Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): health status analysis of a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Improving symptoms is a primary treatment goal in patients with obstructive hypertrophic cardiomyopathy. Currently available pharmacological options for hypertrophic cardiomyopathy are not disease-specific and are often inadequate or poorly tolerated. We aimed to assess the effect of mavacamten, a first-in-class cardiac myosin inhibitor, on patients' health status-ie, symptoms, physical and social function, and quality of life. METHODS: We did a health status analysis of EXPLORER-HCM, a phase 3, double-blind, randomised, placebo-controlled trial. The study took place at 68 clinical cardiovascular centres in 13 countries. Adult patients (≥18 years) with symptomatic obstructive hypertrophic cardiomyopathy (gradient ≥50 mm Hg and New York Heart Association class II-III) were randomly assigned (1:1) to mavacamten or placebo for 30 weeks, followed by an 8-week washout period. Both patients and staff were masked to study treatment. The primary outcome for this secondary analysis was the Kansas City Cardiomyopathy Questionnaire (KCCQ), a well validated disease-specific measure of patients' health status. It was administered at baseline and weeks 6, 12, 18, 30 (end of treatment), and 38 (end of study). Changes from baseline to week 30 in KCCQ overall summary (OS) score and all subscales were analysed using mixed model repeated measures. This study is registered with ClinicalTrials.gov, NCT03470545. FINDINGS: Between May 30, 2018, and July 12, 2019, 429 adults were assessed for eligibility, of whom 251 (59%) were enrolled and randomly assigned. Of 123 patients randomly assigned to mavacamten, 92 (75%) completed the KCCQ at baseline and week 30 and of the 128 patients randomly assigned to placebo 88 (69%) completed the KCCQ at baseline and week 30. At 30 weeks, the change in KCCQ-OS score was greater with mavacamten than placebo (mean score 14·9 [SD 15·8] vs 5·4 [13·7]; difference +9·1 [95% CI 5·5-12·8]; p<0·0001), with similar benefits across all KCCQ subscales. The proportion of patients with a very large change (KCCQ-OS ≥20 points) was 36% (33 of 92) in the mavacamten group versus 15% (13 of 88) in the placebo group, with an estimated absolute difference of 21% (95% CI 8·8-33·4) and number needed to treat of five (95% CI 3-11). These gains returned to baseline after treatment was stopped. INTERPRETATION: Mavacamten markedly improved the health status of patients with symptomatic obstructive hypertrophic cardiomyopathy compared with placebo, with a low number needed to treat for marked improvement. Given that the primary goals of treatment are to improve symptoms, physical and social function, and quality of life, mavacamten represents a new potential strategy for achieving these goals. FUNDING: MyoKardia, a Bristol Myers Squibb company.

Contemporary Challenges in Polycythemia Vera Management From the Perspective of Patients and Physicians.

Although polycythemia vera (PV) is a chronic and incurable disease, effective management can allow most patients to maintain functional lives with near-normal life expectancy. However, there remain several inter-related factors that contribute to many ongoing challenges associated with the management of PV, which this review aims to explore. First, as a disease hallmarked by constitutive activation of the JAK/STAT pathway, PV is often accompanied by inflammatory symptoms that negatively impact quality of life. Next, patients often require recurrent therapeutic phlebotomies to maintain their hematocrit below the 45% threshold that has been associated with a decreased risk of thrombotic events. The need to closely monitor hematocrit and perform conditional therapeutic phlebotomies ties patients to the healthcare system, thereby limiting their autonomy. Furthermore, many patients describe therapeutic phlebotomies as burdensome and the procedure is often poorly tolerated, further contributing to quality-of-life decline. Phlebotomy needs can be reduced by utilizing cytoreductive therapy; however, standard first-line cytoreductive options (i.e., hydroxyurea and interferon) have not been shown to significantly improve symptom burden. Collectively, current PV management, while reducing thrombotic risk, often has a negative impact on patient quality of life. As researchers continue to advance towards the goal of developing a disease-modifying therapy for patients with PV, pursuit of nearer-term opportunities to shift the current treatment paradigm towards improving symptoms without compromising quality of life is also warranted, for example, by reducing or eliminating the frequent use of phlebotomy.

