Recommendations from the Spanish Academy of Dermatology and Venereology Psoriasis Working Group on the Management of Patients with Cancer and Psoriasis. / Recomendaciones del Grupo de Psoriasis de la Academia Española de Dermatología y Venereología sobre el manejo de la psoriasis en pacientes oncológicos.

Several studies suggest that patients with psoriasis have a higher incidence of neoplasms, especially of the skin, which could be associated with the use of therapies to treat psoriasis. Furthermore, the evidence available on the safety profile of some treatments in this context, and the management of these patients is scarce, which is why clinical practice guidelines with recommendations on the management of psoriasis in cancer patients are ambiguous. This study provides recommendations on the management and use of the therapies currently available for these patients. They are the result of a Delphi consensus reached by 45 dermatologists of the Spanish Academy of Dermatology and Venereology Psoriasis Working Group, whose goal is to help specialists in the field in their decision-making processes.

Validation of the Spanish Version of the PURE-4 Questionnaire for the Early Detection of Psoriatic Arthritis in Psoriatic Patients. / Validación de la versión española del cuestionario PURE-4 para la detección precoz de la artritis psoriásica en pacientes con psoriasis.

BACKGROUND AND OBJECTIVE: Psoriasis often precedes the onset of psoriatic arthritis (PsA), so dermatologists often face the challenge of early identifying signs of PsA in patients with psoriasis. Our aim was to validate the Spanish version of the PURE-4 questionnaire as a screening tool for PsA, evaluate its performance in terms of sensitivity, specificity, feasibility, reliability, and build validity. METHODS: This was a cross-sectional, observational, multicenter trial of adult patients with psoriasis. Initially, patients were assessed by a dermatologist and completed 2 self-administered versions (in print and online) of the PURE-4 questionnaire. Afterwards, the rheumatologist, blinded to the PURE-4 results, assessed the presence/absence of PsA, being the reference to determine the performance of the PURE-4 questionnaire. RESULTS: A total of 268 patients were included (115 [42.9%] women; mean age, 47.1±12.6). The prevalence of PsA according to rheumatologist diagnosis was 12.7% (34 patients). The mean PURE-4 score for patients with psoriasis diagnosed with PsA was 2.3±1.1, and 1.3±1.3 for patients without PsA (P<.001). The cutoff value ≥2 demonstrated the best performance for detecting PsA, with a negative predictive value of 95.1% (95% confidence interval, 90.3-97.6). CONCLUSIONS: The PURE-4 questionnaire demonstrated good performance in detecting PsA, with an optimal cutoff point ≥2. This simple tool could facilitate early referral of patients to the rheumatology unit.

Measurement assessment of Minimal Disease Activity in psoriasis in Spain: a national cross-sectional study. / Valoración de la medida de Actividad Mínima de Enfermedad en Psoriasis en España: estudio transversal nacional.

INTRODUCTION: in 2017, the Spanish Academy of Dermatology and Venereology Psoriasis Working Group (PWG) designed the Minimal Disease Activity (MDA) criteria to determine the level of disease activity. We hereby present the results of an observational, cross-sectional, multicenter study of the nationwide application of these criteria. MATERIAL AND METHODS: we conducted a non-randomized sampling, stratified to achieve autonomic and provincial representation of consecutive patients with psoriasis (Ps) vulgaris without active arthritis. A total of 830 patients were included: 493 men (59.5%), with a mean age of 51.4 years (SD, 14.2), from all autonomous regions of Spain (except for Ceuta and Melilla) and 44 (88%) out of the 50 provinces. A questionnaire was obtained with demographic data, DLQI, subjective assessment-on a scale from 0 to 10-of itching, erythema, desquamation, visibility, and the patients' PASI and BSA. RESULTS: more than 50% failed to meet the MDA criteria (491; 59.2%), with significant differences being reported by region, sex, and age. Additionally, significant differences were reported based on the therapy used (p < 0.001). The use of biological therapies was associated with higher MDA compliance compared to other therapies (59.4% vs 23.3%). No differences were reported among various biological therapies. CONCLUSIONS: the overall rate of MDA compliance is low, with differences being based on geographic location, sex, age, and drug used, yet none of these factors separately justify them.

Definition of minimal disease activity in psoriasis.

