[Translated article] Requirements for Accessing New Dermatology Drugs in Spain: Results of the EQUIDAD Study.

BACKGROUND: Although the Spanish Ministry of Health prepares national therapeutic positioning reports (TPRs) and drug reimbursement policies, each of the country's 17 autonomous communities (ACs) is responsible for health care services and prescription requirements in its territory. The aim of the EQUIDAD study was to describe and explore potential differences in prescription requirements for new dermatology drugs across the autonomous communities. MATERIAL AND METHODS: Cross-sectional study conducted in April and May, 2023. Two dermatologists with management responsibilities from each autonomous community reported on territorial and more local prescription requirements for drugs covered by national TPRs issued between 2016 and 2022. RESULTS: Thirty-three researchers from 17 autonomous communities participated. The data submitted revealed between-community inequities in access to new drugs. Overall, 64.7% of the regions imposed additional prescription requirements to those mentioned in the TPRs for psoriasis. This percentage was lower for atopic dermatitis (35.3%) and melanoma (11.8%). The most common requirement for accessing a new drug was a previous prescription for another drug. Differences and additional requirements were also detected at the local level (i.e., differences between hospitals within the same autonomous community). CONCLUSIONS: Spain's autonomous communities have multiple regional and local prescription requirements that are not aligned with national TPR recommendations. These differences result in inequitable access to new drugs for both patients and practitioners across Spain.

Requirements for Accessing New Dermatology Drugs in Spain: Results of the EQUIDAD Study. / Condicionantes de acceso a nuevos medicamentos dermatológicos en España: resultados del proyecto EQUIDAD.

BACKGROUND: Although the Spanish Ministry of Health prepares national therapeutic positioning reports (TPRs) and drug reimbursement policies, each of the country's 17 autonomous communities (ACs) is responsible for health care services and prescription requirements in its territory. The aim of the EQUIDAD study was to describe and explore potential differences in prescription requirements for new dermatology drugs across the autonomous communities. MATERIAL AND METHODS: Cross-sectional study conducted in April and May, 2023. Two dermatologists with management responsibilities from each autonomous community reported on territorial and more local prescription requirements for drugs covered by national TPRs issued between 2016 and 2022. RESULTS: Thirty-three researchers from 17 autonomous communities participated. The data submitted revealed between-community inequities in access to new drugs. Overall, 64.7% of the regions imposed additional prescription requirements to those mentioned in the TPRs for psoriasis. This percentage was lower for atopic dermatitis (35.3%) and melanoma (11.8%). The most common requirement for accessing a new drug was a previous prescription for another drug. Differences and additional requirements were also detected at the local level (i.e., differences between hospitals within the same autonomous community). CONCLUSIONS: Spain's autonomous communities have multiple regional and local prescription requirements that are not aligned with national TPR recommendations. These differences result in inequitable access to new drugs for both patients and practitioners across Spain.

Narrative Review and Update on Biologic and Small Molecule Drugs for Hidradenitis Suppurativa: An Entity With a Promising Future. / [Artículo traducido] Revisión narrativa y actualización en fármacos biológicos y de pequeña molécula para el tratamiento de la hidradenitis supurativa: una entidad con un futuro prometedor.

Hidradenitis suppurativa (HS) is a chronic inflammatory entity characterized by the appearance of multiple nodules, abscesses, and fistulas, predominantly in apocrine regions. In addition to its dermatological involvement, it is associated with multiple systemic comorbidities. Its treatment is combined: topical pharmacological, systemic pharmacological and surgical. Regarding biologic or small molecule drugs, currently only adalimumab is approved. A narrative review of the literature on biological or small molecule drugs used in the treatment of hidradenitis suppurativa is presented. The arsenal we found is large, with multiple targets: inhibitors of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-17, IL-23, IL-1, inhibitors of the janus kinase (JAK) pathway, and multiple other drugs in study. New prospective studies and comparative trials are needed to analyze the effectiveness and safety of these treatments, in an entity with a promising future.

Narrative Review and Update on Biologic and Small Molecule Drugs for Hidradenitis Suppurativa: An Entity With a Promising Future.

Hidradenitis suppurativa (HS) is a chronic inflammatory entity characterized by the appearance of multiple nodules, abscesses, and fistulas, predominantly in apocrine regions. In addition to its dermatological involvement, it is associated with multiple systemic comorbidities. Its treatment is combined: topical pharmacological, systemic pharmacological and surgical. Regarding biologic or small molecule drugs, currently only adalimumab is approved. A narrative review of the literature on biological or small molecule drugs used in the treatment of hidradenitis suppurativa is presented. The arsenal we found is large, with multiple targets: inhibitors of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-17, IL-23, IL-1, inhibitors of the janus kinase (JAK) pathway, and multiple other drugs in study. New prospective studies and comparative trials are needed to analyze the effectiveness and safety of these treatments, in an entity with a promising future.