Clinical Outcomes, Resource Utilization, and Treatment Over the Disease Course of Symptomatic Obstructive Hypertrophic Cardiomyopathy in the United States.

We sought to describe the clinical outcomes, resource utilization, and treatment options for patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) over the course of their disease. Adults with obstructive HCM who were symptomatic were identified from the IBM MarketScan Commercial and Medicare supplemental database (January 2009 to March 2019). The index date was the initial obstructive HCM diagnosis date. Patients were required to have ≥12-month continuous eligibility before and after the index date. Incidence rates (IRs) and cumulative risk of cardiovascular events, healthcare resource utilization, and pharmacotherapy were assessed after index and compared with matched controls. Among 4,617 eligible patients with obstructive HCM, 2,917 (63.2%, mean age 60, 47.2% women) were symptomatic at index date. The most common cardiovascular events were atrial fibrillation/flutter (IR:1.421 per person-year [PPY], heart failure (IR: 0.895 PPY), and dyspnea (IR:0.797 PPY). Patients incurred higher resource use with frequent tests and monitoring, hospitalizations (0.454 PPY), and emergency room visits (0.611 PPY). The use of pharmacotherapy increased from 61.2% in the 6-month preindex period to 83.9% in the 6-month postindex period and remained stable after diagnosis. These events ranged from 3 to over 60-fold higher compared with controls, with the largest difference observed in arrhythmic events. The majority of patients were symptomatic at the time of obstructive HCM diagnosis, resulting in significantly increased cardiovascular complications and frequent disease monitoring after diagnosis versus controls. In conclusion, healthcare resource utilization was substantial, and these findings suggest a higher clinical and economic burden over the disease course among patients with symptomatic obstructive HCM, despite current treatment.

Frequency and clinicoeconomic impact of delays to definitive diagnosis of obstructive hypertrophic cardiomyopathy in the United States.

AIMS: The diagnostic history in the years leading up to the definitive diagnosis of patients with obstructive hypertrophic cardiomyopathy (HCM) has not been studied. METHODS: Patients with a delay in the definitive diagnosis of obstructive HCM from January 2009 to March 2019 were identified in the US IBM MarketScan Commercial and Medicare Supplemental Databases if they had an alternative diagnosis indicating a misdiagnosis during the 24 months before the definitive obstructive HCM diagnosis. Resource use and costs associated with the delay were estimated during the same period. RESULTS: Of 3,888 eligible patients with obstructive HCM, 59.5% had a delay in definitive diagnosis. Patients received a mean of 4.0 misdiagnoses before the definitive obstructive HCM diagnosis, most of which were other cardiovascular conditions. Consequently, 15.7% of patients may have received inappropriate treatment. Approximately 78.4% of patients visited a cardiologist (mean 4.7 visits) before the definitive obstructive HCM diagnosis. Additionally, 26.8% and 32.1% of patients had an inpatient and emergency room visit, respectively. Annualized healthcare costs associated with the delay were $4,379 per patient. LIMITATIONS: The current study used administrative claims data for a commercially insured population. Therefore, the results may not be generalizable to other populations (e.g. those insured by Medicare or Medicaid and the uninsured). Like other database studies, the current study may have suffered from miscoding or undercoding, which may have caused misclassification of patients. Owing to insufficient data, the study could not evaluate all potential consequences of a delay in definitive diagnosis. CONCLUSIONS: Most patients with obstructive HCM had a delay of ≤ 2 years before receiving the definitive diagnosis. The diagnostic journey involved multiple potential misdiagnoses, predominantly cardiovascular, as well as a substantial clinical and economic burden on patients and the healthcare system.

Assessing health-related quality-of-life in patients with symptomatic obstructive hypertrophic cardiomyopathy: EQ-5D-based utilities in the EXPLORER-HCM trial.

