Fabrizio De Benedetti, MD, PhD, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy, presented efficacy and safety results from A Randomized, Placebo-Controlled Study to Evaluate the Effect of Tocilizumab (TCZ) on Disease Response in Patients With Active Systemic Juvenile Idiopathic Arthritis (sJIA), With an Open-Label Extension to Examine the Long-Term Use of Tocilizumab [TENDER; NCT00642460].

In the TENDER trial, 112 patients aged 2 to 17 years with active, refractory sJIA (≥ 6 months; inadequate response to previous anti-inflammatory drugs [NSAIDs] and oral corticosteroids [oral CS]) were randomly assigned 2:1 to TCZ (n=75; 8 mg/kg if body weight ≥30 kg; 12 mg/kg if body weight <30 kg) or placebo (n=37) every 2 weeks for 12 weeks in Part 1. All patients received open-label TCZ in Part 2 (to 104 weeks). Stable doses of NSAIDs and methotrexate were continued, with oral CS tapering permitted according to predefined criteria.

The data were cut for each ongoing patient at the Week 104 infusion, based on date of randomization, with baseline in the longer-term extension considered the first dose of TCZ.

At the data cutoff (May 31, 2011), 61 patients had received at least 104 weeks of treatment; 32 of the ongoing patients had not yet reached 104 weeks of TCZ treatment; and 20 withdrew, including 1 at Week 104 (safety, 9; insufficient therapeutic response, 5; other nonsafety issues, 6).

Main baseline characteristics included mean disease duration of 5.2 years, mean active joint count of 19.8, and presence of fever (temperature ≥37.5°C in the past 7 days) in 43% of patients. High proportions of those who were treated with TCZ achieved JIA ACR 70/90 responses and maintained these responses over time (Table 1). Mean joint counts decreased over time. By Week 104, 55% of patients had 0 active joints and 31% had inactive disease status. In those patients who were taking oral CS at baseline, 60% was able to discontinue the drugs by Week 104 (Table 1); mean oral CS dose decreased from 0.30 mg/kg/day at baseline to 0.04 mg/kg/day at Week 104.

Forty-seven serious adverse events (SAEs) occurred in 35 patients (Table 2); 15 SAEs were considered by the investigator to be related (remotely, possibly, or probably) to TCZ. Twenty-two serious infection AEs were reported in 20 patients; 8 were reported as being related to TCZ (gastroenteritis, otitis media, pharyngotonsillitis, septic arthritis, streptococcal sepsis, tonsillitis, upper respiratory infection, varicella), and all but 1 resolved (patient death). At the data cutoff, 3 patients died (1, suspected tension pneumothorax; 1, road traffic accident [both reported as unrelated]; 1 suspected streptococcal sepsis [possibly treatment-related]).

Excessive interleukin-6 (IL-6) production has been implicated in the pathogenesis of sJIA. TENDER study data show that treatment up to 104 weeks with the IL-6 inhibitor TCZ is highly effective, with a favorable risk-benefit ratio in patients with severe, refractory, persistent sJIA.