Primary Cutaneous Lymphoma Registry of the Spanish Academy of Dermatology and Venereology (AEDV): Data for the First 5 Years. / Registro de linfomas cutáneos primarios (RELCP) de la AEDV: datos tras 5 años de funcionamiento.

BACKGROUND AND OBJECTIVE: Primary cutaneous lymphomas (PCL) are uncommon. Observations based on the first year of data from the Spanish Registry of Primary Cutaneous Lymphomas (RELCP, in its Spanish abbreviation) of the Spanish Academy of Dermatology and Venereology (AEDV) were published in February 2018. This report covers RELCP data for the first 5 years. PATIENTS AND METHODS: RELCP data were collected prospectively and included diagnosis, treatments, tests, and the current status of patients. We compiled descriptive statistics of the data registered during the first 5 years. RESULTS: Information on 2020 patients treated at 33 Spanish hospitals had been included in the RELCP by December 2021. Fifty-nine percent of the patients were men; the mean age was 62.2 years. The lymphomas were grouped into 4 large diagnostic categories: mycosis fungoides/Sézary syndrome, 1112 patients (55%); primary B-cell cutaneous lymphoma, 547 patients (27.1%); primary CD30+lymphoproliferative disorders, 222 patients (11%), and other T-cell lymphomas, 116 patients (5.8%). Nearly 75% of the tumors were registered in stage I. After treatment, 43.5% achieved complete remission and 27% were stable at the time of writing. Treatments prescribed were topical corticosteroids (1369 [67.8%]), phototherapy (890 patients [44.1%]), surgery (412 patients [20.4%]), and radiotherapy (384 patients [19%]). CONCLUSION: The characteristics of cutaneous lymphomas in Spain are similar to those reported for other series. The large size of the RELCP registry at 5 years has allowed us to give more precise descriptive statistics than in the first year. This registry facilitates the clinical research of the AEDV's lymphoma interest group, which has already published articles based on the RELCP data.

Risk of a Second Skin Cancer in a Cohort of Patients With Nonmelanoma Skin Cancer -Basal Cell Carcinoma or Squamous Cell Carcinoma-Treated With Mohs Micrographic Surgery: A National Prospective Cohort Study. / Riesgo de aparición de segundas neoplasias cutáneas en una cohorte de pacientes diagnosticados de carcinoma queratinocítico (carcinoma basocelular y carcinoma epidermoide) tratados con cirugía de Mohs. Estudio de cohortes prospectivo nacional.

OBJECTIVE: Patients with nonmelanoma skin cancer (NMSC)-ie, basal cell carcinoma (BCC) or squamous cell carcinoma (SCC)-have an increased risk of developing a second skin cancer. The aim of this study was to describe the frequency, incidence per 1000 person-years, and predictors of a second skin cancer in a cohort of patients with NMSC treated with Mohs micrographic surgery (MMS). MATERIAL AND METHODS: Prospective study of a national cohort of patients with NMSC who underwent MMS at 22 Spanish hospitals between July 2013 and February 2020; case data were recorded in the REGESMOHS registry. The study variables included demographic characteristics, frequency and incidence per 1000 person-years of second skin cancers diagnosed during the study period, and risk factors identified using mixed-effects logistic regression. RESULTS: We analyzed data for 4768 patients who underwent MMS; 4397 (92%) had BCC and 371 (8%) had SCC. Mean follow-up was 2.4 years. Overall, 1201 patients (25%) developed a second skin cancer during follow-up; 1013 of the tumors were BCCs (21%), 154 were SCCs (3%), and 20 were melanomas (0.4%). The incidence was 107 per 1000 person-years (95% CI, 101-113) for any cancer, 90 per 1000 person-years (95% CI, 85-96) for BCC, 14 (95% CI, 12-16) per 1000 person-years for SCC, and 2 (95% CI, 1-3) per 1000 person-years for melanoma. More men than women developed a subsequent skin cancer (738 [61%] vs 463 [39%]). The main risk factors were a history of multiple tumors before diagnosis (relative risk [RR], 4.6; 95% CI, 2.9-7.1), immunosuppression (RR, 2.1; 95% CI, 1.4-3.1), and male sex (RR, 1.6; 95% CI, 1.4-1.9). CONCLUSION: Patients have an increased risk of developing a second tumor after MMS treatment of NMSC. Risk factors are a history of multiple tumors at diagnosis, immunosuppression, and male sex.

Clinical Practice Guideline on Melanoma From the Spanish Academy of Dermatology and Venereology (AEDV). / Guía de práctica clínica de melanoma de la Academia Española de Dermatología y Venereología.

