Treat-and-Extend Regimen Superior in First Year of DME Treatment

Pierre-Henry Gabrielle, MD, PhD

Credit: LinkedIn

Visual and anatomic outcomes were relatively better in eyes with diabetic macular edema (DME) treated with an intensive intravitreal vascular endothelial growth factor (VEGF) inhibitor regimen in the first year of treatment, according to new findings.¹

Results from a 12-month analysis of eyes with DME identified modest visual acuity (VA) gains, regardless of the number of visits where intravitreal therapy was delivered but showed a slight benefit in favor of the more intensive group, with more injections given at fewer visits.

“These results indicate that for DME, a proactive treat-and-extend protocol yields superior results with fewer visits compared with less intensive treatment regimens in the first year of treatment,” wrote the investigative team, led by Pierre-Henry Gabrielle, MD, PhD, department of ophthalmology, Dijon University Hospital.

Randomized controlled trials have proven the benefit of fixed monthly or every-other-month interval regimens of VEGF inhibitors for visual acuity outcomes.² Still, real-world data have been unable to replicate these findings, stemming from challenges in the burden of appointments for patients, who may have health or mobility issues in coming for a visit.

A movement toward the personalization of healthcare delivery has led to individualized regimens for the treatment of DME, including pro re nata (PRN), where patients are treated only when their disease is active, or a treat-and-extend regimen when the interval between treatments is extended until disease activity is re-identified.³

Clinical trial data of individualized treat-and-extend dosing for DME have shown similar long-term visual and anatomical outcomes to fixed or PRN dosing, with fewer visits and a greater number of injections.⁴ However, the potential beneficial effect of treat-and-extend in managing DME in routine practice is not well understood.¹

In the current analysis, Gabrielle and colleagues sought to compare the one-year treatment outcomes of eyes with DME treated in routine practice with VEGF inhibition, based on the number of visits where treatments were delivered. The cohort study used data from the prospective Fight Retinal Blindness! (FRB) registry, collecting information on visual acuity outcomes, type of treatment given, and central subfield thickness (CST).

All eyes receiving aflibercept 2 mg, bevacizumab 1.25 mg, or ranibizumab 0.5 mg for DME between October 2015 and October 2021 were eligible for study inclusion, to allow for ≥12 months of follow-up after starting treatment. Ultimately, 2288 treatment-naive eyes with DME starting intravitreal VEGF inhibitor therapy during the study period were included in the analysis.

Eyes were separated into two groups according to the median number of injections per visit (median, 67%): Group A (n = 1172) had fewer than the median injections per visit and Group B (n = 1116) had more than the median. Patients had a mean VA and CST at baseline of 64.6 letters and 404 µm, respectively.

Upon analysis, Group B demonstrated moderately greater visual improvement than Group A (mean change, 5.2 letters vs. 3.6 letters; P = .005), as well as a moderately greater reduction in CST (mean change, –85 vs. –69; P = .002) after 12 months. Group B also received significantly more injections (7 vs. 4; P <.001), with a lower interval from the last injection to the final 12-month visit (mean, 24 vs. 125 days; P <.001), compared with Group A.

Gabrielle and colleagues identified a moderate, positive correlation between the number of injections received over 12 months of treatment and the change in VA (P <.001). Eyes with thicker CST at baseline generally received more injections during the study period.

After adjusting for relevant clinical characteristics, the team found eyes with DME receiving more injections over 12 months exhibited moderately greater mean VA improvement (P = .010) and moderately greater reduction in CST (P <.001) at 12 months.

Gabrielle and colleagues indicated the primary advantage of proactive treat-and-extend regimens centers around reducing clinical visits, ultimately lessening the appointment burden and ensuring treatment will be delivered at most visits.

“The main disadvantage of proactive treat-and-extend regimens relates to the marginally higher number of intravitreal injections required, although this appears to translate to improved visual outcomes in the first year of therapy in routine clinical practice,” they wrote.

References

1. _{Mehta H, Gabrielle PH, Hashimoto Y, et al. One-year anti-VEGF therapy outcomes in diabetic macular edema based on treatment intensity: Data from the FRB! registry. Ophthalmol Retina. Published online April 12, 2024. doi:10.1016/j.oret.2024.04.008}
2. _{Mehta H, Nguyen V, Barthelmes D, et al. Outcomes of Over 40,000 Eyes Treated for Diabetic Macula Edema in Routine Clinical Practice: A Systematic Review and Meta-analysis. Adv Ther. 2022;39(12):5376-5390. doi:10.1007/s12325-022-02326-8}
3. _{Chaudhary V; Chair, Retina Evidence Trials InterNational Alliance (R.E.T.I.N.A.) Study Group. Treat & extend in neovascular age-related macular degeneration: how we got here and where do we go next?. Eye (Lond). 2023;37(4):581-583. doi:10.1038/s41433-022-02221-0}
4. _{Arnold JJ, Campain A, Barthelmes D, et al. Two-year outcomes of "treat and extend" intravitreal therapy for neovascular age-related macular degeneration. Ophthalmology. 2015;122(6):1212-1219. doi:10.1016/j.ophtha.2015.02.009}