Dose reduction is a feasible strategy in patients with plaque psoriasis who achieve sustained response with secukinumab: a retrospective, multicenter cohort study in daily practice setting.

BACKGROUND: Biological therapy dose modification is a common practice in the long-term treatment of plaque psoriasis. OBJECTIVE: The objective of the study was to determine prevalence, characteristics of patients, effectiveness, treatment survival of secukinumab dose reduction (SEC-DR) strategy and assess its safety and cost implications. METHODS: A retrospective, observational, multicenter cohort study was conducted in patients with plaque psoriasis treated with secukinumab and up to 2 years of follow-up. RESULTS: In 63/347 patients with an initial standard dose regimen, SEC-DR was tried at any moment in 18.2% of them after sustained response. In 51 patients, the interval between administrations was increased while in 12 patients, monthly dose was reduced to 150 mg. Successful SEC-DR was achieved in 77.8% of the patients, with sustained PASI response to the end of the study. Survival of secukinumab treatment and safety profile were not compromised by DR. The use of DR saved 33% of the cost, including failures in which standard treatment was resumed. LIMITATIONS: The proper of the study designed and the arbitrary definition of "DR success." CONCLUSION: Off-label SEC-DR strategy was used in patients with sustained response to standard dose regimen; this strategy showed long-term efficacy without compromising treatment survival or worsening the safety profile while also being cost saving.

Safety of biologic therapy in combination with methotrexate in moderate to severe psoriasis: a cohort study from the BIOBADADERM registry.

BACKGROUND: Safety is an important consideration in decisions on treatment for patients with moderate-to-severe psoriasis and the study of drug safety is the main purpose of the BIOBADADERM registry. The combination of a biologic agent and a conventional systemic drug [generally methotrexate (MTX)] is a common treatment in clinical practice. However, there is a paucity of evidence from real-world practice on the safety of such combination regimens in the treatment of psoriasis. OBJECTIVES: The primary objective of this study was to ascertain whether the use of regimens combining biologic drugs with MTX in the management of moderate-to-severe psoriasis increases the risk of adverse events (AEs) or serious AEs (SAEs). We compared monotherapy using tumour necrosis factor (TNF), interleukin (IL)-17 and IL-23 inhibitors with the use of the same drugs in combination with MTX. METHODS: Using data from the BIOBADADERM registry, we compared biologic monotherapies with therapies that were combined with MTX. We estimated adjusted incidence rate ratios (aIRR) using a random effects Poisson regression with 95% confidence intervals for all AEs, SAEs, infections and serious infections and other AEs by system organ class. RESULTS: We analysed data from 2829 patients and 5441 treatment cycles, a total of 12 853 patient-years. The combination of a biologic with MTX was not associated with statistically significant increases in overall risk of AEs or SAEs in any treatment group. No increase in the total number of infections or serious infections in patients receiving combined therapy was observed for any group. However, treatment with a TNF inhibitor combined with MTX was associated with an increase in the incidence of gastrointestinal AEs (aIRR 2.50, 95% CI 1.57-3.98; P < 0.002). CONCLUSIONS: The risk of AEs and SAEs was not significantly increased in patients with moderate-to-severe psoriasis receiving different classes of biologic drugs combined with MTX compared with those on biologic monotherapy.

Neural Networks-Based On-Site Dermatologic Diagnosis through Hyperspectral Epidermal Images.

Cancer originates from the uncontrolled growth of healthy cells into a mass. Chromophores, such as hemoglobin and melanin, characterize skin spectral properties, allowing the classification of lesions into different etiologies. Hyperspectral imaging systems gather skin-reflected and transmitted light into several wavelength ranges of the electromagnetic spectrum, enabling potential skin-lesion differentiation through machine learning algorithms. Challenged by data availability and tiny inter and intra-tumoral variability, here we introduce a pipeline based on deep neural networks to diagnose hyperspectral skin cancer images, targeting a handheld device equipped with a low-power graphical processing unit for routine clinical testing. Enhanced by data augmentation, transfer learning, and hyperparameter tuning, the proposed architectures aim to meet and improve the well-known dermatologist-level detection performances concerning both benign-malignant and multiclass classification tasks, being able to diagnose hyperspectral data considering real-time constraints. Experiments show 87% sensitivity and 88% specificity for benign-malignant classification and specificity above 80% for the multiclass scenario. AUC measurements suggest classification performance improvement above 90% with adequate thresholding. Concerning binary segmentation, we measured skin DICE and IOU higher than 90%. We estimated 1.21 s, at most, consuming 5 Watts to segment the epidermal lesions with the U-Net++ architecture, meeting the imposed time limit. Hence, we can diagnose hyperspectral epidermal data assuming real-time constraints.

Secukinumab is effective and safe in the long-term treatment of plaque psoriasis in a daily practice setting: Multicenter study in 384 Spanish patients.

