Recent Developments in the Treatment of Lupus Disease

Ioana Moldovan, Emmanuel Katsaros
European Musculoskeletal Review, 2012;7(1):18-21
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Abstract

New advances in the pathogenesis of systemic lupus erythematosus (SLE) and the recent US Food and Drug Administration approval of belimumab, a B-cell therapy, mark a new era in the treatment of SLE. Other B-cell targeted therapies, such as rituximab and epratuzumab, are promising candidates that encourage further research into B-cell treatments. Interferon-alpha seems to play an important role in SLE. A recent trial of sifalimumab, an anti-interferon-α monoclonal antibody, demonstrated improvements in clinical outcomes in patients with cutaneous disease. Other trials of biologics, such as tocilizumab and abatacept, possibly warrant further clinical studies. Meanwhile, the role of mycophenolate mofetil in induction and maintenance therapy for lupus nephritis has been better defined. This article provides an update on the therapies for SLE.
Keywords
Lupus, therapies, B cells, biologics, immunosuppressives
Disclosure Ioana Moldovan is conducting clinical trials with Johnson & Johnson Pharmaceuticals, UCB Pharma and Genentech and has served as a consultant for Abbott. Emmanuel Katsaros is conducting clinical trials with MedImmune and received a grant from Forest Pharmaceuticals.
Received: December 01, 2011 Accepted January 26, 2012
Correspondence: Ioana Moldovan, 11234 Anderson Street, Room 1521, Loma Linda, CA 92354, US. E: ioanamold@yahoo.com

Systemic lupus erythematosus (SLE) is the prototypical autoimmune disease, characterised by production of antibodies against various nuclear antigens and affecting a multitude of organ systems. Given the complexity of the disease, clinicians have encountered various challenges in finding new therapies for SLE, including good outcome measures in clinical trials. For many years, the only Food and Drug Administration (FDA)-approved therapies for lupus in the US were prednisone, hydroxychloroquine and aspirin. However, the encouraging results of recent clinical trials, leading to the approval of belimumab in SLE, as well as the new advances in understanding the disease pathogenesis, are grounds to say that we are living in an exciting era for lupus therapies. The goal of our article is to provide an overview of the latest advances in the treatment of lupus.

B-cell Targeted Therapies

The presence of autoantibodies against various nuclear antigens is a major characteristic of SLE. Since B cells play a central role in the immune system production of antibodies, they are an attractive target for therapies in lupus. In past years, multiple case reports and open-label trials have suggested a benefit in selectively targeting B cells in SLE refractory to conventional therapies. The successful approval of belimumab, an anti-B-lymphocyte stimulator (BLyS) antibody, by the FDA in March 2011, as the first new therapy for lupus in over 50 years, strongly supports the importance of researching B-cell targeted therapies in SLE. Two different mechanisms of modulating B-cell activity have been studied: peripheral depletion or modulation of B cells and interfering with B-cell survival factors such as B-lymphocyte activating factor (BAFF) and a proliferation-inducing ligand (APRIL).1 Depletion is achieved through monoclonal antibodies directed against surface markers present at various stages of B-cell development. Modulation of BAFF can be achieved through monoclonal antibodies directed against BAFF itself or the BAFF receptors on B cells.

Rituximab

Rituximab (RTX) is a chimeric monoclonal antibody against CD20, present since the early stages of B-cell development and on mature B cells, but not on plasma cells. Numerous case reports and series, as well as a few open-label studies, have described improvement in both renal and non-renal SLE in patients treated with RTX.2,3 Recently, two large randomised double-blind placebo-controlled clinical trials were designed to assess the efficacy and safety of RTX in SLE.

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