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Purpose Estimate effects of ranibizumab on diabetic retinopathy (DR) severity in US Hispanic and non-Hispanic white persons with center-involved diabetic macular edema (DME) causing vision impairment for whom ranibizumab treatment would be considered. Patients and methods This model simulated DR severity outcomes over 2 years in the better-seeing eye using US census, National Health and Nutrition Examination Survey, Wisconsin Epidemiologic Study of Diabetic Retinopathy, and Los Angeles Latino Eye Study data. Baseline DR severity estimated from Diabetic Retinopathy Clinical Research Network trial data. Changes in DR severity after 2 years, with/without monthly ranibizumab (0.3 or 0.5 mg), were estimated from Phase III clinical trial data (RIDE/RISE) using a 2-dimensional Monte Carlo simulation model. Number of patients over a 2-year period for whom 1) DR severity worsening was avoided, 2) DR severity improved, and 3) selected clinical events related to proliferative DR (PDR) occurred, was estimated. Results An estimated 37,274 US Hispanic and non-Hispanic white persons were projected to have DR with center-involved DME and be eligible for ranibizumab treatment. The number of persons with moderately severe non-proliferative DR (NPDR) or less severe DR at baseline who would worsen to PDR and experience a PDR complication over 2 years would be reduced from 437 with no ranibizumab to 19 with ranibizumab (95% reduction; 95% simulation interval [SI], 79-100%). The number of persons with severe NPDR or less severe DR at baseline who would be expected to improve by ≥2 DR severity levels over 2 years would increase from 1706 with no ranibizumab to 13,042 with ranibizumab (682% increase; 95% SI, 478-967%). Conclusion This model estimates that ranibizumab treatment in US Hispanic and non-Hispanic white patients with center-involved DME causing vision impairment would potentially reduce the number of patients with worsening DR and potentially increase the number with DR improvements.

Aims: Protocol T (NCT01627249) was a head-to-head study conducted by the Diabetic Retinopathy Clinical Research Network that compared intravitreal aflibercept, bevacizumab, and ranibizumab for the treatment of diabetic macular edema (DME). A cost-effectiveness analysis accompanying the 1-year data of Protocol T revealed that aflibercept was not cost-effective vs ranibizumab for all patients, but could have been cost-effective in certain patient sub-groups if the 1-year results were extrapolated out to 10 years. The present study evaluated the cost-effectiveness of US Food and Drug Administration-approved anti-vascular endothelial growth factor agents (ranibizumab, aflibercept) for treatment of DME using the 2-year data from Protocol T. Methods: Costs of aflibercept 2.0 mg or ranibizumab 0.3 mg, visual acuity (VA)-related medical costs, and quality-adjusted life-years (QALYs) were simulated for eight VA health states. Treatment, adverse event management, and VA-related healthcare resource costs (2016 US dollars) were based on Medicare reimbursement and published literature. VA-related health utilities were determined using a published algorithm. Patients were stratified by baseline VA: 20/40 or better; 20/50 or worse. Results: Total 2-year costs were higher, and QALYs similar, for aflibercept vs ranibizumab in the full cohort ($44,423 vs $34,529; 1.476 vs 1.466), 20/40 or better VA sub-group ($40,854 vs $31,897; 1.517 vs 1.519), and 20/50 or worse VA sub-group ($48,214 vs $37,246; 1.433 vs 1.412), respectively. Incremental cost-effectiveness ratios in the full cohort and 20/50 or worse VA sub-group were $986,159/QALY and $523,377/QALY, respectively. These decreased to $711,301 and $246,978 when analyses were extrapolated to 10 years. Limitations: Key potential limitations include the fact that VA was the only QALY parameter analyzed and the uncertainty surrounding the role of better- and worse-seeing eye VA in overall functional impairment. Conclusions: This analysis suggests that aflibercept is not cost-effective vs ranibizumab for patients with DME, regardless of baseline vision.

