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• W3044648386 abstract "We appreciate the interest in our Viewpoint1Mehta P Cron RQ Hartwell J Manson JJ Tattersall RS Silencing the cytokine storm: the use of intravenous anakinra in haemophagocytic lymphohistiocytosis or macrophage activation syndrome.Lancet Rheumatol. 2020; 2: e358-e367Summary Full Text Full Text PDF PubMed Scopus (161) Google Scholar on the use of intravenous anakinra in cytokine storm syndromes. Yvan Jamilloux and colleagues contribute to continuing discussions regarding the terminology of hyperinflammatory disorders;2Nikiforow S Berliner N To “lump” or to “split” in macrophage activation syndrome and hemophagocytic lymphohistiocytosis.Arthritis Rheumatol. 2020; 72: 206-209Crossref PubMed Scopus (6) Google Scholar we suggest a unifying umbrella term of cytokine storm syndromes. We feel that it is the concept of hyperinflammation that is crucial; the conditions characterised by hyperinflammation overlap, and we endorse shared clinical and scientific learning. We agree with Jamilloux and colleagues that a subgroup of patients with severe COVID-19-associated hyperinflammation might benefit from immunomodulation, but we caution against prematurely predicting optimal immunomodulatory therapies on the basis of systemic cytokine concentrations measured from peripheral blood, as local (eg, pulmonary) cytokinaemia might be more informative. The focus on inhibition of IL-6 early in the COVID-19 pandemic might be because of, at least in part, the relative ease of measurement of IL-6 and access to drug supply (tocilizumab is widely available in China), rather than a true hypothesised advantage of blocking IL-6 in preference to a different cytokine. Nihal Martis and Alexandra Audemard-Verger discuss the timing of intervention (subclinical compared with fulminant hyperinflammatory states) and the relative merits of corticosteroids and anakinra, and suggest that anakinra should be reserved for rheumatic triggers. We have described a potential window of opportunity to reduce the risk of progression and high mortality in cytokine storm syndromes.3Mehta P Porter JC Manson JJ et al.Therapeutic blockade of granulocyte macrophage colony-stimulating factor (GM-CSF) in COVID-19-associated hyperinflammation: opportunities and challenges.Lancet Respir Med. 2020; (published online June 16.)https://doi.org/10.1016/S2213-2600(20)30267-8Summary Full Text Full Text PDF Scopus (92) Google Scholar Although steroid-free treatment regimens are difficult to achieve, we would emphasise the increased risk of infection with high-dose steroids, and the risk of masking signs of infection with IL-6 blockade (suppression of C-reactive protein or fever) as important considerations. The use of anakinra in cytokine storm syndromes should not be confined to presentations with a rheumatic cause. Of the eight reported cases using intravenous anakinra (at the time of writing the Viewpoint), an equal number of cases had an infectious (three of eight patients) and rheumatological (three of eight patients) cause, and one patient had both an infection and a rheumatological condition (cytomegalovirus and vasculitis). As we mention in our Viewpoint, the efficacy of anakinra in non-rheumatic hyperinflammation was shown in post-hoc analyses of bacterial sepsis trials, and data suggest that IL-1 blockade might have a role in the neurotoxicity secondary to chimeric antigen receptor T-cell therapy for refractory leukaemia or lymphoma. Additionally, cohort studies of 81 patients with severe COVID-19 suggested an efficacy signal with anakinra use.4Huet T Beaussier H Voisin O et al.Anakinra for severe forms of COVID-19: a cohort study.Lancet Rheumatol. 2020; 2: e393-e400Summary Full Text Full Text PDF PubMed Scopus (452) Google Scholar, 5Cavalli G De Luca G Campochiaro C et al.Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study.Lancet Rheumatol. 2020; 2: e325-e331Summary Full Text Full Text PDF PubMed Scopus (732) Google Scholar Data from controlled trials of anakinra in patients with COVID-19 are eagerly anticipated. PM is a Medical Research Council GlaxoSmithKline EMINENT clinical training fellow with project funding outside the submitted work, receives co-funding from the UK National Institute for Health Research University College London Hospitals Biomedical Research Centre, and is on a scientific advisory board for Swedish Orphan Biovitrum (SOBI). RQC is co-principal investigator of an investigator initiated clinical trial funded by Swedish Orphan Biovitrum (SOBI), is on the advisory board for SOBI (<US$5000), and is on the clinical trial adjudication committee for Pfizer. RST is a member of the UK systemic autoinflammatory disease network, whose meetings are funded by an unrestricted educational grant from SOBI. JH and JJM declare no competing interests. Silencing the cytokine storm: the use of intravenous anakinra in haemophagocytic lymphohistiocytosis or macrophage activation syndromeThe term cytokine storm syndromes describes conditions characterised by a life-threatening, fulminant hypercytokinaemia with high mortality. Cytokine storm syndromes can be genetic or a secondary complication of autoimmune or autoinflammatory disorders, infections, and haematological malignancies. These syndromes represent a key area of interface between rheumatology and general medicine. Rheumatologists often lead in management, in view of their experience using intensive immunosuppressive regimens and managing cytokine storm syndromes in the context of rheumatic disorders or infection (known as secondary haemophagocytic lymphohistiocytosis or macrophage activation syndrome [sHLH/MAS]). Full-Text PDF Intravenous anakinra for cytokine storm syndromesWe read with interest the Viewpoint by Puja Mehta and colleagues1 on the use of intravenous anakinra in secondary haemophagocytic lymphohistiocytosis or macrophage activation syndrome (sHLH/MAS), in which they suggest a framework for the management of cytokine storm syndromes. Full-Text PDF Intravenous anakinra for cytokine storm syndromesIn their Viewpoint on cytokine storm syndromes, Puja Mehta and colleagues1 stated that “there is a critical need and growing call for unified nomenclature (such as cytokine storm syndromes)”. Although we agree that a multidisciplinary effort is needed to analyse and classify these conditions, we have concerns about unifying them all under a single umbrella. Indeed, cytokine storm syndromes currently encompass several different conditions with extremely varied causes, pathophysiological processes, or prominant cytokines. Full-Text PDF" @default.
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• W3044648386 title "Intravenous anakinra for cytokine storm syndromes – Authors' reply" @default.
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