AIMS: To assess the effects of mavacamten on health-related quality-of-life (HRQoL) in symptomatic obstructive hypertrophic cardiomyopathy (HCM) and estimate health utilities by New York Heart Association (NYHA) functional class. MATERIALS AND METHODS: Patients with symptomatic obstructive HCM were randomized to 30 weeks of mavacamten or to placebo treatment, with or without beta-blocker or calcium channel blocker monotherapy, in EXPLORER-HCM (ClinicalTrials.gov identifier: NCT03470545). Health utility was measured using the EuroQoL 5-dimension 5-level (EQ-5D-5L) index score with the US value set. The 30-week changes in EQ-5D-5L index score and EuroQoL visual analog scale (EQ-VAS) score were compared between the two arms using linear regression, and the proportions of patients with a meaningful improvement were compared using logistic regression. The meaningful change thresholds were estimated using both distribution- and anchor-based approaches. Mean utilities by NYHA class were estimated for each arm using a generalized estimating equation. RESULTS: Compared with placebo (N = 89), patients receiving mavacamten (N = 96) had significantly greater 30-week improvement in EQ-5D-5L index score (mavacamten = 0.084; placebo = 0.009; adjusted difference = 0.073 [95% confidence interval = 0.027-0.118]) and EQ-VAS score (mavacamten = 8.5; placebo = 0.7; adjusted difference = 7.5 [95% confidence interval = 1.8-13.2]), and a significantly higher proportion of these patients showed meaningful improvement in EQ-5D-5L index score and EQ-VAS score. Both outcomes were correlated with the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ CSS) and HCM Symptom Questionnaire Shortness-of-Breath (HCMSQ SoB) subscore, two patient-reported anchor variables. Additionally, mean utilities significantly decreased with higher NYHA functional class (values for NYHA class I, II, and III/IV - mavacamten = 0.950, 0.866, and 0.708; placebo = 0.952, 0.850, and 0.704). CONCLUSIONS: Compared with placebo, mavacamten significantly improved EQ-5D-5L index score and EQ-VAS score - and thus HRQoL - among patients with symptomatic obstructive HCM. Patients with a higher NYHA functional class had a lower health utility value.

Longitudinal Psychometric Analysis of the Hypertrophic Cardiomyopathy Symptom Questionnaire (HCMSQ) Using Outcomes from the Phase III EXPLORER-HCM Trial.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) symptoms include shortness of breath (SOB), fatigue, chest pain, palpitations, dizziness, and fainting. The HCM Symptom Questionnaire (HCMSQ), the only patient-reported outcome instrument designed to specifically measure HCM symptoms, yields four domain scores (SOB, tiredness, cardiovascular symptoms, syncope) and a total score. We evaluated the longitudinal psychometric properties of the HCMSQ using baseline to week 30 data from the phase III EXPLORER-HCM trial (NCT03470545). METHODS: Test-retest reliability was assessed via intraclass correlation of patients with stable Patient Global Impression of Change (PGIC) and Patient Global Impression of Severity (PGIS) responses. Sensitivity to change was assessed via Spearman correlations with the Kansas City Cardiomyopathy Questionnaire (KCCQ-23) and the EuroQoL visual analogue scale (EQ VAS), and via one-way ANOVA comparing change groups defined on clinical (New York Heart Association [NYHA] class, left ventricular outflow tract [LVOT] gradient, peak oxygen consumption [pVO2]) and patient-reported (PGIS, PGIC) variables. Meaningful change thresholds were established via PGIC/PGIS. RESULTS: All HCMSQ scores showed strong evidence of test-retest reliability (intraclass correlation coefficient > 0.70). Sensitivity to change was demonstrated with mostly strong/moderate correlations with KCCQ-23 and EQ VAS, and significant differences (p ≤ 0.05) in PGIS, PGIC, pVO2, and NYHA (except tiredness domain) change categories, but not LVOT gradient. Clinically meaningful score reductions were ≥1 point for tiredness and cardiovascular symptoms domains, ≥ 2.5 points for SOB domain, and ≥2 points for total score. CONCLUSIONS: Results suggest that HCMSQ is fit for purpose in capturing HCM symptoms and may provide evidence of treatment benefit from the patients' perspectives.

Treatment Changes, Healthcare Resource Utilization, and Costs Among Patients with Symptomatic Obstructive Hypertrophic Cardiomyopathy: A Claims Database Study.

