Elsevier

The Lancet

Volume 382, Issue 9894, 31 August–6 September 2013, Pages 809-818
The Lancet

Series
Systemic lupus erythematosus and other autoimmune rheumatic diseases: challenges to treatment

https://doi.org/10.1016/S0140-6736(13)60889-2Get rights and content

Summary

Increased understanding of the molecular mechanisms underlying the pathogenenesis of autoimmune rheumatic diseases has led to targeted biological treatments that modulate various aspects of the immune response. These new treatments, together with more judicious use of other immunosuppressive drugs, have resulted in marked improvements in morbidity and mortality. Although belimumab, an agent that inhibits B-cell survival, is the first drug to be approved by the US Food and Drug Administration for the treatment of systemic lupus erythematosus in 50 years, many other immunological targets are under investigation. We discuss the recent advances in the biological treatment of autoimmune rheumatic diseases, with a particular focus on systemic lupus erythematosus.

Introduction

The prognosis of patients with autoimmune rheumatic diseases has improved substantially. In the 1950s, the 4 year survival for patients with systemic lupus erythematosus was 50%, now 15 year survival is 85%.1 In this part of the Series on autoimmune rheumatic diseases, we briefly review the treatment of these disorders, focusing mainly on systemic lupus erythematosus, and highlight the recent advances that have been made in biological treatments.

Section snippets

Pharmacological management

The mechanisms of action and indications for the drugs used to treat autoimmune rheumatic diseases are diverse. The table summarises the commonly prescribed conventional drugs available for the treatment of systemic lupus erythematosus. The main advances in the past decade in the conventional management of systemic lupus erythematosus have included studies showing efficacy for mycophenolate as an induction agent for lupus nephritis7, 10 and the equivalent efficacy of low-dose cyclophosphamide

New biological treatments

Improved understanding of the immune response and abnormalities in apoptosis have allowed the recognition of cells and molecules that are crucial to the development of systemic lupus erythematosus and other autoimmune rheumatic diseases. Increased recognition of the multifaceted role that B cells have in the pathophysiology of systemic lupus erythematosus has led to the development of several novel treatments, notably rituximab and belimumab. The failure of some other agents targeted at

Controversies about the use of biological agents for autoimmune rheumatic diseases

By contrast with the highly successful introduction of biological drugs for the treatment of rheumatoid arthritis, the use of these drugs in systemic lupus erythematosus, Sjögren's syndrome, myositis, and vasculitis has remained more problematic. Some notable successes of clinical trials have been belimumab in systemic lupus erythematosus and rituximab in antineutrophil cytoplasmic antibody-positive vasculitis; however, several frustrating failures have also been reported including the use of

Conclusions

We are at a challenging crossroads with regards to the treatment of autoimmune rheumatic diseases. The limit of what conventional drugs can achieve has probably been reached. Improved understanding of the aetiopathogenesis of these diseases with the introduction of more targeted biological treatment is beginning to show some encouraging signs of improvement in the outlook for these patients. However, this improvement is still lagging behind what has been achieved in the past decade for

Search strategy and selection criteria

We searched PubMed for articles published in English between Jan 1, 2005, and Feb 27, 2013, and Summon Search between Jan 1, 2005, and Feb 27, 2013, with the search terms “systemic lupus erythematosus” and “lupus” in combination with the terms “management” and “biologics”. We also searched the references of articles identified by this strategy and selected those that were relevant.

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