Characteristics and Treatment Patterns of Patients with Diabetic Macular Edema Non-Responsive to Anti-Vascular Endothelial Growth Factor Treatment in Ontario, Canada

Abstract

Purpose

To understand the demographics, clinical characteristics, treatment patterns, visual and anatomic responses of patients with diabetic macular edema (DME) initially treated with anti-vascular endothelial growth factor (anti-VEGF) agents in the real-world clinical setting.

Patients and Methods

This retrospective cohort study used electronic health records to identify consecutively presenting patients with DME who received their first documented anti-VEGF injection (index injection) on or after 1 October 2015 and before 30 September 2016 (index period) at 4 clinical sites in Ontario, Canada. Patients receiving anti-VEGF injections in the study eye were followed for ≥18 months. After the first 3 monthly injections, patients were classified as “responder” (≥20% reduction in central retinal thickness [CRT] from index date) or “nonresponder” (<20% reduction in CRT) to anti-VEGF treatment.

Results

At 12 months, change from baseline (CFB) in best visual acuity (BVA) of responders (n = 30) was mean (SD) 12.8 (13.00) letters; CFB in nonresponders (n = 56) was 3.2 (16.3) letters. Sensitivity analyses stratified by initial BVA were supportive. Mean (SD) change in CRT (μm) was −160.4 (111.4) in responders and −62.2 (98.6) in nonresponders. While changes in anti-VEGF therapy were lower in responders versus nonresponders (10.0% vs 23.2%), mean number of injections was similar (8.3 in each cohort).

Conclusion

Despite receiving a substantial number of injections and requiring changes in therapy more frequently, nonresponders showed a lack of clinically meaningful change in BVA and CRT. Nonresponders could be identified after 3 anti-VEGF injections. There remains an unmet need for treatment options in patients with DME who show a nonresponse after 3 months of anti-VEGF treatment.

Keywords:

• real-world evidence
• diabetic macular edema
• drug therapy
• anti-vascular endothelial growth factor
• visual acuity

Abbreviations

BVA, best visual acuity; BCVA, best-corrected visual acuity; CADTH, Canadian Agency for Drugs and Technologies in Health; CFB, change from baseline; CRT, central retinal thickness; DME, diabetic macular edema; EHR, electronic health records; ETDRS, Early Treatment Diabetic Retinopathy Study; HbA1c, glycosylated hemoglobin; OCT, optical coherence tomography; SD, standard deviation; VA, visual acuity; VEGF, vascular endothelial growth factor.

Data Sharing Statement

AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual, and trial-level data (analysis data sets), as well as other information (eg, protocols and Clinical Study Reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications. These clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). Data requests can be submitted at any time, and the data will be accessible for 12 months, with possible extensions considered. For more information on the process, or to submit a request, visit the following link: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html.

Ethics Approval and Informed Consent

Approval of the protocol was obtained from a centralized independent institutional review board (Advarra, Columbia, MD). Since the collected data were retrospective and anonymized, written informed patient consent was waived.

Acknowledgments

Allergan, an AbbVie company, and the authors thank the patients, study sites, and investigators who participated in this study. This work was presented in part at the 2021 Canadian Agency for Drugs and Technologies in Health (CADTH) Virtual Symposium, November 2–4, 2021. Medical writing support was provided by Evidence Scientific Solutions, Inc., Philadelphia, PA, and funded by Allergan (an AbbVie company).

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis, and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agreed to be accountable for all aspects of the work.

Disclosure

Financial arrangements of the authors with companies whose products may be related to the present report are listed as declared by the authors: SS has served as a speaker for AbbVie, Bayer, and Novartis, and a consultant for Bayer, Novartis, and Ripple Therapeutics. KK has served as a consultant to Alcon, Allergan (an AbbVie company), Bayer, Novartis, and received a research grant from Bayer. BS-M serves as a consultant for AbbVie and is an employee of Noesis Healthcare Technologies. DM is a consultant for AbbVie and is an employee of Genesis Research. TK, CZ, and AA are full-time employees of AbbVie and may own AbbVie stock/share options. The authors report no other conflicts of interest in this work.

Additional information

Funding

Allergan, an AbbVie company, funded this study and participated in the study design, research, analysis, data collection, interpretation of data, and the review and approval of the manuscript. All authors had access to relevant data and participated in the drafting, review, and approval of the manuscript.