RATIONALE: ACE2, a critical SARS-CoV-2 entry receptor, has reduced expression in those with allergic sensitizations. Consequently, SARS-CoV-2 infections may impact patients with allergic asthma (AA) or no evidence of allergic asthma (NEAA) differently. We explore demographics of SARS-CoV-2-infected AA and NEAA patients. METHODS: Retrospective data were obtained from the US-representative COVID-19 Optum Electronic Health Record dataset through 10/15/2020. Index was the earliest date of presumed diagnosis or laboratory-confirmed SARS-CoV-2 infection (CDC guidelines) from 02/20/2020, defined as (1) diagnosis code of U07.1/U07.2, or (2) positive diagnostic test for SARS-CoV-2, (3) diagnosis code of B97.29 without a negative molecular SARS-CoV-2 test within a 14-day window (+/-7 days). Patients SARS-CoV-2-positive with evidence of moderate-to-severe asthma at any time (ICD-10 J45.4X or J45.5X) were included. AA was defined as positive specific IgE (≥0.35 kU/L) serum test or skin prick test (code 95004) ordered by a specialist (eg, allergist, pulmonologist, dermatologist) or omalizumab use. NEAA was defined as failing to meet the AA definition and patients with allergic comorbidities were excluded. Baseline demographic and clinical characteristics were obtained 6-12 months before COVID-19 diagnosis. RESULTS: The database included 242,280 SARS-CoV-2-positive patients;569 (0.2%) had evidence of comorbid AA and 3137 (1.3%) had asthma and NEAA. For AA patients, mean (SD) age at index was 48.2 (18.2) years;70.3% were female, with 54.3% White, 26.4% Black, and 12.5% Hispanic (Table 1). Most AA patients were from the US Midwest and Northeast (80.5%). NEAA patients had similar demographics: mean (SD) age at index was 50.7 (19.5) years;67.6% female;with 60.0% White, 21.5% Black, and 13.0% Hispanic;and 81.5% were from the US Midwest and Northeast. A greater proportion of patients had severe asthma in AA versus NEAA groups (220/569 [38.7%] versus 457/3137 [14.6%]). More patients with AA versus NEAA used asthma biologic treatment (62/569 [10.9%] vs 27/3137 [0.9%]). Comorbid conditions (hypertension, diabetes, pregnancy, chronic obstructive pulmonary disease, and Charlson Comorbidity Index), body mass index, and smoking history were comparable between groups. A higher proportion of NEAA patients were current smokers. CONCLUSIONS: A smaller proportion of patients with SARS-CoV-2 infection in this retrospective analysis had comorbid AA versus NEAA, whereas patient demographics and comorbidities were generally comparable between groups. Differences included the proportion of patients with severe asthma and biologic treatment use (greater in AA), and current smoking (lower in AA). The observed lower prevalence of AA versus NEAA in SARS-CoV-2-positive patients warrants further investigation.

Background Chronic spontaneous urticaria (CSU), also known as chronic idiopathic urticaria, may produce hives, itch, and angioedema. The Urticaria Activity and Impact Measure (U-AIM) is a newly developed 9-item patient-reported measure designed for use in routine clinical practice to assess CSU activity and impact during the previous 7 days. Objective To evaluate validity, responsiveness, and clinically meaningful change of the U-AIM. Methods Data from a 24-week, open-label, single-arm period of a randomized, placebo-controlled study of omalizumab were used to assess the psychometric properties of U-AIM items for itch, hives, and angioedema. Results A total of 206 patients (75% female; mean age, 44.6 years) were enrolled. At baseline, U-AIM results included prevalent severe itch (55%) and more than 12 hives (67%), angioedema (15%), and bother by itch (84%), hives (84%), and angioedema (49%). The Urticaria Patient Daily Diary (UPDD) mean weekly scores were 15.4 (itch severity), 16.8 (number of hives), and 32.2 (Urticaria Activity Score [UAS7]). At baseline, week 12, and week 24, U-AIM itch and hives items and UAS7 proxy scores (the sum of itch severity and number of hives during 7 days) demonstrated strong correlation coefficients with their corresponding measures from the UPDD (itch severity: 0.634–0.806; hives number: 0.735–0.843; UAS7 proxy: 0.724–0.852). Changes in U-AIM scores differentiated patients by their perspective of symptom improvement. Meaningful change thresholds were established for itch severity and number of hives scores (range, 0.8–1.0 for both) and the UAS7 proxy score (range, 10.5–12.5). Conclusion The U-AIM is valid and responsive to change and may help clinicians monitor CSU activity and track treatment effectiveness.

