Antivascular endothelial growth factor agents for wet age-related macular degeneration: an IRIS registry analysis.

OBJECTIVE: To evaluate treatment patterns and outcomes of patients in the United States who received antivascular endothelial growth factor (anti-VEGF) agents for wet age-related macular degeneration (AMD). DESIGN: Retrospective study PARTICIPANTS: Patients with wet AMD. METHODS: Using the Intelligent Research in Sight Registry, we studied patients with wet AMD who received ≥1 anti-VEGF injection, who were ≥50 years old, and with ≥1.5 years of follow-up. Patients were grouped based on follow-up duration (in years): ≥1.5 (cohort 1), ≥2.5 (cohort 2), and ≥3.5 (cohort 3). RESULTS: Patient characteristics were similar between treatment groups. 36.8%, 34.5%, and 39.2% of ranibizumab, aflibercept, and all anti-VEGF eyes, respectively, had an injection interval <8 weeks in length at the end of year 1. Results were similar at year 2 and 3. In cohorts 1-3, visual acuity (VA) changes from baseline ranged from 0.3 to 0.7 (year 1), -1.3 to -1.7 (year 2), and -2.8 to -3.1 (year 3) Early Treatment Diabetic Retinopathy Study letters. By the end of year 3, 41%, 39%, and 42% of ranibizumab, aflibercept, and all anti-VEGF eyes, respectively, had discontinued treatment (no injection for >6 months). CONCLUSION: Approximately one-third of eyes had injection intervals <8 weeks in length at the end of year 1. VA was slightly better at the end of year 1 and declined after the first year despite treatment. By the end of year 3, more than one-third of eyes had discontinued treatment. Given the high treatment burden, wet AMD patients may benefit from more durable approaches that require less frequent dosing.

Safety Outcomes of Brolucizumab in Neovascular Age-Related Macular Degeneration: Results From the IRIS Registry and Komodo Healthcare Map.

IMPORTANCE: Limited data exist on the real-world safety outcomes of patients with neovascular age-related macular degeneration treated with brolucizumab (Beovu). OBJECTIVE: To determine the real-world incidence of intraocular inflammation (IOI), including retinal vasculitis (RV) and/or retinal vascular occlusion (RO), for patients with neovascular age-related macular degeneration who underwent brolucizumab treatment. Additionally, potential risk factors associated with these adverse events were evaluated. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included patients with neovascular age-related macular degeneration in the Intelligent Research in Sight (IRIS) Registry and Komodo Healthcare Map. Patients initiating and receiving 1 or more brolucizumab injections from October 8, 2019, to June 5, 2020, with up to 6 months of follow-up were included. INTERVENTION: Brolucizumab injections. MAIN OUTCOME AND MEASURES: Incidence of IOI (including RV) and/or RO and RV and/or RO and risk stratification for the identified risk factors. RESULTS: Of 10 654 and 11 161 included eyes (from the IRIS Registry and Komodo Health database, respectively), the median follow-up times were 97 and 95 days. Most eyes switched from another anti-vascular endothelial growth factor agent (9686 of 10 654 [90.9%] and 10 487 of 11 161 [94.0%], respectively), most commonly aflibercept (7160 of 9686 [73.9%] and 7156 of 10 487 [68.2%]), and most were from women (6105 of 10 654 [57.3%] and 6452 of 11 161 [57.8%]). The overall incidence of IOI and/or RO was 2.4% (255 of 10 654 eyes) and 2.4% (268 of 11 161 eyes) for the IRIS and Komodo groups, respectively, and RV and/or RO, 0.6% (59 of 10 654 eyes and 63 of 11 161 eyes), respectively. Patients with a history of IOI and/or RO in the 12 months before brolucizumab initiation had an increased observed risk rate (8.7% [95% CI, 6.0%-11.4%] and 10.6% [95% CI, 7.5%-13.7%]) for an IOI and/or RO event in the 6 months following the first brolucizumab treatment compared with patients without prior IOI and/or RO (2.0% in both data sets). There was an increased estimated incidence rate in women (2.9% [95% CI, 2.5%-3.3%] and 3.0% [95% CI, 2.6%-3.4%]) compared with men (1.3% [95% CI, 1.0%-1.7%] and 1.4% [95% CI, 1.0%-1.7%]), but this risk was not as large as that of a prior IOI and/or RO. Similar findings were observed for patients with RV and/or RO events. CONCLUSIONS AND RELEVANCE: The incidence rate of IOI and/or RO was approximately 2.4%. Patient eyes with IOI and/or RO in the 12 months prior to first brolucizumab injection had the highest observed risk rate for IOI and/or RO in the early months after the first brolucizumab treatment. However, given study limitations, the identified risk factors cannot be used as predictors of IOI and/or RO events, and causality with brolucizumab cannot be assessed.

