PO.6.130 Rapid efficacy of anifrolumab in multiple subtypes of recalcitrant cutaneous lupus erythematosus parallels discrete changes in transcriptomic and cellular biomarkers

BackgroundCutaneous lupus eyrthematosus (CLE) is frequently refractory to immunosuppressive therapies including B-cell depletion, but this varies by morphology with the chronic discoid (DLE) subtype being particularly resistant. Local production and response to type-I interferon (IFN-I) is implicated in all subtypes of CLE. Therapeutic blockade of the IFN-I receptor with anifrolumab has direct effects on IFN-I signaling, and subsequent more widespread effects on other immune functions regulated by IFN-I.Response to anifrolumab by lesion subtype have not been described, and it is unclear which effects of IFN-blockade are responsible for cutaneous response. We hypothesise that the efficacy of anifrolumab will differ dependent on the relative contribution of direct IFN-I effects vs. the downstream immunostimulatory effects of IFN-I on other immune functions.ObjectivesTo evaluate the effect of anifrolumab on (i) rituximab-refractory CLE; (ii) on DLE; (iii) to compare clinical responses with IFN-specific biomarkers and transcriptomic evaluation of broader immune responses; (iv) to compare early and late immunophenotypic and clinical responses.MethodsSLE patients with active recalcitrant CLE received anifrolumab 300 mg IV every 4 weeks and evaluated using the Cutaneous lupus erythematosus disease area and severity index (CLASI) and dermatology life quality index (DLQI). Fluorescence intensity of tetherin (CD317), a cell surface interferon biomarker, was evaluated by multiparameter flow cytometry of peripheral blood mononuclear cells (PBMCs). Previously validated IFN-Scores-A and B, in addition to gene expression scores annotated to Inflammation, Myeloid lineage and Plasmablasts modules [3], were measured in PBMCs using customised Taqman array at serial time points.Results7 patients (DLE n=5, chillblain/nodular vasculitis n= 1, subacute CLE n=1) have commenced therapy. Median number of previously failed standard therapies is 6, including rituximab in 6/7 patients, belimumab in 2/7 and thalidomide in 4/7. Three patients required long-term oral prednisolone >10 mg daily. Median baseline CLASI activity score was 17 and DLQI was 17/30.Rapid clinical responses were evident at 1 month, with more rapid effects observed in patients with SCLE and DLE compared with chillblain lesions. Median fall in CLASI activity score at 1 month was 6 points with a median percentage change from baseline of 31%. In all patients, a rapid and marked suppression of IFN-Score-A (mean differen