Clinical practice guidelines and recommendations for the management of patients with systemic lupus erythematosus: a critical comparison

Date
2020Author(s)
Izcovich, A.
Alarcón, G.S.
Gómez-Puerta, J.A.
Pons-Estel, G.J.
Ugarte-Gil, M.F.
Cardiel, M.H.
Pons-Estel, B.A.
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Substantial evidence implicates type 1 IFN (IFN-1) in the pathophysiology of SLE and this has led to the development of several therapeutic strategies for lupus that target the IFN-1 pathways . In particular, it has recently been reported that the therapeutic monoclonal antibody anifrolumab showed efficacy in meeting its primary endpoint in a phase III clinical trial in active lupus. Anifrolumab targets the IFN-1 receptor and thereby inhibits the activity of all species of IFN-1 (α, β and ω). Overall, anifrolumab has shown greater promise in lupus than the therapeutic monoclonal antibodies that directly target only IFN-α (i.e. sifalimumab, rontalizumab). This is not surprising, as although many studies have concentrated on the role of IFN-α derived from plasmacytoid dendritic cells in lupus, it is now apparent that IFN-β and IFN-ω are also important in the pathophysiology. With regard to the signalling pathways that are triggered in lupus to generate IFN-1 production, emphasis has been placed on the role of the DNA sensor Toll-like receptor 9 (TLR9). However, there is increasing evidence for involvement of the RNA sensor TLR3, RNA sensors such as retinoic acid–inducible gene 1 (RIG-1)/melanoma differentiation-associated protein 5 (MDA-5) that stimulate mitochondrial antiviral signalling (MAVS) and the DNA sensors such as cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS) that stimulate stimulator of interferon genes (STING) [4–6]: all three pathways act via the signalling molecule TANK-binding kinase 1 (TBK-1). Indeed, the IFN-1 gene signature in peripheral blood mononuclear cells of childhood-onset lupus patients can be down-regulated by the TBK-1 inhibitor BX795 [5]. These and other findings have raised the potential of TBK-1 inhibitors as therapeutic agents for lupus...
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