All Posts tagged Medicine

Cost-effectiveness of Aflibercept, Bevacizumab, and Ranibizumab for Diabetic Macular Edema Treatment

Arecent Diabetic Retinopathy Clinical Research Network (DRCR.net) comparative effectiveness trial found that for patients with diabetic macular edema (DME) and approximate Snellen equivalent baseline visual acuity (VA) of 20/50 or worse aflibercept produced greater mean VA gains at 1 year than bevacizumab or ranibizumab. In contrast, no difference in mean VA improvement was identified for patients with baseline VAs of 20/32 to 20/40.1

These agents also vary substantially in cost. O nthe basis of 2015 wholesale acquisition costs, aflibercept (2.0 mg) costs $1850,2 ranibizumab (0.3mg) costs $1170,2 and bevacizumab repackaged at compounding pharmacies into syringes for ophthalmologic use containing 1.25mg of bevacizumab costs approximately $6 0per dose.3 Considering that these medicines may be given 9 to 11 times in the first year of treatment1 and, on average, 17 times during 5 years,4 total costs can be substantial. In 2010, when these intravitreous agents were being used predominantly for age-related macular degeneration, ophthalmologic use of anti–vascular endothelial growth factor (VEGF)therapy cost approximately $2 billion or one-sixth of the entire Medicare Part B drug budget.3 In 2013, Medicare Part B expenditures for aflibercept and ranibizumab alone totaled $2.5 billion.5 Given these costs, the DRCR.net investigators believed it was important to analyze the relative cost-effectiveness of treating DME using each agent.

Full Paper: Cost-effectiveness of Aflibercept, Bevacizumab, and Ranibizumab for Diabetic Macular Edema Treatment
(385K PDF)

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Topical Dorzolamide-Timolol With Intravitreous Anti–Vascular Endothelial Growth Factor for Neovascular Age-Related Macular Degeneration

Importance

There is a subset of eyes with neovascular age-related macular degeneration (AMD) that have persistent exudation despite fixed-interval intravitreous anti–vascular endothelial growth factor (VEGF) injections.

Objective

To evaluate the effect of topical dorzolamide hydrochloride–timolol maleate on anatomic and functional outcomes in eyes with neovascular AMD and incomplete response to anti-VEGF therapy.

Design, Setting, and Participants

An exploratory, prospective single-arm interventional study at a tertiary referral academic private practice. Patients with neovascular AMD and persistent macular edema despite fixed-interval intravitreous anti-VEGF therapy were enrolled. Baseline spectral-domain optical coherence tomography and clinical data, including visual acuity and intraocular pressure, were obtained at enrollment and from one visit before enrollment. The study was performed at the Retina Service of Wills Eye Hospital and the offices of Mid Atlantic Retina from February 1, 2015, through September 30, 2015. Patients were followed up for at least 2 visits after enrollment. Central subfield thickness, maximum subretinal fluid height, and maximum pigment epithelial detachment height from spectral-domain optical coherence tomography were recorded at each visit. INTERVENTIONS Enrolled eyes received a regimen of topical dorzolamide-timolol twice daily and continued to receive the same intravitreous anti-VEGF therapy at the same interval as received before enrollment for the duration of the study.

Main Outcomes and Measures

Change in central subfield thicknesswas the primary outcome measure. Changes in maximum subretinal fluid height, maximum pigment epithelial detachment height, and visual acuity were the secondary outcome measures.

Results

Ten patients (10 eyes) completed the study. The mean age of the patients was 78.2 years (age range, 65-91 years), and 6 were male. Eight eyes received intravitreous aflibercept, and 2 eyes received intravitreous ranibizumab. All study eyes had been receiving long-term anti-VEGF therapy with the same medication before study enrollment for a mean of 21.9 injections. The mean central subfield thickness decreased from 419.7 μmat enrollment to 334.1 μm at the final visit (P = .01). The mean maximum subretinal fluid height decreased from 126.6 μmat enrollment to 49.5 μm at the final visit (P = .02). The mean maximum pigment epithelial detachment height decreased from 277.4 μmat enrollment to 239.9 μmat the final visit (P = .12). The mean logMAR visual acuity were 0.54 at enrollment and 0.48 at the final visit (P = .60).

Conclusions and Relevance

These data suggest that topical dorzolamide-timolol may reduce central subfield thickness and subretinal fluid in eyes with persistent exudation despite consistent, fixed-interval intravitreous anti-VEGF treatment for neovascular AMD.

