title: Anti-IP-10 antibody (BMS-936557) for ulcerative colitis: a phase II randomised study.
abstract: OBJECTIVE
  Interferon-γ-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.
  
  
  METHODS
  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 μg/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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00656890.
authors: Immunology Institute, Mount Sinai School of Medicine, , New York, New York, USA.
authors: Lloyd
authors: L
authors: Mayer
authors: William J
authors: WJ
authors: Sandborn
authors: Yuriy
authors: Y
authors: Stepanov
authors: Karel
authors: K
authors: Geboes
authors: Robert
authors: R
authors: Hardi
authors: Michael
authors: M
authors: Yellin
authors: Xiaolu
authors: X
authors: Tao
authors: Li An
authors: LA
authors: Xu
authors: Luisa
authors: L
authors: Salter-Cid
authors: Sheila
authors: S
authors: Gujrathi
authors: Richard
authors: R
authors: Aranda
authors: Allison Y
authors: AY
authors: Luo
mesh_terms: D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D054357:Chemokine CXCL10 / Q000037:antagonists & inhibitors*; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000473:pathology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy; D057194:Intention to Treat Analysis; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; C587732:BMS-936557; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10
keywords: Antibody Targeted Therapy; Ulcerative Colitis