Drugs in early clinical development for Systemic Lupus Erythematosus

ABSTRACT

Introduction: While immunosuppressive therapy has positively impacted the prognosis of systemic lupus erythematosus (SLE), many patients still do not respond to traditional therapy. Thus, active SLE disease remains a significant problem. Furthermore, conventional immunosuppressive treatments for SLE are associated a high risk of side effects. These issues call for improvement in our current therapeutic armamentarium.

Areas covered: In this review, the authors highlight the recent developments in therapies for SLE, and present an overview of drugs which are in early clinical development for SLE. There are many new therapeutic approaches being developed, including those focused on B-cell targets, T-cell downregulation, co-stimulatory blockade, anti-cytokine agents, and kinase inhibition, and Toll-like receptor inhibition. They also discuss peptide therapy as a potential method to re-establish immune tolerance, and some of the challenges ahead in developing and testing novel agents for SLE.

Expert opinion: Many novel agents are currently in development for SLE, but this encouraging news is tempered by several disappointments in clinical trials and provides a timely moment to reflect on the future of therapeutic development in SLE. It seems likely that biological heterogeneity between patients is a major contributor to difficulty in drug design in SLE.

KEYWORDS:

• Systemic lupus erythematosus
• cytokine
• t cell
• b cell

Article highlights

• Despite conventional therapies for systemic lupus erythematosus (SLE), many patients have ongoing disease activity.

• Many novel agents are currently in development for SLE.

• Advances in the understanding of the immunological pathways that underlie SLE have opened new opportunities for therapeutic targets.

• Biological therapy has shown efficacy and safety, and is promising in SLE.

• Biological heterogeneity between patients likely represents a major limitation to previous clinical trials in SLE.

This box summarizes key points contained in the article.

Declaration of interest

S Appenzeller has received support through the Fundação Apoio À Pesquisa Estado São Paulo-Brasil (FAPESP 2008/02917-0 and 2009/06049-6 and 2009/15286-1) and the Conselho Nacional Pesquisa Desenvolvimento-Brasil (CNPq) (300447/2009-4 and 471343/2011-0 and 302205/2012-8, 473328/2013-5 and 304255/2015-7). TB Niewold has received support through the National Institutes of Health grants (AR060861, AR057781, AR065964, AI071651), the Rheumatology Research Foundation, the CureJM Foundation, the Mayo Clinic Foundation, and the Lupus Foundation of Minnesota. TB Niewold has also received research grants from EMD Serono and Janssen Pharmaceuticals. 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.