TENDER Trial: Tocilizumab Highly Effective for Systemic JIA

ATLANTA – Tocilizumab was highly effective for the treatment of systemic juvenile idiopathic arthritis, according to findings from the 12-week, double-blind, placebo-controlled portion of the phase III TENDER trial. The anti–interleukin-6 receptor antibody already is approved for use in the treatment of adults with rheumatoid arthritis.

Of 112 children with systemic JIA who are enrolled in the ongoing multinational trial, the 75 who were randomized to receive tocilizumab treatment were significantly more likely than the 37 who received placebo to experience JIA ACR 30 (defined as a 30% improvement in signs and symptoms of disease, according to criteria of the American College of Rheumatology) and to be free of fever at 12 weeks; 85% vs. 20% of patients in the treatment and placebo groups, respectively, achieved JIA ACR 30, according to Dr. Fabrizio De Benedetti said at the annual scientific meeting of the American College of Rheumatology.

Additionally, significantly more of the treatment group patients, compared with controls, achieved JIA ACR 50, ACR 70, and ACR 90 responses (85% vs. 11%, 71% vs. 8%, and 37% vs. 5%, respectively), said Dr. De Benedetti, who is director of the division of rheumatology at Ospedale Pediatrico Bambino Gesù in Rome.

In separate analyses, patients in the active-treatment group who had fever, anemia, or thrombocytosis at baseline were significantly more likely than controls with those conditions at baseline to have normal temperature, normal hemoglobin levels, and normal platelet counts at 12 weeks, he noted.

A post hoc analysis demonstrated that the findings of significant improvement with treatment vs. placebo persisted irrespective of baseline characteristics including active joint count and prior biologic-treatment use. For example, ACR 30 plus absence of fever was achieved by 90% of treated patients with 0-9 active joints, 82% of those with 10-29 active joints, and 80% of those with 30-71 active joints, Dr. De Benedetti said.

Study participants are children aged 2-17 years with active systemic JIA of at least 6 months’ duration and with inadequate response to previous NSAIDS and corticosteroids. They were randomly assigned to receive placebo or tocilizumab infusion every 2 weeks. Those who weighed at least 30 kg received 8 mg/kg, and those who weighed less than 30 kg received 12 mg/kg; dosing was based on models developed from prior studies.

Treatment was generally safe; four serious adverse events occurred, including urticaria and angioedema in one patient, varicella in one patient, and bacterial arthritis in one patient. All resolved without sequelae, he said.

The findings of this portion of the TENDER trial confirm those from two smaller trials of tocilizumab in children, including a Japanese phase III, placebo-controlled trial, he noted.

“Tocilizumab appears to be highly effective in the short-term treatment of systemic JIA; it improves systemic and laboratory features of the disease, and there were no differences based on baseline disease characteristics or by prior use of biologic treatment,” Dr. De Benedetti said, adding that no new tocilizumab safety signals, compared with what is known in adults, emerged in this study.

“Obviously, we are waiting for the long-term analysis from the long-term extension part of the study,” he said.

A 5-year open-label extension phase is currently underway.

The TENDER trial is sponsored by Roche, the maker of tocilizumab (Actemra). Dr. De Benedetti disclosed that he has received consulting fees or other payment from Bristol-Myers Squibb Co., Hoffmann-La Roche, and Pfizer Inc. He also has received research grants from Hoffmann-La Roche.

ATLANTA – Tocilizumab was highly effective for the treatment of systemic juvenile idiopathic arthritis, according to findings from the 12-week, double-blind, placebo-controlled portion of the phase III TENDER trial. The anti–interleukin-6 receptor antibody already is approved for use in the treatment of adults with rheumatoid arthritis.

Of 112 children with systemic JIA who are enrolled in the ongoing multinational trial, the 75 who were randomized to receive tocilizumab treatment were significantly more likely than the 37 who received placebo to experience JIA ACR 30 (defined as a 30% improvement in signs and symptoms of disease, according to criteria of the American College of Rheumatology) and to be free of fever at 12 weeks; 85% vs. 20% of patients in the treatment and placebo groups, respectively, achieved JIA ACR 30, according to Dr. Fabrizio De Benedetti said at the annual scientific meeting of the American College of Rheumatology.

Additionally, significantly more of the treatment group patients, compared with controls, achieved JIA ACR 50, ACR 70, and ACR 90 responses (85% vs. 11%, 71% vs. 8%, and 37% vs. 5%, respectively), said Dr. De Benedetti, who is director of the division of rheumatology at Ospedale Pediatrico Bambino Gesù in Rome.

In separate analyses, patients in the active-treatment group who had fever, anemia, or thrombocytosis at baseline were significantly more likely than controls with those conditions at baseline to have normal temperature, normal hemoglobin levels, and normal platelet counts at 12 weeks, he noted.

