Sonidegib as a Locally Advanced Basal Cell Carcinoma Therapy in Real-life Clinical Setting: A National Multicentre Study. / [Artículo traducido] Sonidegib para el tratamiento del carcinoma basocelular avanzado en práctica clínica real: estudio nacional multicéntrico.

BACKGROUND: Basal cell carcinoma (BCC) is the most prevalent cancer. A minority of BCCs have an aggressive behaviour (laBCC) and may require hedgehog pathway inhibitors such as sonidegib as its treatment. OBJECTIVE: To describe the use of sonidegib in a large number of patients and provide more data on its real-life efficacy and safety profile. METHODS: We conducted a retrospective and multicentric study that included patients treated with sonidegib. Epidemiological, effectiveness and safety data were collected. RESULTS: A total of 82 patients with a mean age of 73.9 years were included. Ten patients had Gorlin syndrome. Median treatment duration was 6 months. Median follow-up duration was 34.2 months. Globally, 81.7% of the patients showed clinical improvement (52.4% partial response and 29.3% complete response), 12.2% clinical stability and 6.1% disease progression. There was no statistically significant difference in clinical improvement between the 24 h and 48 h sonidegib posology. After 6 months of treatment, 48.8% of the patients discontinued sonidegib. Prior vismodegib treatment and recurrent primary BCC were associated with a poorer response to sonidegib. At 6 months of treatment, 68.3% of the patients experienced at least one adverse effect. CONCLUSION: Sonidegib shows good effectiveness and acceptable safety profile in usual clinical practice.

Sonidegib as a Locally Advanced Basal Cell Carcinoma Therapy in Real-life Clinical Setting: A National Multicentre Study.

BACKGROUND: Basal cell carcinoma (BCC) is the most prevalent cancer. A minority of BCCs have an aggressive behaviour (laBCC) and may require hedgehog pathway inhibitors such as sonidegib as its treatment. OBJECTIVE: To describe the use of sonidegib in a large number of patients and provide more data on its real-life efficacy and safety profile. METHODS: We conducted a retrospective and multicentric study that included patients treated with sonidegib. Epidemiological, effectiveness and safety data were collected. RESULTS: A total of 82 patients with a mean age of 73.9 years were included. Ten patients had Gorlin syndrome. Median treatment duration was 6 months. Median follow-up duration was 34.2 months. Globally, 81.7% of the patients showed clinical improvement (52.4% partial response and 29.3% complete response), 12.2% clinical stability and 6.1% disease progression. There was no statistically significant difference in clinical improvement between the 24h and 48h sonidegib posology. After 6 months of treatment, 48.8% of the patients discontinued sonidegib. Prior vismodegib treatment and recurrent primary BCC were associated with a poorer response to sonidegib. At 6 months of treatment, 68.3% of the patients experienced at least one adverse effect. CONCLUSION: Sonidegib shows good effectiveness and acceptable safety profile in usual clinical practice.

Systemic therapies for Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: a SCORTEN-based systematic review and meta-analysis.

BACKGROUND: The SCORTEN score is a specific predictor of mortality for patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). There is little evidence in support of the common immunomodulating therapies for SJS/TEN. OBJECTIVES: To systematically assess the effectiveness of several therapies for SJS/TEN through the SCORTEN score. METHODS: Databases were searched for original studies on the use of SCORTEN. Six meta-analyses were carried out on patients with SJS/TEN who received supportive care only or in combination with immunomodulating drugs: corticosteroids, cyclosporine, etanercept, immunoglobulins or a combination of corticosteroids with immunoglobulins. A multivariate meta-regression and a network meta-analysis were also performed. RESULTS: Of 3893 studies identified, fifty-two involving 2466 patients with SJS/TEN were preselected. Data from thirty-eight of these studies (1827 patients) were finally pooled, and results [log(SMR)] from meta-analyses were as follows: -0.13 (95% CI, -0.42,0.16) for corticosteroids, -0.39 (95% CI, -0.87,0.09) for immunoglobulins, 0.13 (95% CI, -0.15,0.40) for supportive treatment, -0.88 (95% CI, -1.47, -0.29) for cyclosporine, -0.95 (95% CI, -1.82, -0.07) for etanercept and - 0.56 (95% CI, -0.94, -0.19) for immunoglobulins plus corticosteroids. The meta-regression analysis confirmed that cyclosporine and immunoglobulins plus corticosteroids were associated with less deaths than predicted by SCORTEN. In the network meta-analysis, no treatment achieved a significant reduction in the SMR. LIMITATIONS: Heterogeneity and quality of the included studies. CONCLUSIONS: Some treatments for SJS/TEN show a better performance, but there is not sufficient evidence to recommend its widespread use in all patients.

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.

Accuracy of SCORTEN to predict the prognosis of Stevens-Johnson syndrome/toxic epidermal necrolysis: a systematic review and meta-analysis.

BACKGROUND: The SCORTEN score is a specific predictor of the probability of death for patients diagnosed with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). OBJECTIVES: To evaluate the overall accuracy of SCORTEN and the influence of several moderators such as age, sex, geographical region and age of the study. METHODS: A systematic search was performed on MEDLINE, The Cochrane Library, EMBASE, SCOPUS and Web of Knowledge, with no restriction on language (last update 5 February 2019 for all databases). Original studies on the use of SCORTEN were eligible. The standardized mortality ratio (SMR), defined as the quotient between the number of deaths observed and the number expected following SCORTEN, was taken as the measurement of analysis. RESULTS: Sixty-four papers were part of the main meta-analysis carried out in the study. A pooled log(SMR) of -0.0889 (95% CI: -0.2023 to 0.0245) was obtained, suggesting a reasonable behaviour of SCORTEN as a predictor of mortality. The possible influence of several factors in the accuracy of SCORTEN was studied by means of meta-regression models. Multivariate meta-regression allowed finding that the mean age of the patients and the ending year of the study are the only factors that significantly influence SCORTEN predictions. The mean age of the group of patients was associated with a significant increase in the observed/expected ratio, whereas a progressive reduction in the observed/expected ratio can be appreciated over the years. Finally, an underestimation of mortality was found for SCORTEN values of 3 or less and the opposite for those above 3 (SCORTEN range: 0-7). CONCLUSIONS: The rarity of the disease and the heterogeneity of the studies included are major limitations. Despite the overall remarkable accuracy displayed by SCORTEN, the influence of several factors, as comorbidities (e.g. renal impairment), involved body surface area and patient's age, seem of enough relevance to consider a redefinition of the scale.

Cyclosporine 0.1% (Ikervis®) treatment in steroid-dependent dupilumab-associated conjunctivitis. / Tratamiento con ciclosporina al 0,1% (Ikervis®) en conjuntivitis corticodependiente asociada a dupilumab.

Dupilumab is a drug that has recently been approved by the Food and Drug Administration (FDA) and European Medical Agency (EMA) for the treatment of moderate-to-severe atopic dermatitis in adults. An increase in frequency of conjunctivitis related to dupilumab treatment has been reported in recent publications and clinical trials. We report two steroid-dependent cases satisfactorily treated with cyclosporine 0.1% (Ikervis®). To our knowledge there are no reported cases of dupilumab-associated conjunctivitis treated with cyclosporine 0.1% (Ikervis®).