Voraporn Chaikitmongkol, MD, discussed step therapy and reported the results of a major study, the Diabetic Retinopathy Clinical Research (DRCR) Protocol AC, at the 38th Asia-Pacific Academy of Ophthalmology Congress, in Kuala Lumpur, Malaysia.
Step therapy requirements by insurance companies are controversial because physicians may not want to begin treating diabetic macular edema (DME) with the least costly therapy and work up to the much more costly therapies (aflibercept, Eylea, Regeneron; and ranibizumab, Lucentis, Genentech) for patients who do not have a satisfactory response to bevacizumab (Avastin, Genentech). Many prefer to start with a drug that they believe will benefit their patients’ visual acuity (VA) sooner than later.
Voraporn Chaikitmongkol, MD, discussed step therapy and reported the results of a major study, the Diabetic Retinopathy Clinical Research (DRCR) Protocol AC, at the 38th Asia-Pacific Academy of Ophthalmology Congress, in Kuala Lumpur, Malaysia. She is an Associate Professor of Ophthalmology, Retina Division, Department of Ophthalmology, Faculty of Medicine Chiang Mai University in Chiang Mai, Thailand.
The problem is that for eyes with a baseline VA of 20/50 or worse, it is unknown if this strategy compromises long-term VA relative to aflibercept monotherapy.
The DRCR Protocol AC was a randomized trial that evaluated aflibercept vs bevacizumab plus aflibercept if needed in 312 eyes with center-involved DME and moderate vision loss (VA 20/50 to 20/320). The primary outcome measure was the mean change in VA (AUC) over 2 years. Bevacizumab was administered first.
Patients were switched to aflibercept if all of the following criteria were satisfied at 12 weeks or longer:
At 12 weeks or longer, the eyes assigned to receive bevacizumab first that met the switch criteria received 2 initial monthly aflibercept injections, then continued with aflibercept injections throughout the study according to the protocol retreatment regimen.
The results of the comparison of aflibercept monotherapy with bevacizumab first indicated that the difference in the mean change in the VA (area under the curve) from baseline through 2 years was non-significant (p=0.37), with respective letter increases of +15 and +14. At 2 years, the percentage of patients with 20/20 or better VA, 20/40 or better, and 20/200 or worse for the 2 treatments were very similar as were the changes in the CST at 2 years and the resolution of the center-involved DME.
Chaikitmongkol summarized, “About 70% of patients in the bevacizumab group were switched to aflibercept during the 2-year study, with more than half (57%) of these patients switched between 12 and 24 weeks. These results expand our understanding of how and whether clinical outcomes differ using different anti-VEGF treatment strategies for DME.”
The take-home messages from this trial were that there were no significant differences in visual outcomes over 2 years in eyes treated with aflibercept monotherapy compared with eyes treated with bevacizumab first. Initiating therapy with bevacizumab and switching to aflibercept as done in this trial is a safe and effective alternative to aflibercept monotherapy in eyes with moderate vision loss due to center-involved DME.