Full Paper: Topical Dorzolamide-Timolol With Intravitreous Anti–Vascular Endothelial Growth Factor for Neovascular Age-Related Macular Degeneration
(371K PDF)

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Conversion to Aflibercept After Prior Anti-VEGF Therapy for Persistent Diabetic Macular Edema

Diabetic Macular Edema (DME) is the leading cause of visual impairment in patients with diabetic retinopathy.1 In 2010, approximately 20.6 million out of a projected 92.6 million adults with diabetic retinopathy worldwide were estimated to have concurrent DME.2 This global healthcare burden will likely continue to increase at alarming rates, as some models estimate the number of diabetics will double by the year 2030.3

With the Early Treatment Diabetic Retinopathy Study (ETDRS) in the 1980s,4 macular laser photocoagulation became the mainstay of DME management, and it remained the standard of care in the decades that followed. The advent of intravitreal pharmacotherapy agents, primarily driven by the class of vascular endothelial growth factor (VEGF) inhibitors, has since revolutionized how this condition is treated. Validated through the RISE and RIDE phase 3 clinical trials,5 ranibizumab (Lucentis; Genentech, South San Francisco, California, USA) became the first VEGF inhibitor approved by the Food & Drug Administration (FDA) for this indication in 2012.

While off-label, bevacizumab (Avastin; Genentech) has been evaluated through smaller trials, such as the BOLT study.6 Most recently, aflibercept (Eylea; Regeneron, Tarrytown, New York) gained FDA approval to treat DME in July 2014 with the VIVID and VISTA phase 3 clinical trials.7,8

While there is ample evidence supporting the safety and efficacy of the 3 anti-VEGF agents in the management of DME, a head-to-head comparison only recently became available when the Diabetic Retinopathy Clinical Research Network (DRCR) published the 1-year outcomes of its Comparative Effectiveness Study of Intravitreal Aflibercept, Bevacizumab, and Ranibizumab for DME (Protocol T).9 The results demonstrated that when baseline visual acuity (VA) loss was mild (›20/ 40), there was no clinical difference between the 3 medications. However, when the initial acuity loss was more severe (‹20/50), a greater visual benefit was derived from aflibercept.9

Since the FDA approval of aflibercept for DME, and in light of Protocol T’s findings, many retinal specialists are converting eyes from ranibizumab or bevacizumab to aflibercept with the goal of optimizing treatment outcomes, particularly in cases of refractory DME. In the current study, we evaluated the short-term functional and anatomic responses of patients with persistent DME after multiple previous anti-VEGF injections that were converted to aflibercept therapy.

Full Paper: Conversion to Aflibercept After Prior Anti-VEGF Therapy for Persistent Diabetic Macular Edema
(1.78M PDF)

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Genetic Testing for Age-Related Macular Degeneration Not Indicated Now

Age-related macular degeneration is a very common condition that is caused by a complex interplay of genetic and environmental factors. It is likely that, in the future, genetic testing will allow physicians to achieve better clinical outcomes by administering specific treatments to patients based on their genotypes. However, improved outcomes for genotyped patients have not yet been demonstrated in a prospective clinical trial, and as a result, the costs and risks of routine genetic testing currently outweigh the benefits for patients with age-related macular degeneration.

Full Paper: Genetic Testing for Age-Related Macular Degeneration Not Indicated Now
(197K PDF)

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Repeated Intravitreous Ranibizumab Injections for Diabetic Macular Edema and the Risk of Sustained Elevation of Intraocular Pressure or the Need for Ocular Hypotensive Treatment

Importance

For the management of retinal disease, the use of intravitreous injections of anti–vascular endothelial growth factor has increased. Recent reports have suggested that this therapymay cause sustained elevation of intraocular pressure (IOP) and may potentially increase the risk of glaucoma for patients with retinal disease. OBJECTIVE To assess the risk of sustained IOP elevation or the need for IOP-lowering treatments for eyes with diabetic macular edema following repeated intravitreous injections of ranibizumab.

Design, Setting, and Participants

An exploratory analysiswas conducted within a Diabetic Retinopathy Clinical Research Network randomized clinical trial. Study enrollment dates were from March 20, 2007, to December 17, 2008. Of 582 eyes (of 486 participants) with center-involved diabetic macular edema and no preexisting open-angle glaucoma, 260 were randomly assigned to receive a sham injection plus focal/grid laser treatment, and 322 were randomly assigned to receive ranibizumab plus deferred or prompt focal/grid laser treatment.

Main Outcomes and Measures

The cumulative probability of sustained IOP elevation, defined as IOP of at least 22mmHg and an increase of at least 6mmHg from baseline at 2 consecutive visits, or the initiation or augmentation of ocular hypotensive therapy, through 3 years of follow-up.

Results

The mean (SD) baseline IOP in both treatment groups was 16 (3)mmHg (range, 5-24mmHg). The cumulative probability of sustained IOP elevation or of initiation or augmentation of ocular hypotensive therapy by 3 years, after repeated ranibizumab injections, was 9.5%for the participants who received ranibizumab plus prompt or deferred focal/grid laser treatment vs 3.4%for the participants who received a sham injection plus focal/grid laser treatment (difference, 6.1%[99%CI, −0.2%to 12.3%]; hazard ratio, 2.9 [99% CI, 1.0-7.9]; P = .01). The distribution of IOP and the change in IOP from baseline at each visit through 3 years were similar in each group.

