Dataset Information

Use of Bevacizumab and Ranibizumab for Wet Age-Related Macular Degeneration: Influence of CATT Results and Introduction of Aflibercept.

ABSTRACT: PURPOSE: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. DESIGN:Retrospective analysis of treatment patterns. METHODS: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. RESULTS: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. CONCLUSIONS: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.

SUBMITTER: Pershing S

PROVIDER: S-EPMC6856411 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Use of Bevacizumab and Ranibizumab for Wet Age-Related Macular Degeneration: Influence of CATT Results and Introduction of Aflibercept.

Pershing Suzann S Talwar Nidhi N Armenti Stephen T ST Grubbs Joseph J Rosenthal Julie M JM Dedania Vaidehi S VS Stein Joshua D JD

American journal of ophthalmology 20190515

<h4>Purpose</h4>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.<h4>Design</h4>Retrospective analysis of treatment patterns.<h4>Methods</h4>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 ...[more]

PMID: 31100217

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Project description:BackgroundClinical trials have established the efficacy of ranibizumab for the treatment of neovascular age-related macular degeneration (AMD). In addition, bevacizumab is used off-label to treat AMD, despite the absence of similar supporting data.MethodsIn a multicenter, single-blind, noninferiority trial, we randomly assigned 1208 patients with neovascular AMD to receive intravitreal injections of ranibizumab or bevacizumab on either a monthly schedule or as needed with monthly evaluation. The primary outcome was the mean change in visual acuity at 1 year, with a noninferiority limit of 5 letters on the eye chart.ResultsBevacizumab administered monthly was equivalent to ranibizumab administered monthly, with 8.0 and 8.5 letters gained, respectively. Bevacizumab administered as needed was equivalent to ranibizumab as needed, with 5.9 and 6.8 letters gained, respectively. Ranibizumab as needed was equivalent to monthly ranibizumab, although the comparison between bevacizumab as needed and monthly bevacizumab was inconclusive. The mean decrease in central retinal thickness was greater in the ranibizumab-monthly group (196 μm) than in the other groups (152 to 168 μm, P=0.03 by analysis of variance). Rates of death, myocardial infarction, and stroke were similar for patients receiving either bevacizumab or ranibizumab (P>0.20). The proportion of patients with serious systemic adverse events (primarily hospitalizations) was higher with bevacizumab than with ranibizumab (24.1% vs. 19.0%; risk ratio, 1.29; 95% confidence interval, 1.01 to 1.66), with excess events broadly distributed in disease categories not identified in previous studies as areas of concern.ConclusionsAt 1 year, bevacizumab and ranibizumab had equivalent effects on visual acuity when administered according to the same schedule. Ranibizumab given as needed with monthly evaluation had effects on vision that were equivalent to those of ranibizumab administered monthly. Differences in rates of serious adverse events require further study. (Funded by the National Eye Institute; ClinicalTrials.gov number, NCT00593450.).