Purpose Estimate effects of ranibizumab on diabetic retinopathy (DR) severity in US Hispanic and non-Hispanic white persons with center-involved diabetic macular edema (DME) causing vision impairment for whom ranibizumab treatment would be considered. Patients and Methods This model simulated DR severity outcomes over 2 years in the better-seeing eye using US census, National Health and Nutrition Examination Survey, Wisconsin Epidemiologic Study of Diabetic Retinopathy, and Los Angeles Latino Eye Study data. Baseline DR severity estimated from Diabetic Retinopathy Clinical Research Network trial data. Changes in DR severity after 2 years, with/without monthly ranibizumab (0.3 or 0.5 mg), were estimated from Phase III clinical trial data (RIDE/RISE) using a 2-dimensional Monte Carlo simulation model. Number of patients over a 2-year period for whom 1) DR severity worsening was avoided, 2) DR severity improved, and 3) selected clinical events related to proliferative DR (PDR) occurred, was estimated. Results An estimated 37,274 US Hispanic and non-Hispanic white persons were projected to have DR with center-involved DME and be eligible for ranibizumab treatment. The number of persons with moderately severe non-proliferative DR (NPDR) or less severe DR at baseline who would worsen to PDR and experience a PDR complication over 2 years would be reduced from 437 with no ranibizumab to 19 with ranibizumab (95% reduction; 95% simulation interval [SI], 79–100%). The number of persons with severe NPDR or less severe DR at baseline who would be expected to improve by ≥2 DR severity levels over 2 years would increase from 1706 with no ranibizumab to 13,042 with ranibizumab (682% increase; 95% SI, 478–967%). Conclusion This model estimates that ranibizumab treatment in US Hispanic and non-Hispanic white patients with center-involved DME causing vision impairment would potentially reduce the number of patients with worsening DR and potentially increase the number with DR improvements.

Chronic spontaneous urticaria (CSU), also known as chronic idiopathic urticaria, may produce hives, itch, and angioedema. The Urticaria Activity and Impact Measure (U-AIM) is a newly developed 9-item patient-reported measure designed for use in routine clinical practice to assess CSU activity and impact during the previous 7 days.To evaluate validity, responsiveness, and clinically meaningful change of the U-AIM.Data from a 24-week, open-label, single-arm period of a randomized, placebo-controlled study of omalizumab were used to assess the psychometric properties of U-AIM items for itch, hives, and angioedema.A total of 206 patients (75% female; mean age, 44.6 years) were enrolled. At baseline, U-AIM results included prevalent severe itch (55%) and more than 12 hives (67%), angioedema (15%), and bother by itch (84%), hives (84%), and angioedema (49%). The Urticaria Patient Daily Diary (UPDD) mean weekly scores were 15.4 (itch severity), 16.8 (number of hives), and 32.2 (Urticaria Activity Score [UAS7]). At baseline, week 12, and week 24, U-AIM itch and hives items and UAS7 proxy scores (the sum of itch severity and number of hives during 7 days) demonstrated strong correlation coefficients with their corresponding measures from the UPDD (itch severity: 0.634-0.806; hives number: 0.735-0.843; UAS7 proxy: 0.724-0.852). Changes in U-AIM scores differentiated patients by their perspective of symptom improvement. Meaningful change thresholds were established for itch severity and number of hives scores (range, 0.8-1.0 for both) and the UAS7 proxy score (range, 10.5-12.5).The U-AIM is valid and responsive to change and may help clinicians monitor CSU activity and track treatment effectiveness.

Introduction The understanding of asthma pathophysiology has evolved over time, impacting investigation of asthma biologics. Differences in eligibility criteria amongst trials for patients with diverse asthma severity and phenotypes have resulted in relevant differences in baseline characteristics. A systematic literature review explored these differences. Methods PubMed, EMBASE, Cochrane, ClinicalTrials.gov, and conferences were searched from 2003 onwards. Randomized controlled trials (RCTs) were included with: ≥24 weeks’ duration; biologic (omalizumab [OMA]/dupilumab [DUPI]/benralizumab [BENRA]/mepolizumab [MEPO]/reslizumab [RESLI]) + daily high-dose ICS + ≥1 controller; adults ≥18 years with moderate/severe uncontrolled asthma and evidence of Type 2 inflammation (eg, blood eosinophils). Results 27 RCTs (9 OMA/3 DUPI/6 BENRA/7 MEPO/2 RESLI) were included. Overall, BENRA/MEPO/RESLI trials enrolled patients with more severe asthma than OMA/DUPI (Table 1). Per inclusion criteria, the number of prior exacerbations was higher in BENRA/MEPO versus OMA/DUPI/RESLI trials. Baseline blood eosinophil levels varied between trials, but were highest in RESLI. There was a trend towards higher baseline FEV1 in OMA/RESLI trials compared with others. Most patients received medium/high dose ICS + LABAs, with more patients in MEPO trials receiving maintenance OCS. Conclusions Transitivity, an important assumption in network meta-analysis (NMA), requires populations and study designs be sufficiently similar or have differences that can be adjusted for by accepted methods. Substantial heterogeneity in baseline characteristics existed between trials of asthma biologics and OMA. These characteristics are potential treatment effect modifiers with limited evidence for adjustment. Therefore, comparison of OMA to other asthma biologics through NMA is not clinically valid and inconsistent with best practices. Table 1. Summary of eligibility criteria and baseline patient characteristics across randomized controlled trials of biologic agents in moderate-to-severe asthma.