OBJECTIVE: To generate an operational definition to adequately reflect the construct 'Minimal Disease Activity (MDA)' in psoriasis. METHODS: A systematic review of domains included in clinical trials of psoriasis was presented to a panel of dermatologists and patients. Further domains were elicited by panel discussions. Domains (and instruments measuring these) were items of two consecutive Delphi rounds targeting dermatologists from the Psoriasis Group of the Spanish Academy of Dermatology and Venereology and patients from the Acción Psoriasis association. The instruments selected were used to generate 388 patient vignettes. The expert group then classified these vignettes as 'No MDA/MDA/Unclassifiable'. The items were further reduced by factorial analysis. Using the classification variable as gold standard, several operational constructions were tested in regression models and ROC curves and accuracy was evaluated with area under the curve (AUC). RESULTS: The following domains were included: itching, scaling, erythema and visibility by 0-10 scales, extension by BSA, impact on quality of life by DLQI, special location and presence of arthritis as yes/no. The definition with the highest AUC and best balance between sensitivity and specificity was the one including no presence of arthritis plus at least three others below the upper limit of the 95% confidence interval (AUC, 0.897; sensitivity, 95.2%, specificity, 84.1%). CONCLUSION: This study provides, for the very first time, the construct of 'Minimal Disease Activity' in psoriasis as agreed by dermatologists and patients. MDA is defined as absence of active arthritis plus 3 out of 6: itching ≤ 1/10; scaling ≤ 2/10; redness ≤ 2/10; visibility ≤ 2/10; BSA ≤ 2; DLQI ≤ 2; and no lesions in special locations. By design, domains are representative of disease impact. This MDA definition may be used as a measure of adequate management and replace other subjective or restrictive tools.

Real-world effectiveness and safety of apremilast in psoriasis at 52 weeks: a retrospective, observational, multicentre study by the Spanish Psoriasis Group.

BACKGROUND: Little has been published on the real-world effectiveness and safety of apremilast in psoriasis. OBJECTIVES: To evaluate the effectiveness, safety and drug survival of apremilast at 52 weeks in patients with moderate to severe plaque psoriasis or palmoplantar psoriasis in routine clinical practice. METHODS: Retrospective, multicentre study of adult patients with moderate to severe plaque psoriasis or palmoplantar psoriasis treated with apremilast from March 2016 to March 2018. RESULTS: We studied 292 patients with plaque psoriasis and 85 patients with palmoplantar psoriasis. The mean (SD) Psoriasis Area and Severity Index (PASI) score was 10.7 (7.0) at baseline and 3.0 (4.2) at 52 weeks. After 12 months of treatment, 73.6% of patients had a PASI score of 3 or less. In terms of relative improvement by week 52, 49.7% of patients achieved PASI-75 (≥75% reduction in PASI score) and 26.5% achieved PASI-90. The mean physician global assessment score for palmoplantar psoriasis fell from 4.2 (5.2) at baseline to 1.3 (1.3) at week 52. Overall drug survival after 1 year of treatment with apremilast was 54.9 %. The main reasons for treatment discontinuation were loss of efficacy (23.9%) and adverse events (15.9%). Almost half of the patients in our series (47%) experienced at least one adverse event. The most common events were gastrointestinal problems. CONCLUSIONS: Apremilast may be a suitable alternative for the treatment of moderate to severe psoriasis and palmoplantar psoriasis. Although the drug has a good safety profile, adverse gastrointestinal effects are common.

Initial results of ixekizumab efficacy and safety in real-world plaque psoriasis patients: a multicentre retrospective study.

BACKGROUND: Ixekizumab (anti-IL17A) is effective as treatment for moderate-to-severe plaque psoriasis, but real-life data on effectiveness and safety are currently very limited. OBJECTIVE: To evaluate the efficacy and safety of ixekizumab in a cohort of real-life plaque psoriasis patients. METHODS: Retrospective chart review of 100 patients with moderate-to-severe plaque psoriasis treated with ixekizumab at seven Spanish dermatological centres. RESULTS: According to the as observed analysis, the percentage of patients achieving a 75% and 90% of reduction from the baseline score of Psoriasis Area and Severity Index (PASI) was 87.5%-50.0% at week 12-16; 88.3%-58.4% at week 24 and 82.9%-58.5% at week 52, respectively. The mean ± standard deviation (SD) score of PASI at baseline was 12.9 ± 9.2, and it declined rapidly after ixekizumab administration to 1.9 ± 4.0 (P < 0.001) at week 12-16 and was maintained at 1.7 ± 4.1 and 1.8 ± 2.9 at week 24 and 52, respectively. Ixekizumab response was not affected by clinical variables like body mass index, disease duration or the presence of psoriatic arthritis. However, the bio-naive group showed significantly higher PASI 75 response rate at week 12-16 compared to patients previously exposed to biologic agents (P = 0.037). Twenty-six (26%) patients experienced adverse events (AEs) during the follow-up period, being most of them of mild-to-moderate intensity. The most common AE was local reaction at the site of injection (14/26; 53.8%). At the end of the observational period, 15 (15%) patients discontinued ixekizumab treatment due to limited clinical improvement (n = 11), adverse events (n = 3) or lost to follow-up (n = 1) within a mean ± SD time of 6.0 ± 3.9 months. CONCLUSION: The present study illustrates the initial experience with ixekizumab in real-world clinical practice confirming its usefulness and safety in the management of plaque psoriasis patients.

