title: Review article: applying pharmacokinetics to optimise dosing of anti-TNF biologics in acute severe ulcerative colitis.
abstract: BACKGROUND
  Acute severe ulcerative colitis (ASUC), the most aggressive presentation of ulcerative colitis (UC), occurs in 15% of adults and children with UC. First line therapy with intravenous corticosteroids is ineffective in half of adults and one-third of children. Therapeutic monoclonal antibodies against TNF (anti-TNF therapy) are emerging as a common treatment for ASUC due to their similar efficacy to calcineurin inhibitors and more favourable adverse effect profile.
  
  
  OBJECTIVE
  To comprehensively review the evidence for anti-TNF therapy for ASUC in children and adults with regard to outcomes and pharmacokinetics.
  
  
  METHODS
  PubMed and recent conference proceedings were searched using the terms 'ulcerative colitis', 'acute severe ulcerative colitis', 'anti-TNF', 'pharmacokinetics' and the generic names of specific anti-TNF agents.
  
  
  RESULTS
  Outcomes after anti-TNF therapy for ASUC remain suboptimal with about one half of children and adults undergoing colectomy. While several randomised controlled trials have demonstrated the efficacy of anti-TNF therapy for ambulatory patients with moderate to severely active UC, patients in these studies were less ill than those with ASUC. Patients with ASUC may exhibit more rapid clearance of anti-TNF biologics due to pharmacokinetic mechanisms influenced by disease severity.
  
  
  CONCLUSIONS
  Conventional weight-based dosing effective in patients with moderately to severely active UC, may not be equally effective in those with acute severe ulcerative colitis. Personalised anti-TNF dosing strategies, which integrate patient factors and early measures of pharmacokinetics and response, hold promise for ensuring sustained drug exposure and maximising early mucosal healing in patients with acute severe ulcerative colitis.
authors: Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors: M J
authors: MJ
authors: Rosen
authors: P
authors: P
authors: Minar
authors: A A
authors: AA
authors: Vinks
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001688:Biological Products / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D002648:Child; D003082:Colectomy; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000503:physiopathology; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D001688:Biological Products; D005938:Glucocorticoids; D014409:Tumor Necrosis Factor-alpha