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Background: Numerous inclusion and exclusion criteria are involved in phase III moderate to severe psoriasis trials investigating the safety and efficacy of biologics. This questions the generalization of results. Methods: In this cohort study, we applied inclusion/exclusion criteria for phase III trials from original protocols (adalimumab – REVEAL, ustekinumab – PHOENIX, brodalumab – AMAGINE, secukinumab FIXTURE) to all patients enrolled in the PsoBioTeq prospective registry who received a biological agent for the first time between July 2012 and November 2017. We then compared the efficacy, drug survival and occurrence of adverse events between patients who satisfied/did not satisfy the eligibility criteria for these phase III trials. Results: A total of 1267 patients were enrolled, of whom 993 (78.4%) were not eligible for at least one RCT (randomized controlled trial) and 251 (19.1%) did not meet the PASI/PGA severity requirements. Apart from disease severity, the most frequent criteria resulting in exclusion were as follows: non‐plaque psoriasis (12.6%), significant cardiac disease (8.4%), significant liver disease (7.3%), elevated liver enzymes (4.9–9.6%) and personal history of diabetes (9.2%). There was no difference in drug survival between the two groups. The incidence ratio of adverse events was significantly lower in eligible versus non‐eligible patients [0.78 (95% CI 0.62–0.97) (P = 0.03)]. Conclusion: The majority of patients treated with biologics in the PsoBioTeq real‐life registry would not have been eligible for phase III moderate to severe psoriasis trials. Patients not eligible for psoriasis phase III clinical trials have a higher incidence of adverse events. [ABSTRACT FROM AUTHOR]

Background: Congenital ichthyoses (CI) comprise a heterogeneous group of genetic diseases requiring lifelong treatment and having a major effect on quality of life. Conventional treatments reduce scaling and skin discomfort; however, they usually have little or no effect on erythema and pruritus. The identification of cytokine alterations in CI raised the possibility of repurposing available biologics. Several case reports in the literature report successes using different biologics., Objective: We aimed to report the effects of biologics in real life., Methods: This was a retrospective, observational, international multicenter study of patients with CI treated with at least one biologic for a minimum of 3 months. The effect of the biologics was evaluated using an Investigator Global Assessment-Change (IGA-C) scale. A comprehensive literature search was performed in parallel., Results: A total of 98 patients were included, with a mean age of 19.7 years and both sexes equally represented. Patients with Netherton syndrome (NS) or congenital ichthyosiform erythroderma (CIE) represented the majority of patients (30% and 21.4%, respectively). Most patients (84.7%) had a severe or very severe form of CI. The most frequently used biologics were inhibitors targeting interleukin-17 (IL-17), IL-12/IL-23, or the IL-4 receptor. The mean duration of treatment was 22+20.1 months. There were 45 responders (45.9%), including 18 patients (18.3%) who were good responders; all had an erythrodermic CI subset and received one of the three main biologics. In 2 NS and CIE, IL-12/IL-23 and IL-4 receptor inhibitors tended to be most effective. Review of the literature revealed a shorter mean duration of use of biologics (11.5+8.5 months) and higher percentage of responders (85.7%), suggesting reporter bias., Conclusion: This series identified subsets of CI that may respond to biologics and will aid in designing future clinical trials of biologics for CI., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: BRAF and MEK inhibitors have been approved for use in metastatic melanoma therapies. All of them are administered as oral capsules or pills. We report two cases treated applying an alternative method of vemurafenib or debrafenib-trametinib administration in patients unable to swallow., Case Report: The first case involved a 38-year-old man who was referred to a dermatologist for dysphagia and anorexia. After a computerized tomography (CT) scan it was concluded that the dysphagia was due to compression by mediastinal metastasis in a context of metastatic BRAF mutant melanoma. The second case involved a 35-year-old man who was diagnosed in March 2017 with melanoma of the back of the hand. Several months later a positron emission tomography (PET)/CT scan was performed. It revealed multiple disseminated metastasis. Management & Outcome: The first patient presented total dysphagia and was unable to swallow pills. It was decided to dissolve vemurafenib in order to facilitate administration. Dysphagia was improved 48 hours later, and oral feeding was reintroduced. Due to severe tablet phobia, the second patient was unable to swallow pills. Dabrafenib capsules were emptied and trametinib pills were grinded. One month later, we noted improved health associated with reduction of the metastases., Discussion: Our study highlights the possibility of crushing or dissolving BRAF and MEK inhibitors in metastatic melanoma patients for whom it is impossible to swallow pills, eliciting a response and achieving significant if temporary clinical benefit.