Objective Geographic atrophy (GA) is a progressive, irreversible advanced form of age-related macular degeneration. There is limited information on the burden of illness of GA from patient, caregiver, and eye care professional perspectives. This study identifies key factors that should be included for assessment in future studies of patients with GA. Methods In this cross-sectional qualitative study, patients with symptomatic GA (n = 8), their caregivers (n = 6), and eye care professionals who treat patients with GA (n = 5) were interviewed at US sites. Interview guides were designed to evaluate the understanding of the disease, costs and burden of illness, use of vision aids or services, and impact on emotional or psychological well-being and on daily activities. Results Half of the patients mentioned social, psychological, or helplessness issues. Patients reported the impact of GA on sports and outdoor hobbies, meals or food preparation, religious activities, and long-distance travel. Patients reported having stopped driving or changing driving patterns as a major concern. 38% of all patients reported previously modifying their work schedules due to vision impairment. All patients reported the use of at least one vision aid, with 88% of patients purchasing the aids out of pocket. Caregivers reported modifying their schedules to provide assistance as needed and expressed frustration over their inability to improve patients’ health. Eye care professionals noted the emotional impact of vision loss, accidents, and injuries, and identified mental health as a key topic for patients with GA. Conclusions Although limited by size, this study indicates that GA has a major negative impact on patients’ and caregivers’ social functioning and health-related quality of life. This study has identified indirect resource use, including caregiving needs, and direct patient out-of-pocket costs as factors relevant to patients with GA. Future larger studies are needed to further characterize the burden of illness of GA for patients and caregivers.

Diabetes mellitus remains the leading cause of new cases of blindness among US adults. Routine dilated eye examinations can facilitate early detection and intervention for diabetes-related eye disease, providing an opportunity to reduce the risk for diabetes-related blindness in working-aged Americans. The Healthcare Effectiveness Data and Information Set (HEDIS) established criteria for performing dilated eye examination in patients with diabetes.To obtain information about adherence and nonadherence to diabetic eye examinations among insured patients to understand the barriers to routine dilated eye examinations, and to identify ways to improve the quality of care for these patients.This retrospective claims analysis is based on administrative claims from the HealthCore Integrated Research Database, a broad database representing claims from a large commercially insured population. Patients with diabetes and who had ≥1 dilated eye examinations between August 1, 2011, and July 31, 2013, were defined as adherent to the HEDIS recommendations. The analysis was augmented with findings from focus groups. The patient focus groups included adherent and nonadherent patients. The provider focus group participants were general practice or internal medicine physicians and ophthalmologists who provided medical care for the study population. For the administrative claims analysis, comparisons between the adherent and nonadherent patients were performed usingOf 339,646 patients with diabetes identified in a claims data set, 43% were adherent and 57% were nonadherent to the HEDIS eye examination performance measure. The common barriers to routine eye examination cited by 29 patients across 4 focus groups included a lack of understanding of insurance benefits (N = 15), a lack of awareness of the importance of dilated eye examinations (N = 12), and time constraints (N = 12). The common barriers cited by 18 providers included the patient's level of education (N = 13), eye examinations as a lower priority than the management of other diabetes-related health issues (N = 12), and a lack of symptoms (N = 11).Several reasons for patient nonadherence to routine eye examination were identified, including a lack of understanding of insurance benefits, a lack of awareness or low prioritization of having an examination, patient education level, time constraints, and a lack of symptoms. These may be considered by providers and payers when developing programs to increase the rates of eye examinations and improve outcomes among patients with diabetes.

