New directions in the treatment of systemic lupus erythematosus

ABSTRACT

Objective: The aim of this review is to provide an up-to-date overview of treatment approaches for systemic lupus erythematosus (SLE), highlighting the multiplicity and heterogeneity of clinical symptoms that underlie therapeutic decisions. Discussion will focus on the spectrum of currently available therapies, their mechanisms and associated side-effects. Finally, recent developments with biologic treatments including rituximab, epratuzumab, tumor necrosis factor (TNF) inhibitors, and belimumab, will be discussed.

Research design and methods: A MEDLINE literature search for ‘systemic lupus erythematosus’ and ‘damage’ and ‘treatment’ was undertaken for 1996–2008. Secondary citations were obtained from selected manuscripts. Individual case studies were excluded.

Findings: SLE is an autoimmune disease involving multiple organ systems, a clinical pattern of flares and remissions, and the presence of anti-nuclear autoantibodies. Whereas early symptoms most frequently involve the skin and joints, disease morbidity and mortality are usually associated with cardiovascular events and damage to major organs, particularly the kidneys. Many of the current therapeutic options are considered to be inadequate because of toxicities, accrual of organ damage, and insufficient control of the underlying disease pathology.

Improved understanding of SLE pathogenesis and immunology has led to the identification of new treatment targets. Current interest is mainly focused on the targeted immunosuppressive actions provided by biologic therapy. Although the potential long-term beneficial or harmful effects of the new molecular treatments are unclear, their precise molecular targeting may reveal key relationships within the immune system and advance the cause of individualized molecular medicine.

Conclusions: Biologic compounds that target specific immunologic mechanisms offer a new paradigm in the treatment of SLE, one that may, at best, reverse the course of the disease and, at the very least, might provide some new alternatives to reduce symptoms and limit tissue damage without undue contribution to overall morbidity and mortality.

Key words: :

• Biologic therapy
• CD20
• Etiology
• Pathogenesis
• Systemic lupus erythematosus

Transparency

Declaration of funding

Funding for medical writing assistance was provided by Genentech, Inc.

Declaration of financial/other relationships

K.K. and J.T.M. have disclosed that they have no relevant financial relationships.

All peer reviewers receive honoraria from CMRO for their review work. Peer Reviewer 1 and Peer Reviewer 2 have disclosed they have no relevant financial relationships.

Acknowledgments

Medical writing assistance for this manuscript was furnished by Matthew Pugh of Adelphi Communications, with financial support provided by Genentech.