Tocilizumab linked to high-level disease control in polyarticular-course JIA
Patients with polyarticular-course juvenile idiopathic arthritis achieved high-level disease control for up to 2 years when treated with tocilizumab, according to data published in Arthritis & Rheumatology.
“Children with rheumatoid factor–positive polyarticular JIA, rheumatoid-factor–negative polyarticular JIA, or extended oligoarticular JIA can be referred to as having polyarticular-course JIA (pcJIA); these patients are at risk for progressive joint damage, functional disability, and growth impairment,” Hermine I. Brunner, MD, MSc, of the Cincinnati Children’s Hospital Medical Center, and colleagues wrote. “Indeed, up to 30% of patients with pcJIA continue to experience active arthritis despite the use of disease-modifying antirheumatic drugs (DMARDs), such as methotrexate (MTX), and/or biologic therapies, such as anti–tumor necrosis factor agents and cytotoxic T-lymphocyte–associated protein-4 blockade.”
They added: “A randomized, double-blind, placebo-controlled, phase 3 withdrawal trial of the IL-6 receptor inhibitor tocilizumab in patients with pcJIA (CHERISH) demonstrated improvements in JIA-ACR responses, and significantly more placebo-treated than tocilizumab-treated patients experienced JIA flare during the 24-week, double-blind withdrawal period, showing that treatment with tocilizumab for up to 40 weeks was effective for improving the signs and symptoms of pcJIA in children with inadequate response to MTX.”
To examine the 2-year safety and efficacy of tocilizumab (Actemra, Genentech) among patients with polyarticularcourse JIA, Brunner and colleagues analyzed data from the CHERISH study. In part one of that study, 188 patients aged 2 to 17 years with active polyarticular-course JIA, who were unresponsive to methotrexate, were treated with 16 weeks of open-label intravenous tocilizumab. The 166 participants who achieved at least a JIA-ACR30 response at week 16 were then randomly assigned to receive either tocilizumab or placebo in part two.
Participants remained in part 2 until week 40 or the occurrence of a JIA flare. A total of 160 patients entered part 3 of the study, in which all participants received open-label tocilizumab. At week 104, researchers assessed efficacy using JIA-ACR50/70/90 response rates, as well as whether participants achieved inactive disease status and the Juvenile Arthritis Disease Activity Score71 (JADAS71). They assessed safety among the all-exposure population, per 100 patient-years of exposure.
According to the researchers, among the 188 patients in the modifiedintenttotreat group who received tocilizumab, JIAACR50/70/90 response rates were 80.3%, 77.1% and 59.6% respectively, at week 104. In addition, the median JADAS71 decreased from 3.6 at week 40 to 0.7 at week 104, and 51.1% of patients achieved inactive disease. In all, 31 of 66 patients who were receiving glucocorticoids discontinued them.
The adverse-event rate was 406.5 per 100 patient-years, while the rate for serious adverse events was 11.1 per 100 patient-years. The rate of infections was 151.4 per 100 patient-years, while the serious infections rate was 5.2 per 100 patient-years.
“This study has demonstrated that improvements in the signs and symptoms of pcJIA in children treated with tocilizumab were maintained or improved over longer-term treatment up to 2 years,” Brunner and colleagues wrote. “And that the safety profile of tocilizumab remained consistent with that established in a much larger number of adults with RA, with no evidence of increasing toxicities over this period of time.”