The comparative effectiveness and cost-effectiveness of ranibizumab for neovascular macular degeneration revisited

BACKGROUND: To compare a near decade of follow-up, newer control cohort data, use of both the societal and third party insurer cost perspectives, and integration of unilateral/bilateral therapy on the comparative effectiveness and cost-effectiveness of intravitreal ranibizumab therapy for neovascular, age-related macular degeneration (AMD). METHODS: Value-Based Medicine(®), 12-year, combined-eye model, cost-utility analysis employing MARINA and HORIZON clinical trial data. Preference-based comparative effectiveness outcomes were quantified in (1) QALY (quality-adjusted life-year) gain, and (2) percent improvement in quality-of-life, while cost-effectiveness outcomes were quantified in (3) the cost-utility ratio (CUR) and financial return-on-investment (ROI) to society. RESULTS: Using MARINA and HORIZON trial data and a meta-analysis control cohort after 24 months, ranibizumab therapy conferred a combined-eye patient value (quality-of-life) gain of 16.3%, versus 10.4% found in 2006. The two-year direct ophthalmic medical cost for ranibizumab therapy was $46,450, a 33.8$242,920/QALY, indicating a $282,517 financial return-on-investment (ROI), or 12.3$21,199/QALY utilizing all direct, medical costs, to $69,591/QALY using direct ophthalmic medical costs. CONCLUSIONS: Ranibizumab therapy for neovascular AMD in 2015, considering treatment of both eyes, conferred greater patient value gain (comparative effectiveness) and improved cost-effectiveness than in 2006, as well as a large monetary return-on-investment to the Gross Domestic Product and nation’s wealth. The model herein integrates important novel features for neovascular age-related macular degeneration, vitreoretinal cost effectiveness analyses, including: (1) treatment of both eyes, (2) a long-term, untreated control cohort, and (3) the use of societal costs

Composite Indices Using 3 or 4 Components of the Core Data Set Have Similar Predictive Ability to Measure Disease Activity in RA: Evidence from the DANCER and REFLEX Studies

Background. Understanding how disease-assessment indices perform in rheumatoid arthritis (RA) clinical trials can inform their use in routine practice. The study objective was to assess the capacity of combinations of RA Core Data Set measures to distinguish rituximab from control treatment.Methods. Post hoc analysis of two randomised clinical trials was used. Composite Efficacy Indices were derived by combining three or four RA Core Data Set measures from three possible sources: physician, patient, and laboratory.Results. All 105 Composite Efficacy Indices evaluated significantly distinguished rituximab from control treatment (P&lt;10−7). Generally, indices containing measures from three different sources had a greater capacity to distinguish rituximab from control treatment than indices containing three measures from one source. Composite Efficacy Indices performed as well as validated indices such as DAS28, RAPID3, and CDAI.Conclusions. All indices composed of three or four RA Core Data Set measures have a similar capacity to detect treatment differences. These results suggest that the precise measurement used is less important than whether any measurement is performed, although selection should be consistent for each patient. Therefore, the choice of assessment tool should not be limited to a prescribed list and should instead be left to the clinician’s discretion.</jats:p

Safety and Efficacy of Ixoberogene Soroparvovec in Neovascular Age-Related Macular Degeneration in the United States (OPTIC): A Prospective, Two-Year, Multicentre Phase 1 Study

Background Gene therapy, successfully used in rare, monogenetic disorders, may prove to be a durable management approach for common, polygenetic conditions, including neovascular age-related macular degeneration (nAMD). Repeated injections, oftentimes monthly, and possibly for decades, of vascular endothelial growth factor antagonists (anti-VEGF), is the standard for nAMD. We hypothesised that an in-office, intravitreal administration of ixoberogene soroparvovec (ixo-vec, formerly ADVM-022), a single-dose gene therapy encoding for the proven anti-VEGF protein, aflibercept, would transform retinal cells to continually produce aflibercept to minimise treatment burden in nAMD. Methods In this two-year, open-label, prospective, multicentre phase 1 study, patients with nAMD responding to antiVEGF were assigned to four cohorts differing by ixo-vec dose (2 × 1011 vs 6 × 1011 vector genomes (vg/eye)) and prophylactic steroids (oral prednisone vs topical difluprednate). The primary outcome was the type, severity, and incidence of ocular and systemic adverse events (AEs); secondary endpoints included vision, central subfield thickness (CST), and the number of supplemental injections. This study was registered with ClinicalTrials.gov, NCT03748784. Findings Thirty patients with nAMD were enrolled between November 14, 2018 and June 30, 2020 at nine study sites in the United States. No systemic ixo-vec related AEs were noted. Across both dose groups the most common adverse event was anterior chamber cell, which was reported in 11 participants in the 6 × 1011 dose group and in 7 participants in the 2 × 1011 dose group; intraocular inflammation was responsive to topical corticosteroids, with no anterior chamber cells or vitreous cells observed in 2 × 1011 vg/eye patients at the end of the study. Vision and CST remained stable throughout two years with annualised anti-VEGF injections reduced by 80% (10.0 mean annualised anti-VEGF injections to 1.9) in 2 × 1011 vg/eye and 98% (9.8 mean annualised anti-VEGF injections to 0.2) in 6 × 1011 vg/eye cohorts. Interpretation Ixo-vec was generally well-tolerated, maintained vision, and improved anatomical outcomes in nAMD, with a substantial reduction in anti-VEGF injections. A single administration of an in-office gene therapy, with vectorised protein with an already established clinical benefit, has the potential to revolutionise the management of common ocular disorders requiring ongoing, frequent therapeutic interventions

Dilated Eye Exam Compliance for Persons With Diabetes Mellitus in a Managed Care Setting

Background/Aims: National practice guidelines recommend regular dilated eye examinations for persons with diabetes mellitus (DM). Regular exams can identify the presence of diabetic eye diseases leading to early detection and treatment along with vision preservation. We aimed to: 1) assess compliance with guideline-recommended dilated eye exams among persons with DM, and 2) determine the factors associated with noncompliance. Methods: Kaiser Permanente Southern California members aged ≥ 18 years with DM identified from January 2009 to December 2010 were followed until disenrollment or study end date (December 2013). Dilated eye exams were identified from CPT-4, ICD-9 procedure codes and retinal photographs. Compliance with guidelines over the entire duration of follow-up was the binary outcome of interest. A patient was defined as compliant when having at least one exam in each 12-month period if there was evidence of retinopathy, or at least one exam in each 24-month period if there was no evidence of retinopathy. Multivariate logistic regressions were used to investigate patient demographics and other baseline characteristics associated with noncompliance. Results: Among the 204,073 eligible patients, mean age ± standard deviation was 61 ± 13 years and 48% were female. The median follow up was 4.8 years, and overall, 71.1% of patients were compliant with dilated eye exams, including 27.7% who received an eye exam every year and 4.4% who never received a dilated eye exam. At baseline 13% of patients had retinopathy, while an additional 20% of patients developed retinopathy during follow-up time. Noncompliant patients were more likely to be younger, black, male, smokers, and have a Medicare plan, a lower income, a lower education and a higher specialist co-payment plan. In addition, these patients were less likely to be adherent to antidiabetes medications, on statin medications, take a diabetes education class and have other eye diseases; however, they were more likely to use insulin, have retinopathy, have nephropathy, and have a lower comorbidity index. Discussion: During nearly 5 years of follow-up, 28.9% of person’s with DM were noncompliant with dilated eye exam guidelines. Future research should focus on eye disease outcomes associated with noncompliance and the development of interventions to address modifiable factors associated with noncompliance