Tocilizumab Helped Kids With sJIA Catch Up on Growth

WASHINGTON – Tocilizumab for the treatment of systemic juvenile idiopathic arthritis was associated with significant catch-up growth at 2-year follow-up in the vast majority of children who participated in the pivotal phase III TENDER study.

Treatment with the interleukin-6 (IL-6) receptor inhibitor, which is marketed as Actemra, also significantly increased insulinlike growth factor-1 (IGF-1) levels and osteocalcin/C-telopeptide of type 1 collagen (OC/CTX-1) ratios, suggesting that the therapy has beneficial effects on growth hormone axis and bone metabolism, reported Dr. Fabrizio De Benedetti, speaking at the annual meeting of the American College of Rheumatology.

The findings are important because systemic juvenile idiopathic arthritis (sJIA) has a significant impact on the growing skeleton and is associated with impaired linear growth and systemic osteoporosis, he explained.

Height measurements at baseline in 112 children aged 2-17 years who were enrolled in the study showed profound growth failure, with most having height velocity well below normal for age and gender. However, during treatment, most patients had above normal height velocities: 85% of girls and 73% of boys experienced catch-up growth, said Dr. De Benedetti of Ospedale Pediatrico Bambino Gesu, Rome.

In 86 children from the study who were below Tanner stage 4 development at baseline, the 0.61 mean improvement in height standard deviation score at 2-year follow-up was statistically significant, and although mean corticosteroid dose was higher in the first year of treatment (0.13 mg/kg per day vs. 0.05 mg/kg per day), mean height velocities were comparable in both years, at 5.8 cm and 6.3 cm, respectively, he noted.

IGF-1 standard deviation score increased from a mean of –1.1 at baseline to 0.0 at 2 years, and OC/CTX-1 ratio increased significantly, suggesting an increase in osteoblast activity relative to osteoclast activity.

Improvements in the Juvenile Arthritis Disease Activity Score–71 (JADAS-71) during the first year correlated with increases in height velocities during that year, as did younger age at baseline.

Tocilizumab, which was approved by the U.S. Food and Drugs Administration in 2010 for the treatment of rheumatoid arthritis, received an expanded approval for the treatment of sJIA in April 2011, based on 12-week results from the randomized, placebo-controlled TENDER study. Treatment was shown in that phase, as well as in an open-label long-term extension phase, to be safe and effective for the management of sJIA. Two-year findings of the study, which included children with active refractory disease, were reported at the 2011 annual meeting of the American College of Rheumatology.

Data collection will continue through 5 years of follow-up, allowing a more comprehensive analysis of growth outcomes, said Dr. De Benedetti, the lead investigator for the TENDER study.

Dr. De Benedetti disclosed that he has received research grants and/or consulting fees from Abbott, BMS, Novartis, NovImmune, Pfizer, Roche Pharmaceuticals, and Sobi. The TENDER study was sponsored by Roche, the maker of tocilizumab.

WASHINGTON – Tocilizumab for the treatment of systemic juvenile idiopathic arthritis was associated with significant catch-up growth at 2-year follow-up in the vast majority of children who participated in the pivotal phase III TENDER study.

Treatment with the interleukin-6 (IL-6) receptor inhibitor, which is marketed as Actemra, also significantly increased insulinlike growth factor-1 (IGF-1) levels and osteocalcin/C-telopeptide of type 1 collagen (OC/CTX-1) ratios, suggesting that the therapy has beneficial effects on growth hormone axis and bone metabolism, reported Dr. Fabrizio De Benedetti, speaking at the annual meeting of the American College of Rheumatology.

The findings are important because systemic juvenile idiopathic arthritis (sJIA) has a significant impact on the growing skeleton and is associated with impaired linear growth and systemic osteoporosis, he explained.

Height measurements at baseline in 112 children aged 2-17 years who were enrolled in the study showed profound growth failure, with most having height velocity well below normal for age and gender. However, during treatment, most patients had above normal height velocities: 85% of girls and 73% of boys experienced catch-up growth, said Dr. De Benedetti of Ospedale Pediatrico Bambino Gesu, Rome.

In 86 children from the study who were below Tanner stage 4 development at baseline, the 0.61 mean improvement in height standard deviation score at 2-year follow-up was statistically significant, and although mean corticosteroid dose was higher in the first year of treatment (0.13 mg/kg per day vs. 0.05 mg/kg per day), mean height velocities were comparable in both years, at 5.8 cm and 6.3 cm, respectively, he noted.