Subclinical enthesopathy of extensor digitorum tendon is highly prevalent and associated with clinical and ultrasound alterations of the adjacent fingernails in patients with psoriatic disease.

BACKGROUND: Nail psoriasis disease is associated with an increased probability of psoriatic arthritis, and its clinical signs may have different correlates with the pathogenesis of adjacent bone destruction and have different prognostic value. Recent publications about psoriasis and nail psoriatic disease describe different ultrasonographic findings but the relationship between these ungueal alterations measured by ultrasonography and the presence of enthesopathy of the extensor digitorum has yet to be discovered. OBJECTIVE: To describe which ultrasonographic characteristics of nail psoriasis are associated with the presence of subclinical enthesopathy in patients with PsO and asymptomatic PsA. METHODS: Patients with psoriasis and asymptomatic psoriatic arthritis were included in the prospective study. Demographic, clinical data and PASI and NAPSI indexes were recorded of all the patients in the assessment visit. The US assessment included Achilles tendon, extensor digitorum tendon and US scan of the nail plate, nail matrix, nail bed and adjacent skin over nail matrix of the five nails of each hand. RESULTS: Forty-eight patients were included in the study; 33 of them presented ultrasound evidence of extensor digitorum tendon enthesopathy. Nails of the patients with subclinical enthesopathy had a higher NAPSI and skin thickness than the nails of the patients without subclinical enthesopathy (P = 0.047). Patients with asymptomatic enthesopathy had significantly thicker proximal nail folds (1.44 ± 0.312 vs. 1.23 ± 0.27, P = 0.023). Nail beds and matrices were also thicker but the differences were not statistically significant (1.77 ± 0.27 vs. 1.74 ± 0.21, P = 0.66, and 1.79 ± 0.28 vs. 1.67 ± 0.19, P = 0.10, respectively). No statistically significant differences in the trilaminar structure were found between both groups. Patients with and without asymptomatic enthesopathy of extensor digitorum tendons did not statistically differ as regards ultrasonographic alterations of the Achilles tendons (60.6% vs. 46.4%, P 0.368). CONCLUSION: Enthesopathy abnormalities can be detected by US in patients with psoriasis without musculoskeletal complaints frequently. There is a close relationship between subclinical enthesopathy of the extensor digitorum tendon and the presence of nail alterations. Further studies are required to research what implications have the presence of these ungual alterations measured by US, and how it affects later development of a PsA.

Model for assessing the efficiency of biologic drugs in the treatment of moderate to severe psoriasis for one year in clinical practice in Spain.

INTRODUCTION: Most economic evaluations in the literature on the subject of biologic therapy for the treatment of psoriasis do not reflect normal clinical practice or consider the cost of patient management. OBJECTIVE: The objective of the present study is to establish a model for assessing the efficiency of biologic therapies in the treatment of psoriasis taking into account the cost of managing treatment which, in routine clinical practice, depends on patient response. METHODS: We developed a model based on a decision tree that incorporates the probability of treatment response or failure with adalimumab, etanercept, infliximab, and ustekinumab after 24 weeks of therapy (end of the induction phase). The probability in each case was calculated using data from a meta-analysis. The following direct health costs were taken into account: the cost of drugs and their administration in euro (2015). Our analysis was based on the cost of 12 months of treatment administered in a hospital setting. RESULTS: According to the proposed model, the mean cost per year by initial treatment strategy was lowest for patients who started treatment with ustekinumab, although the percentage cost difference between ustekinumab and infliximab or adalimumab was less than 3%. With a fixed budget of €1,000,000, the initial treatment option that would achieve success in the largest number of patients for one year would, according to this model, be ustekinumab (66 patients), followed by infliximab (n = 62), adalimumab (n = 59), and etanercept (n = 50). Sensitivity analysis confirmed the reliability of these results. However, considering the confidence intervals of the incremental efficacy observed in the meta-analysis, the differences found are probably not significant in all the possible binary comparisons. Likewise, possible differences in actual price structures, populations, and the strategies and therapeutic objectives of each hospital could all give rise to considerable variations in real life. CONCLUSIONS: The cost of managing treatment in patients who fail to achieve an acceptable response during the induction phase should also be considered since such costs are a determining factor in any assessment of treatment efficiency. To achieve the optimum allocation of resources and to treat more patients efficiently, the information provided by this analysis should be cross-checked with real data taken from actual clinical practice in Spain collected in each geographical region and hospital.

