key: cord-0709324-rf6y3wvc authors: Mehta, Puja; Cron, Randy Q; Hartwell, James; Manson, Jessica J; Tattersall, Rachel title: Intravenous anakinra for cytokine storm syndromes – Authors' reply date: 2020-07-21 journal: Lancet Rheumatol DOI: 10.1016/s2665-9913(20)30215-0 sha: fddbef3abe44f3b6e684fdfc4623658733022701 doc_id: 709324 cord_uid: rf6y3wvc nan We appreciate the interest in our Viewpoint 1 on the use of intravenous anakinra in cytokine storm syndromes. Yvan Jamilloux and colleagues con tribute to continuing discussions regarding the terminology of hyper inflammatory disorders; 2 we suggest a unifying umbrella term of cytokine storm syndromes. We feel that it is the concept of hyperinflammation that is crucial; the conditions charac terised by hyperinflammation overlap, and we endorse shared clinical and scientific learning. We agree with Jamilloux and col leagues that a subgroup of patients with severe COVID19associated hyperinflammation might benefit from immunomodulation, but we caution against prematurely pre dicting optimal immunomodulatory therapies on the basis of systemic cytokine concentrations meas ured from peripheral blood, as local (eg, pulmonary) cytokinaemia might be more informative. The focus on inhi bition of IL6 early in the COVID19 pandemic might be because of, at least in part, the relative ease of measurement of IL6 and access to drug supply (tocilizumab is widely available in China), rather than a true hypothesised advantage of block ing IL6 in preference to a different cytokine. Nihal Martis and Alexandra AudemardVerger discuss the timing of intervention (subclinical com pared with fulminant hyperinflamma tory 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 mor tality in cytokine storm syndromes. 3 Although steroidfree treatment regimens are difficult to achieve, we would emphasise the increased risk of infec tion with highdose steroids, and the risk of masking signs of infection with IL6 blockade (suppression of Creactive protein or fever) as impor tant considerations. The use of anakinra in cytokine storm syndromes should not be con fined to presentations with a rheu matic 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 rheu matological condition (cytomegalovirus and vasculitis). As we mention in our Viewpoint, the efficacy of anakinra in nonrheumatic hyperinflammation was shown in posthoc analyses of bacterial sepsis trials, and data suggest that IL1 blockade might have a role in the neurotoxicity secondary to chimeric antigen receptor Tcell therapy for refractory leukaemia or lymphoma. Additionally, cohort studies of 81 patients with severe COVID19 suggested an efficacy signal with ana kinra use. 4, 5 Data from controlled trials of anakinra in patients with COVID19 are eagerly anticipated. PM is a Medical Research Council GlaxoSmithKline EMINENT clinical training fellow with project funding outside the submitted work, receives cofunding 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 coprincipal investigator of an investigator initiated clinical trial funded by Swedish Orphan Biovitrum (SOBI), is on the advisory board for SOBI (