GLASGOW -- The efficacy of tocilizumab (Actemra) for systemic juvenile idiopathic arthritis (JIA) has been maintained for 5 years, a three-part phase III study has shown.
Among a cohort of 92 children with systemic JIA who completed the first 2 years of a trial known as TENDER, the American College of Rheumatology (ACR) 30% improvement response was met by all patients at that time point, while ACR 50, 70, and 90 responses were seen in 100%, 94.4%, and 76.4%, respectively, according to Eileen Baildam, MD, of Alder Hey Children's Hospital in Liverpool.
"The 2-year results demonstrated that the IL-6 receptor inhibitor tocilizumab was effective -- extremely effective, actually -- in the treatment of severe systemic JIA, which really is one of the worst diseases we treat in pediatric rheumatology.
"It's easy to forget how severe it was before we had treatments like this that have altered the disease course," she added.
At 5 years, among the 29 patients who continued on the standard regimen of tocilizumab, ACR 70 and 90 responses were still high, at 83% and 60%, respectively, she reported at the annual meeting of the British Society for Rheumatology here.
TENDER was a three-part study that initially enrolled 112 patients with severe, persistent systemic JIA. In part 1, they were randomized to receive placebo or tocilizumab, 8 mg/kg every 2 weeks for those weighing 30 kg or more, and 12 mg/kg every 2 weeks for those weighing less than 30 kg. At the end of that 12-week phase, in part 2, all patients received open-label tocilizumab with weight-based dosing through week 104.
In part 3, which continued through week 260, those patients who achieved clinically inactive disease had the option of an alternative dosing schedule, receiving the medication but at 3- to 4-week intervals and then possibly tapering all their medications.
Among the 89 patients who entered part 3 of the trial, 50 continued on the 2-week interval dosing, while 39 had been in full clinical remission for at least 12 weeks and opted for the alternative schedule.
Of the 39 who went on the alternative prolonged dosing schedule, 32 completed the study. But those patients were not included in this part 3 analysis, so the efficacy reports for the last part of the study "most certainly represent an underestimation of the efficacy of the treatment," Baildam said.
Among the children who entered part 3, the mean age was 9.5 and disease duration was 5 years. The patients had severe disease, with 19 to 20 active joints and erythrocyte sedimentation rates averaging 57 mm/h, and 40% reported fevers during the previous week.
Among patients who continued on the 2-week dosing, 32 completed the study. Of that group, 27% had clinically inactive disease at 5 years.
Among the 66 patients who completed the study, 31 had been taking oral steroids and 34 had been on methotrexate. A total of 17 of the patients were able to stop the steroids and six stopped methotrexate. In addition to the patients who no longer were taking steroids, another 40% had decreased the dose, and the average methotrexate dose had decreased from 10.1 to 5.1/m2/week.
The most common severe adverse events were gastroenteritis and varicella.
Serious adverse events occurred at rates of 23.3/100 patient-years at year 2 and at rates of 21.9/100 patient years at year 5, while serious infections were seen at rates of 10.9/100 and 10.1/100 patient years, respectively.
By year 5, there had been four deaths -- one from sepsis, which was considered possibly treatment-related.
There also had been three cases of macrophage activation syndrome, "as one would expect, in this severe group of patients," she said.
Neutropenia and liver function abnormalities occurred, with one-quarter of patients having grade 3 neutrophil reductions, and 10% to 11% of patients had small increases in their alanine aminotransferase levels.
"This was a landmark study of systemic JIA and biologics -- the first one to be licensed for use in systemic JIA. It's a really important study," she concluded.
Baildam reported financial relationships with Roche and Chugai.
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