areas (55 treated with DWSL and 56 with Nd:YAG) from 26 patients were analyzed. The median number of laser sessions was 2 (interquartile range [IQR] 2-4; mean 2.90 vs 2.88, respectively). The median improvement score, irrespective of location, was significantly higher for Nd:YAG compared to DWSL: 3 (IQR 2-3; mean 2.61) vs 2 (IQR 2-3; mean 2.32), p=0.031. Both FACE-Q index and Skindex-29 test results improved significantly (p<0.001), and 92.4% patients reported a high degree of satisfaction (≥8). No severe adverse events were reported. CONCLUSIONS: DWSL and Nd:YAG laser are convenient, safe and effective treatment options for mucocutaneous telangiectases in HHT patients. However, Nd:YAG delivered better results with better tolerability. QoL was significantly improved by both treatments.

Comparative Treatment of Mucocutaneous Lesions in Hereditary Haemorrhagic Telangiectasia Patients With Dual Sequential Pulsed Dye Laser and Neodymium: Yttrium-Aluminium-Garnet Versus Neodymium: Yttrium-Aluminium-Garnet Laser Alone: A Double-Blind Randomized Controlled Study With Quality-of-Life Evaluation.

BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) is characterized by the presence of telangiectases and larger arteriovenous malformations in different organs. Mucocutaneous telangiectases can bleed and become an aesthetic concern, impairing quality of life (QoL). However, the best treatment approach has not been defined yet. OBJECTIVE: To evaluate the efficacy and safety of dual wavelength sequential 595/1064nm laser (DWSL) compared to 1064nm laser (Nd:YAG) alone. Secondarily, to evaluate QoL impairment in HHT patients, and its improvement with laser therapy. METHODS: A comparative randomized split-body double-blinded prospective study (DWSL vs Nd:YAG). Demographic, clinical and treatment characteristics were recorded. The severity and degree of improvement were evaluated by three blinded examiners who scored pre-treatment and post-treatment pictures on a 5-point scale. Patients fulfilled Skindex-29 and FACE-Q® tests and assessed procedure-associated pain and patient satisfaction. RESULTS: 111 treatment areas (55 treated with DWSL and 56 with Nd:YAG) from 26 patients were analyzed. The median number of laser sessions was 2 (interquartile range [IQR] 2-4; mean 2.90 vs 2.88, respectively). The median improvement score, irrespective of location, was significantly higher for Nd:YAG compared to DWSL: 3 (IQR 2-3; mean 2.61) vs 2 (IQR 2-3; mean 2.32), p=0.031. Both FACE-Q index and Skindex-29 test results improved significantly (p<0.001), and 92.4% patients reported a high degree of satisfaction (≥8). No severe adverse events were reported. CONCLUSIONS: DWSL and Nd:YAG laser are convenient, safe and effective treatment options for mucocutaneous telangiectases in HHT patients. However, Nd:YAG delivered better results with better tolerability. QoL was significantly improved by both treatments.

Persistence and effectiveness of guselkumab treatment in patients with moderate-to-severe plaque psoriasis in a non-interventional real-world setting: The SPRING study.

BACKGROUND: Guselkumab is a monoclonal antibody that blocks the IL-23 pathway with proven efficacy and tolerability in the treatment of moderate-to-severe plaque psoriasis. OBJECTIVES: To assess the persistence, effectiveness and safety of guselkumab in patients with moderate-to-severe psoriasis in real clinical practice in Spain. METHODS: SPRING was a Phase IV, retrospective and non-interventional study analysing patients with moderate-to-severe plaque psoriasis who had initiated guselkumab under clinical practice conditions at least 12 months before inclusion in the study. The primary endpoint was persistence (non-persistence: discontinuation or interruption ≥90 days). Effectiveness was assessed using the Psoriasis Area Severity Index (PASI) and Investigator Global Assessment (IGA). Dermatology Life Quality Index (DLQI) and safety were also evaluated. RESULTS: A total of 284 patients were included between September 2020 and June 2021. The 1-year probability of persistence was 89.6% (86.1%-93.3%). The 1-year probability of persistence was also calculated according to prior biologic treatment, being 90.3% for biologic-naïve patients and 89.5% for patients who received one or more biologic therapies before guselkumab. Additionally, patients were also classified based on the frequency of the administration of guselkumab treatment; the 1-year probability of persistence was 91.9% in patients receiving guselkumab according to the Summary of Product Characteristics and 89.3% in patients with lengthened intervals of administration. After 1 year, PASI 90 was achieved by 56.4% of patients, IGA 0/1 response and BSA <3% were achieved by 65.5% and 77.8% of patients, respectively, and 65.8% achieved a minimal clinically significant difference (>4-point reduction) in the DLQI score at 1 year. Twenty-six adverse reactions (4 of them serious) were reported in 16 patients. CONCLUSIONS: This study suggests that guselkumab has high persistence in real clinical practice in Spain, independently of the previous biologic treatments and changes in the frequency of treatment. Effectiveness and safety are consistent with previously published data.

