IL-17 Inhibition: A Valid Therapeutic Strategy in the Management of Hidradenitis Suppurativa

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a significant negative impact on the quality of life of patients. To date, the therapeutic landscape for the management of the disease has been extremely limited, resulting in a profound unmet need. Indeed, adalimumab, an anti-tumor necrosis factor (TNF)-α monoclonal antibody, is the only approved biologic agent for HS, obtaining a therapeutic response in only 50% of HS patients. Numerous clinical trials are currently ongoing to test novel therapeutic targets in HS. The IL-17-mediated cascade is the target of several biologic agents that have shown efficacy and safety in treating moderate-to-severe HS. Both bimekizumab and secukinumab, targeting IL-17 in different manners, have successfully completed phase III trials with promising results; the latter has recently been approved by EMA for the treatment of HS. The aim of this review is to summarize the current state of knowledge concerning the relevant role of IL-17 in HS pathogenesis, highlighting the key clinical evidence of anti-IL-17 agents in the treatment of this disease

Anti-IL-17A blockade did not significantly reduce inflammatory lesions in a placebo-controlled pilot study in adult patients with moderate to severe acne

BACKGROUND\nMETHODS\nRESULTS\nCONCLUSIONS\nCJM112 is a potent anti-IL-17A monoclonal antibody, whose clinical efficacy in psoriasis was recently documented. This study aimed to assess the effect of IL-17A blockade, using CJM112, in patients with moderate to severe acne.\nA randomized, placebo-controlled, double-blind, parallel-group, proof-of-concept study was conducted on patients with moderate to severe acne. Patients received CJM112 300 mg, 75 mg, or placebo subcutaneously during Treatment Period1 (0-12 weeks). Patients receiving placebo were re-randomized to receive CJM112 300 mg or 75 mg during Treatment Period 2 (12-24 weeks). The primary endpoint was the number of inflammatory facial lesions at Week 12.\nAs the futility criterion was met during the interim analysis, only 52/75 (69.3%) patients were recruited. In total, 48/52 (92.3%) and 26/41 (63.4%) completed Treatment Periods 1 and 2, respectively. All groups exhibited a reduction in facial inflammatory lesions, with no difference observed between CJM112 and placebo (CJM112 300 mg 27.6 ± 20.7; CJM112 75 mg 30.4 ± 34.8; placebo 23.6 ± 13.6; primary endpoint). Additionally, no differences were observed between groups in other secondary and exploratory endpoints at Week 12.\nAnti-IL-17A therapy was not significantly different compared to the placebo in reducing inflammatory lesions in patients with moderate to severe acne.Pharmacolog

New perspectives on the treatment of hidradenitis suppurativa

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by the presence of painful nodules, abscesses, chronically draining fistulas, and scarring in apocrine gland-bearing areas of the body. The exact pathogenesis of HS is not yet well understood, but there is a consensus in considering HS a multifactorial disease with a genetic predisposition, an inflammatory dysregulation, and an influence of environmental modifying factors. Therapeutic approach of HS is challenging due to the wide clinical manifestations of the disease and the complex pathogenesis. This review describes evidence for effectiveness of current and emerging HS therapies. Topical therapy, systemic treatments, biological agents, surgery, and light therapy have been used for HS with variable results. Adalimumab is the only US Food and Drug Administration (FDA) approved biologic agent for moderate-to-severe HS, but new therapeutic options are being studied, targeting different specific cytokines involved in HS pathogenesis. Comparing treatment outcomes between therapies is difficult due to the lack of randomized controlled trials. Treatment strategy should be selected in concordance to disease severity and requires combination of treatments in most cases

The role of inflammation in autoimmune disease: a therapeutic target

Autoimmune diseases (AIDs) are immune disorders whose incidence and prevalence are increasing year by year. AIDs are produced by the immune system’s misidentification of self-antigens, seemingly caused by excessive immune function, but in fact they are the result of reduced accuracy due to the decline in immune system function, which cannot clearly identify foreign invaders and self-antigens, thus issuing false attacks, and eventually leading to disease. The occurrence of AIDs is often accompanied by the emergence of inflammation, and inflammatory mediators (inflammatory factors, inflammasomes) play an important role in the pathogenesis of AIDs, which mediate the immune process by affecting innate cells (such as macrophages) and adaptive cells (such as T and B cells), and ultimately promote the occurrence of autoimmune responses, so targeting inflammatory mediators/pathways is one of emerging the treatment strategies of AIDs. This review will briefly describe the role of inflammation in the pathogenesis of different AIDs, and give a rough introduction to inhibitors targeting inflammatory factors, hoping to have reference significance for subsequent treatment options for AIDs

Understanding efficacy-safety balance of biologics in moderate-to-severe pediatric psoriasis

