Tocilizumab Efficacy and Safety for sJIA Sustained at 2 Years

CHICAGO – Tocilizumab remained highly effective with a favorable risk-benefit ratio after 2 years of continuous treatment in 61 patients with severe, refractory systemic juvenile idiopathic arthritis, according to findings from the ongoing phase III TENDER trial.

The proportion of the patients who achieved the efficacy end point of ACR Pediatric 70 and ACR Pedi 90 (indicating 70% and 90% improvement, respectively, in the signs and symptoms of disease on the American College of Rheumatology pediatric evaluation scale) at 104 weeks of treatment was 88% and 71%, respectively. Mean joint counts decreased over time as well, with 55% of the patients having zero active joints, and 31% achieving inactive disease status by 104 weeks, according to Dr. Fabrizio De Benedetti, who reported his findings at the annual meeting of the American College of Rheumatology.

Additionally, 60% of patients who were on oral corticosteroids at baseline were able to discontinue that treatment by 104 weeks, and among those who continued on oral corticosteroids, the mean dose decreased from 0.30 mg/kg per day at baseline to 0.04 mg/kg per day, said Dr. Benedetti of Ospedale Pedatrico Bambino Gesu in Rome.

Tocilizumab is an interleukin-6 receptor inhibitor, which was approved by the Food and Drug Administration in April for use in children aged 2 years and older with systemic juvenile idiopathic arthritis (sJIA). It is also approved for adults with rheumatoid arthritis. The drug was shown to be effective in children in the first of three parts of the 5-year multicenter TENDER trial; those 12-week results were reported at ACR 2010.

Of 75 patients who received tocilizumab during that first part of the trial, 71% achieved ACR Pedi 70 and 37% achieved ACR Pedi 90, 16% had zero active joints, and none of the patients achieved inactive disease status.

The effects of treatment improved or were maintained over time, Dr. Benedetti said.

For example, ACR Pedi 70 and ACR Pedi 90 were achieved in 87% and 63%, respectively, of 106 patients receiving tocilizumab at 52 weeks, and in 87% and 71% of 101 patients receiving tocilizumab at 78 weeks, he said.

In the patients on active treatment at 104 weeks, 47 serious adverse events occurred (in 35 patients); 15 of these were considered by the investigators to be remotely, possibly, or probably related to tocilizumab. Additionally, 22 serious infections were reported in 20 patients, with 8 of those considered to be related to tocilizumab. All but one infection (which resulted in death) resolved; in all, three deaths occurred in the patients treated for 104 weeks, and one of those (which was a case of suspected streptococcal sepsis) was possibly treatment related. The rates of serious adverse events, serious adverse events attributable to the study drug, and serious infections were not increased, compared with rates in the initial 12-week part of the trial, he said.

Patients included in the TENDER trial were children aged 2-17 years with active, refractory sJIA (defined as disease duration of 6 months or longer with inadequate response to previous NSAIDs and oral corticosteroids). For part 1 of the trial, participants were randomized 2:1 to receive tocilizumab treatment or placebo every 2 weeks for 12 weeks. Tocilizumab dosing was based on body weight (8 mg/kg for those weighing 30 kg or greater, and 12 mg/kg for those weighing less than 30 kg). All patients, including those who escaped to open-label treatment in part 1, also entered part 2, during which they received open-label tocilizumab to week 104.

Patients were allowed to continue on stable doses of NSAIDs and methotrexate, with oral corticosteroid tapering. The 104-week analysis included those patients who completed all 104 weeks of treatment; 32 of 112 patients had not yet reached that treatment duration at the data cutoff, and 20 patients had withdrawn because of safety concerns, insufficient therapeutic response, or other nonsafety reasons (including one who withdrew at 104 weeks, but who was included in the analysis).

The findings of part 2 of the TENDER trial indicate that the response to tocilizumab is sustained, with no significant change in the safety profile, during long-term treatment in patients with sJIA, Dr. Benedetti said.

Furthermore, responses are maintained across a wide variety of baseline disease characteristics, according to findings of a post hoc analysis reported separately at ACR 2011 by Dr. De Benedetti.

In that analysis, which was performed at 52 weeks, trends were seen in regard to improved response based on joint count at baseline, disease duration, patient age, oral corticosteroid dose, and methotrexate use, but the differences did not reach statistical significance for those or for a number of other characteristics, including region, fever status, C-reactive protein levels, and previous biologic treatment, he said.

The TENDER trial is sponsored by Roche, the maker of tocilizumab. Dr. Benedetti disclosed relationships with Abbott Laboratories, Bristol-Myer Squibb, Hoffmann-La Roche, Novartis, Novimmune, Pfizer, Roche, and SOBI.