Etanercept in the treatment of psoriatic arthritis.

The aim of the present review is to provide an update on the most important recent studies on the use of etanercept in psoriatic arthritis (PsA). Using various assessment tools, such as the Disease Activity Score 28-joint count (DAS28), the PsA Response Criteria (PsARC), and the American College of Rheumatology (ACR) score, several authors have shown that etanercept can reduce the signs and symptoms of psoriatic arthritis and inhibit radiographic progression in studies with follow-up periods of up to 2 years. There is evidence that etanercept is effective in the treatment of psoriatic enthesitis, dactylitis, and axial joint disease as well as in disease affecting the skin and nails. In clinical trials, etanercept had a safety profile similar to that of placebo and this profile did not change over time. Cost-effectiveness models have found etanercept to be the most cost-effective tumor necrosis factor inhibitor in patients with psoriatic arthritis and mild to moderate psoriasis. Etanercept has a favorable risk-benefit profile in the short term. The concomitant use of methotrexate does not alter etanercept survival.

Long-term study of infliximab for psoriasis in daily practice: drug survival depends on combined treatment, obesity and infusion reactions.

BACKGROUND: Infiximab has been shown to be highly effective in phase III clinical trials, but limited information is available regarding drug survival and maintenance of efficacy beyond 1 year in real-life clinical setting. OBJECTIVES: To analyse the efficacy and safety of infliximab in a large number of patients with a long follow-up and to identify clinical factors associated with long-term drug survival. METHODS: A retrospective review of patients with moderate-to-severe psoriasis treated with infliximab from March 2004 to August 2012 at a tertiary dermatology centre was carried out. RESULTS: In total, 63 treatment courses with infliximab were administered to 56 patients. The mean duration of treatment was 31.6 months. The only significant positive predictor of drug survival was combination treatment [hazard ratio (HR) vs. monotherapy 2.90, 95% confidence interval (CI) 1.42­5.92]. Significant negative predictors of drug survival were obesity (HR 0.40, 95% CI 0.19­0.87) and infusion reactions (HR 0.40, 95% CI 0.19­0.87). Infusion reactions occurred in 13 (23%) of our patients and were a reason for discontinuation of treatment in 5. CONCLUSIONS: This retrospective review of a cohort of patients with moderate-to-severe psoriasis treated with infliximab in daily practice shows that the PASI75 response rates at 24 and 52 weeks of treatment are similar to those of the pivotal studies, but 37 courses of treatment (59%) had to be discontinued after a median of 12 months. The major cause for discontinuation was loss of response, in 18 cases. Combination treatment, obesity and infusion reactions were found to be predictors of drug survival.

Psoriatic arthritis: an update.

Advances in our understanding of the pathogenesis of psoriatic arthritis and clinical aspects of the disease justify the present review. Studies have identified common inflammatory pathways related to the innate immune response, such as the IL-12/IL-23 axis, along with numerous genes that affect susceptibility to both diseases and influence phenotypic development. Interest has grown in biomarkers that can be used for early diagnosis or prognosis or to predict joint destruction and the response to treatment. Recent reports describe important differences between the effects of disease-modifying antirheumatic drugs and biologics on the process of new bone formation. Other issues that have been discussed include the need for reliable screening methods, particularly for early detection of oligoarticular arthritis, and for protocols to guide referral to specialists, especially in newly created multidisciplinary practices.

Vismodegib: a review.

In January 2012, vismodegib (Erivedge, manufactured by Genentech) became the first selective inhibitor of the Hedgehog signaling pathway to be approved by the US Food and Drug Administration for the treatment of locally advanced and metastatic basal cell carcinoma. The drug selectively binds to Smoothened, a 7-helix transmembrane receptor, thereby inhibiting activation of transcription factors of the glioma-associated oncogene family and suppressing tumor proliferation and growth. Studies published to date have assessed the efficacy of vismodegib according to clinical and radiologic outcomes but little information is available on the molecular mechanisms underpinning the proven clinical efficacy of the drug. This review will cover recent data on the Hedgehog signaling pathway and data from clinical trials with vismodegib in the treatment of basal cell carcinoma, and will consider its use in other types of tumor.

Adalimumab for the treatment of psoriasis in real life: a retrospective cohort of 119 patients at a single Spanish centre.

