Juvenile RA/Pediatric Rheumatology
Sangeeta Sule, M.D.
Abstract 722: Rapid Improvement of Signs and Symptoms Associated with Systemic Juvenile Idiopathic Arthritis (sJIA) by Interleukin-6 (IL-6) Blockade - Results from a Tocilizumab sJIA Phase III Clinical Trial
Authors: Shumpei Yokota1, Tomoyuki Imagawa1, Masaaki Mori1, Syuji Takei2, Yoshifumi Kawano2, Naomi Iwata3, Minako Tomiita4, Mari Miyoshi5, Yuko Aihara6, Takuji Murata7, Daiki Abukawa8, Norihiro Nishimoto9, Tadamitsu Kishimoto9. 1Departmet of Pediatrics, Yokohama City University School of medicine, Yokohama, Japan; 2Kagoshima University School of Medicine, Kagoshima, Japan; 3Aichi Children's Health and Medical Center, Obu, Japan; 4Chiba University, Chiba, Japan; 5Kobe Children's Hospital, Kobe, Japan; 6Yokohama City University Medical Center, Yokohama, Japan; 7Osaka Medical College, Takatsuki, Japan; 8Miyagi Children's Hospital, Sendai, Japan; 9Osaka University, Osaka, Japan
Purpose: In previous studies, IL-6 has been shown to be important in the pathogenesis of sJIA and IL-6 blockade with tocilizumab is effective in controlling the disease. The authors report on the results of a Phase III double-blind, randomized, placebo-controlled study with tocilizumab in sJIA.
Methods: Patients with sJIA diagnosed according to ILAR criteria with a CRP >1.5 mg/dl and inadequate response to oral steroids were enrolled. Patients initially received 8 mg/kg of tocilizumab intravenously every other week for 6 weeks. After this, patients who met the responder criteria (at least JIA30 response and CRP<0.5 mg/dl) entered the double-blind phase. Patients were randomized to receive either 8 mg/kg of tocilizumab or placebo every other week for 12 weeks. If patients failed to maintain the responder criteria during the double-blind phase, they were withdrawn from the study.
Results: 56 patients entered the open-label period. At baseline, mean age was 8.3 years, mean duration of sJIA was 4.5 years and mean steroid dose was 0.51 mg/kg/day. 91.1% met JIA30 response, 85.7% met JIA50, and 67.9% met JIA70 response in the open-label period. 43 patients met the responder criteria and agreed to participate in the double-blind phase. 20 were randomized to tocilizumab and 23 to placebo. 4 of 20 (20%) were withdrawn from the study compared to 19 of 23 (82.6%) of the placebo group (p<0.001). Only one patient in each group was withdrawn due to an AE.
Conclusions: Treatment with tocilizumab at 8 mg/kg intravenously every other week was well tolerated and resulted in rapid improvement in children with sJIA.
Editorial Comments: This is an encouraging study of an IL-6 inhibitor in the treatment of systemic onset JIA. The responses to treatment were impressive with 67.9% meeting JIA70 response in the open-label phase. From the abstract, it is not clear if patients continued on other medications for JIA or if there was a differential response in those continued on other medications (such as methotrexate or oral prednisone). Also, adult RA patients treated with tocilizumab had reported increases in cholesterol and LFTs. There is no mention of cholesterol levels or LFTs in this study. We eagerly await the manuscript for further information.