Pharmacotherapy for Neovascular Age-Related Macular Degeneration: An Analysis of the 100% 2008 Medicare Fee-For-Service Part B Claims File

doi:10.1016/j.ajo.2010.11.017

American Journal of Ophthalmology

Volume 151, Issue 5, May 2011, Pages 887-895.e1

https://doi.org/10.1016/j.ajo.2010.11.017 Get rights and content

Purpose

To describe the usage patterns of pharmacological treatments for neovascular age-related macular degeneration (AMD) in Medicare fee-for-service beneficiaries.

Design

Retrospective review of all Medicare fee-for-service Part B claims for neovascular AMD during 2008.

Methods

Medicare beneficiaries having undergone treatment were identified. The data collected for each visit for a given beneficiary included age, race, gender, Medicare region, state/zip code of residence, date of visit, whether or not the beneficiary had a treatment, the type and amount of drug, and dollars paid by Medicare. The main outcome measures were the number and rate of treatments, the types of drugs used for treatment, and the payments for these drugs.

Results

Of the 222 886 unique beneficiaries, 146 276 (64.4%) received bevacizumab and 80 929 (35.6%) received ranibizumab. A total of 824 525 injections were performed with 480 025 injections of bevacizumab (58%) and 336 898 injections of ranibizumab (41%). National rates of injections per 100 000 fee-for-service Part B Medicare beneficiaries for bevacizumab and ranibizumab were 1506 and 1057, respectively. Total payments by Medicare were $20 290 952 for bevacizumab and $536 642 693 for ranibizumab. In 39 out of 50 states, the rate of injection was higher for bevacizumab compared with ranibizumab.

Conclusions

In 2008, bevacizumab was used at a higher rate than ranibizumab for the treatment of neovascular AMD. Even though bevacizumab accounted for 58% of all injections, Medicare paid $516 million more for ranibizumab than bevacizumab. These data suggest that despite its off-label designation, intravitreal bevacizumab is currently the standard-of-care treatment for neovascular AMD in the United States.

Section snippets

Methods

The 100% fee-for-service Part B Medicare claims file for calendar year 2008, updated as of July 1, 2009, was used for this report. Since data from the entire fee-for-service Medicare population was used for this report and sampling was not performed, standard deviations and confidence intervals are not appropriate in this analysis.

This fee-for-service claims file includes beneficiaries who have their claims reported directly to CMS for 80% coverage of costs and does not include beneficiaries

Results

A total of 222 886 unique Medicare beneficiaries were identified who had the diagnosis of neovascular AMD and who received 1 or more injections or infusions for this diagnosis among 31 879 444 Part B Medicare beneficiaries in 2008 (Figure 1). Of these beneficiaries, 9041 had injections in both right and left eyes, though not necessarily at the same time during 2008. Nine hundred ninety-seven unique beneficiaries had bevacizumab injected in one eye and ranibizumab injected in the other eye at

Discussion

When a physician decided to use anti-VEGF therapy for the treatment of neovascular AMD in a Medicare fee-for-service Part B beneficiary during 2008, approximately 64% of these unique Medicare beneficiaries received bevacizumab compared with 36% receiving ranibizumab. Even though more bevacizumab was used, Medicare paid $516 million more for ranibizumab compared with bevacizumab in 2008. When the usage patterns for one drug versus the other were compared throughout the US, there were obvious

Ross J. Brechner is an Ophthalmologist and Lead Medical Officer at Medicare writing National Coverage Decisions, Centers for Medicare and Medicaid Services, Woodlawn, Maryland. He is a graduate of Princeton and has graduate level training in Biostatistics and Epidemiology. He is also analyzing the 100% Part B Medicare fee-for-service claims files with a focus on Ophthalmology. He practiced Ophthalmology for 25 years and has always been active in international medicine.