Brolucizumab vs aflibercept and ranibizumab for neovascular age-related macular degeneration: a cost-effectiveness analysis.

BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of blindness worldwide and is the most common cause of blindness in developed countries. Despite antivascular endothelial growth factor (anti-VEGF) therapy demonstrating improvements in visual and anatomical outcomes, unmet needs remain. Brolucizumab-dbll (ie, brolucizumab), a VEGF inhibitor for treatment of neovascular (wet) AMD and recently approved by the FDA for its treatment of wet AMD, attempts to mitigate treatment burden through less frequent injections. OBJECTIVE: To assess the incremental cost-effectiveness of brolucizumab compared with aflibercept and ranibizumab, given similar costs per injection and the potential for longer dosing intervals based on phase 3 clinical trial data. METHODS: A Markov model was developed to model the treatment of wet AMD patients with brolucizumab vs aflibercept and vs ranibizumab over a lifetime time horizon (base case) and 5-year time horizon (scenario analysis). The Markov model consisted of 3 primary health states: on treatment, off treatment, and death. Markov substates (5 total) described visual acuity (VA) ranging from no vision impairment to blindness. These VA-based substates were defined by best-corrected visual acuity (BCVA) values measured using Early Treatment Diabetic Retinopathy Study letters. Fixed-dosing regimens for each therapy were included in the model: dosing every 4 weeks (q4w) for the first 3 months followed by dosing q8w/q12w for brolucizumab, dosing q4w for the first 3 months followed by dosing q8w for aflibercept, and q4w for ranibizumab. RESULTS: In the base case, brolucizumab was less costly than aflibercept ($63,614 vs $72,189), and brolucizumab generated 0.0079 more quality-adjusted life-years (QALYs) than aflibercept (4.580 vs 4.572). Lower total costs with brolucizumab were driven by reduced drug costs ($56,432 vs $64,057), reduced administration costs ($6,013 vs $6,825), and reduced monitoring costs ($1,168 vs $1,306). When evaluating the cost-effectiveness of brolucizumab over a 5-year time horizon, brolucizumab was less costly than aflibercept ($44,644 vs $50,772) and generated an additional 0.0049 QALYs (2.953 vs 2.948). Additionally, brolucizumab was less costly than ranibizumab ($63,614 vs $128,163) and generated 0.0078 more QALYs than ranibizumab (4.580 vs 4.572) in the base case. Lower total costs with brolucizumab were driven by reduced drug costs ($56,432 vs $114,516), reduced administration costs ($6,013 vs $11,541), and reduced monitoring costs ($1,168 vs $2,107). When evaluating the cost-effectiveness of brolucizumab over a 5-year time horizon, brolucizumab was less costly than ranibizumab ($44,644 vs $89,665), and brolucizumab generated an additional 0.0046 QALYs (2.953 vs 2.948). CONCLUSIONS: Brolucizumab can be cost saving and cost-effective compared with aflibercept and ranibizumab in the treatment of wet AMD. DISCLOSURES: Novartis Pharmaceuticals Corporation provided funding to Xcenda for the cost-effectiveness analysis and preparation of this manuscript. Carlton is an employee of Xcenda. Agashivala is employed by Novartis Pharmaceuticals Corporation; Yu was an employee of Novartis Pharmaceutical Corporation at the time of this study. Hassan reports personal fees from iOPEN, BVI/Visitrec, ArcticDx, Bayer, F. Hoffmann-La Roche Ltd, Broadspot, BMC, Katalyst Surgical, Alcon, Vitreq, Surgicube, personal Ocugenix, Regeneron, Allergan, Oculus Surgical, Novartis, Genentech, and Eyepoint, unrelated to this work. Wykoff reports personal fees from Corcept Therapeutics, DORC, EyePoint, Gyroscope, IVERIC Bio, Merck, Notal Vision, ONL Therapeutics, Oxurion, Palatin, PolyPhotonix, Takeda, Thea Open Innovation; grants from Aerie Pharmaceuticals, Aldeyra, Gemini Therapeutics, Graybug Vision, IONIS Pharmaceutical, LMRI, Mylan, Neurotech Pharmaceuticals, Outlook Pharmaceuticals, Samsung Bioepis, Senju, Taiwan Liposome Company, Xbrane BioPharma, Santen; and grants and personal fees from Adverum, Allergan, Apellis, Chengdu Kanghong Biotechnologies (KHB), Clearside Biomedical, Genentech, Kodiak Sciences, NGM Biopharmaceuticals, Novartis, Opthea, Recens Medical, Regenxbio, Roche, and Regeneron, unrelated to this work. This research was presented as a virtual poster at the AMCP 2020 Annual Meeting, April 2020.