Statins and psoriasis: Position statement by the Psoriasis Task Force of the European Academy of Dermatology and Venerology.

BACKGROUND: Psoriasis is associated with an increased mortality risk, with cardiovascular disease being the leading excess cause (in a dose-response manner with psoriasis severity). Statins have demonstrated a reduction in all-cause mortality with no excess of adverse events among the general population. The underuse of interventions in cardiovascular prevention, such as statins, for patients with psoriasis may be the result of an insufficient evaluation. OBJECTIVES: To provide the dermatologist with a tool for systematizing the treatment of dyslipidemia in psoriasis, which generally escapes the scope of dermatological practice, and to facilitate decision-making about the referral and treatment of patients. METHODS: The Psoriasis Task Force of the European Academy of Dermatology and Venereology performed this two-phase study to achieve a consensus and create recommendations on the use of statin therapy in patients with psoriasis. The first phase included a systematic review to identify a list of outline concepts and recommendations according to guidelines. The second phase consisted in a two-round Delphi study to evaluate those recommendations not literally taken from guidelines. RESULTS: A list of 47 concepts and recommendations to be followed by dermatologists involved in the treatment of patients with moderate-severe psoriasis was created. It included six main concepts about cardiovascular risk and psoriasis, six items related with the role of low-density lipoprotein cholesterol (LDL-c) and the benefits of statin treatment in psoriasis patients, eight recommendations about how cardiovascular risk should be assessed, three on the role of non-invasive cardiovascular imaging, three on LDL-c thresholds, eight key points related to statin prescription, 10 on statin treatment follow-up and three on patient referral to another specialist. CONCLUSIONS: The application of this position statement (close final list of concepts and recommendations) will help dermatologists to manage dyslipidemia and help psoriasis patients to reduce their cardiovascular risk.

Updated Position of the Spanish Psoriasis Group (GPs) on the Use of Biosimilar Drugs in Moderate to Severe Psoriasis. / Actualización en el posicionamiento del Grupo Español de Psoriasis (GPS) en la utilización de medicamentos biosimilares en psoriasis moderada-grave.

The advent of biosimilar drugs and their use in routine clinical practice has revolutionized the management of moderate to severe psoriasis and led to changes in the positioning of the existing molecules used to control this condition. Evidence from clinical trials complemented by real-world experience has helped to clarify concepts and has significantly changed the use and positioning of biologic agents in this setting. The present document is an update on the position of the Spanish Psoriasis Working Group regarding the use of biosimilar drugs, which takes into account this new situation.

Nail Psoriasis. / Psoriasis ungueal.

Nail involvement in psoriasis is common. It is seen in up to 80% of patients with psoriatic lesions and may be the only manifestation in 6% of cases. Nail psoriasis is correlated with more severe disease, characterized by earlier onset and a higher risk of psoriatic arthritis. Accordingly, it can also result in significant functional impairment and reduced quality of life. Psoriasis involving the nail matrix causes pitting, leukonychia, red lunula and nail dystrophy, while nail bed involvement causes splinter hemorrhages, onycholysis, oil spots (salmon patches), and subungual hyperkeratosis. Common evaluation tools are the Nail Psoriasis Severity Index (NAPSI), the modified NAPSI, and the f-PGA (Physician's Global Assessment of Fingernail Psoriasis). Treatment options include topical therapy, intralesional injections, and systemic and biologic agents. Treatment should therefore be assessed on an individualized basis according to the number of nails involved, the part of the nail or nails affected, and the presence of concomitant nail and/or joint involvement.

