Patient Preferences in the Management of Wet Age-Related Macular Degeneration: A Conjoint Analysis.

INTRODUCTION: To identify patient preference drivers related to the management of wet age-related macular degeneration (wet AMD). METHODS: In this cross-sectional study, a self-explicated 'conjoint analysis' survey was administered online to eligible patients with wet AMD (receiving anti-vascular endothelial growth factor [VEGF] treatment for at least 12 months) from the USA, Canada, UK, France, Spain, Germany, Italy, Japan, Taiwan, and Australia. The survey consisted of six domains with 21 attributes, which were selected on the basis of a literature review, social media listening, and tele-interviews/discussions with patients, clinical experts, and patient groups. Utility and relative importance scores were generated for each attribute and utility difference significance testing was performed using 'unequal variances t tests'. The Patient Activation Measure (PAM-13) questionnaire was administered to assess patients' knowledge, skill, and confidence in self-management. RESULTS: A total of 466 patients (mean age, 68 years; women, 54%; binocular wet AMD, 28%) with an average anti-VEGF treatment duration of 3.9 years completed the survey. The most important preference domains were 'treatment effects on vision' (non-significant) and 'vision-related symptom burdens' (p < 0.001), followed by 'treatment risk' (p < 0.05), 'impact on daily activities' (p < 0.05), 'burden of clinic/hospital visits' (p < 0.001), and 'impact on psychological well-being'. The five most important attributes in order of importance were clarity of vision, treatment effect on symptoms, quality of vision, time to treatment effect, and time to re-administration. The two most important attributes globally were also in the top three attributes across countries. The majority of participants in the study were level 3 or level 4 of the PAM-13 questionnaire. CONCLUSIONS: This study identified the most important disease and treatment attributes to patients using patient-centred methods. The data showed the degree of harmonization of preferences across geographies and that participants actively adopt behaviours required for improved treatment outcomes. The identified preference drivers may inform future clinical development.

SIERRA-AMD: A Retrospective, Real-World Evidence Study of Patients with Neovascular Age-Related Macular Degeneration in the United States.

PURPOSE: Characterize real-world baseline visual acuity (VA) and anti-vascular endothelial growth factor (VEGF) treatment patterns in neovascular age-related macular degeneration patients in 2012-2015. DESIGN: Retrospective, multicenter, noninterventional real-world evidence study. PARTICIPANTS: A total of 98 821 eyes from 79 885 patients receiving intravitreal anti-VEGF therapy. METHODS: Anonymized patient data routinely collected over 5 years were extracted from 58 United States centers to a central database using an electronic medical records system. MAIN OUTCOME MEASURES: Baseline VA, VA change from baseline, treatment frequencies, annual anti-VEGF injections, bilateral treatment frequencies, annual total clinic visits, and noninjection clinic visits. RESULTS: Baseline characteristics were comparable across years. Baseline VAs (Mean±standard deviation [SD] Early Treatment Diabetic Retinopathy Study [ETDRS] letters) were similar for 2012, 2013, and 2014 (53.6±23.3, 53.2±23.4, and 53.1±23.6, respectively), but was lower for 2015 (50.7±24.4). In eyes with 4-year follow-up, VA changes from baseline (ETDRS letters) were least squares means of +1.1 (95% confidence interval [CI], 1.0;1.3), -1.3 (95%CI, -1.5;-1.0), and -3.1 (95%CI, -3.5;-2.7), and -5.2 (95%CI, -6.0;-4.3) for years 1-4. Mean±SD number of injections was 7.5±1.9, 6.7±2.1, 6.6±2.3, and 6.4±2.3 for years 1-4. By year 4, 36.7% of eyes had ≤8-week dosing intervals (q8w) and 21.2% had ≥12-week dosing intervals. Eyes treated q8w increased 40% from Year 1 (32.4%) to Year 4 (45.3%). Baseline bilateral treatment frequency was 6.1%. Of the patients treated bilaterally, 32.0% received the first treatment in the better-seeing eye, and 68.0% received first treatment in an eye with vision the same as or worse than the fellow-eye. This trend was evident across all index years. CONCLUSIONS: This real-world study describes the treatment burden, initiation and monitoring patterns, and VA outcomes at a scale and timeframe that has not been previously reported. In this cohort, baseline VA was similar for the index years 2012-2014, but lower for 2015. In patients with 4-year follow-up, both VA and injection frequency declined, whereas the proportion of eyes treated more frequently than the recommended q8w interval increased. The reduction in dosing intervals may be a consequence of intensification of treatment due to year-on-year VA loss and disease progression.

