Sirukumab : a novel therapy for lupus nephritis?

Expert Opin Investig Drugs. 2014 Oct;23(10):1449-55. doi: 10.1517/13543784.2014.950837. Epub 2014 Sep 5.

Abstract

Introduction: Lupus nephritis (LN) is a significant contributor to morbidity and mortality in systemic lupus erythematosus (SLE). Current therapies for LN are limited by significant toxicities and high rates of relapse. A clear and present need exists for the development of effective, targeted and well-tolerated treatment strategies for LN.

Areas covered: In this review, the authors examine sirukumab , a monoclonal antibody with high affinity for IL-6, as a novel agent with potential for use in the treatment of SLE and LN in particular. Their review focuses on the available data on the use of sirukumab in patients. Data from Phase I trials would indicate that sirukumab is generally safe and well tolerated. This review also reports the dose-dependent decreases in absolute neutrophil count and platelet count. To date, data for sirukumab in the treatment of SLE and LN are limited, but preliminary data suggest improvement in patient-reported outcomes, and transient improvement in clinical parameters.

Expert opinion: Considering scientific literature regarding IL-6 and the IL-6 receptor antagonist tocilizumab, one could extrapolate that sirukumab has the potential to treat LN by acting acutely and locally at the site of renal injury, as well as chronically by modulating the abnormal B- and T-cell subsets observed in SLE patients. However, the clinical efficacy of sirukumab in SLE and LN, in particular, remains to be seen in Phase III trials, and efficacy data in both the induction and maintenance phases of LN treatment will be of interest.

Keywords: IL-6; biologic; human; lupus nephritis; monoclonal antibody; sirukumab; systemic lupus erythematosus; therapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • B-Lymphocyte Subsets / pathology
  • Humans
  • Interleukin-6 / immunology*
  • Lupus Erythematosus, Systemic / drug therapy
  • Lupus Erythematosus, Systemic / physiopathology
  • Lupus Nephritis / drug therapy*
  • Lupus Nephritis / physiopathology
  • T-Lymphocyte Subsets / pathology

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Interleukin-6
  • sirukumab