• Arthritis Clinical Trials

Treatment with tocilizumab, a humanized monoclonal antibody that interrupts interleukin-6-mediated signaling, results in meaningful improvement of polyarticular-course juvenile idiopathic arthritis (pcJIA) following methotrexate failure, with treatment responses maintained to at least 40 weeks, said Hermine I. Brunner, MD, MSc, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

The finding comes from A Study of Tocilizumab in Patients with Active Polyarticular-Course Juvenile Idiopathic Arthritis [CHERISH; NCT00988221], a 3-part trial in which patients aged 2 to 17 years with pcJIA who had at least 5 joints with active arthritis were randomized to treatment with tocilizumab 8 mg/kg or 10 mg/kg, depending on body weight, or placebo after an open-label run-in. To be eligible, patients had to have an inadequate response to or an inability to tolerate methotrexate and had to be on a maximum stable dose of oral corticosteroids (10 mg/day or 0.2 mg/kg/day—whichever was lower).

In Part 1 of the study, 188 patients received intravenous infusion of tocilizumab (8 mg/kg for patients ≤30 kg, 8 mg/kg or 10 mg/kg for patients <30 kg) in an open-label fashion for 16 weeks. In Part 2, 166 patients who had an adequate response in Part 1 were randomized to receive either tocilizumab at the same dosage as in Part 1 or placebo, every 4 weeks for up to 24 weeks. In Part 3, patients will receive tocilizumab at the same dosage as in Part 1, every 4 weeks for up to another 64 weeks. Standard-of-care therapy was continued throughout the study. Data from Parts 1 and 2 were presented by Dr. Brunner.

The primary efficacy endpoint was the proportion of patients with JIA American College of Rheumatology 30 (ACR30) flares on tocilizumab versus placebo in the 160 patients who completed Part 2 (Weeks 16 to 40). Significantly fewer patients randomized to tocilizumab had a JIA ACR30 flare compared with those randomized to placebo: 26% versus 48%, respectively. The adjusted difference in the mean risk of flares between groups was −0.21 (95% CI, −0.35 to −0.08; p=0.0024).

The percentage of patients who demonstrated improvements in JIA ACR30/50/70/90 responses at Week 16 was lower among the patients randomized to 8 mg/kg tocilizumab who weighed <30 kg compared with the other 2 tocilizumab treatment groups.

At Week 40, 74% of patients assigned to tocilizumab maintained a JIA ACR30 response, 73% maintained a JIA ACR50 response, 65% maintained a JIA ACR70 response, and 40% maintained a JIA ACR90 response.

Infections and infestations were the most common adverse event in patients on active treatment, occurring at a rate of 163.7 per 100 patient-years. There were no deaths during the study.

• © 2012 MD Conference Express®