ReviewAnti-interferon alpha treatment in SLE

•IFNα and plasmacytoid dendritic cells (pDC) are important treatment targets in SLE.•Antibodies against IFNα and its receptor have been used to block the IFNα pathway.•TLR7 and 9 inhibition is another strategy to block IFNα production by pDC.•Anti-IFNα agents in early clinical trials appear safe and suppress IFN signature.•More data are required to assess the safety and efficacy of IFNα inhibitors.

Several studies in the last decade have highlighted the role of the type I interferon (IFN-I) pathway, and particularly interferon alpha (IFNα) in SLE pathogenesis. As a result, a multitude of potential treatments targeting IFNα have emerged in the last few years, a few of which have already completed phase II clinical trials. Some of the treatment strategies have focused on blocking IFNα or its receptor and others the plasmacytoid dendritic cell (pDC), which is the principal IFNα producing cell. In this review, we will discuss the evidence supporting a pathogenic role of IFNα and pDC in SLE, provide an update on the current status of these therapeutic strategies, and discuss the potential advantages and disadvantages of each therapeutic approach.