Objective To assess retinal vein occlusion (RVO) clinical features to create a simulation model quantifying the preference-based, patient value gain (benefit) and cost-utility (cost-effectiveness) of RVO therapy. Design Retrospective analysis data integrated with patient utilities and an ocular cost-utility model for RVO. Participants One thousand consecutive Wills Eye Hospital Retina Service RVO patients seen from January 2010 through April 2011. Methods Value-Based Medicine analysis assessing the demographic features and vision in affected eyes and fellow eyes of RVO patients. Main Outcome Measures Presenting vision, final vision, conversion incidence of fellow eyes to RVO, and patient value gain in quality-adjusted life-years (QALYs). Results Among 1000 patients, 332 (33.2%) presented with central retinal vein occlusion (CRVO), 53 (5.3%) with hemiretinal vein occlusion (HRVO), and 615 (61.5%) with branch retinal vein occlusion (BRVO). Mean follow-up for the entire RVO cohort was 3 years. One hundred and one patients (10.1%) had bilateral baseline RVO and, among the 826 unilateral cases seen more than once, 37 (4.5%) developed a fellow-eye RVO, a unilateral-to-bilateral conversion rate of 1.5%/year. Among the 101 baseline bilateral cases, 66% (66/101) had the same RVO variant bilaterally (CRVO/CRVO, HRVO/HRVO, or BRVO/BRVO). Mean CRVO baseline vision was 20/63 −2 and final vision was 20/63 −1 ( P = 0.16). Thirty percent of patients had less than or equal to baseline fellow-eye vision. Within combined HRVO/BRVO cohorts, mean baseline vision was 20/50 −2 and final vision was 20/50 +1 ( P = 0.0004). Thirty percent of patients also had less than or equal to baseline fellow-eye vision. The proportion of RVO patients with fellow-eye vision less than or equal to the RVO primary-eye baseline vision increased to 44% by year 16. Conclusions Thirty percent of all RVO patients had less than or equal to baseline vision in the fellow eye. Among unilateral RVO cases, 1.5%/year developed fellow-eye RVO. These findings have implications for cost-utility analysis, because bilateral vision loss yields greater QALY loss and an increased financial burden compared with unilateral loss. Referent to total therapeutic QALY gain (100%), if a treated RVO was always considered the better-seeing eye, the actual clinical scenario demonstrates that the average CRVO patient gains 38% as much value and the average HRVO/BRVO patient gains 37% as much.

This paper sought to review the literature on complementary and alternative medicine (CAM) use by patients with colorectal cancer (CRC). Methods A systematic search of Pubmed and Embase was conducted to identify the relevant literature. Study investigators reviewed the titles of identified articles and one abstracted data from the eligible studies. Of the 39 English and French citations screened, 4 observational studies were included. Results Up to 75% of CRC patients reported using at least one CAM. The bio-based and mind–body therapies were the most commonly used. Nearly half of the studies showed that patients used CAM to improve general health and well-being. Conclusions Future research may focus on how CAM use affects quality of life over time and in relation to changing health states, cancer stage and treatment to enable health care professionals to better inform CRC patients of the CAMs that may be helpful at particular points during the disease and treatment trajectories.

Purpose To assess the incremental, comparative effectiveness (patient value gain) and cost effectiveness (financial value gain) associated with 0.3-mg intravitreal ranibizumab injection therapy versus sham therapy for diabetic macular edema (DME). Design Value-Based Medicine (Center for Value-Based Medicine, Flourtown, PA) 14-year, cost-utility analysis using patient preferences and 2012 United States real dollars. Participants Published data from the identical Ranibizumab Injection in Subjects with Clinically Significant Macular Edema with Center Involvement Secondary to Diabetes Mellitus (RISE and RIDE) clinical trials. Methods An incremental cost-utility analysis was performed using societal and third-party insurer cost perspectives. Costs and outcomes were discounted with net present value analysis at 3% per annum. Main Outcome Measures The incremental comparative effectiveness was measured in: (1) quality-adjusted life year (QALY) gain and (2) percent patient value (quality-of-life) gain. Cost effectiveness was quantified with the cost-utility ratio (CUR) measured as $/QALY. Results The 14-year, incremental patient value gain conferred by intravitreal ranibizumab therapy for diabetic maculopathy was 0.9981 QALY, equating to an 11.6% improvement in quality of life. The direct, ophthalmic medical cost for ranibizumab therapy in 1 eye was $30 116, whereas for 2 eyes it was $56 336. The direct, nonophthalmic, medical costs saved from decreased depression, injury, skilled nursing facility admissions, nursing home admissions, and other vision-associated costs totaled $51 758, resulting in an overall direct medical cost of $4578. The net mean societal cost for bilateral ranibizumab therapy was −$30 807. Of this total, decreased caregiver costs accrued a $31 406 savings against the direct medical costs, whereas decreased wage losses accrued a $3978 savings. The third-party insurer CUR for bilateral ranibizumab therapy was $4587/QALY. The societal cost perspective for bilateral therapy was −$30 807/QALY, indicating that ranibizumab therapy dominated sham therapy because it conferred both a positive QALY gain of 0.9981 and a financial value gain (positive financial return on investment) of $30 807 referent to the direct ophthalmic medical costs expended. Conclusions Intravitreal ranibizumab therapy for the treatment of DME confers considerable patient (human) value gain. It also accrues financial value to patients, public and private insurers, and society.