INTRODUCTION: There is limited evidence on therapies for obstructive hypertrophic cardiomyopathy (HCM), and data regarding treatment patterns and cost are scarce. This study assessed treatment patterns and economic outcomes in patients with symptomatic obstructive HCM. METHODS: Adults with symptomatic obstructive HCM as per study design and treated with pharmacotherapies [beta blockers (BBs), calcium channel blockers (CCBs), BB + CCB, or disopyramide] or procedures (septal reduction therapy, heart transplantation, implantable cardioverter-defibrillator, and pacemaker implantation) were identified from the IBM® MarketScan® Commercial and Medicare Supplemental database (January 2009-March 2019). Patients had 12-month continuous eligibility before and after (study period) treatment initiation (index treatment). Healthcare resource utilization (HRU), costs, and treatment changes were assessed. RESULTS: Of the 4883 patients included in the analysis, 85% received pharmacotherapies (BB 52.5%; CCB 11.7%; BB + CCB 17.7%; disopyramide 2.4%) and 15.7% underwent procedures. During the study period, 38, 34, and 100% of all patients had ≥ 1 inpatient stay, emergency room (ER) visit, and outpatient visit, respectively; mean total healthcare costs were US$53,053. Patients undergoing procedures had the highest HRU and costs across groups. Among patients receiving pharmacotherapies, HRU was lowest with BBs and highest with disopyramide. Treatment changes were observed in 43.8% of patients receiving pharmacotherapies. CONCLUSIONS: Patients experienced high rates of treatment changes, and the economic burden associated with symptomatic obstructive HCM increased as therapy escalated. More effective therapies are needed to stabilize or decrease the economic burden of obstructive HCM.

Projecting the Long-term Clinical Value of Mavacamten for the Treatment of Obstructive Hypertrophic Cardiomyopathy in the United States: An Assessment of Net Health Benefit.

PURPOSE: The aim of the study was to project the long-term net health benefits of mavacamten for the treatment of symptomatic obstructive hypertrophic cardiomyopathy (HCM) in the United States. METHODS: A Markov model with 4 mutually exclusive health states (New York Heart Association [NYHA] functional classes I, II, and III/IV and death) was developed to project the life-years (LYs) and quality-adjusted life-years (QALYs) over a lifetime horizon for patients with symptomatic obstructive HCM receiving mavacamten with or without ß-blocker (BB) or calcium channel blocker (CCB) monotherapy or placebo with or without BB or CCB monotherapy. The model simulated a patient cohort with a starting age of 59 years and 41% women. Transition probabilities across NYHA functional classes were estimated using data from the Phase III Clinical Study to Evaluate Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy (EXPLORER-HCM) and the EXPLORER long-term extension (EXPLORER-LTE) cohort from the Long-term Safety Extension Study of Mavacamten in Adults who Have Completed MAVERICK-HCM or EXPLORER-HCM (MAVA-LTE) trial and were extrapolated after week 30. The mortality risks of NYHA functional class I were assumed to be the age- and sex-specific mortality risks of the US general population. The mortality risks for NYHA class II and III/IV were estimated using those for class I in conjunction with the relative mortality risks derived using patients with obstructive HCM from a large real-world registry. Health state utilities for each treatment were estimated from EXPLORER-HCM. Both LYs and QALYs were aggregated over a lifetime for each treatment arm, discounted at 3% annually, and compared between the 2 arms. Sensitivity analyses were conducted to evaluate the robustness of the model findings. FINDINGS: Over a lifetime, treatment with mavacamten with or without BB or CCB monotherapy was associated with 3.67 incremental LYs compared with placebo with or without BB or CCB monotherapy (13.00 vs 9.33 LYs). Compared with individuals in the placebo group, patients in the mavacamten group were projected to spend 6.17 additional LYs in NYHA functional class I and 0.04 and 2.46 fewer LYs in NYHA functional classes II and III/IV, respectively. With utilities incorporated, mavacamten with or without BB or CCB monotherapy was associated with 4.17 additional QALYs compared with placebo with or without BB or CCB monotherapy (11.74 vs 7.57 QALYs). In the sensitivity analyses, incremental benefits ranged from 1.55 to 6.21 LYs and from 2.48 to 6.19 QALYs across the scenarios. IMPLICATIONS: This model projected substantial net health benefits associated with mavacamten for symptomatic obstructive HCM owing to improved patient survival and quality of life. The projected QALY gain underscored the likely long-term clinical value of mavacamten in symptomatic obstructive HCM.