IGF-1 standard deviation score increased from a mean of –1.1 at baseline to 0.0 at 2 years, and OC/CTX-1 ratio increased significantly, suggesting an increase in osteoblast activity relative to osteoclast activity.

Improvements in the Juvenile Arthritis Disease Activity Score–71 (JADAS-71) during the first year correlated with increases in height velocities during that year, as did younger age at baseline.

Tocilizumab, which was approved by the U.S. Food and Drugs Administration in 2010 for the treatment of rheumatoid arthritis, received an expanded approval for the treatment of sJIA in April 2011, based on 12-week results from the randomized, placebo-controlled TENDER study. Treatment was shown in that phase, as well as in an open-label long-term extension phase, to be safe and effective for the management of sJIA. Two-year findings of the study, which included children with active refractory disease, were reported at the 2011 annual meeting of the American College of Rheumatology.

Data collection will continue through 5 years of follow-up, allowing a more comprehensive analysis of growth outcomes, said Dr. De Benedetti, the lead investigator for the TENDER study.

Dr. De Benedetti disclosed that he has received research grants and/or consulting fees from Abbott, BMS, Novartis, NovImmune, Pfizer, Roche Pharmaceuticals, and Sobi. The TENDER study was sponsored by Roche, the maker of tocilizumab.

WASHINGTON – Tocilizumab for the treatment of systemic juvenile idiopathic arthritis was associated with significant catch-up growth at 2-year follow-up in the vast majority of children who participated in the pivotal phase III TENDER study.

Treatment with the interleukin-6 (IL-6) receptor inhibitor, which is marketed as Actemra, also significantly increased insulinlike growth factor-1 (IGF-1) levels and osteocalcin/C-telopeptide of type 1 collagen (OC/CTX-1) ratios, suggesting that the therapy has beneficial effects on growth hormone axis and bone metabolism, reported Dr. Fabrizio De Benedetti, speaking at the annual meeting of the American College of Rheumatology.

The findings are important because systemic juvenile idiopathic arthritis (sJIA) has a significant impact on the growing skeleton and is associated with impaired linear growth and systemic osteoporosis, he explained.

Height measurements at baseline in 112 children aged 2-17 years who were enrolled in the study showed profound growth failure, with most having height velocity well below normal for age and gender. However, during treatment, most patients had above normal height velocities: 85% of girls and 73% of boys experienced catch-up growth, said Dr. De Benedetti of Ospedale Pediatrico Bambino Gesu, Rome.

In 86 children from the study who were below Tanner stage 4 development at baseline, the 0.61 mean improvement in height standard deviation score at 2-year follow-up was statistically significant, and although mean corticosteroid dose was higher in the first year of treatment (0.13 mg/kg per day vs. 0.05 mg/kg per day), mean height velocities were comparable in both years, at 5.8 cm and 6.3 cm, respectively, he noted.

IGF-1 standard deviation score increased from a mean of –1.1 at baseline to 0.0 at 2 years, and OC/CTX-1 ratio increased significantly, suggesting an increase in osteoblast activity relative to osteoclast activity.

Improvements in the Juvenile Arthritis Disease Activity Score–71 (JADAS-71) during the first year correlated with increases in height velocities during that year, as did younger age at baseline.

Tocilizumab, which was approved by the U.S. Food and Drugs Administration in 2010 for the treatment of rheumatoid arthritis, received an expanded approval for the treatment of sJIA in April 2011, based on 12-week results from the randomized, placebo-controlled TENDER study. Treatment was shown in that phase, as well as in an open-label long-term extension phase, to be safe and effective for the management of sJIA. Two-year findings of the study, which included children with active refractory disease, were reported at the 2011 annual meeting of the American College of Rheumatology.

Data collection will continue through 5 years of follow-up, allowing a more comprehensive analysis of growth outcomes, said Dr. De Benedetti, the lead investigator for the TENDER study.

Dr. De Benedetti disclosed that he has received research grants and/or consulting fees from Abbott, BMS, Novartis, NovImmune, Pfizer, Roche Pharmaceuticals, and Sobi. The TENDER study was sponsored by Roche, the maker of tocilizumab.