COPENHAGEN — The anti-interleukin-6 receptor monoclonal antibody tocilizumab represents “a major breakthrough” in the treatment of systemic-onset juvenile idiopathic arthritis, according to Dr. Shumpei Yokota, speaking at the annual European Congress of Rheumatology.
New data from an open-label extension trial of patients with systemic juvenile idiopathic arthritis (sJIA) who previously participated in phase II and phase III trials of the biologic agent confirmed the results of the earlier studies; the data demonstrated significant improvement in clinical responses among children who were refractory to conventional therapy, reported Dr. Yokota, professor of pediatrics at Yokohama (Japan) City University.
In addition, the findings from the extension study showed that the “acceptable safety profile” of tocilizumab therapy is maintained up to 3 years, he said.
In the double-blind, withdrawal phase III trial reported last year, 56 children (aged 2-19 years) with sJIA who didn't respond to conventional treatment received three doses of tocilizumab (8 mg/kg every 2 weeks) during a 6-week, open-label lead-in phase.
Patients who achieved an American College of Rheumatology (ACR) Pediatric 30 response and had a C-reactive protein concentration (CRP) of less than 5 mg/dL were then either randomized to placebo or continued on tocilizumab treatment for a 12-week, double-blind phase.
Patients responding to tocilizumab during the double-blind phase of the study who needed further treatment were enrolled in an open-label extension phase for up to 3 years (Lancet 2008;371:998-1006).
“At the end of the open-label lead-in phase, ACR Pedi 30, 50, and 70 were achieved by 91%, 86%, and 68% patients, respectively,” Dr. Yokota said. Of the 43 patients who continued to the double-blind phase and were included in the efficacy analysis, significantly more patients in the tocilizumab group, compared with the placebo group, maintained an ACR Pedi 30 response and a CRP level less than 1.5 mg/dL (80% vs. 17%, respectively). By week 48 of the open-label extension phase, 100%, 95%, and 90% of the patients achieved ACR Pedi 30, 50, and 70, respectively, he said.
To evaluate the longer-term efficacy and safety of the treatment, Dr. Yokota and colleagues analyzed the outcomes of 67 patients who previously participated in the phase II and phase III trials who were eligible to receive tocilizumab.
“Safety end points included the incidence of serious adverse events and death, and efficacy end points were the ACR Pedi 30, Pedi 50, Pedi 70, and Pedi 90 criteria,” he said.
Of the 67 patients included in the 3-year analysis of continuous tocilizumab therapy, 9 patients discontinued treatment, including 4 who experienced serious adverse events, 4 who developed anti-tocilizumab antibodies, and 1 in whom the treatment was no longer effective, Dr. Yokota said.
The median duration of tocilizumab treatment was 185 weeks, he noted.
In the 3-year analysis, the overall rate of serious adverse events—including anaphylactic reaction, gastrointestinal hemorrhage, bronchitis, and gastroenteritis—was 35.5 per 100 patient-years, Dr. Yokota reported, noting that “there were no cases of opportunistic infections, malignancies, autoimmune diseases, or reported deaths.”
Among the frequently observed nonsevere adverse events were nasopharyngitis, upper respiratory tract infection, and gastroenteritis, he said.
Regarding efficacy, 96%, 96%, 88%, and 73% of patients, respectively, achieved ACR Pedi 30, 50, 70, and 90 by at week 168. “During the long-term treatment, 77% of them had reduced doses of corticosteroids at week 168 and tocilizumab was ceased in eight patients because of continuous remission,” said Dr. Yokota.
The findings indicate that tocilizumab produces “favorable levels of clinical improvements in the signs and symptoms of systemic juvenile idiopathic arthritis with acceptable safety” up to 3 years, Dr. Yokota concluded.
Dr. Yokota disclosed no financial conflicts of interest with respect to his presentation. Chugai Pharmaceutical Co. sponsored the phase III trial.