Validation of the Kansas City Cardiomyopathy Questionnaire in Symptomatic Obstructive Hypertrophic Cardiomyopathy.

BACKGROUND: The primary goal for treating patients with obstructive hypertrophic cardiomyopathy (oHCM) is to improve their symptoms, function, and quality of life. Although the Kansas City Cardiomyopathy Questionnaire (KCCQ) is a valid, reliable, and sensitive measure for other etiologies of heart failure, its appropriateness for patients with oHCM is unknown. OBJECTIVES: The purpose of this study was to establish the interpretability, validity, reliability, and responsiveness of the KCCQ in patients with oHCM. METHODS: Cognitive debriefing of the KCCQ was performed in 26 patients with oHCM. The validity, reliability, responsiveness, and interpretability of the KCCQ were tested in 196 participants from the EXPLORER-HCM trial by comparing each scale with relevant comparators, describing the internal reliability and the mean change in stable patients, and comparing the mean change in patients who reported different degrees of clinical change using a patient-reported global impression of change (PGIC). RESULTS: All KCCQ domains demonstrated strong correlations with external standards of symptoms, function, social limitation, and quality of life, including a recently designed instrument measuring symptoms not captured by the KCCQ (P < 0.0001 for all). Mean changes in stable patients were nonsignificant, ranging from 0.21 to 2.3 points (P > 0.30 for all), with high intraclass correlation coefficients. The mean changes in patients with small, moderate, and large clinical changes were consistent with the 5-, 10-, and 20-point mean differences observed in other etiologies of heart failure. CONCLUSIONS: The KCCQ is well understood by patients with oHCM and has strong evidence of good psychometric performance. It can not only serve as a relevant endpoint in clinical trials of oHCM therapy, but may also prove useful in the clinical care of patients with oHCM. (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy [EXPLORER-HCM]; NCT03470545).

Clinical and economic burden of obstructive hypertrophic cardiomyopathy in the United States.

AIMS: Obstructive hypertrophic cardiomyopathy (oHCM) is a disease of the cardiomyocyte in which dynamic left ventricular outflow track obstruction may lead to heart failure, valvular disease, and sudden death. Little is known about healthcare resource utilization (HRU) and costs associated with oHCM. This study investigated the clinical and economic burden of oHCM in patients with or without symptoms associated with oHCM. METHODS: We used the US IBM MarketScan Commercial and Medicare Supplemental database to identify patients with oHCM (January 2009-March 2019). Control patients without cardiomyopathy were matched to each patient with oHCM based on age, sex, region, and index year (3:1 ratio). One-year HRU and cost data were compared between all oHCM, symptomatic oHCM, and asymptomatic oHCM subgroups, and their respective controls. RESULTS: Among 11,401 eligible patients with oHCM (mean age 57 years, 42% female), 5,667 (50%) were symptomatic (23% chest pain, 57% dyspnea, 29% fatigue, 17% syncope). oHCM was associated with significant increases in all-cause hospitalizations, hospital days, outpatient visits, and total healthcare costs (mean ± standard deviation: $26,929 ± 77,720 vs. $6,808 ± 25,712, p<.001) compared with matched controls. These differences were driven mainly by the clinical and economic burden of symptomatic oHCM, which was associated with significant increases in 1-year hospitalization rates (38.0 vs. 6.9%), hospital days (3.7 ± 9.9 vs. 0.4 ± 3.0), and total healthcare costs ($43,586 ± 103,756 vs. $6,768 ± 27,618; all p<.001). Adjustment for comorbidities had minimal impact on these differences. LIMITATIONS: The use of claims data relies on International Classification of Diseases (ICD-9 and ICD-10) diagnosis codes, which might be inaccurate. Only commercially insured patients were included. CONCLUSION: In a real-world population, oHCM was associated with substantial increases in HRU and incremental costs of ∼$20,000/year when compared with matched controls-a difference that increased to ∼$35,000/year among symptomatic patients. Further studies are warranted to understand the potential impact of specific therapies on HRU and the economic burden of oHCM.