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Retinal vascular diseases such as neovascular age-related macular degeneration (nAMD) are the leading cause of blindness worldwide. They can be treated with intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents by inhibiting VEGF which is a major agent of abnormal blood vessel growth. However, because of drug's short half-life, clinical treatment often requires monthly repeated intravitreal injections, causing treatment burden and undertreatment. Among various kinds of drug carriers, in situ forming hydrogels have been studied as potential intravitreal drug carriers for the high drug loading, easy injection, controlled drug release, and protection of encapsulated drugs from the environment. However, gelation time, crosslinking degree, and drug release patterns following injection of a liquid that will be subsequently gelled in situ are susceptible to be hindered by dilution of the hydrogel precursor solution with body fluids (e.g., blood or vitreous). Here, we report an injectable pre-crosslinked hydrogel rod to overcome the limitations of in situ forming hydrogels and to extend intravitreal half-life of anti-VEGF for reducing intraocular injection frequency. Hydrogel rods can be simply prepared using in situ forming hydrogels, and injectable using a designed rod injector. The adjustable crosslinking degree of hydrogel rods easily controlled bevacizumab release profiles in a sustained manner. Compared with in situ forming hydrogels, hydrogel rods effectively reduced initial burst release, and showed sustained release with long-term drug efficacy in vitro. From the 4-month in vivo pharmacokinetic analysis, following the intravitreal injection of hydrogel rods, the half-life of bevacizumab in the vitreous and retina was significantly extended, and drug elimination to aqueous humor was effectively reduced. Finally, intraocular stability, degradation, and inflammatory response of hydrogel rods were evaluated. We expect that the hydrogel rod can be a potential drug delivery system for the treatment of nAMD and other conditions that need long-term and local sustained drug administration.
Herein, we report an injectable pre-crosslinked hydrogel rod based on an in situ forming hydrogel to achieve intravitreal long-acting anti-VEGF delivery to reduce injection frequency and improve the long-term visual outcomes of patients with retinal vascular diseases. Hydrogel rods were readily prepared using removable molds and injected using customized injectors. Compared to the in situ forming hydrogel, hydrogel rods showed significantly reduced initial burst release, controllable release profiles for several months, physical stability, and a long-acting anti-angiogenic effect. Animal studies demonstrated that the hydrogel rods dramatically prolonged the intraocular drug half-life while significantly reducing drug elimination for up to four months. Moreover, the biodegradability and safety of the hydrogel rods suggest their suitability as an advanced intravitreal DDS for treating retinal vascular diseases.
Social, political, and economic determinants of access to biologics: A scoping review of structural determinants in the clinical disparities literature
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The number of biologics among new medication approvals is increasing. Social, political, and economic factors influence access to these expensive medications. Disparities in access to new medications can exacerbate health disparities. The notion of “structural determinants” provides a theoretical framework for broadly evaluating the integration of upstream social, political, and economic determinants in the clinical study of access.
To review the literature on access to FDA approved biologic medications with particular focus on the integration of social, political, and economic determinants into study design and interpretation.
We used PRISMA guidelines to review studies on racial and socioeconomic disparities in biologic access through August 2020. We assessed whether the design or interpretation of studies considered key economic determinants of access: the biologics supply chain, trade agreements, patents, drug research and development, insurance reimbursement, and non-insurance drug policies.
100 studies met our inclusion criteria. Sixty-six studies considered insurance reimbursement, but trade law, patents, and other key economic determinants were rarely considered. The literature focuses on a small number of older biologics.
A small number of studies model the integration of structural determinants into clinical research on access to biologics, but overall this literature has many limitations and lacks integration of structural determinants. Increased interdisciplinary collaboration, availability of manufacturer data, and use of disease registries can help create structurally grounded understandings of the relationship between the political economy of expensive medications and clinical disparities.
