The DRCR Retina Network recently reported findings from their trial Protocol AB,1 wherein they investigated the effect of initial treatment with intravitreal injections of aflibercept, 2 mg, vs pars plana vitrectomy (PPV) plus panretinal photocoagulation (PRP) for nonclearing vitreous hemorrhage secondary to proliferative diabetic retinopathy.1 They found no statistically significant differences in visual acuity between these treatment strategies for the primary outcome, the mean change in visual acuity over 24 weeks, or a secondary end point, the mean change at 104 weeks. Given that visual acuity outcomes were not superior in one group vs the other, we evaluated the cost-effectiveness of each strategy under Medicare, the largest insurance payer in the US, as a factor to consider when choosing between these alternative treatment approaches.
A literature search capturing all studies from January 2008 to December 2020 was performed to find preexisting calculations of total Medicare reimbursement for intravitreal aflibercept, including both medication and administration costs, and combined PPV plus PRP. Then, the mean number of PPV plus PRP procedures was calculated from the original Protocol AB report supplement1 by totaling the number of reported surgeries and dividing by the number of participants. Because other factors, such as adverse events, cataract extraction (31% vs 27%), and tractional detachment repair (12% vs 13%), did not differ significantly between the treatment groups, their cost differences were excluded from this analysis. The costs of postoperative medications were not considered because they were not standardized. The costs of office visits (including postoperative visits), in-office testing, indirect costs (such as caregiver costs), and geographic factors that may modulate Medicare reimbursement were also not included. Then, these total costs of each administration of therapy were calculated using the Medicare reimbursement values, using Excel version 2103 (Microsoft). Data collection occurred within the past 2 years.
Protocol AB included 205 participants (205 eyes) (mean [SD] age, 57 [11] years; 115 men [56.1%]). Including medication and administration costs, intravitreal aflibercept, 2 mg, cost a mean of $1953.2 Mean total costs for PPV plus PRP performed in facility settings (ie, in a hospital) and nonfacility settings (ie, in an ambulatory surgical center) were $4796 and $3145, respectively.3 The initial aflibercept group required means (SDs) of 8.9 (4.6) injections and 0.45 (0.70) PPVs over 104 weeks. The initial PPV plus PRP group required means (SDs) of 2.3 (4.3) injections and 1.18 (0.47) PPVs, including initial PPVs, over 104 weeks. Using these values, initial PPV plus PRP saved a mean (SD) of $9389 ($12 946) over 104 weeks when performed in a facility and a mean (SD) of $10 594 ($12 580) when performed in a nonfacility setting, compared with the initial aflibercept group (Table).
While the PPV plus PRP–first strategy was not shown to have superior visual acuity outcomes compared with the aflibercept-first strategy for nonclearing vitreous hemorrhage in proliferative diabetic retinopathy, this analysis shows the therapeutic cost of performing a surgical intervention first is about half that of initial medical therapy. It is difficult to extrapolate these results across the US health system, because the incidence of nonclearing vitreous hemorrhage from proliferative diabetic retinopathy is unknown, to our knowledge.
We acknowledge potential advantages to an aflibercept-first strategy for selected patients, such as those not healthy enough for an operative procedure. Furthermore, Protocol AB only studied participants up to 104 weeks; the cost analysis and visual acuity results may differ beyond this period, when the rate of injections could increase or decrease. Finally, it is possible that intravitreal bevacizumab, which is substantially less costly than aflibercept, may have economic advantages compared with PPV plus PRP first. However, a cost analysis of an intravitreal bevacizumab–first strategy cannot be done, because such a strategy, to our knowledge, has not been studied. Differential visual acuity outcomes when comparing bevacizumab with aflibercept have been shown with diabetic macular edema4 and macular edema secondary to central retinal vein occlusion.5 Given the financial disadvantages, transience of aflibercept’s effects, and potential consequences of noncompliance with follow-up in the clinical practice setting, we believe clinicians should strongly consider these findings when recommending a treatment strategy for patients similar to those enrolled in Protocol AB.6
Accepted for Publication: April 1, 2021.
Published Online: May 27, 2021. doi:10.1001/jamaophthalmol.2021.1565
Corresponding Author: Thomas J. Wubben, MD, PhD, Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan, 1000 Wall St, Ann Arbor, MI 48105 (twubben@med.umich.edu).
Author Contributions: Drs Young and Johnson had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Young, Wubben.
Acquisition, analysis, or interpretation of data: Young, Johnson.
Drafting of the manuscript: Young.
Critical revision of the manuscript for important intellectual content: All authors.
Administrative, technical, or material support: Young.
Supervision: Johnson, Wubben.
Conflict of Interest Disclosures: Dr Johnson reports receiving personal fees for serving on data and safety monitoring boards for ACI Clinical, Amgen, Pfizer, and Aura Biosciences and grants from Apellis as a site principal investigator for a clinical trial, all outside the submitted work. Dr Wubben reports having participated in the Allergan Fostering Innovative Retina Stars of Tomorrow program, outside the submitted work. No other disclosures were reported.
Disclaimer: The views expressed in this article are those of the authors and do not necessarily reflect the positions or policies of the University of Michigan Health System or the Kellogg Eye Center.
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