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory skin disease affecting both adults and children. To better understand the efficacy-safety profile of biologics in children with moderate-to-severe psoriasis, this study aimed to analyze efficacy and safety data of randomized controlled trials (RCTs) performed in pediatric psoriasis and to compare efficacy outcomes in children with those in adults. METHODS: RCTs investigating biologics in children with moderate-to-severe psoriasis were identified in a systematic literature review. PASI75/90 treatment responses at weeks 11/12 were analyzed comparing biologics with control arms. Serious adverse events (SAEs) were analyzed at the end of each study. Efficacy data from RCTs in adults with psoriasis were selected for the same biologics. Risk ratios (RR) of selected RCTs were pooled together in a statistical random effects model using the inverse variance method. RESULTS: For children, there were 1 etanercept, 2 secukinumab, 1 ixekizumab and 1 ustekinumab placebo-controlled RCTs and 1 adalimumab RCT using methotrexate as reference arm at weeks 11/12. For adults, out of 263 RCTs, 7 adalimumab and 15 etanercept (TNF inhibitors) and 4 ixekizumab and 12 ustekinumab (IL-17 and IL-12/23 inhibitors) RCTs reported PASI75/90 efficacy responses at weeks 11/12. Regarding efficacy, all biologics showed improved PASI responses over control arms. RRs ranges were 2.02-7.45 in PASI75 and 4.10-14.50 in PASI90. The highest PASI75 responses were seen for ustekinumab 0.375 mg/kg (RR = 7.25, 95% CI 2.83-18.58) and ustekinumab 0.75 mg/kg (RR = 7.45, 95% CI 2.91-19.06) in the CADMUS study. The highest PASI90 response was seen for ixekizumab (RR = 14.50, 95% CI 4.82-43.58) in the IXORA-PEDS study. SAE incidences in pediatric and adult arms with biologics were 0 to 3% except for a pediatric arm with adalimumab 0.40 mg/kg (8%). For adults, pooled RR also showed improved PASI responses over placebo for all biologics, with highest PASI75 response observed for ixekizumab (pooled RR = 16.18, 95% CI 11.83-22.14). CONCLUSION: Both adults and children with psoriasis show superior efficacy with biologics compared to control arms after 3 months of treatment with SAE incidences in the low percentages. Additional longer-term clinical studies are warranted to fully understand the overall efficacy-safety profile of biologics in children with moderate-to-severe psoriasis

Biologic drugs in the treatment of chronic inflammatory pulmonary diseases: recent developments and future perspectives

Chronic inflammatory diseases of the lung are some of the leading causes of mortality and significant morbidity worldwide. Despite the tremendous burden these conditions put on global healthcare, treatment options for most of these diseases remain scarce. Inhaled corticosteroids and beta-adrenergic agonists, while effective for symptom control and widely available, are linked to severe and progressive side effects, affecting long-term patient compliance. Biologic drugs, in particular peptide inhibitors and monoclonal antibodies show promise as therapeutics for chronic pulmonary diseases. Peptide inhibitor-based treatments have already been proposed for a range of diseases, including infectious disease, cancers and even Alzheimer disease, while monoclonal antibodies have already been implemented as therapeutics for a range of conditions. Several biologic agents are currently being developed for the treatment of asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and pulmonary sarcoidosis. This article is a review of the biologics already employed in the treatment of chronic inflammatory pulmonary diseases and recent progress in the development of the most promising of those treatments, with particular focus on randomised clinical trial outcomes

Redacción y Traducción de Artículos Originales en Dermatología: estudio de necesidades y secuencias retóricas.