Practical update of the Recommendations Published by the Psoriasis Group of the Spanish Academy of Dermatology and Venereology (GPS) on the Treatment of Psoriasis with Biologic Therapy. Part 1. Concepts and General Management of Psoriasis with Biologic Therapy. / Actualización práctica de las recomendaciones del Grupo de Psoriasis de la Academia Española de Dermatología y Venereología (GPS) para el tratamiento de la psoriasis con terapia biológica. Parte 1. «Conceptos y manejo general de la psoriasis con terapia biológica¼.

BACKGROUND AND OBJECTIVES: A new, updated AEDV Psoriasis Group consensus document on the treatment of moderate to severe psoriasis was needed owing to the approval, in recent years, of a large number of new drugs and changes in the treatment paradigm. METHODOLOGY: The consensus document was developed using the nominal group technique and a scoping review. First, a designated coordinator selected a group of Psoriasis Group members for the panel. The coordinator defined the objectives and key points for the document and, with the help of a documentalist, conducted a scoping review of articles in Medline, Embase, and the Cochrane Library up to January 2021. The review included systematic reviews and meta-analyses as well as clinical trials not included in those studies and high-quality real-world studies. National and international clinical practice guidelines and consensus documents on the management of moderate to severe psoriasis were also reviewed. Based on these reviews, the coordinator drew up a set of proposed recommendations, which were then discussed and modified in a nominal group meeting. After several review processes, including external review by other GPs members, the final document was drafted. RESULTS: The present guidelines include general principles for the treatment of patients with moderate to severe psoriasis and also define treatment goals and criteria for the indication of biologic therapy and the selection of initial and subsequent therapies. Practical issues, such as treatment failure and maintenance of response, are also addressed.

Practical Update of the Guidelines Published by the Psoriasis Group of the Spanish Academy of Dermatology and Venereology (GPs) on the Treatment of Psoriasis With Biologic Agents: Part 2 - Management of Special Populations, Patients With Comorbid Conditions, and Risk. / Actualización práctica de las recomendaciones del Grupo de Psoriasis de la Academia Española de Dermatología y Venereología (GPS) para el tratamiento de la psoriasis con terapia biológica. Parte 2 «Manejo de poblaciones especiales, pacientes con comorbilidad y gestión del riesgo¼.

BACKGROUND AND OBJECTIVES: Since its inception, the Psoriasis Group (GPs) of the Spanish Academy of Dermatology and Venereology (AEDV) has worked to continuously update recommendations for the treatment of psoriasis based on the best available evidence and incorporating proposals arising from and aimed at clinical practice. An updated GPs consensus document on the treatment of moderate to severe psoriasis was needed because of changes in the treatment paradigm and the approval in recent years of a large number of new biologic agents. METHODOLOGY: The consensus document was developed using the nominal group technique complemented by a scoping review. First, a designated coordinator selected a group of GPs members for the panel based on their experience and knowledge of psoriasis. The coordinator defined the objectives and key points for the document and, with the help of a documentalist, conducted a scoping review of articles in Medline, Embase, and the Cochrane Library up to January 2021. The review included systematic reviews and meta-analyses as well as clinical trials not included in those studies and high-quality real-world studies. National and international clinical practice guidelines and consensus documents on the management of moderate to severe psoriasis were also reviewed. The coordinator then drew up a set of proposed recommendations, which were discussed and modified in a nominal group meeting. After several review processes, including external review by other GPs members, the final document was drafted. RESULTS: The present guidelines include updated recommendations on assessing the severity of psoriasis and criteria for the indication of systemic treatment. They also include general principles for the treatment of patients with moderate to severe psoriasis and define treatment goals for these patients as well as criteria for the indication and selection of initial and subsequent therapies Practical issues, such as treatment failure and maintenance of response, are also addressed.

Long-term efficacy and safety of brodalumab in moderate-to-severe plaque psoriasis: a post hoc pooled analysis of AMAGINE-2 and -3.

