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Malgré les traitements disponibles, le lupus érythémateux systémique (LES) actif et corticodépendant constitue un défi thérapeutique majeur. Cette revue systématique avait pour objectif de proposer une mise à jour des thérapies ciblées en développement clinique dans le LES, avec une attention particulière accordée aux traitements les plus prometteurs. Nous avons mené une revue systématique des thérapies ciblées en développement clinique dans le LES à partir du registre des essais cliniques clinicaltrials.gov (date de la recherche : 28 août 2022). Les thérapies ciblées (médicaments conçus pour bloquer des molécules, récepteurs ou voies de signalisation spécifiques impliqués dans le développement du LES) ont été extraites. Pour chaque médicament évalué, seule l'étude ayant atteint la phase de développement clinique la plus avancée a été prise en compte. Sur un total de 203 essais cliniques consacrés au LES, nous avons identifié 92 thérapies ciblées différentes (58 DMARD biologiques [bDMARD] et 34 DMARD synthétiques ciblés [tsDMARD]). Les médicaments analysés ont atteint la phase I (n = 20), Ia/IIb (n = 6), II (n = 51), II/III (n = 1), III (n = 13) et IV (n = 1). Les essais correspondants étaient en cours de recrutement (n = 31), actifs mais au recrutement clos (n = 8), au recrutement à venir (n = 4), en recrutement par invitation (n = 2), complétés (n = 31), arrêtés prématurément (n = 12) et abandonnés dans 1 cas (statut inconnu dans 3 cas). Les principales stratégies thérapeutiques en développement dans le LES ciblent les cytokines/chimiokines pro-inflammatoires ou leurs récepteurs (n = 19), les voies de signalisation intracellulaire (n = 18), les lymphocytes B (n = 14) ou plasmocytes (n = 7), les molécules de co-stimulation des cellules T/B (n = 10), les protéines du complément (n = 5), les lymphocytes T (n = 2), les cellules dentritiques plasmacytoïdes (n = 2) ainsi que de nombreuses autres cibles de l'immunité (n = 15). La grande diversité des médicaments en développement dans le LES devrait permettre d'améliorer les stratégies Treat-to-Target avec pour objectif de modifier la maladie. L'identification de biomarqueurs compagnons sera nécessaire afin de mieux caractériser l'hétérogénéité du LES et d'optimiser le choix du traitement le plus adapté à chaque patient. Despite available therapies, persistently active and corticosteroid-dependent Systemic Lupus Erythematosus (SLE) represent a significant therapeutic challenge. The purpose of this systematic review was to provide an updated view of targeted therapies currently in clinical development in SLE, with a special focus on the most promising ones. We performed a systematic review of targeted therapies in clinical development in SLE in clinicaltrials.gov (search date: 28th of August 2022). Targeted therapies (defined as drugs specifically designed to block certain molecules, receptors, or pathways involved in the development of SLE) were extracted. For each investigational drug, we considered only the study at the most advanced stage of clinical development. The systematic review yielded a total of 92 targeted therapies (58 biological DMARDs [bDMARDs] and 34 targeted synthetic [ts]DMARDs) assessed in a total of 203 clinical trials. The candidate drugs reached phase I (n = 20), Ia/IIb (n = 6), phase II (n = 51), phase II/III (n = 1), phase III (n = 13) and phase IV (n = 1). These trials were reported as recruiting (n = 31), active but not recruiting (n = 8), not yet recruiting (n = 4), enrolling by invitation (n = 2), completed (n = 31), prematurely terminated (n = 12) and withdrawn in 1 (status unknown in 3). The main investigational drugs for SLE target inflammatory cytokines, chemokines or their receptors (n = 19), intracellular signaling pathways (n = 18), B cells (n = 14) or plasma cells (n = 7), T/B cells costimulation molecules (n = 10), complement molecules (n = 5), T lymphocytes (n = 2), plasmacytoid dendritic cells (n = 2), as well as various other immune targets (n = 15). The pipeline of investigational drugs in SLE is highly diversified and will hopefully enable more optimal Treat-To-Target with the goal of disease modification. Companion biomarkers will be needed to better characterized SLE heterogeneity and optimize treatment selection at the individual-patient level. [ABSTRACT FROM AUTHOR]

The development of new targeted therapies in non-small cell lung carcinoma (NSCLC) depends on a better understanding of the molecular basis of carcinogenesis, a knowledge of the role of molecular aberrations in disease progression and the development of molecular biology platforms with the capacity to identify new biomarkers. In the current article, we review the techniques routinely used in cancer molecular biology platforms as well as new techniques under development. These new NSCLC biomarkers have been made available to clinicians and biologists in parallel with the development of targeted drugs. New molecular abnormalities of EGFR exon 20, HER2, MET, RET, BRAF, ROS1 and NTRK have been identified and there have been clinical trials of the most innovative targeted drugs., (Copyright © 2021 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

The treatment of atopic dermatitis in adults is based on the use of topical steroids and emollients. When AD is resistant to a well-conducted topical treatment, phototherapy or systemic treatments can be used: ciclosporin, methotrexate, azathioprine or mycophenolate mofetil. The therapeutic landscape of adult AD is about to change and even be revolutionized by the imminent arrival of new treatments: topical phosphodiesterase 4 inhibitors, topical or systemic JAK inhibitors, anti-IL-4 and/or antiIL-13 biotherapies (dupilumab, tralokinumab, lebrikizumab), anti-IL-31 (nemolizumab), anti-TSLP., (© 2017 Elsevier Masson SAS. Tous droits réservés.)