PLAIN LANGUAGE SUMMARYObstructive hypertrophic cardiomyopathy (oHCM) is a medical condition in which the heart muscle becomes abnormally thick and can cause partial blockage of blood flow out of the heart. Some patients experience symptoms (such as shortness of breath, chest pain, and fatigue) from this condition while others do not. Little is known about the healthcare resource utilization (HRU) and costs associated with oHCM, and if there are any differences between patients with oHCM who experience symptoms versus those who are asymptomatic. Therefore, we performed a study to investigate the clinical and economic burden of oHCM in patients with or without symptoms associated with oHCM. Based on insurance claims data, ∼50% of all patients with diagnosed oHCM are symptomatic. Symptomatic patients experience nearly 8 times as many hospitalizations and cost the healthcare system >$35,000 per year more than matched controls. In contrast, asymptomatic patients with oHCM have a much smaller difference in HRU and costs (∼$3,600/year) compared with matched controls. The results of this study suggest that effective therapies for oHCM may provide economic value, even if the impact of therapy is limited solely to the relief of symptoms.

Vision-related function after ranibizumab treatment by better- or worse-seeing eye: clinical trial results from MARINA and ANCHOR.

OBJECTIVE: To examine the effects of ranibizumab on the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) scores in neovascular age-related macular degeneration (AMD) according to whether the study eye was the better- or worse-seeing eye at baseline. DESIGN: Within 2 randomized, double-masked clinical trials (MARINA and ANCHOR), the NEI VFQ-25 was administered at 0, 1, 2, 3, 6, 9, 12, 18, and 24 months. PARTICIPANTS: We included 646 MARINA and 379 ANCHOR patients. INTERVENTION: Patients were randomized 1:1:1 to monthly intravitreal ranibizumab (0.3 or 0.5 mg) or control (sham injections for MARINA; photodynamic therapy [PDT] with verteporfin for ANCHOR). MAIN OUTCOME MEASURES: Mean change from baseline in NEI VFQ-25 scores at 12 and 24 months. RESULTS: Across all treatment arms, 21% to 38% of enrolled eyes were the better-seeing eye. At the 24-month follow-up visit, mean change in composite scores with ranibizumab seemed to be better than control for both better-seeing eyes (8.4 [95% confidence interval (CI), 5.2-11.6], 7.5 [95% CI, 3.7-11.4], and -9.4 [95% CI, -12.5 to -6.3] for the 0.3-mg, 0.5-mg, and sham groups, respectively) and worse-seeing eyes (1.7 [95% CI, -1.1 to 4.4], 1.7 [95% CI, -0.7 to 4.1], and -5.4 [95% CI, -7.9 to -2.8] for the 0.3-mg, 0.5-mg, and sham groups, respectively) in MARINA, as well as the better-seeing eye in ANCHOR (11.3 [95% CI, 5.3-17.3], 13.3 [95% CI, 7.7-19.0], and -2.7 [95% CI, -9.0 to 3.7] for the 0.3-mg, 0.5-mg, and PDT groups, respectively). When the worse-seeing eye was treated in ANCHOR, such differences could not be detected at 24 months (1.3 [95% CI, -1.7 to 4.2], 2.6 [95% CI, -1.1 to 6.3], and 0.1 [95% CI, -3.5 to 3.7] for the 0.3-mg, 0.5-mg, and PDT groups, respectively). CONCLUSIONS: Analysis of patient perception of vision-related function in phase III trials evaluating ranibizumab for neovascular AMD demonstrates improved patient-reported outcomes regardless of whether the treated eye is the better- or worse-seeing eye at onset of treatment, and supports treatment of such lesions with ranibizumab, even those in the worse-seeing eye. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Improved vision-related function after ranibizumab treatment of neovascular age-related macular degeneration: results of a randomized clinical trial.