Clinical manifestations of intravitreal bortezomib injection
2020, American Journal of Ophthalmology Case Reports
To describe the clinical presentation and ocular manifestations of intravitreal bortezomib.
Retrospective chart review of five patients who inadvertently received intravitreal injection of bortezomib, instead of bevacizumab, showed that all patients presented hyperacutely within 24–72 hours of the injection with pain and severe vision loss. Examination revealed a fibrinous anterior uveitis, corneal edema, and choroidal effusion associated with a shallow anterior chamber and secondary angle closure glaucoma. Significant vitritis was notably absent. Severe retinal vascular attenuation and optic atrophy, and sometimes even retinal infarction or detachment, followed. Four of the five patients rapidly progressed to no light perception vision. Vitreous gram stain and cultures were negative in all eyes.
Intravitreal bortezomib is severely toxic to the eye. Special safeguards should be instituted for the dispensing of intravitreal medications.
Use of Bevacizumab and Ranibizumab for Wet Age-Related Macular Degeneration: Influence of CATT Results and Introduction of Aflibercept
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Citation Excerpt :
Before the CATT trial, there was no strong level 1 evidence evaluating the safety or efficacy of ranibizumab vs bevacizumab for retinal disease. Factors that may have influenced ophthalmologists' decisions to use one agent vs the other included the results of earlier studies, costs of purchasing and storing these agents, reimbursement for administration of one agent vs the other, financial incentives for making bulk purchases or purchasing these medications using credit cards, the medicolegal environment where the ophthalmologist was practicing (given that only ranibizumab was approved by the FDA), input from pharmaceutical representatives, the location where the ophthalmologist did his or her fellowship training, preferences of the attendings who trained him or her, preferences of other ophthalmologists in the same practice or geographic community, insurance tiering and other policies, and/or whether the ophthalmologist's patients could afford the copays for the more expensive agent.1–3,17–23 The publication of CATT results offered strong evidence of similar efficacy and relatively similar safety profiles between bevacizumab and ranibizumab.
To assess whether publication of Comparison of Age-related macular degeneration Treatment Trial (CATT) results and introduction of aflibercept to the marketplace affected intravitreal bevacizumab and ranibizumab utilization.
Retrospective analysis of treatment patterns.
We calculated weekly bevacizumab and ranibizumab utilization during 3 timeframes: (1) before CATT publication, (2) between CATT publication (April 28, 2011) and assignment of a unique aflibercept billing code (January 1, 2013), and (3) afterward for 164,188 Medicare beneficiaries with neovascular macular degeneration receiving ≥1 anti–vascular endothelial growth factor injection(s) from January 1, 2008 to December 31, 2014. We identified ophthalmologists who predominantly (≥80%) administered bevacizumab or ranibizumab and evaluated changes in preferences over the 3 periods. We replicated analyses on 881,381 commercially insured beneficiaries.
Among 317 ophthalmologists administering predominantly ranibizumab to Medicare beneficiaries pre-CATT, 221 (69.7%) reduced ranibizumab use post-CATT, whereas 96 (30.3%) continued using ranibizumab ≥80% of the time. Findings were reversed among 1041 ophthalmologists who predominantly administered bevacizumab pre-CATT—777 (74.6%) continued bevacizumab-predominant use while 264 (25.4%) reduced bevacizumab use post-CATT. Among the 145 ophthalmologists who predominantly administered ranibizumab before aflibercept's availability, 77 (53.1%) reduced ranibizumab utilization and 68 (46.9%) continued using ranibizumab ≥80% of the time after aflibercept became available. Corresponding numbers among the 909 ophthalmologists who predominantly administered bevacizumab pre-aflibercept were 381 (41.9%) reducing and 528 (58.1%) continuing bevacizumab-predominant use. Similar results were observed for commercially insured patients.
Many ophthalmologists who favored ranibizumab switched to bevacizumab after CATT publication, while most who favored bevacizumab before CATT publication continued favoring it afterward. Aflibercept's introduction had little impact on preferences for ranibizumab or bevacizumab.
Lessons Learned From Avastin and OCT–The Great, the Good, the Bad, and the Ugly: The LXXV Edward Jackson Memorial Lecture
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Citation Excerpt :