Project description:BackgroundThe relative efficacy and safety of intravitreous aflibercept, bevacizumab, and ranibizumab in the treatment of diabetic macular edema are unknown.MethodsAt 89 clinical sites, we randomly assigned 660 adults (mean age, 61±10 years) with diabetic macular edema involving the macular center to receive intravitreous aflibercept at a dose of 2.0 mg (224 participants), bevacizumab at a dose of 1.25 mg (218 participants), or ranibizumab at a dose of 0.3 mg (218 participants). The study drugs were administered as often as every 4 weeks, according to a protocol-specified algorithm. The primary outcome was the mean change in visual acuity at 1 year.ResultsFrom baseline to 1 year, the mean visual-acuity letter score (range, 0 to 100, with higher scores indicating better visual acuity; a score of 85 is approximately 20/20) improved by 13.3 with aflibercept, by 9.7 with bevacizumab, and by 11.2 with ranibizumab. Although the improvement was greater with aflibercept than with the other two drugs (P<0.001 for aflibercept vs. bevacizumab and P=0.03 for aflibercept vs. ranibizumab), it was not clinically meaningful, because the difference was driven by the eyes with worse visual acuity at baseline (P<0.001 for interaction). When the initial visual-acuity letter score was 78 to 69 (equivalent to approximately 20/32 to 20/40) (51% of participants), the mean improvement was 8.0 with aflibercept, 7.5 with bevacizumab, and 8.3 with ranibizumab (P>0.50 for each pairwise comparison). When the initial letter score was less than 69 (approximately 20/50 or worse), the mean improvement was 18.9 with aflibercept, 11.8 with bevacizumab, and 14.2 with ranibizumab (P<0.001 for aflibercept vs. bevacizumab, P=0.003 for aflibercept vs. ranibizumab, and P=0.21 for ranibizumab vs. bevacizumab). There were no significant differences among the study groups in the rates of serious adverse events (P=0.40), hospitalization (P=0.51), death (P=0.72), or major cardiovascular events (P=0.56).ConclusionsIntravitreous aflibercept, bevacizumab, or ranibizumab improved vision in eyes with center-involved diabetic macular edema, but the relative effect depended on baseline visual acuity. When the initial visual-acuity loss was mild, there were no apparent differences, on average, among study groups. At worse levels of initial visual acuity, aflibercept was more effective at improving vision. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01627249.).

Project description:ObjectiveTo describe effects of ranibizumab and bevacizumab when administered monthly or as needed for 2 years and to describe the impact of switching to as-needed treatment after 1 year of monthly treatment.DesignMulticenter, randomized clinical trial.ParticipantsPatients (n = 1107) who were followed up during year 2 among 1185 patients with neovascular age-related macular degeneration who were enrolled in the clinical trial.InterventionsAt enrollment, patients were assigned to 4 treatment groups defined by drug (ranibizumab or bevacizumab) and dosing regimen (monthly or as needed). At 1 year, patients initially assigned to monthly treatment were reassigned randomly to monthly or as-needed treatment, without changing the drug assignment.Main outcome measuresMean change in visual acuity.ResultsAmong patients following the same regimen for 2 years, mean gain in visual acuity was similar for both drugs (bevacizumab-ranibizumab difference, -1.4 letters; 95% confidence interval [CI], -3.7 to 0.8; P = 0.21). Mean gain was greater for monthly than for as-needed treatment (difference, -2.4 letters; 95% CI, -4.8 to -0.1; P = 0.046). The proportion without fluid ranged from 13.9% in the bevacizumab-as-needed group to 45.5% in the ranibizumab monthly group (drug, P = 0.0003; regimen, P < 0.0001). Switching from monthly to as-needed treatment resulted in greater mean decrease in vision during year 2 (-2.2 letters; P = 0.03) and a lower proportion without fluid (-19%; P < 0.0001). Rates of death and arteriothrombotic events were similar for both drugs (P > 0.60). The proportion of patients with 1 or more systemic serious adverse events was higher with bevacizumab than ranibizumab (39.9% vs. 31.7%; adjusted risk ratio, 1.30; 95% CI, 1.07-1.57; P = 0.009). Most of the excess events have not been associated previously with systemic therapy targeting vascular endothelial growth factor (VEGF).ConclusionsRanibizumab and bevacizumab had similar effects on visual acuity over a 2-year period. Treatment as needed resulted in less gain in visual acuity, whether instituted at enrollment or after 1 year of monthly treatment. There were no differences between drugs in rates of death or arteriothrombotic events. The interpretation of the persistence of higher rates of serious adverse events with bevacizumab is uncertain because of the lack of specificity to conditions associated with inhibition of VEGF.