OBJECTIVE: To examine the effects of ranibizumab on patient-reported visual function using the National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25) in patients with neovascular age-related macular degeneration (AMD). DESIGN: In MARINA, a randomized, double-masked clinical trial, 716 patients with AMD with recent disease progression and minimally classic or occult with no classic lesion component were randomized 1:1:1 to monthly intravitreal ranibizumab (0.3 or 0.5 mg) or sham injections. The NEI VFQ-25 was administered at 0, 1, 2, 3, 6, 9, 12, 18, and 24 months. Main Outcome Measure Mean change from baseline in NEI VFQ-25 scores at 12 and 24 months. RESULTS: At 12 months, ranibizumab-treated patients (0.3 mg [n = 238] and 0.5 mg [n = 240]) had mean improvements in NEI VFQ-25 composite scores of +5.2 (95% confidence interval [CI], 3.5 to 6.9) and +5.6 (95% CI, 3.9 to 7.4), respectively; sham-injected patients (n = 238) had a mean decline of -2.8 (95% CI, -4.6 to -1.1; P < .001 vs each dose). Ranibizumab-treated patients were more likely to improve in near activities, distance activities, and vision-specific dependency through 24 months. CONCLUSIONS: In MARINA, ranibizumab-treated patients were more likely than sham-treated patients to report visual function improvements at 12 and 24 months. APPLICATION TO CLINICAL PRACTICE: Treatment of neovascular AMD with ranibizumab can improve patient-reported visual function in a meaningful way compared with sham treatments. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00056836.

Validation of the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) in age-related macular degeneration.

PURPOSE: Patient-reported measures of visual function are increasingly incorporated into clinical trials of new treatments for age-related macular degeneration (AMD). Limited information is available regarding the associations between distance visual acuity (VA), reading speed, or contrast sensitivity and the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) subscales judged relevant to these measures. This study's objective was to evaluate such associations along with questions on restricted activity days. METHODS: This cross-sectional study was conducted in patients with clinical diagnoses of neovascular AMD. Patient-reported outcome measures included the NEI VFQ-25 and restricted activity days. Clinical assessments included best-corrected visual acuity (BCVA), reading speed, and contrast sensitivity. The better-seeing eye was defined based on the BCVA of each patient. Psychometric properties of the NEI VFQ-25 were examined; analyses a priori focused on the Near Activities, Distance Activities, and Vision-Specific Dependency subscales. RESULTS: The final study group included 92 participants (mean age, 78 years). Cronbach's α for the subscales ranged from 0.67 to 0.92. The NEI VFQ-25 overall composite, Near Activities, Distance Activities, and Vision-Specific Dependency scores were correlated with BCVA (r = -0.48 to -0.54, all P < 0.0001), reading speed (r = 0.43 to 0.56, all P < 0.0001), and contrast sensitivity (r = -0.39 to -0.46, all P < 0.001) of the better-seeing eye and with restricted activity days (r = -0.52 to -0.55, all P < 0.0001). CONCLUSIONS: This study provides additional evidence supporting the validity of the NEI VFQ-25 in neovascular AMD patients by demonstrating correlations with a spectrum of vision measurements and a daily function measure.

Improved vision-related function after ranibizumab vs photodynamic therapy: a randomized clinical trial.

OBJECTIVE: To compare patient-reported visual function in those with neovascular age-related macular degeneration treated with ranibizumab or verteporfin photodynamic therapy (PDT). DESIGN: Multicenter, double-masked, phase 3 trial (ANCHOR). Participants were randomized in a 1:1:1 ratio to receive 0.3 or 0.5 mg of intravitreal ranibizumab plus sham verteporfin or sham injections plus active verteporfin monthly. The National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) was administered at baseline and 1, 2, 3, 6, 9, 12, 18, and 24 months. MAIN OUTCOME MEASURE: Mean change from baseline in NEI VFQ-25 scores at 12 months. RESULTS: At 12 months, patients treated with ranibizumab (0.3 mg [n = 137] or 0.5 mg [n = 139]) had mean improvements in NEI VFQ-25 composite scores of 5.9 (95% confidence interval [CI], 3.6 to 8.3) and 8.1 (95% CI, 5.3 to 10.8) points, respectively; patients treated with PDT (n = 142) had a mean improvement of 2.2 points (95% CI, -0.3 to 4.7; vs 0.5 mg of ranibizumab, P < .001; vs 0.3 mg of ranibizumab, P = .003). At each dose through 24 months, patients treated with ranibizumab were more likely to improve in most subscales, including the prespecified subscales (near activities, distance activities, and vision-specific dependency). CONCLUSIONS: Patients treated with ranibizumab were more likely to report clinically meaningful improvements in visual function through 24 months compared with those treated with verteporfin PDT. Application to Clinical Practice Ranibizumab treatment in neovascular age-related macular degeneration can improve patient-reported visual function. Trial Registration clinicaltrials.gov Identifier: NCT00061594.