A post hoc analysis demonstrated that the findings of significant improvement with treatment vs. placebo persisted irrespective of baseline characteristics including active joint count and prior biologic-treatment use. For example, ACR 30 plus absence of fever was achieved by 90% of treated patients with 0-9 active joints, 82% of those with 10-29 active joints, and 80% of those with 30-71 active joints, Dr. De Benedetti said.

Study participants are children aged 2-17 years with active systemic JIA of at least 6 months’ duration and with inadequate response to previous NSAIDS and corticosteroids. They were randomly assigned to receive placebo or tocilizumab infusion every 2 weeks. Those who weighed at least 30 kg received 8 mg/kg, and those who weighed less than 30 kg received 12 mg/kg; dosing was based on models developed from prior studies.

Treatment was generally safe; four serious adverse events occurred, including urticaria and angioedema in one patient, varicella in one patient, and bacterial arthritis in one patient. All resolved without sequelae, he said.

The findings of this portion of the TENDER trial confirm those from two smaller trials of tocilizumab in children, including a Japanese phase III, placebo-controlled trial, he noted.

“Tocilizumab appears to be highly effective in the short-term treatment of systemic JIA; it improves systemic and laboratory features of the disease, and there were no differences based on baseline disease characteristics or by prior use of biologic treatment,” Dr. De Benedetti said, adding that no new tocilizumab safety signals, compared with what is known in adults, emerged in this study.

“Obviously, we are waiting for the long-term analysis from the long-term extension part of the study,” he said.

A 5-year open-label extension phase is currently underway.

The TENDER trial is sponsored by Roche, the maker of tocilizumab (Actemra). Dr. De Benedetti disclosed that he has received consulting fees or other payment from Bristol-Myers Squibb Co., Hoffmann-La Roche, and Pfizer Inc. He also has received research grants from Hoffmann-La Roche.

ATLANTA – Tocilizumab was highly effective for the treatment of systemic juvenile idiopathic arthritis, according to findings from the 12-week, double-blind, placebo-controlled portion of the phase III TENDER trial. The anti–interleukin-6 receptor antibody already is approved for use in the treatment of adults with rheumatoid arthritis.

Of 112 children with systemic JIA who are enrolled in the ongoing multinational trial, the 75 who were randomized to receive tocilizumab treatment were significantly more likely than the 37 who received placebo to experience JIA ACR 30 (defined as a 30% improvement in signs and symptoms of disease, according to criteria of the American College of Rheumatology) and to be free of fever at 12 weeks; 85% vs. 20% of patients in the treatment and placebo groups, respectively, achieved JIA ACR 30, according to Dr. Fabrizio De Benedetti said at the annual scientific meeting of the American College of Rheumatology.

Additionally, significantly more of the treatment group patients, compared with controls, achieved JIA ACR 50, ACR 70, and ACR 90 responses (85% vs. 11%, 71% vs. 8%, and 37% vs. 5%, respectively), said Dr. De Benedetti, who is director of the division of rheumatology at Ospedale Pediatrico Bambino Gesù in Rome.

In separate analyses, patients in the active-treatment group who had fever, anemia, or thrombocytosis at baseline were significantly more likely than controls with those conditions at baseline to have normal temperature, normal hemoglobin levels, and normal platelet counts at 12 weeks, he noted.

A post hoc analysis demonstrated that the findings of significant improvement with treatment vs. placebo persisted irrespective of baseline characteristics including active joint count and prior biologic-treatment use. For example, ACR 30 plus absence of fever was achieved by 90% of treated patients with 0-9 active joints, 82% of those with 10-29 active joints, and 80% of those with 30-71 active joints, Dr. De Benedetti said.

Study participants are children aged 2-17 years with active systemic JIA of at least 6 months’ duration and with inadequate response to previous NSAIDS and corticosteroids. They were randomly assigned to receive placebo or tocilizumab infusion every 2 weeks. Those who weighed at least 30 kg received 8 mg/kg, and those who weighed less than 30 kg received 12 mg/kg; dosing was based on models developed from prior studies.

Treatment was generally safe; four serious adverse events occurred, including urticaria and angioedema in one patient, varicella in one patient, and bacterial arthritis in one patient. All resolved without sequelae, he said.

The findings of this portion of the TENDER trial confirm those from two smaller trials of tocilizumab in children, including a Japanese phase III, placebo-controlled trial, he noted.

“Tocilizumab appears to be highly effective in the short-term treatment of systemic JIA; it improves systemic and laboratory features of the disease, and there were no differences based on baseline disease characteristics or by prior use of biologic treatment,” Dr. De Benedetti said, adding that no new tocilizumab safety signals, compared with what is known in adults, emerged in this study.

“Obviously, we are waiting for the long-term analysis from the long-term extension part of the study,” he said.

A 5-year open-label extension phase is currently underway.

The TENDER trial is sponsored by Roche, the maker of tocilizumab (Actemra). Dr. De Benedetti disclosed that he has received consulting fees or other payment from Bristol-Myers Squibb Co., Hoffmann-La Roche, and Pfizer Inc. He also has received research grants from Hoffmann-La Roche.