BACKGROUND: Brodalumab is a monoclonal antibody that blocks multiple interleukin (IL)-17 family cytokines by binding to the shared A subunit of the IL-17 receptor. In Phase 3 trials, brodalumab provided high levels of skin clearance through 52 weeks in patients with moderate-to-severe psoriasis and was generally well tolerated. OBJECTIVES: To assess efficacy response rates and safety outcomes through 120 weeks for patients with moderate-to-severe psoriasis who received brodalumab. METHODS: Safety and efficacy data were pooled for patients from AMAGINE-2 and -3 who received continuous brodalumab 210 mg every 2 weeks, or brodalumab 210 mg every 2 weeks after receiving either brodalumab 140 mg or placebo through Week 12. Efficacy data are presented using observed data, non-responder imputation (NRI) and a combination of NRI and missing at random assumption to account for missing data. Absolute PASI scores are presented using mixed-effect model repeated measure modelling and multiple imputation. RESULTS: Based on observed data at Week 120, 86% of the continuous brodalumab 210 mg group achieved PASI 90 and 74% achieved PASI 100. At Week 12, 58% of this group achieved absolute PASI ≤1; this proportion increased to approximately 80% at Week 52 and persisted through Week 120. Among patients receiving continuous brodalumab 210 mg, median duration of brodalumab exposure was 747 days and the overall exposure-adjusted event rate of treatment emergent adverse events per 100 patient-years was 329. Safety through 120 weeks was comparable to the results of the primary AMAGINE-2 and -3 studies. Patients who switched to brodalumab 210 mg after receiving either brodalumab 140 mg or placebo through Week 12 showed similar skin clearance and safety profiles. CONCLUSIONS: Brodalumab treatment was well tolerated and resulted in high levels of skin clearance that were rapidly achieved and maintained through Week 120, supporting its long-term efficacy and safety profile.

Prevalence of most common skin diseases in Europe: a population-based study.

BACKGROUND: The assessment of the prevalence of diseases is of primary importance in planning health policies. No complete data on the prevalence of skin diseases across European countries are available. OBJECTIVE: To estimate the prevalence of the most frequent skin conditions or diseases in 27 European countries (24 EU countries, plus Norway, Switzerland, and the United Kingdom). METHODS: We conducted a population-based study on representative and extrapolable samples of the general population aged 18 years or more in each of the 27 countries surveyed. Participants were selected using stratified, proportional sampling with a replacement design. Data were collected using a web-based online survey. All participants were asked to fill in a questionnaire with sociodemographic data and to declare if they have had one or more skin conditions or diseases during the previous 12 months. RESULTS: A total of 44 689 participants from 27 countries responded to the questionnaire, 21 887 (48.98%) men and 22 802 (51.02%) women. The proportion of participants who reported having suffered from at least one dermatological condition or disease during the previous 12 months was 43.35% (95% CI: 42.89%, 43.81%). The projection in the total population of the 27 countries included in the study resulted in 185 103 774 individuals affected by at least one dermatological condition or disease. Accordingly, we can estimate that more than 94 million Europeans complain of uncomfortable skin sensations like itch, burning, or dryness. The most frequent conditions were fungal skin infections (8.9%), acne (5.4%), and atopic dermatitis or eczema (5.5%). Alopecia, acne, eczema, and rosacea were more common in women, whereas men were more likely to suffer from psoriasis and sexually transmitted infections. CONCLUSION: Skin diseases are an important public health concern. Their high prevalence has to be taken into account in planning access to dermatological care to address patient needs.

MicroRNA31 and MMP-1 contribute to the differentiated pathway of invasion -with enhanced epithelial-to-mesenchymal transition- in squamous cell carcinoma of the skin.

Epithelial to mesenchymal transition (EMT) is an important mechanism of invasion in cutaneous squamous cell carcinomas (cSCCs) and has been found to be enhanced in tumors originated from actinic keratosis with transformation limited to the basal epithelial layer -differentiated pathway-, compared to cases with invasion subsequent to complete epidermal transformation -classical pathway-. Several microRNAs and proteins can contribute to EMT modulation in cSCCs. MicroRNA21 and microRNA31 are involved in posttranscriptional regulation of protein expression and could play a relevant role in EMT and cSCC progression. Throughout the EMT process upregulation of matrix metalloproteinases (MMPs) enhances invasiveness and MMP-1 and MMP-3 contribute to local invasion, angiogenesis and metastasis in cSCCs. Additionally, cSCC development is associated with PTEN loss and NF-κB, NOTCH-1 and p63 activation. The aim of this work is to identify differences in the expression of those molecules between both pathways of cSCCs development. Eight tissue microarrays from 80 consecutive cSCCs were analyzed using LNA-based miRNA in situ hybridization for miRNA21 and miRNA31 evaluation, and immunohistochemistry for MMP-1, MMP-3, PTEN, NOTCH-1, NF-κB, p63 and CD31. Significantly higher expression of miRNA31 (p < 0.0001) and MMP-1 (p = 0.0072) and angiogenesis (p = 0.0199) were found in the differentiated pathway, whereas PTEN loss (p = 0.0430) was more marked in the classical pathway. No significant differences were found for the other markers. Our findings support a contribution of miRNA31 and MMP-1 in the differentiated pathway, associated to EMT and increased microvascularization. The greater PTEN loss in the classical pathway indicate that its relevance in cSCC is not EMT-related.