Specialist approaches to the diagnosis and treatment of melanoma have undergone many changes. This guideline aims to provide Spanish dermatologists with evidence-based information for resolving the most common doubts that arise in clinical practice. Members of the Spanish Oncologic Dermatology and Surgery Group (GEDOC) with experience treating melanoma were invited to participate in drafting the guideline. The group developed a new guideline on the basis of existing ones, using the ADAPTE collaboration process, first summarizing the care process and posing relevant clinical questions, then selecting guidelines with the best scores according to the AGREE II (Appraisal of Guidelines for Research and Evaluation) tool. Finally, the group searched the selected guidelines for answers to the clinical questions, drafted recommendations, and sent them for external review. The guideline is structured around 21 clinical questions chosen for their relevance to issues that make clinical decisions about the management of melanoma difficult. Evidence from existing guidelines was used to answer the questions. A limitation of this guide derives from the scarce evidence available for answering some questions. Moreover, some areas are changing rapidly, so recommendations must be updated often. The present guideline offers answers to clinical questions about the routine management of melanoma in clinical practice and provides dermatologists with a reference to guide decisions, taking into consideration the resources available and patient preferences.

Systematic review of BRAF/MEK inhibitors-induced Severe Cutaneous Adverse Reactions (SCARs).

Severe cutaneous adverse reactions (SCARs) [Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic syndrome (DRESS), acute generalized exanthematous pustulosis (AGEP), and generalized bullous fixed eruption (GBFE)] are severe drug reactions that often require hospitalization and could be fatal. BRAF and MEK inhibitors (BRAF/MEKi) are a standard of care in patients with BRAF-mutated metastatic melanomas. These agents are administered until disease progression or unacceptable toxicity occurs. This review has focus on BRAF/MEKi-induced SCARs. A systematic search of the following terms: 'vemurafenib', 'cobimetinib', 'dabrafenib', 'trametinib', 'encorafenib', 'binimetinib', 'Acute Generalized Exanthematous Pustulosis', 'Stevens Johnson syndrome', 'Toxic Epidermal Necrolysis', 'Generalized Bullous Fixed Eruption' 'Drug Hypersensitivity Syndrome', and 'DRESS' in simple combination (every drug with each disease) and all in combination, was performed on MEDLINE, EMBASE, Web of Knowledge and The Cochrane Library repositories, with no restriction on language, for original studies. One hundred sixty-eight original articles were found, 26 (retrospective series, case reports and conference abstracts) were selected, and 21 were included in the qualitative synthesis. A total of 31 SCAR cases (23 DRESS and 8 SJS/TEN - 1 SJS and 7 TEN -) were identified. Vemurafenib was the culprit drug in all but one case, which was dabrafenib-induced. Mean time to SCAR onset from drug intake was 15.5 and 11.4 days, for SJS/TEN and DRESS, respectively. For the DRESS cases, hepatic involvement occurred in 96% and renal alterations in 87% of patients. Overall, BRAF/MEKi-induced SCARs are rare. Among them, vemurafenib is the drug that requires more close monitoring for SCARs. Prior immunotherapy can favour SCARs. Vemurafenib DRESS is likely to occur within the first fifteen days of treatment accompanied by hepatic and renal involvement. Following vemurafenib-induced SCAR resolution, switching to dabrafenib seems to be a safe alternative for these patients' treatment.

Sonidegib in the Treatment of Locally Advanced Basal Cell Carcinoma. / Sonidegib en el tratamiento del carcinoma basocelular localmente avanzado.

Sonidegib is an antagonist of the transmembrane protein Smoothened in the Hedgehog signaling pathway. It is indicated for the treatment of locally advanced basal cell carcinoma (BCC) that is not amenable to curative surgery or radiotherapy. Sonidegib's efficacy and safety were demonstrated in the phase 2 BOLT trial, where 61% (95% CI, 48-72%) of patients with locally advanced BCC treated with sonidegib 200 mg achieved an objective response to treatment with a mean time to response of 4 months. The median duration of response was 26.1 months and the median progression-free survival was 22.1 months. The most common adverse events were muscle spasms (54.4%), hair loss (49.4%), and loss of taste (44.3%); most events were grade 1 or 2. In this review, we summarize the main findings on the efficacy, safety, and tolerability of sonidegib and discuss the management of locally advanced BCC with this drug.

Changing Trends in Drug Prescription and Causes of Treatment Discontinuation of First Biologic Over Ten Years in Psoriasis in the Spanish Biobadaderm Registry. / Cambios en las tendencias de la prescripción y causas de la interrupción en los tratamientos biológicos indicados en la psoriasis durante los primeros 10 años. Datos obtenidos del registro español Biobadaderm.

