Survival of medical treatment success in primary open-angle glaucoma and ocular hypertension.

BACKGROUND/AIMS: Topical agents to lower intraocular pressure (IOP) are the most common initial therapeutic measure in glaucoma prevention. This study aims to assess treatment success duration among patients initiating or intensifying topical glaucoma medication. METHODS: Medical records (2013‒2018) for adults initiating/intensifying topical glaucoma medication were extracted from five secondary-care and tertiary-care UK ophthalmology centres. Main study outcomes were time from treatment initiation/intensification to treatment failure (<20% IOP reduction or IOP >21 mm Hg at consecutive clinic visits, or intensification of glaucoma treatment) and time from treatment change to subsequent treatment intensification. RESULTS: Study eyes (n=6587) underwent treatment intensification 0-to-1 glaucoma drop (5358 events), 1-to-2 drops (1469 events) and 2-to-3 drops (857 events) during the observation period. Median time to treatment failure was 1.60 (95% CI 1.57 to 1.65), 1.00 (95% CI 0.94 to 1.07) and 0.92 (95% CI 0.81 to 1.02) years following escalation 0-to-1, 1-to-2 and 2-to-3 drops, respectively. Median time to treatment intensification (non-IOP-based criterion) was 4.68 (95% CI 4.50 to 5.08) years for treatment initiators, 3.83 (95% CI 3.36 to 4.08) years on escalation 1-to-2 drops and 4.35 (95% CI 3.82 to 4.88) years on escalation 2-to-3 drops. On multivariable regression, significant risk factors for both treatment failure and intensification were lower baseline visual field mean deviation, primary open-angle glaucoma and lower eyedrop count in the fellow eye; lower baseline IOP was associated with treatment failure, higher baseline IOP with treatment intensification. CONCLUSION: Large-scale survival analyses provide the expected duration of treatment success from topical glaucoma medication.

Burden of Glaucoma in the United Kingdom: A Multicenter Analysis of United Kingdom Glaucoma Services.

OBJECTIVE: To determine the spectrum of glaucoma-associated health care resource utilization among outpatients attending National Health Service (NHS) hospital glaucoma clinics and the costs of managing glaucoma in this setting. DESIGN: Retrospective observational cohort study using electronic medical record data. SUBJECTS: Patients aged ≥ 18 years attending 5 NHS glaucoma clinics in the United Kingdom (2013‒2018) with ≥ 12 months of continuous electronic medical record data. METHODS: Deidentified Medisoft Ophthalmology electronic medical record data (January 2013‒December 2018) from 43 742 eligible patients were categorized by year of clinic visit. Extracted information included patient demographics, glaucoma diagnoses, topical glaucoma medication prescription start/stop dates, types/numbers of glaucoma clinic visits, glaucoma investigations (visual acuity, intraocular pressure, visual field, and OCT), and glaucoma procedures received over 12 months after the first ("index") visit of the specified year. Direct glaucoma-related health care costs (clinic visits, investigations, procedures, and ongoing glaucoma medication initiated in the clinic) were estimated from event volumes and unit costs (UK national tariffs) and expressed from the direct-payer perspective. MAIN OUTCOME MEASURES: Glaucoma diagnoses and topical glaucoma medication use at the index clinic visit; numbers of glaucoma clinic visits, investigations and procedures; and glaucoma-related health care costs over 12 months postindex. RESULTS: For the 2016 cohort (n = 21 719), the estimated average total cost of NHS-provided glaucoma care over 12 months was £405 per patient (medical staff services £209, glaucoma investigations £126, glaucoma medication £40, glaucoma procedures £26). Among this cohort, 40.8% had ocular hypertension/suspected glaucoma, 70% had 0-to-mild visual field impairment, and 14% had undergone a glaucoma procedure. Over 12 months, patients received (mean) 2.0 glaucoma clinic visits and 1.5 visual field tests, and 7% underwent glaucoma procedure(s). Results were similar for the other years examined. CONCLUSIONS: Cost estimates for managing patients with glaucoma in the UK are required for effective service planning. Appreciable proportions of patients managed in NHS glaucoma clinics may be considered at low risk of blindness (glaucoma suspects and those with ocular hypertension with mild visual field loss) and may be more appropriately managed with alternative, more affordable models of care.