Background: Vismodegib has shown clinical efficacy in the management of locally advanced basal cell carcinomas (laBCC). However, non-response to vismodegib is observed in 2-13.5% of patients in clinical studies. The purpose of this study was to identify factors associated with non-response to vismodegib in patients with laBCC., Methods: We carried out a retrospective multicenter study, including patients with laBCC treated with vismodegib, from July 2011 to May 2019. Response to treatment was assessed according to the RECIST 1.1 criteria. Patients were categorized as responders with a complete response or a partial response or non-responders with a stable disease or a progressive disease according to what has been observed during follow-up. Patient demographics, tumor profile, and treatment modalities were compared in responders and non-responders., Results: Eighty-three patients with laBCC were included in the study. Twenty-five (30.1%) were non-responders to vismodegib. History of treatment with radiotherapy, presence of muscle involvement and intermittent treatment with vismodegib were significantly associated with a non-response (p < 0.001, p = 0.025, p < 0.001). Bone involvement (p = 0.2) and morpheaform IaBCC subtype (p = 0.056) were more frequent in non-responders without reaching statistical significance., Conclusion: In this study, non-response of laBCC to vismodegib therapy was associated with muscle involvement. Previous radiotherapy and intermittent use of vismodegib have been identified as causes favoring non-response to vismodegib. Due to the low numbers of patients included in the study, it is difficult to draw firm conclusions. Further studies are needed to confirm these data., (© 2021 S. Karger AG, Basel.)

Background: Schnitzler syndrome (SchS) is a rare autoinflammatory disease characterized by urticarial exanthema, bone and joint alterations, fever and monoclonal IgM gammopathy. Overactivation of the interleukin(IL)-1 system is reported, even though the exact pathophysiological pathways remain unknown., Objective: To determine ex v ivo cytokine profiles of Peripheral Blood Mononuclear Cells (PBMCs) from SchS patients prior to treatment and after initiation of anti-IL-1 therapy (anakinra). The sera cytokine profile was studied in parallel., Methods: We collected blood samples from thirty-six untreated or treated SchS. PBMCs were cultured with and without LPS or anti-CD3/CD28. Cytokine levels were evaluated in serum and cell culture supernatants using Luminex technology., Results: Spontaneous TNFα, IL-6, IL-1β, IL-1α, and IL-1RA release by PBMCs of SchS patients were higher than in controls. LPS-stimulation further induced the secretion of these cytokines. In contrast, after T-cell stimulation, TNFα, IL-10, IFNγ, IL-17A, and IL-4 production decreased in SchS patients compared to healthy controls, but less in treated patients. Whereas IL-1β serum level was not detected in most sera, IL-6, IL-10, and TNFα serum levels were higher in patients with SchS and IFNγ and IL-4 levels were lower. Of note, IL-6 decreased after treatment in SchS ( p = 0.04)., Conclusion: Our data strengthen the hypothesis of myeloid inflammation in SchS, mediated in particular by IL-1β, TNFα, and IL-6, associated with overproduction of the inhibitors IL-1RA and IL-10. In contrast, we observed a loss of Th1, Th2, and Th17 cell functionalities that tends to be reversed by anakinra., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Masson Regnault, Frouin, Jéru, Delwail, Charreau, Barbarot, Néel, Masseau, Puéchal, Kyndt, Gayet, Lifermann, Asli, Balguerie, Blanchard-Delaunay, Aubin, Rizzi, Rongioletti, Boyé, Gusdorf, Bessis, Morel, Hainaut, Lipsker and Lecron.)