BACKGROUND AND OBJECTIVES: Current psoriasis guidelines do not usually include recommendations about first line classical or biologic treatment. The objectives of this study were: to describe shifts in the prescription of the first biological treatment, and to compare treatment withdrawal and rates of adverse events over ten years. MATERIAL AND METHODS: Biobadaderm registry was analyzed to describe: first biological prescription in bio-naïve patients, adverse events rate and reasons for drug withdrawal comparing three periods of time (2008-2010, 2011-2014, 2015-2018). RESULTS: Anti-TNF drugs were the most prescribed biological drug from 2008 to 2010. Ustekinumab has become the most prescribed first biologic since 2014. The main reasons for drug discontinuation were adverse events, lack of efficacy and remission. In each period any treatment was less likely to be discontinued due to any of these three reasons comparing to the previous period. CONCLUSIONS: The present study identifies trends in prescription of the first biological antipsoriatic drug in clinical practice from 2008 to 2018. It suggests that we have become more comfortable with the safety profile and more exigent with the efficacy of the drugs.

A review of terms used to define cutaneous squamous cell carcinoma with a poor prognosis. / Revisión de los términos que definen un carcinoma epidermoide cutáneo asociado a mal pronóstico.

Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer in humans and its incidence is both underestimated and on the rise. cSCC is referred to in the literature as high-risk cSCC, locally advanced cSCC, metastatic cSCC, advanced cSCC, and aggressive cSCC. These terms can give rise to confusion and are not always well defined. In this review, we aim to clarify the concepts underlying these terms with a view to standardizing the description of this tumor, something we believe is necessary in light of the new drugs that have been approved or are in development for cSCC.

A randomized, intraindividual, non-inferiority, Phase III study comparing daylight photodynamic therapy with BF-200 ALA gel and MAL cream for the treatment of actinic keratosis.

BACKGROUND: The most effective treatment modality for actinic keratosis (AK) is photodynamic therapy (PDT). Major obstacles of PDT are the need of a special illumination device and pain accompanying the illumination. These issues may be overcome by replacing an artificial high-power light source with natural daylight for more extended illumination at lower light doses. OBJECTIVE: To determine whether BF-200 ALA (a nanoemulsion gel containing 7.8% 5-aminolaevulinic acid) is non-inferior to MAL (a cream containing 16% methyl-aminolaevulinate) in the treatment of mild-to-moderate AK with daylight PDT (dPDT). Non-inferiority of the primary efficacy variable (total lesion clearance rate per patient's side 12 weeks after PDT) is established if the mean response for BF-200 ALA is no worse than for MAL, within a statistical margin of Δ = -12.5%. METHODS: The study was performed as an intraindividual comparison with 52 patients in seven centres in Germany and Spain. Each patient received one dPDT. Results include clinical endpoints as well as 1-year follow-up results. RESULTS: Twelve weeks after a single dPDT, 79.8% of the AK lesions treated with BF-200 ALA gel and 76.5% of the lesions treated with MAL cream were completely cleared. The median of differences was 0.0 with a one-sided 97.5% CI of 0.0, establishing non-inferiority (P < 0.0001). Results for secondary efficacy parameters were in line with the primary outcome. Recurrence rates 1 year after the treatment were 19.9% for lesions treated with BF-200 ALA and 31.6% for lesions treated with MAL. Adverse reactions including pain were mostly mild and transient and identical to those previously described for dPDT. CONCLUSION: Daylight PDT of AK with BF-200 ALA is well-tolerated and non-inferior to MAL/dPDT. The study demonstrates a trend towards higher efficacies after 3 months and significantly lower recurrence rates after 1 year follow-up.

Telomerase Expression in a Series of Melanocytic Neoplasms. / Estudio de la expresión de telomerasa en una serie de neoplasias melanocíticas.

BACKGROUND AND OBJECTIVES: Telomerase is an enzyme involved in maintaining the length of telomeres and cell senescence. Numerous studies have shown that in more than 90% of malignant tumors telomerase activity is detected. MATERIAL AND METHODS: Retrospective observational study in a series of 85 cases of primary melanomas, 12 metastatic melanomas, and 22 melanocytic nevi. We used the monoclonal antibody hTERT (human telomerase reverse transcriptase, Rockland) to assess telomerase activity. The SPSS software package was used to analyze data. RESULTS: Telomerase expression was present in all the melanocytic neoplasms analyzed. Expression was heterogenous and moderate or high in the melanomas. In contrast, expression was homogeneous and lower in the nevi. Heterogeneous expression was associated with rapid melanoma growth (P=.028), a Breslow thickness of more than 4 mm (P=.004), mitosis (P=.032), and mutations in the TERT gene (P=.002). Activity was less intense in intradermal nevi, and more intense in compound and dysplastic nevi (P=.054). CONCLUSIONS: Telomerase expression is found in all melanocytic neoplasms but is higher in melanomas than in nevi. A heterogeneous pattern of expression in melanomas is associated with more aggressive tumors.