New data presented at EULAR for the investigational drug canakinumab (ACZ885) from its pivotal Phase III study in patients with systemic juvenile idiopathic arthritis (SJIA) suggest that the agent offers a new treatment option for the most severe form of childhood arthritis.
SJIA is a rare systemic interleukin-1 beta (IL-1 beta)-mediated autoinflammatory disease characterised by daily spiking fevers, rash, chronic pain and arthritis.
Canakinumab is a fully human monoclonal antibody that inhibits IL-1 beta. It is currently licensed in the EU for the treatment of adults and children with cryopyrin associated periodic syndromes (CAPS), another rare inflammatory disorder. A regulatory submission has been made in SJIA.
The Phase III study, presented by Professor Alberto Martini, Professor of Paediatrics at the University of Genoa, showed that 62% of patients treated with canakinumab had inactive disease at the end of the placebo-controlled period.
The trial design was an open-label, single-arm active treatment period followed by a randomised, double-blind, placebo-controlled, event-driven period.
A total of 177 SJIA patients were enrolled in the study. Patients received a subcutaneous dose of canakinumab (4 mg/kg, up to 300 mg) every 4 weeks and if they had been using a corticosteroid at the trial entry, tapered their steroid use until reaching a pre-specified amount or a maximum of 20 weeks had passed without reaching this goal.
Following the open-label phase, patients who had a minimum adapted American College of Rheumatology (ACR) Pediatric 30 criteria at the end of the first phase continued receiving canakinumab or received placebo every 4 weeks until a pre-specified number of flares had occurred.
Professor Martini said: “It is encouraging to see many patients become free of symptoms as this is the aim in clinical practice, and to see a significant number achieve sufficient symptom control to allow them to completely discontinue corticosteroid therapy.”
The primary endpoint result in the first part of the study was met: 45% of patients successfully reduced their use of steroids within 28 weeks of commencing treatment with canakinumab (p<0.0001).
Also, 31% of patients had inactive disease and were nearly three times less likely to suffer a new flare. The most common adverse events were nasopharyngitis, headache and cough.
Clinical remission was maintained for all patients from day 15 onwards in the second part of the study except for one patient who suffered a relapse at day 85.