Observational Study

. 2024 Aug;8(8):733-743.

doi: 10.1016/j.oret.2024.03.014. Epub 2024 Mar 20.

Similar Risk of Kidney Failure among Patients with Blinding Diseases Who Receive Ranibizumab, Aflibercept, and Bevacizumab: An Observational Health Data Sciences and Informatics Network Study

Cindy X Cai¹, Akihiko Nishimura², Mary G Bowring³, Erik Westlund², Diep Tran⁴, Jia H Ng⁵, Paul Nagy⁶, Michael Cook⁷, Jody-Ann McLeggon⁸, Scott L DuVall⁹, Michael E Matheny¹⁰, Asieh Golozar¹¹, Anna Ostropolets¹², Evan Minty¹³, Priya Desai¹⁴, Fan Bu¹⁵, Brian Toy¹⁶, Michelle Hribar¹⁷, Thomas Falconer⁸, Linying Zhang⁸, Laurence Lawrence-Archer¹¹, Michael V Boland¹⁸, Kerry Goetz¹⁹, Nathan Hall²⁰, Azza Shoaibi²⁰, Jenna Reps²⁰, Anthony G Sena²¹, Clair Blacketer²⁰, Joel Swerdel²⁰, Kenar D Jhaveri²², Edward Lee¹⁶, Zachary Gilbert¹⁶, Scott L Zeger², Deidra C Crews²³, Marc A Suchard²⁴, George Hripcsak⁸, Patrick B Ryan²⁰

Affiliations

¹ Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland. Electronic address: ccai6@jhmi.edu.
² Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
³ Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, Maryland.
⁴ Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland.
⁵ Division of Kidney Diseases and Hypertension, Donald and Barbara School of Medicine at Hofstra/Northwell, New York.
⁶ Department of Biomedical Informatics and Data Science, Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, Maryland.
⁷ Johns Hopkins University, Baltimore, Maryland.
⁸ Department of Biomedical Informatics, Columbia University, New York, New York.
⁹ VA Informatics and Computing Infrastructure, US Department of Veterans Affairs, Salt Lake City, Utah; Department of Internal Medicine Division of Epidemiology, University of Utah School of Medicine, Salt Lake City, Utah.
¹⁰ VA Informatics and Computing Infrastructure, Tennessee Valley Healthcare System, Nashville, Tennessee; Department of Biomedical Informatics, Vanderbilt University, Nashville, Tennessee.
¹¹ Odysseus Data Services, Inc., Cambridge, Massachusetts; OHDSI Center at the Roux Institute, Northeastern University, Boston, Massachusetts.
¹² Odysseus Data Services, Inc., Cambridge, Massachusetts.
¹³ O'Brien Center for Public Health, Department of Medicine, University of Calgary, Canada.
¹⁴ Technology / Digital Solutions, Stanford Health Care and Stanford University School of Medicine, Palo Alto, California.
¹⁵ Department of Biostatistics, University of California - Los Angeles, Los Angeles, California.
¹⁶ Roski Eye Institute, Keck School of Medicine, University of Southern California; Los Angeles, California.
¹⁷ National Eye Institute, National Institutes of Health, Bethesda, Maryland; Casey Eye Institute, Oregon Health & Science University, Portland, Oregon.
¹⁸ Mass Eye and Ear, and Harvard Medical School, Boston, Massachusetts.
¹⁹ National Eye Institute, National Institutes of Health, Bethesda, Maryland.
²⁰ Janssen Research and Development, Titusville, New Jersey.
²¹ Janssen Research and Development, Titusville, New Jersey; Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, the Netherlands.
²² Glomerular Center at Northwell Health, Division of Kidney Diseases and Hypertension, Donald and Barbara School of Medicine at Hofstra/Northwell, New York.
²³ Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
²⁴ VA Informatics and Computing Infrastructure, US Department of Veterans Affairs, Salt Lake City, Utah; Department of Biostatistics, University of California - Los Angeles, Los Angeles, California.

PMID: 38519026
PMCID: PMC11298306
DOI: 10.1016/j.oret.2024.03.014

Observational Study

Similar Risk of Kidney Failure among Patients with Blinding Diseases Who Receive Ranibizumab, Aflibercept, and Bevacizumab: An Observational Health Data Sciences and Informatics Network Study

Cindy X Cai et al. Ophthalmol Retina. 2024 Aug.

. 2024 Aug;8(8):733-743.

doi: 10.1016/j.oret.2024.03.014. Epub 2024 Mar 20.

