Intravenous administration of tocilizumab at a dose of 12 mg/kg is safe and effective to treat systemic juvenile idiopathic arthritis patients who are younger than 2, results from a Phase 1 clinical trial show.
The treatment showed a similar pharmacological pattern to that reported previously in older children, with the exception of a higher likelihood of severe hypersensitivity (allergic reactions) in younger patients.
These findings were reported in the study “Intravenous dosing of tocilizumab in patients younger than two years of age with systemic juvenile idiopathic arthritis: results from an open-label phase 1 clinical trial,” which was published recently in the journal Pediatric Rheumatology.
Systemic juvenile idiopathic arthritis (sJIA) had been the most severe and difficult-to-treat form of childhood arthritis because there were limited treatment options. Increased understanding of the underlying mechanisms of sJIA, however, has led to the development of more effective, targeted therapies and improvements in the outcome of patients.
Tocilizumab, known in the U.S. as Actemra (marketed by Genentech) and as RoActemra in Europe (marketed by Roche), is an antibody designed to block the signals of the protein IL-6, which have been shown to play a significant role in sJIA.
The antibody already is approved for the treatment of sJIA in patients ages 2 to 17, based on results from a randomized, controlled Phase 3 clinical trial (NCT00642460). However, sJIA can be diagnosed in even younger patients, who also may exhibit more severe inflammatory features and are at risk for worse outcomes.
A new open-label Phase 1 clinical trial (NCT01455701) was launched in 2012 to explore whether tocilizumab is effective and safe in patients younger than 2.
The team compared the impact of the treatment in this younger population to previous data from children and adolescents (ages 2-17) who participated in the previous Phase 3 study.
In the new Phase 1 study, 11 infants (average age 1.3 years) received 12 mg/kg tocilizumab every two weeks administrated directly into the vein, for a total treatment period of 12 weeks. After completion of this initial assessment, they rolled over for an extension study in which they continued to receive tocilizumab therapy for up to 56 weeks.
Results indicated that during the 12-week main evaluation period tocilizumab had similar pharmacokinetic (how the therapy moves through the body) and pharmacodynamics (how the drug affects the body) in this younger group as was reported in older patients.
Further analysis showed that all infants experienced a reduction in disease activity score throughout the study duration comparable to that in older patients. Median change in Juvenile Arthritis Disease Activity score (JADAS-71) from before the treatment started up until week 12 was of 17.6 in patients younger than 2, and of 26.6 in the older group.
During the overall study duration, the safety safety profile of tocilizumab was comparable to previous reports, with rash being one of the most common adverse side effects — present in 14.3% of the younger participants and 13.5% of the older children.
“During the optional extension period, [tocilizumab] treatment was well tolerated in patients younger than 2 years, and no additional safety signals were noted,” researchers wrote. Still, children younger than 2 were more prone to experience serious hypersensitivity reactions, which occurred at a rate of 27.3%, compared to only 2.6% in the older group.
Supported by these results, the researchers believe that 12 mg/kg of intravenous tocilizumab every two weeks is a safe and effective strategy to treat the younger sJIA population.