Biologicals for the treatment of systemic lupus erythematosus: current status and emerging therapies.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease resulting from the dysregulation of various immunological pathways. There has been major progress in recent years in the understanding of the pathogenesis of SLE, which has led to an emergence of a new class of drugs designed to target specific components of the disease process.Evidence from a number of open-label, uncontrolled studies has supported the use of rituximab (an anti-CD20 monoclonal antibody) in SLE for more than one decade. However, these promising results are in clear contrast with the poor results of the completed Efficacy and Safety of Rituximab in Patients with Severe SLE (EXPLORER) and Efficacy and Safety of Rituximab in Subjects with class III or IV Lupus Nephritis (LUNAR) randomized controlled trials. In contrast to EXPLORER and LUNAR results, controlled trials for belimumab (a fully humanized monoclonal antibody against B lymphocyte stimulator) showed positive results and subsequently, belimumab was the first drug approved for the treatment of SLE patients. This has paved the way for the development of further biological agents, potentially revolutionizing the treatment of SLE. In this study, the potential benefits of novel biological agents are explored, obstacles to the development of a treatment target in SLE are identified, and possible strategies to achieve this goal are discussed.

The efficacy of novel B cell biologics as the future of SLE treatment: a review.

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease with wide ranging multi-systemic effects. Current understanding centralises B cells in SLE pathogenesis with clinical features resulting from autoantibody formation, immune complex deposition, antigen presentation and cytokine activation. Existing standard of care therapies generates adverse side effects; secondary to corticosteroid use and untargeted immunosuppression. The inability to uphold remission and abolish the disease process, in addition to the increasing numbers of patients seen with refractory disease with these therapies, has provoked the development of novel B cell biologics targeting specific pathogenic pathways fundamental to the SLE disease process. Current evidence highlighting the efficacy of Rituximab, Ocrelizumab and Epratuzumab in inducing B cell depletion and achieving disease amelioration through specific B cell surface receptor antagonism is discussed. We review the efficacy of Atacicept, Briobacept and Belimumab in antagonising B lymphocyte stimulator (BLyS) and A proliferation inducing ligand (APRIL), two stimulatory cytokines crucial to B cell survival, growth and function. Two large multicentre randomised controlled trials, BLISS-52 and BLISS-76, have led to FDA approval of Belimumab. Following this breakthrough, other anti-BLyS therapies, Blisibimod and Tabalumab, are currently under Phase III evaluation. Similarly, murine models and Phase I/II trials have demonstrated significant efficacy of Rituximab, Epratuzumab, Briobacept and Atacicept as potential future therapies and we now eagerly await results from Phase III trials. Future research must compare the efficacy of different biologics amongst different patient subpopulations and SLE manifestations, in order to develop clinically and cost effective therapies.