Warning: Undefined variable $zfal in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 525
Deprecated: str_replace(): Passing null to parameter #3 ($subject) of type array|string is deprecated in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 525
Warning: Undefined variable $sterm in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 530
 free
Warning: Undefined variable $sterm in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 531
 free
 free
 
English Wikipedia
Nephropedia Template TP (
Twit Text
DeepDyve
Pubget Overpricing |  
lüll
Anti-IP-10 antibody (BMS-936557) for ulcerative colitis: a phase II randomised study Mayer L; Sandborn WJ; Stepanov Y; Geboes K; Hardi R; Yellin M; Tao X; Xu LA; Salter-Cid L; Gujrathi S; Aranda R; Luo AYGut 2014[Mar]; 63 (3): 442-50OBJECTIVE: Interferon-gamma-inducible protein-10 (IP-10 or CXCL10) plays a role in inflammatory cell migration and epithelial cell survival and migration. It is expressed in higher levels in the colonic tissue and plasma of patients with ulcerative colitis (UC). This phase II study assessed the efficacy and safety of BMS-936557, a fully human, monoclonal antibody to IP-10, in the treatment of moderately-to-severely active UC. DESIGN: In this 8-week, phase II, double-blind, multicentre, randomised study, patients with active UC received placebo or BMS-936557 (10 mg/kg) intravenously every other week. The primary endpoint was the rate of clinical response at Day 57; clinical remission and mucosal healing rates were secondary endpoints. Post hoc analyses evaluated the drug exposure-response relationship and histological improvement. RESULTS: 109 patients were included (BMS-936557: n=55; placebo: n=54). Prespecified primary and secondary endpoints were not met; clinical response rate at Day 57 was 52.7% versus 35.2% for BMS-936557 versus placebo (p=0.083), and clinical remission and mucosal healing rates were 18.2% versus 16.7% (p=1.00) and 41.8% versus 35.2% (p=0.556), respectively. However, higher BMS-936557 steady-state trough concentration (Cminss) was associated with increased clinical response (87.5% vs 37.0% (p<0.001) for patients with Cminss 108-235 mug/ml vs placebo) and histological improvements (73.0% vs 41.0%; p=0.004). Infections occurred in 7 (12.7%) BMS-936557-treated patients and 3 (5.8%) placebo-treated patients. 2 (3.6%) BMS-936557 patients discontinued due to adverse events. CONCLUSIONS: Anti-IP-10 antibody, BMS-936557, is a potentially effective therapy for moderately-to-severely active UC. Higher drug exposure correlated with increasing clinical response and histological improvement. Further dose-response studies are warranted. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT00656890.|*Induction Chemotherapy[MESH]|Administration, Intravenous[MESH]|Adolescent[MESH]|Adult[MESH]|Aged[MESH]|Aged, 80 and over[MESH]|Anti-Inflammatory Agents/*therapeutic use[MESH]|Antibodies, Monoclonal/*therapeutic use[MESH]|Chemokine CXCL10/*antagonists & inhibitors[MESH]|Colitis, Ulcerative/*drug therapy/pathology[MESH]|Double-Blind Method[MESH]|Drug Administration Schedule[MESH]|Female[MESH]|Humans[MESH]|Intention to Treat Analysis[MESH]|Logistic Models[MESH]|Male[MESH]|Middle Aged[MESH]|Severity of Illness Index[MESH]|Treatment Outcome[MESH]|Young Adult[MESH] |
