Targeting Interleukin-6 in Rheumatoid Arthritis

Md Yuzaiful Md Yusof, Paul Emery

Interleukin (IL)-6 is a potent pro-inflammatory agent that plays a crucial role in the pathogenesis of systemic inflammatory disease. Targeting this pathway in rheumatoid arthritis (RA) seems an attractive option as IL-6 is important for both joint destruction and systemic manifestations. Currently, tocilizumab, which binds the IL-6 receptor, is licensed for treatment in active, moderate to severe disease in RA and systemic juvenile idiopathic arthritis (JIA). Several other promising IL-6 blocking agents as well as a subcutaneous form of tocilizumab are currently undergoing phase III clinical trials. The aim of this article is to provide an up-to-date analysis of clinical efficacy and tolerability data concerning the use of IL-6 inhibitors. Data from clinical trials demonstrated that clinical efficacy for tocilizumab, which included improvement in physical function and halting radiographic progression, were comparable to other biologics licensed for use in RA. Patients who should gain most are RA patients with systemic features such as high inflammatory markers and anaemia. Perhaps, the strongest selling point lies in its effectiveness as a monotherapy. This is particularly useful in those who are not tolerating combination treatment with methotrexate. Tocilizumab is one of a few biologics that have been shown to be superior to methotrexate in head-to-head studies. The safety profile of tocilizumab also is comparable to other currently available biologics. There is a small but significant increase in adverse events including infections in patients treated with tocilizumab compared to placebo, particularly in patients who are elderly and those with multiple comorbidities. Elevated lipid profiles are frequent but have not been associated with major cardiovascular events. IL-6 blockade is a major advancement in the treatment of RA as it targets a unique molecule. Over the next few years, evidence will be available on the long-term cardiovascular safety and efficacy of subcutaneous IL-6 blocking agents.