AMSTERDAM — In the first double-blind study evaluating tocilizumab in refractory systemic juvenile idiopathic arthritis, rapid and substantial improvements were seen, suggesting that interleukin-6 blockade is one of the most promising approaches for this condition, Dr. Shumpei Yokota said at the annual European Congress of Rheumatology.
A group of 56 patients with systemic juvenile idiopathic arthritis (JIA) diagnosed according to the criteria of the International League of Associations for Rheumatology were included in the multicenter Japanese study. A total of 62.5% (35) of the patients were female. Their mean age was 8.3 years, and mean disease duration was 4.5 years.
Interleukin (IL)-6 levels were high at baseline, at a mean level of 37.2 pg/mL.
Because this was a pediatric study, there was an initial 6-week lead-in period during which all patients received the active treatment of 8 mg/kg tocilizumab every other week. At the end of this phase, those who responded were randomized to active treatment on the same schedule or placebo for up to 12 weeks.
For patients receiving placebo who flared, the drug was reinstituted as soon as possible said Dr. Yokota of the department of pediatrics, Yokohama City (Japan) University.
At the end of the 6-week open phase of the trial, the JIA core set of responses among the 56 patients were as follows: 51 achieved 30% improvement, 48 achieved 50% improvement, and 38 achieved 70% improvement. Consistent improvements were seen in each core set variable, Dr. Yokota said.
Six patients withdrew during the lead-in phase of the study, and six others were not randomized because their C-reactive protein levels remained high. An additional patient was not considered evaluable because of inadvertent unmasking of the code. During the 12-week double-blind phase, 19 of 23 (82.6%) patients receiving placebo had a flare and were withdrawn, compared with 4 of 20 (20.0%) of those receiving the IL-6 blocker.
In other words, flare was prevented in 80% of the tocilizumab group and in only 17.4% of those in the placebo group, Dr. Yokota said. In addition, JIA-70 responses were seen in 85% of the tocilizumab group, compared with 35% of the placebo group.
One patient in each group withdrew because of adverse events. One patient experienced anaphylactic shock following the second infusion of tocilizumab, and one had a gastrointestinal hemorrhage, probably relating to long-term use of systemic corticosteroids, the investigator noted. The drug was generally well tolerated for periods of up to 18 weeks. Nonetheless, patients undergoing treatment with tocilizumab should be closely monitored, Dr. Yokota said.