Treat and Extend Treatment Interval Patterns with Anti-VEGF Therapy in nAMD Patients.

Treat and extend (T&E) is a standard treatment regimen for treating neovascular age-related macular degeneration (nAMD) with anti-vascular endothelial growth factors (anti-VEGFs), but the treatment intervals attained are not well documented. This retrospective, non-comparative, non-randomised study of eyes with nAMD classified treatment interval sequences in a T&E cohort in Australia using Electronic Medical Records (EMR) data. We analysed data from 632 treatment-naïve eyes from 555 patients injected with ranibizumab, aflibercept or unlicensed bevacizumab between January 2012 and June 2016 (mean baseline age 78.0). Eyes were categorised into non-overlapping clusters of interval sequences based on the first 12 months of follow-up. We identified 523 different treatment interval sequences. The largest cluster of 197 (31.5%) eyes attained an 8-week treatment interval before dropping to a shorter frequency, followed by 168 (26.8%) eyes that did not reach or attained a single 8-week interval at the end of the study period. A total of 65 (10.4%) and 83 (13.3%) eyes reached and sustained (≥2 consecutive injection intervals of the same length) an 8 and 12 weekly interval, respectively. This study demonstrates highly individualised treatment patterns in the first year of anti-VEGF therapy in Australia using T&E regimens, with the majority of patients requiring more frequent injections than once every 8 weeks.

Effectiveness of Continued Ranibizumab Therapy in Neovascular Age-Related Macular Degeneration versus Switch to Aflibercept: Real World Evidence.

PURPOSE: To assess the long-term comparative effectiveness of ranibizumab versus switching to aflibercept in neovascular age-related macular degeneration (nAMD). DESIGN: A 24-month, retrospective, comparative, nonrandomized, matched cohort study. PARTICIPANTS: Patients with nAMD initiated on ranibizumab who remained (nonswitchers) or who switched to aflibercept (switchers) captured from a United States electronic medical records database between July 1, 2011 and October 12, 2014. METHODS: Patient eyes were matched for baseline age, baseline visual acuity (VA), VA at month 3, and duration of follow-up. Matching ratio was 1:2 (switchers: nonswitchers) where possible and 1:1 otherwise. MAIN OUTCOME MEASURES: The primary outcome was VA change from baseline (first injection of ranibizumab) to month 24. Secondary end points were standardized area under the curve of VA change; patient eyes (%) gaining or losing ≥5, ≥10, or ≥15 letters, or with VA of >73 letters at month 24; number of injections and monitoring visits; and analysis of preswitch characteristics. RESULTS: A total of 454 switchers and 750 matched nonswitchers were included. The adjusted difference in mean VA change from baseline to month 24 for switchers to nonswitchers was 0.02 letters (95% confidence interval [CI], -1.63 to 1.68). The upper bound 95% CI (1.68) was below the predefined noninferiority margin of 5 letters. Switchers had a significantly higher annualized number of mean total visits compared with nonswitchers (10.0 vs. 9.0 for year 1; 8.7 vs. 7.4 for year 2), a higher number of injection visits (8.4 vs. 6.7 for year 1; 7.0 vs. 5.1 for year 2), but a lower number of monitoring-only visits (1.6 vs. 2.3 for year 1; 1.7 vs. 2.3 for year 2). During the preswitch period, switchers had a higher number of injection visits (7.6 vs. 6.5), fewer monitoring-only visits (1.5 vs. 2.2), and comparable total visits (9.1 vs. 8.7). Visual acuity change from baseline to switch was similar between switchers and nonswitchers (adjusted least squares mean difference, -1.36 letters; 95% CI, -2.76 to 0.05). CONCLUSIONS: Switching patients from ranibizumab to aflibercept resulted in no difference in VA change compared with those maintained on ranibizumab only. The lower retreatment rate in nonswitchers compared with switchers post switch does not support the view of a longer treatment efficacy.