BACKGROUND: Patients with moderate-to-severe psoriasis treated with adalimumab in daily clinical practice are different from those in clinical trials, and outcomes may differ in different geographical settings. OBJECTIVES: To analyse the efficacy, retention of treatment and adverse events in a cohort of such patients at a referral centre in Barcelona, Spain. METHODS: Data from a cohort of 119 consecutive patients treated between January 2008 and March 2013 were retrospectively collected. Drug survival was analysed by the Kaplan-Meier method with log-rank test and Cox regression. RESULTS: The mean duration of treatment was 25 months (median 22, range 2-60). The 75% improvement in Psoriasis Area and Severity Index (PASI 75) response rates at 16 weeks, 6 months and 1 year of treatment were 64%, 58% and 53%, respectively (intention-to-treat analysis). The corresponding PASI 90 values were 49%, 52% and 50%. Biologic-naive patients (41%) had significantly higher PASI 75 and PASI 90 response rates at 6 months and 1 year. On multivariate analysis, only PASI 90 response at 6 months was significantly associated with treatment retention (P = 0.0009), with a hazard ratio of 7.3 (95% confidence interval 2.3-23.6). Forty-eight adverse events (AEs) occurred in 29 patients, and were serious in eight (0.032 events per patient-year). Paradoxical flares of psoriasis or arthritis were seen in five patients. Infections accounted for seven serious AEs, and were the reason for discontinuation in two patients. CONCLUSIONS: PASI 90 response at 6 months was the only independent variable predicting drug survival on multivariate analysis. Infections, including de novo infection by Mycobacterium tuberculosis, accounted for seven serious AEs.

[Botulinum toxin A for the treatment of familial benign pemphigus]. / Toxina botulínica A en el tratamiento del pénfigo benigno familiar.

Familial benign pemphigus or Hailey-Hailey disease is a rare bullous disease that presents clinically with recurrent flares of erosions and vesicles that mainly affect the skinfolds. Many topical and systemic therapies have been proposed. Hyperhidrosis is one of the factors that can trigger or aggravate a flare-up, and its treatment is therefore important for controlling the disease and preventing further episodes. We report 3 patients with axillary and/or inguinal benign familial pemphigus that responded favorably to treatment with subcutaneous botulinum toxin.

[Psoriatic arthritis: what the dermatologist needs to know, part 1]. / Artritis psoriásica: lo que el dermatólogo debe saber (Parte 1).

Psoriatic arthritis is defined as inflammatory arthritis occurring in patients with psoriasis and is classified as a seronegative spondyloarthropathy associated with human leukocyte antigen B27. Between 25 and 35% of patients with psoriasis go on to develop psoriatic arthritis during the course of their disease. Given that the skin is affected before the joints in most cases, the dermatologist must be able to recognize the signs and symptoms in order to make a diagnosis and start the most appropriate treatment. This review aims to cover key aspects of the initial diagnostic workup and clinical evaluation. It examines the epidemiology, pathogenesis, and manifestations of psoriatic arthritis, as well as the complementary tests and diagnostic tools the dermatologist should be aware of in order to make the correct diagnosis.

[Psoriatic arthritis: what the dermatologist needs to know, Part 2]. / Artritis psoriásica. Lo que el dermatólogo debe saber (Parte 2).

This review aims to cover all aspects related to the treatment of psoriatic arthritis and the evaluation of the response to treatment. We define the various evaluation methods currently used to assess response to treatment in patients with psoriatic arthritis and the complementary examination techniques used to ensure adequate follow-up. These tools enable both the dermatologist and the rheumatologist to carry out an ongoing evaluation of the clinical course, severity, and prognosis of the disease. The treatment lines proposed by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Spanish Society of Rheumatology are discussed. Emerging strategies for treating this condition and improving prognosis are examined.

Psoriatic Arthritis: What the Dermatologist needs to Know, Part 1. / Artritis psoriásica: lo que el dermatólogo debe saber (Parte 1).

Psoriatic arthritis is defined as inflammatory arthritis occurring in patients with psoriasis and is classified as a seronegative spondyloarthropathy associated with human leukocyte antigen B27. Between 25 and 35% of patients with psoriasis go on to develop psoriatic arthritis during the course of their disease. Given that the skin is affected before the joints in most cases, the dermatologist must be able to recognize the signs and symptoms in order to make a diagnosis and start the most appropriate treatment. This review aims to cover key aspects of the initial diagnostic workup and clinical evaluation. It examines the epidemiology, pathogenesis, and manifestations of psoriatic arthritis, as well as the complementary tests and diagnostic tools the dermatologist should be aware of in order to make the correct diagnosis.