title: Safety and efficacy of an oral histone deacetylase inhibitor in systemic-onset juvenile idiopathic arthritis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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(nausea, vomiting, and fatigue) were related to the study drug, but each resolved spontaneously and no patient was withdrawn from the study due to drug-related AEs.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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University Clinic Center, Nis, Serbia. vojinovic.jelena@gmail.com
authors.forename: Jelena
authors.initials: J
authors.lastname: Vojinovic
authors.forename: Nemanja
authors.initials: N
authors.lastname: Damjanov
authors.forename: Carmine
authors.initials: C
authors.lastname: D'Urzo
authors.forename: Antonio
authors.initials: A
authors.lastname: Furlan
authors.forename: Gordana
authors.initials: G
authors.lastname: Susic
authors.forename: Srdjan
authors.initials: S
authors.lastname: Pasic
authors.forename: Nicola
authors.initials: N
authors.lastname: Iagaru
authors.forename: Mariana
authors.initials: M
authors.lastname: Stefan
authors.forename: Charles A
authors.initials: CA
authors.lastname: Dinarello
mesh_terms: D000293:Adolescent; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001171:Arthritis, Juvenile / Q000188:drug therapy*; D002648:Child; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006877:Hydroxamic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D057194:Intention to Treat Analysis; D008297:Male; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C502418:givinostat hydrochloride