Treball Final de Màster Universitari en Traducció Medicosanitària. Codi: SBA032. Curs: 2020/2021El presente trabajo conforma el Trabajo de Fin de Máster elaborado por la alumna Clara López Santamaría y dirigido por el profesor y tutor Vicent Montalt i Resurrecció dentro de lo que establece el plan de estudios del Máster en Traducción Médico-Sanitaria impartido por la Universitat Jaume I de Castelló para el curso académico 2020-2021. Este proyecto responde a una serie de motivaciones. Por otro lado, se enmarca dentro de una motivación personal de la autora por profundizar en los estudios de traducción, especialmente dentro de los estudios de género textual y en particular dentro de los textos médicos especializados. Al mismo tiempo, pretende atender a la solicitud planteada por la Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO Castelló) por la cual se solicitaba realizar un trabajo de investigación de estas características, para poder conocer la realidad que afecta a los investigadores españoles en cuanto a la redacción de artículos originales, en concreto, por parte de los investigadores del área de la dermatología. La realización del presente trabajo está igualmente justificada por varias razones. Primeramente, existe una falta de estudios de este tipo en el campo de la traducción y del análisis textual de géneros especializados. La escasez de estudios que reflejen la realidad planteada por los autores de textos médicos, en este caso investigadores de la rama de la dermatología, es uno de los factores por los cuales el presente estudio puede considerarse como algo valioso e interesante a nivel académico. La necesidad de estudios que combinen una perspectiva real, centrada en lo que realmente necesitan los autores y que se aleje de la teoría puramente dicha es una necesidad innegable en el campo de la traducción donde los estudios se han centrado, mayormente, en exponer casos que no resultan representativos a la realidad que afecta tanto a profesionales de la traducción como a autores. Por otro lado, el presente trabajo se plantea con la intención de que las conclusiones derivadas de sus resultados sean aplicables tanto al ejercicio profesional de la traducción como al de redacción por parte de los investigadores, autores de géneros textuales especializados. En este sentido, este trabajo pretende ser de utilidad en ambos campos. Por último, la realización del presente trabajo se ve justificada en cuanto a que ha sido solicitado por parte de los propios profesionales investigadores a través de la fundación FISABIO Castelló. Para llevarlo a cabo, se ha empleado una metodología en dos estudios sucesivos. Primeramente, se ha planteado un estudio con una metodología cualitativa que consiste en una toma de contacto directa con los profesionales investigadores de la especialidad de dermatología. Mediante la realización de una serie de entrevistas se ha podido acceder a testimonios reales y actualizados para conocer de primera mano cuáles son las mayores dificultades que encuentran los investigadores en activo a la hora de redactar artículos originales. Asimismo, se ha podido conocer el papel que los traductores médicos juegan en el proceso de publicación. Seguidamente, se ha realizado el análisis en profundidad de dichas entrevistas. De esta forma se han podido deducir patrones a raíz de las respuestas aportadas que pueden ser extrapolados a la realidad, siendo comparables con una muestra real de artículos originales en el área de la dermatología. La segunda fase de la metodología empleada es un análisis de un corpus textual bilingüe inglés-español especializado y comparable conformado por doce artículos originales (seis por idioma) de investigación dentro de la especialidad de dermatología. Se trata de un corpus textual especializado porque los textos seleccionados son textos médicos y, es comparable porque los artículos originales que lo conforman son similares en cuanto a su composición y características, de manera que es factible realizar comparaciones a nivel lingüístico y estructural. Mediante el análisis de este corpus de artículos originales se han identificado de patrones secuencias retóricas propios del género textual en aquellas secciones en las que los profesionales entrevistados advirtieron mayores dificultades, pudiendo de este modo sacar conclusiones al respecto. Con todo ello este estudio ha podido sacar una serie de conclusiones sobre cuáles son los aspectos de los artículos originales que más problemas suponen en cuanto a su redacción se refiere, así como las razones que llevan a dichas dificultades y se han podido aislar problemas para que tanto investigadores como traductores puedan resolverlos con mayor acierto y rapidez

First-in-human study demonstrating the safety and clinical efficacy of novel anti-IL-17A monoclonal antibody CJM112 in moderate to severe plaque psoriasis

Background and objective: Anti-IL-17A IgG/κ monoclonal antibody CJM112 binds both IL-17A and IL-17AF. The purpose of this First-in-Human study was to assess CJM112 effects on safety and efficacy in patients with moderate to severe plaque psoriasis. Methods: This study had two parts: single ascending doses of 5–450 mg subcutaneous (s.c.) CJM112 (SAD) and multi-dose parallel groups of CJM112 15 mg, 50 mg and 150 mg s.c. low frequency or high frequency (MD). SAD/MD were double-blind, randomized and placebo-controlled; MD also included a secukinumab 150 mg s.c. arm as an active comparator. Patients 18–65 years with moderate to severe psoriasis were included in this study. The efficacy outcome was the change in Psoriasis Area Severity Index (PASI) from baseline to Week 4 in the SAD part of the study, and from baseline to Week 12 in the MD part. Results: 96 patients were enrolled in this study (SAD, n = 42; MD, n = 54). In SAD, CJM112 doses from 15 mg and above demonstrated higher PASI responses compared with placebo at Week 12. CJM112 450 mg did not add further efficacy, but efficacy duration was prolonged compared with CJM112 150 mg. CJM112 MD resulted in a dose-dependent decrease in PASI over time to Week 12. CJM112 150 mg high frequency did not exceed the effect of CJM112 150 mg low frequency and had similar efficacy to secukinumab 150 mg. The safety profile of CJM112 was as expected for an antibody targeting IL-17A/IL-17AF. Conclusions: CJM112 had clinical efficacy in moderate to severe psoriasis and was generally safe and well tolerated in the doses tested. Additional neutralization of IL-17AF did not translate to increased clinical efficacy compared with secukinumab