New therapies for systemic lupus erythematosus — past imperfect, future tense

The failure of many new, mostly biologic, drugs to meet their primary end points in double-blind clinical trials in patients with systemic lupus erythematosus (SLE) has caused a profound sense of disappointment among both physicians and patients. Arguably, the success of B cell depletion with rituximab in open-label studies and in patients with lupus nephritis in the USA and in difficult-to-treat patients with SLE in the UK, together with the approval of belimumab (which blocks B cell-activating factor (BAFF)) for use in patients with SLE and the recognition that clinical trial design can be improved, have given some cause for hope. However, changes to therapies in current use and the development of new approaches are urgently needed. The results of the latest studies investigating the use of several new approaches to treating SLE are discussed in this Review, including: fully humanized anti-CD20 and anti-CD19 monoclonal antibodies; inhibition of tyrosine-protein kinase BTK; CD40 ligand blockade; interfering with the presentation of antigen to autoreactive T cells using a peptide approach; a receptor decoy approach using an analogue of Fcγ receptor IIB; dual blockade of IL-12 and IL-23; and inhibition of Janus kinases. A series of successive failures of new therapies for systemic lupus erythematosus (SLE) in clinical trials has left clinicians with limited options to treat this disease. Could any of the therapies currently in development offer hope for patients with SLE?