Tocilizumab: molecular intervention therapy in children with systemic juvenile idiopathic arthritis

Abstract

Systemic juvenile idiopathic arthritis (JIA) is a subtype of chronic childhood arthritis of unknown etiology, manifested by long-lasting systemic inflammation and complicated by joint destruction, functional disability and growth impairment. Macrophage activation syndrome is the most devastating complication, which is associated with serious morbidity. IL-6 has been hypothesized to be a pathogenic factor of this disease. The anti-IL-6 receptor monoclonal antibody, tocilizumab, was developed, and we investigated the safety and efficacy of tocilizumab in children with this disorder. The Phase II trial revealed that high-grade fever abruptly subsided and that inflammatory markers were also normalized. The dose of tocilizumab for systemic JIA was revealed to be 8 mg/kg at 2-week intervals. The Phase III trial, a placebo-controlled, double-blind study, indicated that patients in the tocilizumab group had sustained clinical measures of effectiveness and wellbeing, whereas most of those in the placebo group needed rescue treatment. The most common adverse events were symptoms of mild infections and transient increases of alanine aminotransferase. Serious adverse events were anaphylactoid reaction and gastrointestinal hemorrhage. Clinical and laboratory improvement in fever, sickness behavior, C-reactive protein gene expression and chronic inflammatory anemia in children with systemic JIA treated with tocilizumab indicated the possible roles played by IL-6 in this inflammatory disease. Thus, tocilizumab is generally safe and well tolerated. It might be a suitable treatment in the control of this disorder, which has so far been difficult to manage.

Keywords::

• biologic response modifier
• C-reactive protein
• IL-6
• IL-6 receptor
• systemic juvenile idiopathic arthritis
• tocilizumab

Financial & competing interests disclosure

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.