Project description:BACKGROUND:The discussion on the use of bevacizumab is still ongoing and often doctors are deterred from using bevacizumab due to legal or political issues. Bevacizumab is an effective, safe and inexpensive treatment option for neovascular age-related macular degeneration (AMD), albeit unregistered for the disease. Therefore, in some countries ophthalmologists use the equally effective but expensive drugs ranibizumab and aflibercept. We describe the economic consequences of this dilemma surrounding AMD treatment from a societal perspective. METHODS:We modelled cost-effectiveness of treatment with ranibizumab (as-needed), aflibercept (bimonthly) and bevacizumab (as-needed). Effectiveness was estimated by systematic review and meta-analysis. The drug with the most favourable cost-effectiveness profile compared to bevacizumab was used for threshold analyses. First, we determined how much we overspend per injection. Second, we calculated the required effectiveness to justify the current price and the reasonable price for a drug leading to optimal vision. Finally, we estimated how much Europe overspends if bevacizumab is not first choice. RESULTS:Bevacizumab treatment costs €27,087 per year, about €4,000 less than aflibercept and €6,000 less than ranibizumab. With similar effectiveness for all drugs as shown by meta-analysis, bevacizumab was the most cost-effective. Aflibercept was chosen for threshold analyses. Aflibercept costs €943 per injection, but we determined that the maximum price to be cost-effective is €533. Alternatively, at its current price, aflibercept should yield about twice the visual gain. Even when optimal vision can be achieved, the maximum price for any treatment is €37,453 per year. Most importantly, Europe overspends €335 million yearly on AMD treatment when choosing aflibercept over bevacizumab. CONCLUSION:Bevacizumab is the most cost-effective treatment for AMD, yet is not the standard of care across Europe. The registered drugs ranibizumab and aflibercept lead to large overspending without additional health benefits. Health authorities should consider taking steps to implement bevacizumab into clinical practice as first choice.

Project description:BackgroundAnti-vascular endothelial growth factor (anti-VEGF) agents have become the standard of care in neovascular age-related macular degeneration (nAMD). Despite generally excellent response rates to anti-VEGF therapy, some patients do not respond or may respond suboptimally. In the case of refractory or rapidly recurring fluid in nAMD, clinicians may switch to another anti-VEGF agent. TITAN was an observational study that assessed the effectiveness and safety of intravitreal aflibercept (IVT-AFL) in patients with nAMD refractory to ranibizumab who switched to IVT-AFL after less than 12?months of ranibizumab treatment in routine clinical practice in France.MethodsTITAN was an observational, retrospective and prospective 12-month study conducted at 28 centres in France. Patients with nAMD refractory to ranibizumab were enrolled. Patients who were switched from ranibizumab to IVT-AFL were followed for 12?months. Data were obtained from medical records for retrospectively included patients, and at routine follow-up visits for those included prospectively. The main outcome measure was percentage of patients who achieved treatment success (gain of ?1 Early Treatment Diabetic Retinopathy Study letters in best-corrected visual acuity [BCVA] and/or any reduction in central retinal thickness [CRT]) from baseline to 12?months after switching. A sample size of 225 patients was determined based on a 2-sided 95% confidence interval with a width equal to 0.12 when the sample proportion was 0.70.ResultsWe analysed safety data (N =?217) and clinical outcomes from patients in the per-protocol population (n =?125). The mean (standard deviation) number of IVT-AFL injections was 7.5 (2.6). Treatment success was achieved in 68.8% of patients. Mean BCVA change from baseline to Month 12 was +?1.5 letters (P =?0.105) and the mean CRT change was -?45.0??m (P <? 0.001). In a subgroup analysis, in patients who received three initial monthly IVT-AFL injections, mean BCVA gain was 3.3 letters at Month 12 (P =?0.015). Excluding lack of efficacy and inappropriate scheduling of drug administration, the most common adverse event was eye pain (2.3%).ConclusionsSwitching ranibizumab-refractory patients with nAMD to IVT-AFL may improve visual outcomes in some patients, particularly those who receive three initial monthly injections.Trial registrationClinicalTrials.gov , NCT02321241 . First posted: December 22, 2014; Last update posted: July 2, 2018.

Dataset Information

Use of Bevacizumab and Ranibizumab for Wet Age-Related Macular Degeneration: Influence of CATT Results and Introduction of Aflibercept.

Publications

Use of Bevacizumab and Ranibizumab for Wet Age-Related Macular Degeneration: Influence of CATT Results and Introduction of Aflibercept.

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