Anti-VEGF Treatment Patterns in Patients With Wet Age-Related Macular Degeneration in Clinical Practice.

BACKGROUND AND OBJECTIVE: To characterize on-label anti-vascular endothelial growth factor (VEGF) treatment patterns in patients with wet age-related macular degeneration (AMD) in clinical practice in the U.S. PATIENTS AND METHODS: Retrospective cohort analysis using administrative claims data from the IQVIA Open Source Databases. Treatment-naïve patients in the U.S. who received one or more wet AMD-related anti-VEGF injection from July 1, 2013, to April 30, 2017, were included. The main outcome was the injection interval closest to Month 12. RESULTS: This study included 21,960 patients who initiated an anti-VEGF agent (ranibizumab, aflibercept, or bevacizumab): 5,489 initiated aflibercept and 4,253 initiated ranibizumab. Among ranibizumab, aflibercept, and all anti-VEGF eyes, 38.1% (n = 2,035), 33.5% (n = 3,262), and 40.0% (n = 12,505) of patient eyes had injection intervals of less than 8 weeks, respectively, at Month 12 with the mean (standard deviation) number of injections over 12 months being 8.0 (2.4), 7.6 (2.4), and 7.8 (2.5). CONCLUSION: A substantial proportion of patients receive injections more frequently than every 8 weeks within the first year of treatment. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:263-272.].

Evaluation of the 6-item Identify Chronic Migraine screener in a large medical group.

OBJECTIVE: To evaluate the sensitivity and specificity of the 6-item Identify Chronic Migraine screener (ID-CM[6]), designed to improve the detection of chronic migraine (CM). BACKGROUND: CM is often undertreated and underdiagnosed. Survey-based studies have found that approximately 75-80% of people meeting criteria for CM do not report having received an accurate diagnosis. METHODS: This study used claims data of patients enrolled in a large medical group who had at least one medical claim with an International Classification of Diseases 9th/10th revision diagnostic code for migraine in the 12-month prescreening period. The Identify Chronic Migraine survey was administered by e-mail, in-person, or over the telephone to all enrolled patients. A Semi-Structured Diagnostic Interview (SSDI) was administered by telephone by a trained physician. The ID-CM(6) and SSDI classifications of CM status were compared to evaluate sensitivity and specificity of the ID-CM(6) screening tool. RESULTS: The analysis of the ID-CM(6) screening tool included 109 patients, with 65/109 (59.6%) positive for CM based on the SSDI. The mean (standard deviation) age of the patient sample was 49 (15) years and 100/109 (91.7%) were female. Using the SSDI as the diagnostic gold standard, the ID-CM(6) had a sensitivity of 70.8% (46/65) and a specificity of 93.2% (41/44). CONCLUSION: The ID-CM(6) demonstrated acceptable sensitivity and good specificity in determining CM status. The results of this analysis support the real-world utility of the ID-CM(6) as a simple and useful tool to identify patients with CM.

