Clinical management of Lupus patients during the COVID-19 pandemic

Severe acute respiratory syndrome coronavirus (SARS-CoV-2), the virus causing Coronavirus disease 2019 (COVID-19), has had a huge impact on health services with a high mortality associated with complications including pneumonia and acute respiratory distress syndrome. Historical evidence suggests that Lupus patients have a higher incidence of several viral infections. This is likely due to a combination of immune dysfunction, immunosuppressive therapy and excess co-morbidities. In this context there has been concern that Lupus patients may be at a higher risk of developing COVID-19 and suffering a severe disease course. As a result, many Lupus patients have been advised to ‘shield’ by isolating from social contact in the hope that this will reduce the likelihood of infection. Early clinical data does not appear to show that the incidence of COVID-19 is higher in Lupus patients. Reassuringly, the clinical course of COVID-19 in Lupus does not generally seem to be more severe than in the general population. There has been huge interest in repurposing existing drugs as potential treatments, including several used to treat Lupus. Of these, corticosteroids and hydroxychloroquine are the most well researched so far. The current evidence suggests that the corticosteroid dexamethasone improves outcome for the sickest COVID-19 patients requiring respiratory support. Initial reports suggested that hydroxychloroquine could have a positive impact on the course of COVID-19, however larger prospective studies have not supported this. Janus kinase inhibitors, currently being investigated for efficacy in lupus, have been shown to have anti-viral effects in vitro and inhibiting the JAK-STAT pathway may dampen down the host hyper-inflammatory response. Several trials are ongoing to assess the outcome of the use of JAK inhibitors in COVID-19 positive patients. For most patients continuing with their existing therapies to prevent a lupus flare or adverse events associated with sudden corticosteroid withdrawal is important whilst an Individualised risk assessment remains vital.

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An Updated Analysis of In vitro Cytokine Inhibition Profiles of a Number of Janus Kinase Inhibitors at Clinically Meaningful Concentrations

The American Journal of Gastroenterology ◽

10.14309/00000434-201710001-00739 ◽

2017 ◽

Vol 112 ◽

pp. S407

Author(s):

Martin E. Dowty ◽

Tsung H. Lin ◽

Lu Wang ◽

Jason M. Jussif ◽

Li Li ◽

...

Keyword(s):

Kinase Inhibitors ◽

Janus Kinase ◽

Janus Kinase Inhibitors ◽

Cytokine Inhibition

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Janus kinase inhibitors: jackpot or potluck?

Oncology Reviews ◽

10.4081/oncol.2012.187 ◽

2012 ◽

pp. e13

Author(s):

Pavithran Keechilat ◽

Shripad Brahmanand Pande

Keyword(s):

High Risk ◽

Polycythemia Vera ◽

Kinase Inhibitors ◽

Kinase Inhibitor ◽

Myeloproliferative Neoplasms ◽

Primary Myelofibrosis ◽

Janus Kinase ◽

Current Evidence ◽

Federal Drug Administration ◽

Janus Kinase Inhibitors

The reports of a unique mutation in the Janus kinase-2 gene (JAK2) in polycythemia vera by several independent groups in 2005 quickly spurred the development of the Janus kinase inhibitors. In one of the great victories of translational research in recent times, the first smallmolecule Janus kinase inhibitor ruxolitinib entered a phase I trial in 2007. With the approval of ruxolitinib by the US Federal Drug Administration in November 2011 for high-risk and intermediate-2 risk myelofibrosis, a change in paradigm has occurred in the management of a subset of myeloproliferative neoplasms (MPN): primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis. Whereas the current evidence for ruxolitinib only covers high-risk and intermediate-2 risk myelofibrosis, inhibitors with greater potency are likely to offer better disease control and survival advantage in patients belonging to these categories, and possibly to the low-risk and intermediate-1 risk categories of MPN as well. But use of the Janus kinase inhibitors also probably has certain disadvantages, such as toxicity, resistance, withdrawal phenomenon, non-reversal of histology, and an implausible goal of disease clone eradication, some of which could offset the gains. In spite of this, Janus kinase inhibitors are here to stay, and for use in more than just myeloproliferative neoplasms.

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Janus kinase inhibitors: jackpot or potluck?

Oncology Reviews ◽

10.4081/oncol.2012.e13 ◽

2012 ◽

Vol 6 (1) ◽

pp. 13

Author(s):

Pavithran Keechilat ◽

Shripad Brahmanand Pande

Keyword(s):

High Risk ◽

Polycythemia Vera ◽

Kinase Inhibitors ◽

Kinase Inhibitor ◽

Myeloproliferative Neoplasms ◽

Primary Myelofibrosis ◽

Janus Kinase ◽

Current Evidence ◽

Federal Drug Administration ◽

Janus Kinase Inhibitors

The reports of a unique mutation in the Janus kinase-2 gene (<em>JAK2</em>) in polycythemia vera by several independent groups in 2005 quickly spurred the development of the Janus kinase inhibitors. In one of the great victories of translational research in recent times, the first smallmolecule Janus kinase inhibitor ruxolitinib entered a phase I trial in 2007. With the approval of ruxolitinib by the US Federal Drug Administration in November 2011 for high-risk and intermediate-2 risk myelofibrosis, a change in paradigm has occurred in the management of a subset of myeloproliferative neoplasms (MPN): primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis. Whereas the current evidence for ruxolitinib only covers high-risk and intermediate-2 risk myelofibrosis, inhibitors with greater potency are likely to offer better disease control and survival advantage in patients belonging to these categories, and possibly to the low-risk and intermediate-1 risk categories of MPN as well. But use of the Janus kinase inhibitors also probably has certain disadvantages, such as toxicity, resistance, withdrawal phenomenon, non-reversal of histology, and an implausible goal of disease clone eradication, some of which could offset the gains. In spite of this, Janus kinase inhibitors are here to stay, and for use in more than just myeloproliferative neoplasms.

Download Full-text