The economic and humanistic burden of patients in receipt of current available therapies for nAMD.

AIM: To determine the economic and humanistic burden of neovascular age-related macular degeneration (nAMD) in a cohort of patients treated with anti-VEGF in Europe and the US. PATIENTS & METHODS: 79 respondents from the EU and 63 from the US with a self-reported diagnosis of nAMD and in current receipt of treatment, as reported in an international, general population survey, were compared with non-nAMD controls. RESULTS: Anti-VEGF-treated nAMD patients in the EU had a greater utilization of healthcare resources, poorer quality of life and greater overall activity impairment versus non-nAMD controls. In the US cohort, treated nAMD patients had significantly greater resource utilization for ophthalmologist visits only. CONCLUSION: The burden of care associated with nAMD on EU and US healthcare systems, and on patients who are in receipt of nAMD therapy, is significant and likely to be unsustainable.

Dispensing Patterns of Ranibizumab and Aflibercept for the Treatment of Neovascular Age-Related Macular Degeneration: A Retrospective Cohort Study in Australia.

INTRODUCTION: Anti-vascular endothelial growth factor therapy is the standard of care for neovascular age-related macular degeneration (nAMD). The dosage of two licensed agents, ranibizumab and aflibercept, was established through clinical trials; however, it is unclear if either agent is administered as recommended in routine clinical practice. Using pharmacy claims data, we investigated if the dispensing patterns of ranibizumab differ from those of aflibercept 6 and 12 months after treatment initiation. METHODS: Prescription data retrieved from the Australian IMS® AUS LRx database were used to identify nAMD patients with one or more claims for ranibizumab or aflibercept between December 1, 2012, and March 31, 2015, with follow-up of at least 6 months. The number of ranibizumab and aflibercept units dispensed was adjusted for baseline patient Medication-Based Disease Burden Index (MBDBI) scores. No difference in the number of ranibizumab versus aflibercept units dispensed was concluded if the 95% confidence interval (CI) limits of the adjusted mean difference between the study cohorts were 1.00 unit or less. RESULTS: Baseline patient MBDBI scores were similar for the ranibizumab (N = 1235) and aflibercept (N = 959) cohorts. The adjusted mean (standard deviation) number of units dispensed was 5.3 (1.3) versus 5.1 (1.4) at month 6 and 8.9 (2.2) versus 8.9 (2.3) at month 12. The 95% CI limits of the adjusted mean difference did not exceed 1.00 unit dispensed at either time point: 95% CI of 0.09 to 0.32 for an adjusted mean difference of 0.20 at month 6 and -0.23 to 0.30 for an adjusted mean difference of 0.04 at month 12. Mean (standard deviation) dispensing intervals were comparable for both cohorts: 35.3 (19.2) days versus 36.8 (20.0) days at month 6 (adjusted mean difference -1.59 days; 95% CI -2.51 to -0.67 days) and 41.2 (20.9) days versus 41.6 (20.4) days at month 12 (adjusted mean difference -0.40 days; 95% CI -1.70 to 0.91 days). CONCLUSIONS: Ranibizumab and aflibercept are dispensed in a similar manner by Australian pharmacies during the first year of treatment. FUNDING: Novartis Pharma AG.

A Retrospective Study of Ranibizumab Treatment Regimens for Neovascular Age-Related Macular Degeneration (nAMD) in Australia and the United Kingdom.

