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

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. 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. 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.