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 <5, < 3, < 1 and 0, respectively, at month 3. Secukinumab was more effective in biologic-naïve patients and in those with lower Body Mass Index. Secukinumab presented a good long-term safety profile. Secukinumab was effective and safe in a routine clinical setting, in a large cohort of patients with moderate-to-severe plaque psoriasis, in the short-, medium- and long-term (up to 24 months).

Assessing the effect of environmental and socio-economic factors on skin melanoma incidence: an island-wide spatial study in Gran Canaria (Spain), 2007-2018.

INTRODUCTION: Skin melanoma incidence has risen in the last decades becoming a major public health problem in many regions of the world. Geographic variation of rates is not well understood. PURPOSE: To assess the spatial distribution of skin melanoma in Gran Canaria Island (Canary Islands, Spain) and to evaluate the role of environmental, socio-economic, and demographic factors in this distribution. METHODS: We performed a small-area study with disease mapping at the census-tract level (CT) in Gran Canaria between 2007 and 2018. After testing for spatial autocorrelation, we integrated individual-level health data with census-based demographic and socio-economic indicators, and satellite-based environmental data. Finally, we assessed the role of demographic, socio-economic and environmental factors on skin melanoma incidence using a Bayesian analytical framework, with options for non-spatial and spatial random effects. RESULTS: 1058 patients were diagnosed with invasive skin melanoma in the study period and geolocated to a CT (number of CT in Gran Canaria = 565). We found evidence of global spatial autocorrelation in skin melanoma incidence (Moran's I = 0.09, pseudo p-value = 0.001). A few hotspots were detected, fundamentally in urban northern tracts. A radial pattern of high values was also observed in selected ravines with historical isolation. Multivariable conditional autoregressive models identified urbanicity, percent of females, and a high socio-economic status as risk factors for disease. Solar radiation did not show a significant role. CONCLUSION: Urbanicity and a high socio-economic status were identified as the main risk factors for skin melanoma. These associations might reflect differential melanoma susceptibilities or be explained by health inequalities in detection. This study also uncovered high-risk areas in particular ravines. Future targeted research in these regions might help better understand the role of genetic and toxic factors in melanoma pathogenesis.

Fast and sustained improvement of patient-reported outcomes in psoriatic patients treated with secukinumab in a daily practice setting.

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 naïve 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 naïve to biological therapies and with a direct correlation with PASI improvement.

Comorbidity identification and referral in atopic dermatitis: a consensus document.

BACKGROUND: Atopic dermatitis (AD) is associated with different comorbidities. OBJECTIVE: To develop evidence-based and practical recommendations for comorbidity detection in patients with AD in daily practice. METHODS: We employed a modified RAND/UCLA methodology, including a systematic literature review (SLR). A group of six experts on AD was established. We conducted a comprehensive search strategy on Medline, Embase, and Cochrane Library up to June 2020. The selection criteria included studies with AD patients with any comorbidity reporting data on comorbidity prevalence, burden, and management. The included studies quality was assessed. The SLR results were discussed in a nominal group meeting, and several recommendations were generated. The recommendation agreement grade was tested on additional experts through a Delphi process. RESULTS: The recommendations cover the following issues: (1) Which comorbidities should be investigated at the first and subsequent visits; (2) how and when should comorbidities be investigated (screening); (3) how should patients with specific comorbidities be referred to confirm their diagnosis and initiate management; (4) specific recommendations to ensure an integral care approach for AD patients with any comorbidity. CONCLUSIONS: These recommendations seek to guide dermatologists, patients, and other stakeholders in regard to early comorbidity identification and AD patient referral to improve decision-making.

The risk of hepatic adverse events of systemic medications for psoriasis: a prospective cohort study using the BIOBADADERM registry.

BACKGROUND: Limited information is available regarding the risk of incident liver disease in patients with psoriasis receiving systemic therapies. OBJECTIVES: To describe the liver safety findings of conventional and modern systemic therapies for moderate-to-severe psoriasis, and to compare the relative incidence rates of hepatic adverse events (AEs) for each drug. METHODS: All the patients on the BIOBADADERM registry were included. Crude and adjusted incidence rate ratios (cIRR and aIRR, respectively) of hepatic AEs, using anti-TNF drugs as reference, were determined. Outcomes of interest were hypertransaminasemia, nonalcoholic fatty liver disease (NADFLD) and a group of other, less represented, hepatic AEs. RESULTS: Our study included 3,171 patients exposed to systemic drugs (6279 treatment cycles). Incident hypertransaminasemia was the most frequent hepatic AE (incidence rate of 21 per 1000 patients-years [CI 95% 18-23]), followed by NAFLD (8 cases per 1000 patients-years [95% CI 6-10]). Methotrexate (aIRR 3.06 [2.31-4.4]; p = 0.000) and cyclosporine (aIRR 2.37 [1.05-5.35]; p = .0378) were associated with an increased risk for hypertransaminasemia when compared to anti-TNF-α agents. No differences were observed between different groups of biologics. Conventional therapies were not associated with new incident NAFLD. CONCLUSIONS: Comparative information of the incidence of hepatic AEs could facilitate drug selection in moderate-to-severe psoriasis.

