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

Abstract

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.

Keywords:

• B cells
• biologic therapy
• immunosuppression
• lupus
• T cells

Financial & competing interests disclosure

MA Khamashta has received a grant from Bayer. He has also received sponsorship from and served on Advisory Boards for GSK, AstraZeneca and UCB. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Belimumab is the first drug licensed for use in systemic lupus erythematosus (SLE) in more than 50 years.

• Open-label and uncontrolled studies supported the use of B cell-depleting agents in refractory/life-threatening SLE, despite the poor outcome of two randomized controlled trials.

• Careful evaluation of the risk/benefit profiles of biologic agents in SLE is essential.

• Understanding the B cell signaling pathways along with their lupus-relevant molecular aberrations identified may allow for more targeted and rational interventions.

Notes