MADRID – The results of the first trial of a biologic agent in children less than 2 years of age with systemic juvenile idiopathic arthritis (sJIA) suggest that tocilizumab is likely to be effective in this age group.
“sJIA is the most severe form of childhood arthritis, and as you are aware, it’s the most difficult to treat as well,” said Navita L. Mallalieu, PhD, director of clinical pharmacology at Roche Innovation Center New York, the company that funded the study.
Tocilizumab (Actemra) has been available for the treatment of sJIA, both in the United States and the European Union since 2011, she observed at the European Congress of Rheumatology, but only for children aged 2 years or older at the current time.
Because of this prior history of use in sJIA, “we have confidence in the safety profile, and so we were able to go to the next step of testing children who were even younger than 2 years of age,” Dr. Mallalieu said in a video interview.
Dr. Mallalieu presented findings from an open-label, single-arm, phase I trial that evaluated a 12 mg/kg dosing regimen of tocilizumab, which was given intravenously every 2 weeks for 12 weeks. Eleven children were studied who had a mean age of 1.3 years and active disease for at least 1 month despite treatment with glucocorticoids or nonsteroidal anti-inflammatory drugs.
The primary endpoint was the pharmacokinetics of tocilizumab in this younger patient population, and secondary endpoints were safety, pharmacodynamics, and exploring the efficacy over 12 weeks on top of stable background therapy, she explained.
Results showed that tocilizumab in children under 2 years of age could achieve pharmacokinetics similar to those seen in older children in the TENDER trial (N Engl J Med. 2012;367:2385-95), which is the trial that helped the biologic get licensed for use in the older sJIA population. Reductions in soluble interleukin-6 receptor, C-reactive protein, and the erythrocyte sedimentation rate were seen, again to a similar extent as seen in the TENDER trial. There was also an indication that similar reductions in the Juvenile Arthritis Disease Activity Score (JADAS)-71 score could be achieved, Dr. Mallalieu reported.
While the pattern and nature of adverse events were similar to those seen in the TENDER trial, there were more cases of hypersensitivity in this phase I study. Four cases of hypersensitivity were clinically confirmed, three of which were deemed serious. The three serious cases were observed at day 15, with two of the cases associated with multiple signs and symptoms that were confounded by either subclinical macrophage activation syndrome (MAS) or a faster infusion rate. One patient had urticaria and was hospitalized for observation.