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.
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Contributors
All authors were involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. RJC drafted the manuscript and approved the final version to be published. SSG, SEB, JMP, MW, EdeLPC, and CMB critically revised the manuscript for important intellectual content. RJC, MW, SEB, SSG, and CMB conducted the statistical analysis. RJC and SSG obtained funding. RJC supervised the study and is the guarantor.
Funding
This study was funded by the Canadian Institutes of Health Research (CIHR) and the Ontario Ministry of Health and Long-Term Care (MOHLTC). The work was also supported by the Institute for Clinical Evaluative Sciences (ICES), a non-profit research institute funded by the Ontario MOHLTC. RJC is supported by a Clinician Scientist Award from the Southeastern Ontario Academic Medical Organization, which receives funding from the MOHLTC, and holds research grants from the CIHR and the MOHLTC for related work. SSG and SEB are supported by CIHR New Investigator Awards from the Institute of Aging. CMB is supported by a CIHR and Canadian Patient Safety Institute chair in Patient Safety and Continuity of Care.
Data Access and Responsibility
Dr. RJ Campbell had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Conflicts of Interest
RJ Campbell, CM Bell, SE Bronskill, JM Paterson, M Whitehead, EdeL Campbell, and SS Gill have no conflicts of interest.
Role of the Sponsors
The sponsors of this study had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit for publication. The opinions, results, and conclusions reported in this paper are those of the authors and are independent from the funding sources. No endorsement by ICES or the Ontario MOHLTC is intended or should be inferred.
Ethical Approval
The study protocol was approved by the Research Ethics Board at Queen’s University, Kingston, Ontario, Canada (file No. 6004374).
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Campbell, R.J., Bell, C.M., Bronskill, S.E. et al. Adverse Gastrointestinal Events with Intravitreal Injection of Vascular Endothelial Growth Factor Inhibitors: Nested Case–Control Study. Drug Saf 37, 723–733 (2014). https://doi.org/10.1007/s40264-014-0211-6
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DOI: https://doi.org/10.1007/s40264-014-0211-6