Biotherapies in systemic lupus erythematosus: New targets

Systemic lupus erythematosus (SLE) is an autoimmune disease with a polymorphic presentation. The variability in the clinical expression and severity of SLE makes new treatments both essential and challengingto develop. Several biotherapies targeting different pathophysiological pathways have been developedover the past 15 years. The results of Phase II trials were encouraging but rarely borne out by PhaseIII trials. Recent data, which are discussed in detail in this review, allowed belimumab -a monoclonalantibody against BLyS (B-lymphocyte stimulator) -to become the first biotherapy approved for use inSLE. Other molecules targeting B cells include the two anti-BLyS antibodies tabalumab and blisibimod; atacicept, which targets both BLyS and APRIL (a proliferation-inducing ligand); and the monoclonal antibody to CD22 epratuzumab. The rekindling of interest in the B-cell pathway has also driven new clinicalresearch into rituximab, a monoclonal antibody targeting CD20 with evaluations of new strategies. Anew and promising approach is the use of inhibitors of the type 1 interferon (IFN) pathway, of which themost promising is anifrolumab, a monoclonal antibody targeting the type 1 IFN receptor. In this review, we discuss study findings and their clinical relevance, present the most promising targets, and analyzepossible explanations to negative results, such as inappropriate patient selection and treatment responsecriteria or the erratic use of high-dose glucocorticoid therapy. (C) 2016 Societe francaise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.