CHICAGO – Tocilizumab remained highly effective with a favorable risk-benefit ratio after 2 years of continuous treatment in 61 patients with severe, refractory systemic juvenile idiopathic arthritis, according to findings from the ongoing phase III TENDER trial.

The proportion of the patients who achieved the efficacy end point of ACR Pediatric 70 and ACR Pedi 90 (indicating 70% and 90% improvement, respectively, in the signs and symptoms of disease on the American College of Rheumatology pediatric evaluation scale) at 104 weeks of treatment was 88% and 71%, respectively. Mean joint counts decreased over time as well, with 55% of the patients having zero active joints, and 31% achieving inactive disease status by 104 weeks, according to Dr. Fabrizio De Benedetti, who reported his findings at the annual meeting of the American College of Rheumatology.

Additionally, 60% of patients who were on oral corticosteroids at baseline were able to discontinue that treatment by 104 weeks, and among those who continued on oral corticosteroids, the mean dose decreased from 0.30 mg/kg per day at baseline to 0.04 mg/kg per day, said Dr. Benedetti of Ospedale Pedatrico Bambino Gesu in Rome.

Tocilizumab is an interleukin-6 receptor inhibitor, which was approved by the Food and Drug Administration in April for use in children aged 2 years and older with systemic juvenile idiopathic arthritis (sJIA). It is also approved for adults with rheumatoid arthritis. The drug was shown to be effective in children in the first of three parts of the 5-year multicenter TENDER trial; those 12-week results were reported at ACR 2010.

Of 75 patients who received tocilizumab during that first part of the trial, 71% achieved ACR Pedi 70 and 37% achieved ACR Pedi 90, 16% had zero active joints, and none of the patients achieved inactive disease status.

The effects of treatment improved or were maintained over time, Dr. Benedetti said.

For example, ACR Pedi 70 and ACR Pedi 90 were achieved in 87% and 63%, respectively, of 106 patients receiving tocilizumab at 52 weeks, and in 87% and 71% of 101 patients receiving tocilizumab at 78 weeks, he said.

In the patients on active treatment at 104 weeks, 47 serious adverse events occurred (in 35 patients); 15 of these were considered by the investigators to be remotely, possibly, or probably related to tocilizumab. Additionally, 22 serious infections were reported in 20 patients, with 8 of those considered to be related to tocilizumab. All but one infection (which resulted in death) resolved; in all, three deaths occurred in the patients treated for 104 weeks, and one of those (which was a case of suspected streptococcal sepsis) was possibly treatment related. The rates of serious adverse events, serious adverse events attributable to the study drug, and serious infections were not increased, compared with rates in the initial 12-week part of the trial, he said.

Patients included in the TENDER trial were children aged 2-17 years with active, refractory sJIA (defined as disease duration of 6 months or longer with inadequate response to previous NSAIDs and oral corticosteroids). For part 1 of the trial, participants were randomized 2:1 to receive tocilizumab treatment or placebo every 2 weeks for 12 weeks. Tocilizumab dosing was based on body weight (8 mg/kg for those weighing 30 kg or greater, and 12 mg/kg for those weighing less than 30 kg). All patients, including those who escaped to open-label treatment in part 1, also entered part 2, during which they received open-label tocilizumab to week 104.

Patients were allowed to continue on stable doses of NSAIDs and methotrexate, with oral corticosteroid tapering. The 104-week analysis included those patients who completed all 104 weeks of treatment; 32 of 112 patients had not yet reached that treatment duration at the data cutoff, and 20 patients had withdrawn because of safety concerns, insufficient therapeutic response, or other nonsafety reasons (including one who withdrew at 104 weeks, but who was included in the analysis).

The findings of part 2 of the TENDER trial indicate that the response to tocilizumab is sustained, with no significant change in the safety profile, during long-term treatment in patients with sJIA, Dr. Benedetti said.

Furthermore, responses are maintained across a wide variety of baseline disease characteristics, according to findings of a post hoc analysis reported separately at ACR 2011 by Dr. De Benedetti.

In that analysis, which was performed at 52 weeks, trends were seen in regard to improved response based on joint count at baseline, disease duration, patient age, oral corticosteroid dose, and methotrexate use, but the differences did not reach statistical significance for those or for a number of other characteristics, including region, fever status, C-reactive protein levels, and previous biologic treatment, he said.

The TENDER trial is sponsored by Roche, the maker of tocilizumab. Dr. Benedetti disclosed relationships with Abbott Laboratories, Bristol-Myer Squibb, Hoffmann-La Roche, Novartis, Novimmune, Pfizer, Roche, and SOBI.