Effectiveness and safety of guselkumab for the treatment of psoriasis in real-world settings at 24 weeks: A retrospective, observational, multicentre study by the Spanish Psoriasis Group.

Data on the effectiveness and safety of a drug in real-world clinical practice complement the evidence from clinical trials, which are carried out in a different setting. Little has been published on the effectiveness and safety of guselkumab in the treatment of psoriasis in clinical practice. The ojective of this study was to assess the effectiveness and safety of guselkumab at 24 weeks in patients with moderate to severe plaque psoriasis in routine clinical practice. A retrospective, multicentre study of adult patients with moderate to severe plaque psoriasis treated with guselkumab for at least 24 weeks was carried out in Spain. We studied 343 patients, 249 of whom were followed for 24 weeks. By week 24, the mean (SD) psoriasis area severity index (PASI) had decreased from 11.1 (7.3) to 1.7 (2.8) (-9.3; [-10.2;-8.4]), 85.9% of the patients had achieved PASI score of 4 or less and 77.9% a PASI score of 2 or less. In terms of relative PASI response, 59.4% of the patients achieved a PASI-90 response and 49.0% a PASI-100 response. On multivariate analysis, two factors reduced the probability of a PASI of 2 or less at 24 weeks: a BMI ≥30 (OR, 0.44; 95% CI, 0.22-0.88) and a greater previous exposure to biologic therapy (OR, 0.69; 95% CI, [0.56-0.84]). Adverse events were rare (9.9%) and led to withdrawal from treatment in only nine patients (2.6%) by the end of the follow-up period. The results of this study confirm the high efficacy and safety of guselkumab indicated by the clinical trial data. In clinical practice, the absolute PASI score appears to be a better marker of response to treatment than the relative value.

Multicenter Retrospective Study of Secukinumab Drug Survival in Psoriasis Patients in a Daily Practice Setting: A Long-Term Experience in Spain.

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 incidence of skin melanoma in Gran Canaria (Canary Islands, Spain) is lower than expected in Southern Europe despite high-risk environmental conditions: an island-wide cross-sectional study.

BACKGROUND: The Canary Islands are a leading European touristic destination. The ultraviolet index (UVI) in the region is the highest in Spain, and similar to indexes registered in Australia and New Zealand, which hold the highest incidence of skin melanoma worldwide. Yet according to cancer registry data, the incidence in the Canary Islands in the late 1990s was the lowest in Spain (among the lowest in Europe) and about six times lower than in New Zealand. PURPOSE: To analyze the incidence rates of skin melanoma in Gran Canaria island between 2007 and 2018. METHODS: The study was based in the two centres of the Canary Islands' Healthcare Service centralizing melanoma care in Gran Canaria. We analyzed crude and age-standardized (ASR) incidence rates of invasive cutaneous melanoma for the period 2007-2018 following the inclusion criteria of the International Agency for Research on Cancer (IARC). Clinical and histological characteristics of melanoma patients were assessed. RESULTS: A total of 1058 patients were included. The incidence rates obtained matched the latest available Canary Islands' cancer registry data, confirming its reliability (ASR, Segi-Doll world standard population: 6.4 cases per 100,000 habitants for 2008-2012). The incidence was also below the latest IARC predictions for Southern Europe (GLOBOCAN 2018). Histological characteristics of patients were similar to other Southern European series. CONCLUSIONS: The incidence of skin melanoma in Gran Canaria is unexpectedly low for a Southern European population exposed to such a high UVI. Further research in the Canary Islands could provide insight into a better understanding of melanoma pathogenesis.

Curve-Based Classification Approach for Hyperspectral Dermatologic Data Processing.

This paper shows new contributions in the detection of skin cancer, where we present the use of a customized hyperspectral system that captures images in the spectral range from 450 to 950 nm. By choosing a 7 × 7 sub-image of each channel in the hyperspectral image (HSI) and then taking the mean and standard deviation of these sub-images, we were able to make fits of the resulting curves. These fitted curves had certain characteristics, which then served as a basis of classification. The most distinct fit was for the melanoma pigmented skin lesions (PSLs), which is also the most aggressive malignant cancer. Furthermore, we were able to classify the other PSLs in malignant and benign classes. This gives us a rather complete classification method for PSLs with a novel perspective of the classification procedure by exploiting the variability of each channel in the HSI.

Effect of Sex in Systemic Psoriasis Therapy: Differences in Prescription, Effectiveness and Safety in the BIOBADADERM Prospective Cohort.

The effect of sex on systemic therapy for psoriasis has not been well studied. The aim of this study was to analyse a large multicentre Spanish cohort of 2,881 patients with psoriasis (58.3% males), followed from January 2008 to November 2018, to determine whether sex influences prescription, effectiveness of therapy, and the risk of adverse events. The results show that women are more likely than men to be prescribed biologics. There were no differences between men and women in effectiveness of therapy, measured in terms of drug survival. Women were more likely to develop adverse events, but the difference in risk was small and does not justify different management. Study limitations include residual confounding and the use of drug survival as a proxy for effectiveness.