Development of a claims-based algorithm to identify potentially undiagnosed chronic migraine patients.

OBJECTIVE: To develop a claims-based algorithm to identify undiagnosed chronic migraine among patients enrolled in a healthcare system. METHODS: An observational study using claims and patient survey data was conducted in a large medical group. Eligible patients had an International Classification of Diseases, Ninth/Tenth Revision (ICD-9/10) migraine diagnosis, without a chronic migraine diagnosis, in the 12 months before screening and did not have a migraine-related onabotulinumtoxinA claim in the 12 months before enrollment. Trained clinicians administered a semi-structured diagnostic interview, which served as the gold standard to diagnose chronic migraine, to enrolled patients. Potential claims-based predictors of chronic migraine that differentiated semi-structured diagnostic interview-positive (chronic migraine) and semi-structured diagnostic interview-negative (non-chronic migraine) patients were identified in bivariate analyses for inclusion in a logistic regression model. RESULTS: The final sample included 108 patients (chronic migraine = 64; non-chronic migraine = 44). Four significant predictors for chronic migraine were identified using claims in the 12 months before enrollment: ≥15 versus <15 claims for acute treatment of migraine, including opioids (odds ratio = 5.87 [95% confidence interval: 1.34-25.63]); ≥24 versus <24 healthcare visits (odds ratio = 2.80 [confidence interval: 1.08-7.25]); female versus male sex (odds ratio = 9.17 [confidence interval: 1.26-66.50); claims for ≥2 versus 0 unique migraine preventive classes (odds ratio = 4.39 [confidence interval: 1.19-16.22]). Model sensitivity was 78.1%; specificity was 72.7%. CONCLUSIONS: The claims-based algorithm identified undiagnosed chronic migraine with sufficient sensitivity and specificity to have potential utility as a chronic migraine case-finding tool using health claims data. Research to further validate the algorithm is recommended.

Performance-Based Risk-Sharing Arrangements for Pharmaceutical Products in the United States: A Systematic Review.

BACKGROUND: Value for money is a growing necessity in today's U.S. health care system in which drug spending is expected to increase by an average rate of 6.7% yearly through 2025. In response to uncertainty about real-world clinical and economic outcomes for many drugs, health insurers and pharmacy benefit managers (PBMs) have implemented various contracts and arrangements with drug manufacturers that can collectively be described as performance-based risk-sharing arrangements (PBRSAs). Little is known about U.S.-specific PBRSAs for drugs. OBJECTIVES: To conduct a systematic review of U.S.-specific PBRSAs for drugs to describe (a) trends over time and (b) key aspects including outcome measures and terms of arrangements between stakeholders. METHODS: A systematic review was conducted in MEDLINE (January 1, 1946-April 1, 2017), Embase (January 1, 1988-April 1, 2017), and the grey literature (up to April 1, 2017) to identify publicly disclosed PBRSAs. Articles and conference abstracts were included if they were published in English and described a U.S.-specific PBRSA for a drug. Articles and conference abstracts were excluded if they only described a PBRSA similar to a money-back guarantee to patients. They were also excluded if they only described a PBRSA between a PBM and a health insurer in which the latter would receive a discount for patients nonadherent to a drug. Results were summarized as counts and percentages. RESULTS: From the literature review, 26 publicly disclosed PBRSAs were identified. Of these, 16 (62%) were announced or initiated from 2015 to 2017, and 10 (38%) were announced or initiated from 1997 to 2012. Thirteen (50%) PBRSAs involved cardiometabolic indications; 5 (19%) involved oncology indications; and 8 (31%) involved other indications. Categorized by health insurer or PBM, 10 (38%) PBRSAs involved large multistate insurers; 5 (19%) involved the Centers for Medicare & Medicaid Services; 7 (27%) involved regional insurers; 3 (12%) involved PBMs; and 1 (4%) involved multiple unspecified insurers. Regarding the most active drug manufacturers, Amgen initiated 5 (19%) PBRSAs and Novartis initiated 4 (15%). Relative to the initial FDA approval of a treatment, 15 (58%) PBRSAs were announced or initiated within 5 years, and 11 (42%) were announced or initiated more than 5 years later. For data collection, electronic medical record (EMR) data would have been an appropriate source for 12 (46%) PBRSAs; claims data would have been an appropriate source for 11 (42%) PBRSAs; and EMR and claims data would have been appropriate sources for 2 (8%) PBRSAs; no description of the outcome measures was available for 1 (4%) PBRSA. CONCLUSIONS: The number of publicly disclosed U.S.-specific PBRSAs for drugs has increased over the years. This review's findings confirm the interest of stakeholders in such arrangements and their confidence in the use of the selected outcome measures. Each PBRSA represents a timely collaboration among stakeholders to provide access to a drug while generating evidence to better elucidate its clinical and economic value. DISCLOSURES: No funding supported this systematic review. Yu is an employee and shareholder of Allergan. Chin reports personal fees from Formulary Resources. Oh and Farias have nothing to disclose. Study concept and design were primarily contributed by Yu, along with the other authors. All authors contributed to the collection and interpretation of the data. The manuscript was written by Yu, Chin, Oh, and Farias and revised by Yu and Chin, along with the other authors.