CHICAGO – Tocilizumab remained highly effective with a favorable risk-benefit ratio after 2 years of continuous treatment in 61 patients with severe, refractory systemic juvenile idiopathic arthritis, according to findings from the ongoing phase III TENDER trial.

The proportion of the patients who achieved the efficacy end point of ACR Pediatric 70 and ACR Pedi 90 (indicating 70% and 90% improvement, respectively, in the signs and symptoms of disease on the American College of Rheumatology pediatric evaluation scale) at 104 weeks of treatment was 88% and 71%, respectively. Mean joint counts decreased over time as well, with 55% of the patients having zero active joints, and 31% achieving inactive disease status by 104 weeks, according to Dr. Fabrizio De Benedetti, who reported his findings at the annual meeting of the American College of Rheumatology.

Additionally, 60% of patients who were on oral corticosteroids at baseline were able to discontinue that treatment by 104 weeks, and among those who continued on oral corticosteroids, the mean dose decreased from 0.30 mg/kg per day at baseline to 0.04 mg/kg per day, said Dr. Benedetti of Ospedale Pedatrico Bambino Gesu in Rome.

Tocilizumab is an interleukin-6 receptor inhibitor, which was approved by the Food and Drug Administration in April for use in children aged 2 years and older with systemic juvenile idiopathic arthritis (sJIA). It is also approved for adults with rheumatoid arthritis. The drug was shown to be effective in children in the first of three parts of the 5-year multicenter TENDER trial; those 12-week results were reported at ACR 2010.

Of 75 patients who received tocilizumab during that first part of the trial, 71% achieved ACR Pedi 70 and 37% achieved ACR Pedi 90, 16% had zero active joints, and none of the patients achieved inactive disease status.

The effects of treatment improved or were maintained over time, Dr. Benedetti said.

For example, ACR Pedi 70 and ACR Pedi 90 were achieved in 87% and 63%, respectively, of 106 patients receiving tocilizumab at 52 weeks, and in 87% and 71% of 101 patients receiving tocilizumab at 78 weeks, he said.

In the patients on active treatment at 104 weeks, 47 serious adverse events occurred (in 35 patients); 15 of these were considered by the investigators to be remotely, possibly, or probably related to tocilizumab. Additionally, 22 serious infections were reported in 20 patients, with 8 of those considered to be related to tocilizumab. All but one infection (which resulted in death) resolved; in all, three deaths occurred in the patients treated for 104 weeks, and one of those (which was a case of suspected streptococcal sepsis) was possibly treatment related. The rates of serious adverse events, serious adverse events attributable to the study drug, and serious infections were not increased, compared with rates in the initial 12-week part of the trial, he said.

Patients included in the TENDER trial were children aged 2-17 years with active, refractory sJIA (defined as disease duration of 6 months or longer with inadequate response to previous NSAIDs and oral corticosteroids). For part 1 of the trial, participants were randomized 2:1 to receive tocilizumab treatment or placebo every 2 weeks for 12 weeks. Tocilizumab dosing was based on body weight (8 mg/kg for those weighing 30 kg or greater, and 12 mg/kg for those weighing less than 30 kg). All patients, including those who escaped to open-label treatment in part 1, also entered part 2, during which they received open-label tocilizumab to week 104.

Patients were allowed to continue on stable doses of NSAIDs and methotrexate, with oral corticosteroid tapering. The 104-week analysis included those patients who completed all 104 weeks of treatment; 32 of 112 patients had not yet reached that treatment duration at the data cutoff, and 20 patients had withdrawn because of safety concerns, insufficient therapeutic response, or other nonsafety reasons (including one who withdrew at 104 weeks, but who was included in the analysis).

The findings of part 2 of the TENDER trial indicate that the response to tocilizumab is sustained, with no significant change in the safety profile, during long-term treatment in patients with sJIA, Dr. Benedetti said.

Furthermore, responses are maintained across a wide variety of baseline disease characteristics, according to findings of a post hoc analysis reported separately at ACR 2011 by Dr. De Benedetti.

In that analysis, which was performed at 52 weeks, trends were seen in regard to improved response based on joint count at baseline, disease duration, patient age, oral corticosteroid dose, and methotrexate use, but the differences did not reach statistical significance for those or for a number of other characteristics, including region, fever status, C-reactive protein levels, and previous biologic treatment, he said.

The TENDER trial is sponsored by Roche, the maker of tocilizumab. Dr. Benedetti disclosed relationships with Abbott Laboratories, Bristol-Myer Squibb, Hoffmann-La Roche, Novartis, Novimmune, Pfizer, Roche, and SOBI.