WASHINGTON – Tocilizumab led to a rapid clinical improvement in polyarticular juvenile idiopathic arthritis that was sustained at 40 weeks.
Moreover, the interleukin-6 (IL-6) receptor inhibitor was relatively safe in this population, with a profile similar to that of other populations treated with tocilizumab, for instance systemic juvenile idiopathic arthritis (JIA) patients. The Food and Drug Administration approved tocilizumab for use in children with systemic JIA in 2011 and a year earlier for use in adults with moderately to severely active RA.
That was the finding from the phase III CHERISH trial presented here by Dr. Hermine Brunner on Nov. 12 at the annual meeting of the American College of Rheumatology.
Dr. Brunner of the Cincinnati Children’s Hospital Medical Center and her colleagues looked at 188 patients aged 2-17 years with active polyarticular JIA.
For the first 16 weeks, all patients received open-label tocilizumab injections every 4 weeks according to body weight, with patients who were at least 30 kg receiving 8 mg/kg (n = 119) and patients less than 30 kg randomized to receive either 8 mg/kg (n = 34) or 10 mg/kg (n = 35).
The primary end point was achievement of a JIA ACR30 response, indicating a 30% improvement from baseline in at least three of six criteria without a worsening of greater than 30% in one remaining measure, including active joint count, limitation of motion joint count, physician global assessment, patient/parent global assessment, Childhood Health Assessment Questionnaire, and acute-phase reactant level (either erythrocyte sedimentation rate or C-reactive protein).
By the end of the 16 weeks, 93% of the heavier patients (who received 8 mg/kg) had achieved a JIA ACR30 response; 89% of the lighter patients taking 10 mg/kg achieved that level, and 77% of the lighter 8 mg/kg patients.
Moreover, 25% of patients in the heavier group achieved a JIA ACR90 at the end of 16 weeks, as did 31% of the 10 mg/kg lower-weight group and 24% of the 8 mg/kg lower-weight group, reported Dr. Brunner.
At week 16, patients who achieved a JIA-ACR30 response moved on to the second part of the study, a 24-week, double-blind randomization to either placebo or to continue tocilizumab at the same dose.
By week 40, only 54% of placebo patients were at JIA ACR30, compared with 74% of the treatment group (P = .0084).
Moreover, "nearly half" (45%) of the treatment group patients maintained a JIA ACR90 at the end of part two, said Dr. Brunner.
Looking at adverse events, the most commonly reported were infections and infestations, with 164 infections/100-person-years, followed by gastrointestinal disorders, with 71 incidences/100 person-years.
Neutropenia occurred in 3.7% of patients, though Dr. Brunner stated it was "not clearly associated" with any infectious event.
LDL cholesterol levels were elevated to 110 mg/dL or greater in 11.4% of patients, but there were no grade IV lab abnormalities reported, nor were there any deaths in the study.
"The safety profile is quite comparable to what has been seen and reported in other studies" of patients taking tocilizumab, said Dr. Brunner.
However, she added that longer term safety data are forthcoming from this ongoing trial.
Several investigators disclosed multiple relationships to pharmaceutical companies including the maker of tocilizumab, Roche Pharmaceuticals, who also sponsored the study.