PMID- 21538322
OWN - NLM
STAT- MEDLINE
DCOM- 20110805
LR  - 20131121
IS  - 1529-0131 (Electronic)
IS  - 0004-3591 (Linking)
VI  - 63
IP  - 5
DP  - 2011 May
TI  - Safety and efficacy of an oral histone deacetylase inhibitor in systemic-onset 
      juvenile idiopathic arthritis.
PG  - 1452-8
LID - 10.1002/art.30238 [doi]
AB  - 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      to the study drug, but each resolved spontaneously and no patient was withdrawn 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. CONCLUSION: 
      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.
CI  - Copyright (c) 2011 by the American College of Rheumatology.
FAU - Vojinovic, Jelena
AU  - Vojinovic J
AD  - University Clinic Center, Nis, Serbia. vojinovic.jelena@gmail.com
FAU - Damjanov, Nemanja
AU  - Damjanov N
FAU - D'Urzo, Carmine
AU  - D'Urzo C
FAU - Furlan, Antonio
AU  - Furlan A
FAU - Susic, Gordana
AU  - Susic G
FAU - Pasic, Srdjan
AU  - Pasic S
FAU - Iagaru, Nicola
AU  - Iagaru N
FAU - Stefan, Mariana
AU  - Stefan M
FAU - Dinarello, Charles A
AU  - Dinarello CA
LA  - eng
SI  - ClinicalTrials.gov/NCT00570661
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Antirheumatic Agents)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Hydroxamic Acids)
RN  - Z02132R2QQ (givinostat hydrochloride)
SB  - IM
MH  - Adolescent
MH  - Antirheumatic Agents/administration & dosage/*therapeutic use
MH  - Arthritis, Juvenile/*drug therapy
MH  - Child
MH  - Female
MH  - Histone Deacetylase Inhibitors/adverse effects/*therapeutic use
MH  - Humans
MH  - Hydroxamic Acids/adverse effects/*therapeutic use
MH  - Intention to Treat Analysis
MH  - Male
MH  - Treatment Outcome
EDAT- 2011/05/04 06:00
MHDA- 2011/08/06 06:00
CRDT- 2011/05/04 06:00
PHST- 2011/05/04 06:00 [entrez]
PHST- 2011/05/04 06:00 [pubmed]
PHST- 2011/08/06 06:00 [medline]
AID - 10.1002/art.30238 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2011 May;63(5):1452-8. doi: 10.1002/art.30238.