Healthcare burden of pulmonary hypertension owing to lung disease and/or hypoxia.

BACKGROUND: Group 3 pulmonary hypertension (PH) encompasses PH owing to lung diseases and/or hypoxia. Treatment patterns, healthcare resource use, and economic burden to US payers of Group 3 PH patients were assessed. METHODS: This retrospective observational study extracted data from July 1, 2010 to June 30, 2013 from two Truven Health Analytics MarketScan databases. Adult Group 3 PH patients were identified based on claims for PH (ICD-9-CM 416.0/416.8), a related lung disease, and an echocardiogram or right heart catheterization (RHC). The index date was the date of the first PH claim; data were collected for 12 months pre- and post-index. A difference-in-difference approach using generalized estimating equations was done to account for baseline differences. RESULTS: Group 3 PH patients (n = 2,236) were matched 1:1 to controls on lung disease. PH patients had higher all-cause resource utilization and annual healthcare costs ($44,732 vs. $7,051) than controls. Costs were driven by inpatient admissions (35.4% of total costs), prescriptions (33.0%), and outpatient care (26.5%). Respiratory-related costs accounted for 11.4% of post-index annual costs for PH patients. PH diagnosis was not confirmed in the majority of PH patients (<7% RHC use) but nevertheless, 22% of PH patients post-index had claims for drugs approved for the treatment of pulmonary arterial hypertension (PAH). CONCLUSIONS: Group 3 PH poses a significant clinical and economic burden. Given the low use of RHC and the prevalence of PAH-indicated prescriptions that are not currently approved for Group 3 PH, this study suggests some Group 3 PH patients may not be receiving guideline-recommended treatment.

Indirect costs and workplace productivity loss associated with non-Hodgkin lymphoma.

The objective of this study was to examine indirect costs and workplace productivity loss (defined as an aggregate measure of absenteeism, short-term disability, and long-term disability days) associated with non-Hodgkin lymphoma (NHL) from a societal perspective in a commercially insured working-age United States population. The MarketScan(®) Commercial Claims and Encounters and Health and Productivity Management Databases (2007-2013) were used in this study, with controls matched 3:1 to NHL patients. In comparison to controls, NHL patients incurred significantly more workplace productivity loss (31.99 days; 95% CI: 25.24 days, 38.73 days; p < 0.001) and associated indirect costs ($6302.34; 95% CI: $4973.40, $7631.28; p < 0.001) in the 12-month post-diagnosis period when adjusting for covariates. NHL contributes significantly to losses in workplace productivity and higher associated indirect costs.