Risk/benefit profiles similar for subcutaneous, IV tocilizumab in systemic JIA
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Subcutaneous tocilizumab provides similar exposure and risk-benefit profiles as intravenous tocilizumab in patients with systemic juvenile idiopathic arthritis, according to findings published in Rheumatology.
“Phase 3 randomized controlled trials demonstrated that intravenous (IV) tocilizumab (IV-TCZ) was an effective treatment for [systemic JIA (sJIA)], [polyarticular JIA (pJIA)] and rheumatoid arthritis (RA),” Nicolino Ruperto, MD, MPH, of the IRCCS Istituto Giannina Gaslini, in Genoa, Italy, and colleagues wrote.
“In RA, subcutaneous (SC) TCZ (SC-TCZ) has efficacy and safety comparable to those of IV-TCZ. SC injections offer a convenient alternative to IV administration by allowing administration by the patient or caregiver, eliminating the inconvenience of short hospital admission for infusions and reducing the stress of IV administration, which is particularly relevant for younger children,” they added.
To identify optimal dosing regimens for subcutaneous tocilizumab (Actemra, Genentech) among children with systemic or polyarticular JIA, the researchers conducted two 52-week, open-label, multicenter phase 1b trials. In both trials, participants aged 1 to 17 years — or 12 to 17 years in Russia — were enrolled from 24 centers in 11 countries in the Pediatric Rheumatology International Trials Organization (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG) networks. The systemic JIA trial included 51 total patients who had an inadequate response to NSAIDs and glucocorticoids, while the polyarticular study enrolled 52 participants with an inadequate response or intolerance to methotrexate.
Participants in the systemic trial received 162 mg of subcutaneous tocilizumab every week or every 2 weeks depending on body weight — either 30 kg or more, or less than 30 kg — while those in the polyarticular study received the same dose every 2 or 3 weeks. The primary endpoints were pharmacokinetics, pharmacodynamics and safety. In addition, the researchers compared their results to data from phase 3 trials with intravenous tocilizumab in patients with systemic or polyarticular JIA.
According to the researchers, 96% of participants in the systemic trial, and 100% of those in the polyarticular study, achieved the steady-state minimum tocilizumab concentration — greater than 5th percentile — reported in the intravenous data. Pharmacodynamic markers of disease in both trials were similar between body weight groups. Improvements in Juvenile Arthritis Disease Activity Score-71 were comparable between subcutaneous and intravenous data. By week 52, 53% of patients with systemic JIA, and 31% of those with polyarticular disease, achieved clinical remission on treatment.
Subcutaneous safety findings were consistent with intravenous data save for injection site reactions, which were reported by 41.2% and 28.8% of systemic and polyarticular participants, respectively. Meanwhile, infections were reported in 78.4% of patients in the systemic trial, and in 69.2% of patients with polyarticular JIA. Two participants in the systemic trial died, with both deaths were deemed related to tocilizumab.
“Appropriate SC-TCZ dosing regimens were successfully identified from studies in patients with sJIA or pJIA that bridged to data from studies of IV-TCZ,” Ruperto and colleagues wrote. “The overall benefit/risk profile for SC-TCZ was favorable and comparable with that for IV-TCZ in patients with sJIA and in patients with pJIA. These findings highlight the ability of PK/PD bridging to provide a path towards regulatory approval of agents for the treatment of pediatric patients.”
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