Five-Year Cost-effectiveness of Intravitreous Ranibizumab Therapy vs Panretinal Photocoagulation for Treating Proliferative Diabetic Retinopathy: A Secondary Analysis of a Randomized Clinical Trial

Abstract

Importance: The DRCR Retina Network Protocol S randomized clinical trial suggested that the mean visual acuity of eyes with proliferative diabetic retinopathy (PDR) treated with ranibizumab is not worse at 5 years than that of eyes treated with panretinal photocoagulation (PRP). Moreover, the ranibizumab group had fewer new cases of diabetic macular edema (DME) with vision loss or vitrectomy but had 4 times the number of injections and 3 times the number of visits. Although 2-year cost-effectiveness results of Protocol S were previously identified, incorporating 5-year data from Protocol S could alter the longer-term cost-effectiveness of the treatment strategies from the perspective of the health care system.

Objective: To evaluate 5- and 10-year cost-effectiveness of therapy with ranibizumab, 0.5 mg, compared with PRP for treating PDR.

Design, setting, and participants: A preplanned secondary analysis of the Protocol S randomized clinical trial using efficacy, safety, and resource utilization data through 5 years of follow-up for 213 adults diagnosed with PDR and simulating results through 10 years.

Interventions: Intravitreous ranibizumab, 0.5 mg, at baseline and as frequently as every 4 weeks based on a structured retreatment protocol vs PRP at baseline for PDR; eyes in both groups could receive ranibizumab for concomitant DME with vision loss.

Main outcomes and measures: Incremental cost-effectiveness ratios (ICERs) of ranibizumab therapy compared with PRP were evaluated for those with and without center-involved DME (CI-DME) and vision loss (Snellen equivalent, 20/32 or worse) at baseline.

Results: The study included 213 adults with a mean (SD) age of 53 (12) years, of whom 92 (43%) were women and 155 (73%) were white. The ICER of the ranibizumab group compared with PRP for patients without CI-DME at baseline was $582 268 per quality-adjusted life-year (QALY) at 5 years and $742 202/QALY at 10 years. For patients with baseline CI-DME, ICERs were $65 576/QALY at 5 years and $63 930/QALY at 10 years.

Conclusions and relevance: This study suggests that during 5 to 10 years of treatment, ranibizumab, 0.5 mg, as given in the studied trial compared with PRP may be within the frequently cited range considered cost-effective in the United States for eyes presenting with PDR and vision-impairing CI-DME, but not for those with PDR but without vision-impairing CI-DME. Substantial reductions in anti-vascular endothelial growth factor cost may make the ranibizumab therapy cost-effective within this range even for patients without baseline CI-DME.

Trial registration: ClinicalTrials.gov identifier: NCT01489189.

Conflict of interest statement

Conflict of Interest Disclosures: Drs Hutton and Sun reported receiving grants from the JAEB Center for Health Research. Drs Stein, Glassman, and Jampol reported receiving grants from the National Eye Institute (NEI). Dr Glassman also reported receiving grants from Genentech and Regeneron and nonfinancial support from Regeneron. Dr Bressler reported receiving grants from Bayer, Genentech/Roche, Novartis, and Samsung Bioepis. Dr Sun also reported receiving grants from Boehringer Ingelheim, Genentech/Roche, and JDRF; equipment loaned for research from Adaptive Sensory Technologies, Boston Micromachines, and Optovue; nonfinancial support from Boerhinger Ingelheim, Genentech/Roche, Merck, Novartis, and Novo Nordisk; and personal fees from Current Diabetes Reports (as the diabetic retinopathy section editor, 2008-2017), JAMA Ophthalmology (as CME editor), Merck, and Novartis. A complete list of all DRCR.net investigator financial disclosures can be found at http://www.drcr.net.

Figures

Figure 1.. One-Way Sensitivity Analysis of Varying Cost of Anti–Vascular Endothelial Growth Factor (Anti-VEGF) Assuming Effectiveness of Ranibizumab, 0.5 mg

The incremental cost-effectiveness ratios of anti-VEGF therapy vs panretinal photocoagulation. Although there are no official thresholds of cost-effectiveness in the United States, interventions costing less than $50 000 to $150 000 may be considered cost-effective. The orange line represents results for patients with center-involved diabetic macular edema (DME) and vision loss; the blue line, patients without center-involved DME and vision loss.

Figure 2.. Two-Way Sensitivity Analysis of Number of Annual Injections With and Without Baseline Center-Involved Diabetic Macular Edema (DME) and Vision Loss

The colors in the figures represent the incremental cost-effectiveness ratios (ICERs) of therapy with ranibizumab, 0.5 mg, vs panretinal photocoagulation (PRP). Although there are no official thresholds of cost-effectiveness in the United States, interventions costing less than $50 000 to $150 000 may be considered cost-effective. The color scales are an order of magnitude different.

Figure 3.. Cost-effectiveness Acceptability Curves

Results of the Monte Carlo simulation, which simultaneously varied all parameter estimates and created synthetic populations of patients from the trial using bootstrapping. The lines represent the fraction of simulation iterations in which ranibizumab was cost-effective compared with panretinal photocoagulation (y-axis) at various levels of willingness to pay for quality-adjusted life-year (QALY) gains (x-axis). The orange line represents results for patients with center-involved diabetic macular edema (DME) and vision; the blue line, patients without center-involved DME and vision loss.