key: cord-0884835-idd04kh0
authors: Khan, Sujoy
title: Comment on: Gudu T, Stober C, Cope AP et al. Baricitinib set to join the Covid-19 therapeutic arsenal? Rheumatology (Oxford). 2021;60:1585-1587
date: 2021-04-24
journal: Rheumatology (Oxford)
DOI: 10.1093/rheumatology/keab386
sha: e59cfe596e63cc2b44a96575b3544a9b6bee4b9d
doc_id: 884835
cord_uid: idd04kh0

nan

Treatment Trial -2 (ACTT-2) study findings that showed JAK-inhibitor baricitinib and remdisivir can provide a clinically meaningful benefit and safer management approach to severe COVID19 [2] . A hypothetical but possibly real clinical scenario is patients with adult-onset Still's disease (AoSD) presenting with florid cytokine storm typical of autoimmune/inflammatory diseases (AI-MAS-HLH) but with CT imaging suggesting possible COVID19 pathological lesions. Will treatment be according to protocols for autoinflammatory-macrophage activation syndrome-hemophagocytic lymphohistiocytosis (AI-MAS-HLH) or COVID19-related-MAS-HLH? Patients with active AoSD will typically be on immunosuppressive drugs (such as methotrexate) and virally driven hyperinflammation can make clinical symptoms and inflammatory markers quite difficult to interpret which may be further complicated by negative SARS-CoV-2 PCR on nasopharyngeal samples [3] . A triple combination therapy of baricitinib, remdisvir and dexamethasone has the potential to change the way we treat COVID19-MAS-HLH [4] .

Non-aerosol generating procedures such as CT imaging (non-contrast CT chest followed by cardiac CT) has fundamentally changed the way we evaluate patients but persistently negative nasopharyngeal PCR samples for COVID19 may mean performing bronchoalveolar lavage for samples which may prove quite challenging and has its own limitations [5] . We would first need a systematic approach and use existing criteria to diagnose HLH, then re-consider our immunosuppressive strategies. Both conditions, suspected COVID19-MAS-HLH and AI-MAS-HLH, would respond to immunosuppression but the former will benefit from additional anti-viral support such as with remdisivir. Addressing the cytokine storm will determine final outcome and triple combination with baricitinib, remdisivir and dexamethasone appears much safer than using transplant-related protocols routinely used for secondary HLH. Etoposide has serious side effects of lymphocytopenia, derangement in coagulation parameters that would complicate prognostic variables F o r P e e r R e v i e w and patient recovery. Addition of remdisivir in such patients who are COVID19 negative (but high suspicion on imaging studies) will not necessarily add to the risk whilst controlling viral replication if nasopharyngeal PCR samples were negative due to low viral loads or variable shedding. Successful clinical trials with the triple combination will also highlight the potential of added JAK-inhibition that is not in current treatment pathways of HLH.

Baricitinib set to join the Covid-19 therapeutic arsenal?

ACTT-2 Study Group Members. Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19

Managing high clinical suspicion COVID-19 inpatients with negative RT-PCR: a pragmatic and limited role for thoracic CT

Janus Family kinase (JAK) inhibitors in HLH and severe COVID-19

Limited role for bronchoalveolar lavage to exclude COVID-19 after negative upper respiratory tract swabs: a multicentre study