Dr. Dinarello has received consulting fees, speaking fees, and/or honoraria from Italfarmaco SpA, Capstone, and Source MdX (less than $10,000 each).
Safety and efficacy of an oral histone deacetylase inhibitor in systemic-onset juvenile idiopathic arthritis†
Article first published online: 27 APR 2011
Copyright © 2011 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 63, Issue 5, pages 1452–1458, May 2011
How to Cite
Vojinovic, J., Damjanov, N., D'Urzo, C., Furlan, A., Susic, G., Pasic, S., Iagaru, N., Stefan, M. and Dinarello, C. A. (2011), Safety and efficacy of an oral histone deacetylase inhibitor in systemic-onset juvenile idiopathic arthritis. Arthritis & Rheumatism, 63: 1452–1458. doi: 10.1002/art.30238
ClinicalTrials.gov identifier: NCT00570661.
- Issue published online: 27 APR 2011
- Article first published online: 27 APR 2011
- Accepted manuscript online: 18 JAN 2011 12:08PM EST
- Manuscript Accepted: 4 JAN 2011
- Manuscript Received: 22 OCT 2010
- Italfarmaco SpA, Cinisello Balsamo, Italy
- NIH. Grant Number: AF-15614
The current treatment options for systemic-onset juvenile idiopathic arthritis (JIA) are methotrexate, steroids, and biologic agents. This study was undertaken to evaluate the safety of the orally active histone deacetylase inhibitor givinostat (ITF2357) and its ability to affect the disease.
Givinostat was administered orally, for up to 12 weeks at a dosage of 1.5 mg/kg/day, to 17 patients with systemic-onset JIA who had had active disease for ≥1 month. Disease activity was clinically assessed using the American College of Rheumatology Pediatric 30 (ACR Pedi 30), ACR Pedi 50, or ACR Pedi 70 criteria for improvement and a systemic feature score. The primary goal was safety and the primary efficacy end point was the number of patients completing 12 weeks of treatment who were responders.
Givinostat was safe and well tolerated, with adverse events (AEs) being mild or moderate, of short duration, and self-limited. The 17 patients from the intent-to-treat population reported a total of 44 AEs, and the 9 patients in the per-protocol population reported a total of 25. Six AEs in 3 patients (nausea, vomiting, and fatigue) were related to the study drug, but each resolved spontaneously and no patient was withdrawn from the study due to drug-related AEs. In the per-protocol population at week 4, the improvement as measured by the ACR Pedi 30, ACR Pedi 50, and ACR Pedi 70, respectively, was 77.8%, 55.6%, and 22.2%, and this increased further to 77.8%, 77.8%, and 66.7% at week 12. The most consistent finding was the reduction in the number of joints with active disease or with limited range of motion.
After 12 weeks, givinostat exhibited significant therapeutic benefit in patients with systemic-onset JIA, particularly with regard to the arthritic component of the disease, and showed an excellent safety profile.