title: Adverse gastrointestinal events with intravitreal injection of vascular endothelial growth factor inhibitors: nested case-control study.
abstract: BACKGROUND
  Intravenous administration of vascular endothelial growth factor (VEGF)-inhibiting drugs is associated with adverse gastrointestinal (GI) events. Clinical trials of VEGF inhibitors used for the treatment of retinal diseases have suggested higher risks of adverse GI events among patients treated with bevacizumab. However, population-based studies have been lacking.
  
  
  OBJECTIVE
  Our objective was to assess risks for GI adverse events associated with intravitreal injections of VEGF-inhibiting drugs.
  
  
  METHODS
  We conducted a population-based, nested case-control study of 114,427 older adults in Ontario, Canada, with retinal disease identified between 1 November 2005 and 30 April 2011. Of these, 3,582 cases were admitted to hospital or assessed in an emergency department for GI adverse events. Controls were matched to cases on the basis of age, sex, and outcome history.
  
  
  RESULTS
  Patients experiencing adverse events were equally as likely as matched controls to have been exposed to bevacizumab or ranibizumab. Adjusted odds ratios for bevacizumab were 1.05 (95 % confidence interval [CI] 0.69-1.61) for upper GI ulceration, 1.29 (95 % CI 0.86-1.96) for diverticular disease, 1.49 (95 % CI 0.84-2.63) for pancreatitis, 0.82 (95 % CI 0.53-1.29) for cholelithiasis, and 1.45 (95 % CI 0.67-3.12) for cholecystitis. For ranibizumab they were 1.25 (95 % CI 0.88-1.77) for upper GI ulceration, 1.12 (95 % CI 0.83-1.52) for diverticular disease, 0.85 (95 % CI 0.51-1.40) for pancreatitis, 0.77 (95 % CI 0.53-1.11) for cholelithiasis, and 0.83 (95 % CI 0.44-1.56) for cholecystitis. Results were similar when the analysis was restricted to patients only exposed to a single type of VEGF inhibitor.
  
  
  CONCLUSIONS
  In this population-based study, intravitreal injections of bevacizumab and ranibizumab were not associated with increased risks of adverse GI events.
authors.affiliation: Department of Ophthalmology, Queen's University, Kingston, ON, Canada, rob.campbell@queensu.ca.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Campbell
authors.forename: Chaim M
authors.initials: CM
authors.lastname: Bell
authors.forename: Susan E
authors.initials: SE
authors.lastname: Bronskill
authors.forename: J Michael
authors.initials: JM
authors.lastname: Paterson
authors.forename: Marlo
authors.initials: M
authors.lastname: Whitehead
authors.forename: Erica de L
authors.initials: Ede L
authors.lastname: Campbell
authors.forename: Sudeep S
authors.initials: SS
authors.lastname: Gill
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects*; D000068258:Bevacizumab; D016022:Case-Control Studies; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005767:Gastrointestinal Diseases / Q000453:epidemiology* / Q000209:etiology; D006801:Humans; D058449:Intravitreal Injections; D008297:Male; D009864:Ontario / Q000453:epidemiology; D000069579:Ranibizumab; D012164:Retinal Diseases / Q000188:drug therapy*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D000069579:Ranibizumab
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