Drug Safety

, Volume 37, Issue 9, pp 723–733

Adverse Gastrointestinal Events with Intravitreal Injection of Vascular Endothelial Growth Factor Inhibitors: Nested Case–Control Study

  • Robert J. Campbell
  • Chaim M. Bell
  • Susan E. Bronskill
  • J. Michael Paterson
  • Marlo Whitehead
  • Erica de L. Campbell
  • Sudeep S. Gill
Original Research Article

DOI: 10.1007/s40264-014-0211-6

Cite this article as:
Campbell, R.J., Bell, C.M., Bronskill, S.E. et al. Drug Saf (2014) 37: 723. doi:10.1007/s40264-014-0211-6

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.

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Robert J. Campbell
    • 1
    • 2
    • 3
  • Chaim M. Bell
    • 3
    • 4
    • 5
    • 10
    • 11
  • Susan E. Bronskill
    • 3
    • 5
  • J. Michael Paterson
    • 3
    • 5
    • 9
  • Marlo Whitehead
    • 3
    • 8
  • Erica de L. Campbell
    • 1
    • 2
  • Sudeep S. Gill
    • 3
    • 6
    • 7
  1. 1.Department of OphthalmologyQueen’s UniversityKingstonCanada
  2. 2.Department of OphthalmologyHotel Dieu and Kingston General HospitalsKingstonCanada
  3. 3.Institute for Clinical Evaluative Sciences (ICES-Central)TorontoCanada
  4. 4.Department of MedicineUniversity of TorontoTorontoCanada
  5. 5.Institute of Health Policy Management and EvaluationUniversity of TorontoTorontoCanada
  6. 6.Division of Geriatric MedicineQueen’s UniversityKingstonCanada
  7. 7.Division of Geriatric MedicineSt. Mary’s of the Lake HospitalKingstonCanada
  8. 8.Institute for Clinical Evaluative Sciences (ICES@Queen’s)Abramsky Hall, Queen’s UniversityKingstonCanada
  9. 9.Department of Family MedicineMcMaster UniversityHamiltonCanada
  10. 10.Department of MedicineMount Sinai HospitalTorontoCanada
  11. 11.Department of MedicineSt. Michael’s HospitalTorontoCanada