Authors

Affiliations

¹ Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland. Electronic address: ccai6@jhmi.edu.
² Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
³ Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, Maryland.
⁴ Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland.
⁵ Division of Kidney Diseases and Hypertension, Donald and Barbara School of Medicine at Hofstra/Northwell, New York.
⁶ Department of Biomedical Informatics and Data Science, Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, Maryland.
⁷ Johns Hopkins University, Baltimore, Maryland.
⁸ Department of Biomedical Informatics, Columbia University, New York, New York.
⁹ VA Informatics and Computing Infrastructure, US Department of Veterans Affairs, Salt Lake City, Utah; Department of Internal Medicine Division of Epidemiology, University of Utah School of Medicine, Salt Lake City, Utah.
¹⁰ VA Informatics and Computing Infrastructure, Tennessee Valley Healthcare System, Nashville, Tennessee; Department of Biomedical Informatics, Vanderbilt University, Nashville, Tennessee.
¹¹ Odysseus Data Services, Inc., Cambridge, Massachusetts; OHDSI Center at the Roux Institute, Northeastern University, Boston, Massachusetts.
¹² Odysseus Data Services, Inc., Cambridge, Massachusetts.
¹³ O'Brien Center for Public Health, Department of Medicine, University of Calgary, Canada.
¹⁴ Technology / Digital Solutions, Stanford Health Care and Stanford University School of Medicine, Palo Alto, California.
¹⁵ Department of Biostatistics, University of California - Los Angeles, Los Angeles, California.
¹⁶ Roski Eye Institute, Keck School of Medicine, University of Southern California; Los Angeles, California.
¹⁷ National Eye Institute, National Institutes of Health, Bethesda, Maryland; Casey Eye Institute, Oregon Health & Science University, Portland, Oregon.
¹⁸ Mass Eye and Ear, and Harvard Medical School, Boston, Massachusetts.
¹⁹ National Eye Institute, National Institutes of Health, Bethesda, Maryland.
²⁰ Janssen Research and Development, Titusville, New Jersey.
²¹ Janssen Research and Development, Titusville, New Jersey; Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, the Netherlands.
²² Glomerular Center at Northwell Health, Division of Kidney Diseases and Hypertension, Donald and Barbara School of Medicine at Hofstra/Northwell, New York.
²³ Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
²⁴ VA Informatics and Computing Infrastructure, US Department of Veterans Affairs, Salt Lake City, Utah; Department of Biostatistics, University of California - Los Angeles, Los Angeles, California.

PMID: 38519026
PMCID: PMC11298306
DOI: 10.1016/j.oret.2024.03.014

Abstract

Purpose: To characterize the incidence of kidney failure associated with intravitreal anti-VEGF exposure; and compare the risk of kidney failure in patients treated with ranibizumab, aflibercept, or bevacizumab.

Design: Retrospective cohort study across 12 databases in the Observational Health Data Sciences and Informatics (OHDSI) network.

Subjects: Subjects aged ≥ 18 years with ≥ 3 monthly intravitreal anti-VEGF medications for a blinding disease (diabetic retinopathy, diabetic macular edema, exudative age-related macular degeneration, or retinal vein occlusion).

Methods: The standardized incidence proportions and rates of kidney failure while on treatment with anti-VEGF were calculated. For each comparison (e.g., aflibercept versus ranibizumab), patients from each group were matched 1:1 using propensity scores. Cox proportional hazards models were used to estimate the risk of kidney failure while on treatment. A random effects meta-analysis was performed to combine each database's hazard ratio (HR) estimate into a single network-wide estimate.

Main outcome measures: Incidence of kidney failure while on anti-VEGF treatment, and time from cohort entry to kidney failure.

Results: Of the 6.1 million patients with blinding diseases, 37 189 who received ranibizumab, 39 447 aflibercept, and 163 611 bevacizumab were included; the total treatment exposure time was 161 724 person-years. The average standardized incidence proportion of kidney failure was 678 per 100 000 persons (range, 0-2389), and incidence rate 742 per 100 000 person-years (range, 0-2661). The meta-analysis HR of kidney failure comparing aflibercept with ranibizumab was 1.01 (95% confidence interval [CI], 0.70-1.47; P = 0.45), ranibizumab with bevacizumab 0.95 (95% CI, 0.68-1.32; P = 0.62), and aflibercept with bevacizumab 0.95 (95% CI, 0.65-1.39; P = 0.60).

