Expert review of clinical immunology
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Expert Rev Clin Immunol · Sep 2019
ReviewTreatment of systemic necrotizing vasculitides: recent advances and important clinical considerations.
Introduction: Primary systemic necrotizing vasculitides (SNVs) include polyarteritis nodosa, Kawasaki disease, ANCA-associated vasculitides, IgA vasculitis, and cryoglobulinemic vasculitis. All are rare but potentially severe, life-threatening conditions. Evidence-based treatments are well established, but continue to evolve and management requires some expertise. ⋯ Results from ongoing and future trials for vasculitis will likely impact these treatment approaches. Entirely avoiding GC may become possible, perhaps even the next gold standard, if medications such as avacopan are confirmed to be safe and effective. New combination strategies, more individualized for each patient, may also prove to be more effective, faster.
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Expert Rev Clin Immunol · Aug 2019
ReviewTocilizumab for the treatment of chimeric antigen receptor T cell-induced cytokine release syndrome.
Introduction: Cancer-directed immunotherapies are transforming the landscape in oncology as new and exciting therapies move from the laboratory to the bedside. Chimeric antigen receptor T (CAR-T) cells are one of these novel therapies, demonstrating impressive efficacy against B-cell malignancies. With the development of new therapies, it is not uncommon to identify new and unanticipated toxicities. ⋯ Expert opinion: This review describes the recommended management of CRS and CRES and examines the current limitations in management. Alternative therapies for the treatment of CAR-T cell related toxicities are also explored. Furthermore, the review proposes future directions for research.
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Expert Rev Clin Immunol · Mar 2019
ReviewNew frontiers in precision medicine for sepsis-induced immunoparalysis.
In the last decade, the sepsis research field has shifted focus from targeting hyperinflammation to reversing sepsis-induced immunoparalysis. Sepsis-induced immunoparalysis is very heterogeneous: the magnitude and the nature of the underlying immune defects differ considerably between patients, but also within individuals over time. Therefore, a 'one-treatment-fits-all' strategy for sepsis-induced immunoparalysis is bound to fail, and an individualized 'precision medicine' approach is required. ⋯ Finally, we present a contemporary overview of adjuvant immunostimulatory therapies. Expert opinion: The integration of multiple omics techniques offers a systems biology approach which can yield biomarker profiles that accurately and comprehensively gauge the extent and nature of sepsis-induced immunoparalysis. We expect this development to be instrumental in facilitating precision medicine for sepsis-induced immunoparalysis, consisting of the application of targeted immunostimulatory therapies and follow-up measurements to monitor the response to treatment and to titrate or adjust medication.
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Introduction: Tofacitinib and baricitinib have recently been approved as second-line treatments for Rheumatoid arthritis (RA) though their maximum expected efficacy may be limited by dose-related toxicities. Upadacitinib selectively inhibits Janus Kinase 1 (JAK1) which could potentially reduce JAK2 and JAK3-related side effects. Areas covered: In this paper, we review a newly developed oral selective JAK inhibitor, upadacitinib for the treatment of RA. ⋯ The comparison with abatacept is still ongoing. Expert commentary: Upadacitinib has displayed a rapid and favorable efficacy profile in RA but despite being a selective JAK1 inhibitor appears to have a similar safety profile to less-selective Jakinibs. Longer term safety data are awaited.
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Allergic conditions such as asthma and atopic dermatitis have a high prevalence but represent a heterogeneous group of diseases despite similar clinical presentation and underlying pathophysiology. A better understanding of the phenotypes and endotypes of these diseases has driven rapid development of biologic medications targeting many steps of the inflammatory pathways. Areas covered: There are 2 major inflammatory pathways that drive allergic diseases: Type-2 (Th-2) inflammation and non-type 2 inflammation. ⋯ Biologic targets along this pathway include Anti-Immunoglobulin E (IgE), Anti-Interleukin 5 (IL-5), Anti-IL 4, and Anti-IL 13. Although the most study has been done in the realm of severe asthma, biologic targets for other allergic diseases including atopic dermatitis, chronic rhinosinusitis with nasal polyposis, chronic idiopathic urticaria, eosinophilic esophagitis, and eosinophilic granulomatosis with polyangiitis are also discussed. Expert commentary: Novel biologic therapies have emerged over the last several years that have revolutionized the management of patients with refractory allergic disease.