Targeting IL-6 for the treatment of rheumatoid arthritis: Phase II investigational drugs

Abstract

Introduction: IL-6 is a key cytokine in the pathogenesis of rheumatoid arthritis (RA). The clinical efficacy of tocilizumab (TCZ), a humanized anti-IL6-receptor mAb, confirmed the value of IL-6 blockade in this disease. A number of new anti-IL-6 biologics are currently in Phase I – III of clinical development for RA.

Areas covered: This article reviews the available results from Phase II trials of investigational anti-IL-6 agents in RA. The authors discuss the potential relevance of alternative IL-6-blocking agents, with regard to their specific molecular targets in IL-6 signaling pathways and to the main open questions in the clinical research agenda for anti-IL-6 biologics.

Expert opinion: The results of Phase II trials of new anti-IL-6 biologics show promising results in terms of efficacy. The most frequently reported adverse events were not unexpected based on previous experience with TCZ. Further evidence is needed to appraise whether the difference in molecular structure or in the specific target of new anti-IL-6 biologics might result in added therapeutic value over TCZ. New data from Phase III trials that provides a head-to-head comparison against TCZ and anti-TNF agents with or without methotrexate background treatment are expected in the future.

Keywords::

• biological therapies
• clinical trials
• interleukin-6
• rheumatoid arthritis

Acknowledgment

A Thiolat and E Minichiello contributed equally to this work.

Declaration of interest

All of the authors are affiliated with Inserm UMR1125 which has received unrestricted grants from Bristol-Myers Squibb, Chugai, Merck Sharp & Dohme, Pfizer, Roche, UCB Pharmaceuticals. MC Boissier and L Semerano have received speaker fees from Roche. MC Boissier is member of the scientific board of Neovacs (France). 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.

Notes

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