INTRODUCTION: Neovascular age-related macular degeneration (nAMD) is the leading cause of vision loss among persons aged 65 years and older. Anti-vascular endothelial growth factor (anti-VEGF) treatment is the recommended standard of care. The current study compares the effectiveness of ranibizumab in routine clinical practice in two countries that generally apply two different treatment regimens, treat-and-extend (T&E) in Australia or pro re nata (PRN) in the UK. METHODS: This retrospective, comparative, non-randomised cohort study is based on patients' data from electronic medical record (EMR) databases in Australia and the UK. Treatment regimens were defined based on location, with Australia as a proxy for analysing T&E and UK as a proxy for analysing PRN. The study included patients with a diagnosis of nAMD who started treatment with ranibizumab between January 2009 and July 2014. A total of 647 eyes of 570 patients in Australia and 3187 eyes of 2755 patients in the UK with complete 12-months follow-up were analysed. RESULTS: Baseline patient characteristics were comparable between the two cohorts. After 1 year of treatment, T&E-treated eyes achieved higher mean (±SE) visual acuity (VA) gains (5.00 ± 0.54 letters [95% confidence interval (CI) 3.93-6.06]) than PRN-treated eyes [3.04 ± 0.24 letters (95% CI 2.57-3.51); difference in means 2.07 ± 0.69 (95% CI 0.73-3.41), p < 0.001]. Non-inferiority of T&E compared to PRN was concluded based on the change in mean visual acuity gains at 12 months. Over the 12-month follow-up, T&E-treated eyes received a higher mean [±standard deviation (SD)] number of injections (9.29 ± 2.43) than PRN-treated eyes (6.04 ± 2.19) (p < 0.0001). Australian patients had a lower mean (±SD) number of total clinic visits (10.29 ± 2.90) than UK patients (11.47 ± 2.93) (p < 0.0001). CONCLUSION: The higher injection frequency in the T&E cohort may account for the trend toward improved vision. FUNDING: Novartis Pharma AG, Basel, Switzerland.

The Clinical Effectiveness of Ranibizumab Treat and Extend Regimen in nAMD: Systematic Review and Network Meta-Analysis.

INTRODUCTION: Neovascular age-related macular degeneration (nAMD) is a chronic eye condition that causes severe deterioration of vision and ultimately blindness. Two vascular endothelial growth factor inhibitors are approved for nAMD treatment in Europe: ranibizumab and aflibercept. The European license for ranibizumab was updated with an individualized "treat and extend" (T&E) regimen, which involves more proactive treatment based on changes in best corrected visual acuity (BCVA) and/or anatomical outcomes. The aim of this publication is to compare the efficacy of the ranibizumab T&E regimen with other approved dosing regimens for nAMD on the basis of outcomes identified from a systematic review and subsequent NMA. METHODS: Following a systematic search of publications, to identify relevant studies, a repeated-measures network meta-analysis (NMA) was performed to estimate the relative effectiveness of ranibizumab T&E versus approved dosing regimens of ranibizumab and aflibercept. The analysis focused on licensed treatment regimens for nAMD. We examined mean change from baseline in BCVA on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. RESULTS: The systematic literature review identified 22,949 records, of which 23 studies were included in the NMA. At 12 months, the ranibizumab T&E dosing regimen vs ranibizumab pro re nata (PRN) was associated with small differences in change in BCVA, between 1.86 letter gain at 12 months and 2.35 letter gain at 24 months. A similar difference was observed in the aflibercept dosing regimen versus ranibizumab T&E ; 1.94 letter gain at 12 months and 3.31 letter gain at 24 months. All doses of ranibizumab and aflibercept showed similar effectiveness, and the differences between treatment options were not significant. CONCLUSION: This study used novel repeated-measures NMA to synthesize efficacy results when treatment effects were reported at multiple follow-up times. This repeated-measures NMA suggests that treating patients with the ranibizumab T&E regimen yields similar effectiveness compared to other approved ranibizumab and aflibercept dosing regimens for nAMD treatment. FUNDING: Novartis Pharmaceuticals UK Ltd, Surrey, UK.