Our paper was submitted soon after the WSJ article appeared, and Dr Straube left CMS shortly thereafter. Our research was published in the May 2011 issue of the American Journal of Ophthalmology (AJO).38 By the time the paper was published, we had already finished evaluating the 100% CMS database for 2009 and had begun evaluating the 2010 database.
To describe the synergistic benefits and cost savings from the use of optical coherence tomography (OCT) and vascular endothelial growth factor (VEGF) inhibitors, particularly intravitreal bevacizumab, in the treatment of exudative age-related macular degeneration (AMD).
Retrospective literature review and personal perspective.
Retrospective literature review and personal perspective.
The introduction of the first clinically useful OCT instrument coincided with early-phase clinical trials of a drug that would become known as ranibizumab. OCT provided a noninvasive imaging strategy that unambiguously showed the macular fluid associated with exudative AMD and the ability of anti-VEGF therapy to resolve this fluid with concomitant visual acuity improvement. Clinicians came to embrace the use of OCT imaging as the basis for dosing with anti-VEGF drugs, rather than the fixed-interval dosing that was the standard in clinical trials and recommended by industry after approval. But, before ranibizumab was approved for the treatment of exudative AMD, intravenous bevacizumab was approved to treat cancer. Both drugs shared a common molecular lineage, and this led to a clinical trial using intravenous bevacizumab for the treatment of exudative AMD. Intravenous bevacizumab resulted in visual acuity and OCT improvements similar to ranibizumab, and this observation soon led to the intravitreal use of bevacizumab in 2005. Fortuitously, both ranibizumab and bevacizumab were packaged at similar molar concentrations, so similar volumes of both drugs when injected into an eye would result in similar anti-VEGF activity. With ranibizumab not yet commercially available, intravitreal bevacizumab rapidly became adopted worldwide for the treatment of VEGF-driven ocular diseases. Despite numerous attempts by industry and anonymous sources to discredit and prevent its use, bevacizumab spread globally owing to its availability; its low treatment cost, which was $5.50 per 1 mg in the United States; the evidence of efficacy based on OCT imaging and vision improvement; and its perceived safety. In the United States alone, the use of OCT-guided therapy and the use of bevacizumab for the treatment of exudative AMD has saved Medicare over $40 billion since 2008.
The rapid adoption of OCT-guided therapy and the use of intravitreal bevacizumab by the global retinal community has prevented blindness from exudative and neovascular ocular diseases worldwide while saving healthcare providers and patients billions of dollars.
Estimating Medicare and Patient Savings From the Use of Bevacizumab for the Treatment of Exudative Age-related Macular Degeneration
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The Medicare cost savings from the use of bevacizumab in the United States for the treatment of exudative age-related macular degeneration (AMD) were estimated by replacing the use of bevacizumab with ranibizumab and aflibercept.
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Main outcome measures were spending by Medicare as tracked by Current Procedural Terminology (CPT) codes for intravitreal injections (67028) and treatment-specific J-codes (J0178, J2778, J9035, J3490, and J3590) for inhibitors of vascular endothelial growth factor. These claims were identified from the Medicare Provider Utilization and Payment Data from the Centers for Medicare and Medicaid Services among fee-for-service (FFS) Medicare beneficiaries from 2012 to 2015. The 2008 claims were acquired from the 100% fee-for-service (FFS) Part B Medicare Claims File.
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The cost savings from the use of bevacizumab from 2008 to 2015 for Medicare fee-for-service patients undergoing treatment for exudative AMD was estimated at $17.3 billion. Additional savings over the $17.3 billion would have accrued from the use of bevacizumab if diagnostic categories such as diabetic macular edema and retinal vein occlusion were included in this study.

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Original articlePharmacotherapy for Neovascular Age-Related Macular Degeneration: An Analysis of the 100% 2008 Medicare Fee-For-Service Part B Claims File

Purpose

Design

Methods

Results

Conclusions

Section snippets

Methods

Results

Discussion

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Original article
Pharmacotherapy for Neovascular Age-Related Macular Degeneration: An Analysis of the 100% 2008 Medicare Fee-For-Service Part B Claims File