Long-term efficacy and safety of risankizumab for the treatment of moderate-to-severe plaque psoriasis: interim analysis of the LIMMitless open-label extension trial beyond 3 years of follow-up.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease requiring prolonged treatment. New biologic therapies require long-term evaluation to assess the durability of their efficacy and safety profiles over time. OBJECTIVES: To evaluate the long-term efficacy and safety of risankizumab (RZB) for the treatment of psoriasis. METHODS: LIMMitless is an ongoing, phase III, open-label extension study evaluating the long-term efficacy and safety of RZB in adults with moderate-to-severe plaque psoriasis following multiple phase II/III studies. This analysis assessed efficacy through 172 weeks of continuous RZB treatment by examining the proportion of patients achieving ≥ 90% or 100% improvement in Psoriasis Area and Severity Index (PASI 90 and PASI 100), static Physician's Global Assessment of clear or almost clear (sPGA 0/1) and Dermatology Life Quality Index of no effect on quality of life (DLQI 0/1). Safety was assessed by recording adverse events (AEs) through the data cutoff date. The study is registered at ClinicalTrials.gov (identifier: NCT03047395). RESULTS: Of 955 patients randomized to RZB 150 mg in the base studies, 897 patients continued into LIMMitless; 799 patients were still receiving treatment in LIMMitless at the time of data cutoff for this analysis. After 172 weeks of continuous RZB treatment, 85·5% of patients achieved PASI 90, 54·4% achieved PASI 100, 85·2% achieved sPGA 0/1, and 78·4% achieved DLQI 0/1 using modified nonresponder imputation. Rates of AEs leading to discontinuation and AEs of safety interest were low with long-term treatment and comparable with those identified in the base studies. CONCLUSIONS: Overall, long-term continuous RZB was well tolerated and showed high and durable efficacy over 172 weeks.

Complete clearance and Psoriasis Area and Severity Index response for brodalumab and ustekinumab by previous treatment history in AMAGINE-2 and AMAGINE-3.

BACKGROUND: The pathway for treatment of psoriasis is partly dependent upon disease severity, and patients may experience inadequate response at any point along the treatment pathway. Patients who repeatedly fail therapy represent a population in whom effective and well-tolerated treatment options are limited. OBJECTIVES: To investigate and describe patients achieving Psoriasis Area and Severity Index (PASI) 100 and cumulative treatment benefit over time in patients with moderate-to-severe psoriasis receiving brodalumab or ustekinumab by prior treatment. METHODS: We conducted a post hoc analysis of data from two phase 3, randomized, controlled, 52-week AMAGINE trials of brodalumab to describe patients who achieved complete clearance as measured by PASI 100 by prior treatment subgroup (naïve to systemic and biologic treatment, systemic-treated but biologic-naïve, biologic-treated without failure, and biologic-treated with failure). A competing risk model was used to assess cumulative incidence over a 52-week period with outcomes of PASI 100 or inadequate response. Cumulative clinical benefit of treatment was determined with an area under the curve analysis. RESULTS: The 52-week cumulative incidence of patients achieving PASI 100 was consistently higher for brodalumab vs. ustekinumab across treatment pathway subgroups (76% vs. 58% in systemic/biologic-naïve patients, 78% vs. 55% in systemic-treated/biologic-naïve patients, 75% vs. 41% in biologic-treated patients without failure, and 70% vs. 30% in biologic-treated patients with failure). Rates of inadequate response were lower with brodalumab compared with ustekinumab across all subgroups. Cumulative treatment benefit was also higher for all subgroups treated with brodalumab compared with those treated with ustekinumab. CONCLUSION: Treatment with brodalumab was associated with higher levels of complete clearance and greater cumulative benefit over time compared with ustekinumab, in patients with moderate-to-severe psoriasis, regardless of prior treatment experience.