Conclusions and Relevance

In eyes with center-involved diabetic macular edema and no prior open-angle glaucoma, repeated intravitreous injections of ranibizumab may increase the risk of sustained IOP elevation or the need for ocular hypotensive treatment. Clinicians should be aware of this risk and should consider this information when following up with patients who have received intravitreous injections of anti–vascular endothelial growth factor for the treatment of diabetic macular edema.

Full Paper: Repeated Intravitreous Ranibizumab Injections
(231K PDF)

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Ocriplasmin Injection

Two recent articles published in the Archives of Ophthalmology expose the risks of Ocriplasmin injection into the vitreous:

1. Acute Panretinal Structural and Functional Abnormalities After Intravitreous Ocriplasmin Injection — JAMA Ophthalmol. 2014;132(4):484-486.

Conclusion: Retinal dysfunction associated with intravitreous ocriplasmin injection is not limited to the macular region and seems to involve the entire retina. Enzymatic cleavage of intraretinal laminin is a biologically plausible mechanism for acute ocriplasmin retinal toxic effects.

2. Vision Loss After Intravitreal Ocriplasmin: Correlation of Spectral-Domain Optical Coherence Tomography and Electroretinography — JAMA Ophthalmol. 2014;132(4):487-490.

Conclusion: On the basis of these findings, it is possible that ocriplasmin may have a diffuse enzymatic effect on photoreceptors or the retinal pigment epithelium that is not limited to areas of vitreomacular adhesion. The rod photoreceptors may be more susceptible than cone photoreceptors to the effects of ocriplasmin. Further work is needed to understand mechanisms of visual impairment after ocriplasmin.

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Sustained Increased Intraocular Pressure

Sustained Increased Intraocular Pressure Related to Intravitreal Antivascular Endothelial Growth Factor Therapy for Neovascular Age-related Macular Degeneration

The following article, Sustained Increased Intraocular Pressure Related to Intravitreal Antivascular Endothelial Growth Factor Therapy for Neovascular Age-Related Macular Degeneration (J. Glaucoma; Volume 21, Number 4, April/May 2012), makes note of increased intraocular pressure following anti-VEGF drug therapy that we have noted in our practice as well. It appears that after seven (7) shots, there is an increased risk of patients developing sustained elevated intraocular presure, which they have never experienced in the past. The second observation is that it appears patients with an open capsule have an increased risk over patients with intact capsules for this sustained increased intraocular pressure. Most patients respond well to medical therapy with eye drops over time as the pressure goes down, but a few may proceed on to require filtering bleb surgery.

Proposed etiologies for the elevated pressure have been looked for. Researchers began looking for microscopic particulate contaminates. It has been thought that the molecular weight of the drugs may play a role in a blockage of the trabecular meshwork as well as some people thinking that the lubricant primarily used in tuberculin syringes was the culprit. This is the reason that many compounding pharmacies no longer send their drugs in tuperculin syringes.

At this point, the definite etiology for the pressure rise is unknow but is under continued investigation. It is important to note that this is a secondary complication with Avastin, Lucentis, and Eylea therapy that is just now coming to the forefront.

If we can answer any of your questions regarding this form of therapy, please feel free to let us know.

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For Our Patients Receiving Avastin (Bevacizumab)

We are certain our Avastin (bezacizumab) is not counterfeit due to the following:

  1. We only order our Avastin (bezacizumab) from a local compounding pharmacy, accredited by the Professional Compounding Accreditation Board, who receives their supply directly from Genentech, the manufacturer of Avastin (bezacizumab). Each order is shipped in FDA-approved cartons directly from the manufacturer with the words “Genentech” or “Genentech – A Member ofthe Roche Group” printed on the packaging.
  2. FDA-approved Avastin (bezacizumab) contains a six-digit lot number on the product’s packaging and all packaging is printed in English. All lot numbers are logged and confirmed with Genentech as the product is received by the compounding pharmacy.
  3. Counterfeit A vastin (bezacizumab) has letters in the lot numbers and is printed in multiple languages instead of English. Authentic Avastin (bezacizumab) does not have letters in the lot numbers.
  4. The counterfeit product packaging does not come close to looking similar to authentic A vastin (bezacizumab) packaging.

We are certain that our local compounding pharmacy is giving us only FDA-approved Avastin (bezacizumab) direct from the manufacturer.

If you have any further questions, concerns or comments, we will be happy to discuss this matter further with you.

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Preliminary CATT Results

The Preliminary CATT (Comparison of AMD Treatment Trials) results are in and they support the use of either Avastin or Lucentis for the treatment of neovascular AMD. The May 2011 edition of the New England Journal of Medicine contained an editorial written by Philip J. Rosenfeld, M.D., Ph.D. which stated, “The CATT data support the continued global use of intravitreal bevacizumab as an effective, low-cost alternative to ranibizumab.”

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