PReS-FINAL-2166: Long-term safety and effectiveness of anti-interleukin-6 receptor monoclonal antibody, tocilizumab, in patients with systemic juvenile idiopathic arthritis in Japan

Introduction

Systemic-onset juvenile idiopathic arthritis (sjia) is a form of childhood chronic arthritis of unknown etiology with systemic manifestations such as remittent fever and erythematous rash, lymph adenopathy, hepatosplenomegaly, and/or serositis. Tocilizumab (TCZ) is a humanized anti-IL-6 receptor monoclonal antibody that has been approved for the treatment of patients with sjia. Results of the lead-in phase; the placebo-controlled, double-blind phase; and the first 48 weeks of an open-label extension have been already published.

Objectives

To assess the long-term safety and effecacy of tocilizumab in sjia.

Methods

The long-term extension phase of two pivotal studies (Phase II study with 11 patients and Phase III study with 56 patients) in patients with active sjia was analyzed. Patients received open-label tocilizumab (8 mg/kg, every 2 wks). Assessments included ACR Pedi 30/50/70 responses, adverse events (aes), laboratory parameters, oral corticosteroid dose reductions, and growth rates (the latter compared with national standards).

Results

In total, 67 patients were enrolled. Median duration of exposure was 3.4 years. Event rates of aes and serious aes were 803.7/100 patient-years (pys) and 34.7/100 pys, respectively. The most common serious aes were infections (13.2/100 pys). Mean liver enzyme levels basically remained stable over the course of the study. Grade 3 elevations in alanine and aspartate aminotransferase levels occurred in six (9.0%) and four (6.0%) patients, respectively. Mean total cholesterol levels also were not increased during the study, although eight (11.9%) patients experienced grade 2 elevations in total cholesterol. ACR Pedi response rates were maintained throughout the study: at week 168, ACR Pedi 30/50/70 response rates were 80.3%, 80.3%, and 75.4%, respectively. Tocilizumab completely blocked the production of C-reactive protein and serum amyloid A in sjia. Twenty-two (32.8%) patients discontinued corticosteroids during tocilizumab therapy. Of 52 patients completing the week 168 visit, 40 (76.9%) reduced corticosteroid doses by at least 50%, and 33 (63.5%) patients by 70%. Significant improvement was seen in changes in height velocity (HV) SDS from 1 year prior to 1 year after baseline. HV-SDS continued to improve through the studies of toiclizumab treatment.

Conclusion

Tocilizumab had an acceptable safety profile, was associated with sustained clinical improvement, and reduced systemic corticosteroid dose in children with sjia. Also, catch-up growth was observed in patients under the treatment with tocilizumab.

Disclosure of interest

S.Yokota Consultant for: an advisory board from Chugai Pharmaceuticals; joint patent holder for tocilizumab for treatment of systemic juvenile idiopathic arthritis., T. Nozawa: None declared., T. Kanetaka: None declared., K. Yamazaki: None declared., T. Sato: None declared., N. Sakurai: None declared., M. Kikuchi: None declared.