Conclusions: There was no substantially different relative risk of kidney failure between those who received ranibizumab, bevacizumab, or aflibercept. Practicing ophthalmologists and nephrologists should be aware of the risk of kidney failure among patients receiving intravitreal anti-VEGF medications and that there is little empirical evidence to preferentially choose among the specific intravitreal anti-VEGF agents.

Financial disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Keywords: Anti-vascular endothelial growth factor; Big data; Informatics; Kidney failure; OHDSI; OMOP.

PubMed Disclaimer

Conflict of interest statement

Cai: Grant support from Regeneron

Ng: J.H. Ng received consultancy fees from Vifor Pharmaceuticals. She is the founder of PublishedMD Consulting LLC.

DuVall: Dr. DuVall reports grants from Alnylam Pharmaceuticals, Inc., Astellas Pharma, Inc., AstraZeneca Pharmaceuticals LP, Biodesix, Inc, Celgene Corporation, Cerner Enviza, GSK PLC, IQVIA Inc., Janssen Pharmaceuticals, Inc., Novartis International AG, Parexel International Corporation through the University of Utah or Western Institute for Veteran Research outside the submitted work within the past 24 months.

Matheny: VA ORD research infrastructure funding for VINCI

Golozar: Employee of Odysseus Data Servicees

Minty: Previous: Janssen (analytics consulting, outside the scope of this work); Orpyx Medical Technologies (outside scope)

Toy: Alimera (Advisory board), Eyepoint (Advisory board)

Boland: Carl Zeiss Meditec (consulting, speaking);Topcon Healthcare (consulting); Janssen (consulting); Allergan (consulting)

Hall: Employee of and shareholder of Johnson & Johnson

Shoaibi: Employee and stockholder of janssen pharmaceutics

Reps: Employee of and shareholder of Johnson & Johnson

Sena: Employee of and shareholder of Johnson & Johnson

Blacketer: Employee of and shareholder of Johnson & Johnson

Swerdel: Employee of and shareholder of Johnson & Johnson

Jhaveri: Consultant for GSK, PMV pharma, Calliditas, George Clinicals

Crews: Baxter (research grant funding)

Suchard: MAS receives grants and contracts from the US Food & Drug Administration and Janssen Research & Development outside the scope of this work.

Ryan: Employee of and shareholder of Johnson & Johnson

Figures

**Figure 1:**
Proportion of patients with baseline kidney diseases comparing those who did and did not develop kidney failure in each exposure group (ranibizumab, aflibercept, and bevacizumab) within each database. Abbreviations: CUMC = Columbia University Medical Center, CCAE = IBM Health MarketScan Commercial Claims and Encounters Database, MDCD = IBM Health MarketScan Multi-State Medicaid Database, MDCR = IBM Health MarketScan Medicare Supplemental and Coordination of Benefits Database, JHME = Johns Hopkins Medical Enterprise, JMDC = Japan Medical Data Center, USC = University of Southern California, Optum^® EHR = Optum^® de-identified Electronic Health Record data set, Clinformatics^® = Optum’s de-identified Clinformatics^® Data Mart Database - Socio-economic Status, NEU = IQVIA PharMetrics^® Plus for Academics Database, VA = Department of Veterans Affairs

**Figure 2:**
Hazard ratio (HR) estimates for the risk of kidney failure among new users of monthly anti-VEGF medications while on treatment comparing ranibizumab, aflibercept, and bevacizumab. Results from each database are provided as well as the meta-analytic estimates. Abbreviations: Clinformatics^® = Optum’s de-identified Clinformatics^® Data Mart Database – Socio-economic Status, MDCR = IBM Health MarketScan Medicare Supplemental and Coordination of Benefits Database, MDCD = IBM Health MarketScan Multi-State Medicaid Database, CCAE = IBM Health MarketScan Commercial Claims and Encounters Database, NEU = IQVIA PharMetrics^® Plus for Academics Database, VA = Department of Veterans Affairs The incidence of kidney failure is 678 per 100,000 patients who receive intravitreal anti-vascular endothelial growth factor agents. The risk of kidney failure appears similar among those who receive ranibizumab, aflibercept, or bevacizumab.

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References

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Similar Risk of Kidney Failure among Patients with Blinding Diseases Who Receive Ranibizumab, Aflibercept, and Bevacizumab: An Observational Health Data Sciences and Informatics Network Study

Affiliations

Similar Risk of Kidney Failure among Patients with Blinding Diseases Who Receive Ranibizumab, Aflibercept, and Bevacizumab: An Observational Health Data Sciences and Informatics Network Study

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

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Grants and funding

LinkOut - more resources

Full Text Sources