Tocilizumab: The evidence for its place in the treatment of juvenile idiopathic arthritis
Juvenile idiopathic arthritis (JIA) is one of the most common chronic diseases with childhood onset. It comprises different subtypes of which the systemic onset subtype is often resistant to treatment. With the advent of biological treatment with tumor necrosis factor-alpha (TNFalpha)-inhibitors, the clinical outcome of JIA has improved considerably, but only for subtypes other than systemic JIA. Substantial evidence shows that the proinflammatory cytokine interleukin-6 (IL-6) plays a pivotal role in systemic JIA. The blockage of IL-6 action by tocilizumab, a humanized anti-IL-6-receptor monoclonal antibody, could therefore be an effective treatment of systemic JIA. The purpose of this article was to review the clinical trials of tocilizumab and to discuss its place in the treatment of JIA with the focus on the systemic onset of disease. Two phase II studies and one phase III clinical trial of tocilizumab demonstrating the clinical efficacy and safety in systemic onset JIA have been published. Within those studies, sustained and high response rates of clinical improvement have been achieved with American College of Rheumatology Pediatric criteria (ACRPed) 30, 50, and 70 observed in 98%, 94%, and 90% of patients, respectively, after 48 weeks. One study regarding the clinical efficacy of tocilizumab for the treatment of oligo- and polyarticular JIA has been presented only as a conference abstract. The very promising results seen so far in patients with severe systemic JIA and acceptable tolerability gives tocilizumab a central role in the future therapy in controlling this disease. No other biological therapy has achieved similar high response rates when treating with tocilizumab 8 mg/kg every two weeks to patients with systemic onset JIA, but direct comparison of the efficacy of different biological agents are not yet available.