Topical Medication Adherence and Visual Field Progression in Open-angle Glaucoma: Analysis of a Large US Health Care System.

PRCIS: Modeling of visual field and pharmacy data (Kaiser Permanente, 2001 to 2014) from open-angle/pseudoexfoliation glaucoma patients in clinical practice indicated a significant inverse association between the level of medication adherence and rate of visual field progression. PURPOSE: The aim was to quantify the effect of nonadherence to topical hypotensive medication on glaucomatous visual field progression in clinical practice. METHODS: Retrospective analysis of combined visual field and pharmacy data from Kaiser Permanente Southern California's HealthConnect electronic health record database. Patients with a diagnosis of primary open-angle glaucoma or pseudoexfoliation glaucoma (2001 to 2011) and ≥3 subsequent visual field tests of the same Swedish Interactive Threshold Algorithm type were followed up from first medication fill to final visual field test. Medication adherence (proportion of days covered) was estimated from pharmacy refill data. A conditional growth model was used to estimate the effect of adherence level in modifying the progression of mean deviation over time after adjusting for potential confounders, including age, sex, race/ethnicity, baseline glaucoma severity, and comorbidity. RESULTS: In total, 6343 eligible patients were included in the study and followed for (mean) 5.8 years; average treatment adherence during follow-up was 73%. After controlling for confounders and the interaction between time and baseline disease severity, the model indicated that mean deviation progression was significantly (P=0.006) reduced by 0.006 dB per year for each 10% (absolute) increase in adherence. Model estimates of time to glaucoma progression (mean deviation change -3 dB from baseline) were 8.3 and 9.3 years for patients with adherence levels of 20% and 80%, respectively. CONCLUSIONS: Improving patient adherence to topical glaucoma medication may result in slower deterioration in visual function over time.

Comparing Healthcare Resource Utilization and Costs for Patients with Normal Tension Glaucoma Across Levels of Severity: A Retrospective Cohort Study.

PURPOSE: To estimate the healthcare resource utilization (HCRU) and costs for patients with normal tension glaucoma (NTG) as well as their payers across various levels of disease severity. PATIENTS AND METHODS: Our study was a retrospective cohort study of 6330 US NTG patients. Patients were enrolled if they were 40 years or older and had two or more qualifying NTG diagnoses within the enrollment period, October 1st, 2015 to December 31st, 2017. Our analysis was carried out for two cohorts - those with unilateral disease and those with bilateral disease. Baseline demographic and clinical characteristics were assessed for a 12-month pre-index period. The follow up period was 12-months post-index. We employed generalized linear models to model HCRU and costs. RESULTS: Patients with severe, bilateral disease, filled more than two additional prescriptions annually (2.5, p<0.001, 95% CI [2.0, 3.1]) when compared to their mild counterparts and accounted for 111 (p<0.001, 95% CI [83.5, 139.1]) extra days of supply of glaucoma medications. These patients face an adjusted $187 (p<0.001, 95% CI [145, 229]) more out-of-pocket (OOP), and payers an additional $598 (p<0.001, 95% CI [$370, $826]), than their counterparts with a mild diagnosis on an annual basis. Total annual payer costs, on average (SD) for those with severe bilateral NTG were $1175 ($2222). CONCLUSION: Our results suggest that patient and payer burden is significantly greater for those with severe disease compared to those with mild NTG. The excess burden is attributed to additional HCRU and the associated financial burden. Payers experienced a much larger financial burden from patients with severe disease compared to those with mild NTG. Approximately half of the cost differences can be attributed to additional prescription use.

Clinical and Economic Burden of Glaucoma by Disease Severity: A United States Claims-Based Analysis.

PURPOSE: To provide updated estimates of the clinical and economic burden in patients with ocular hypertension (OHT) or open-angle glaucoma (OAG) by disease severity in the United States and to estimate incremental costs associated with disease progression. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with 1 or more International Classification of Diseases, 10th Revision, Clinical Modification, diagnoses for OAG or OHT who are 40 years of age or older. METHODS: Patients were identified from IQVIA's PharMetrics Plus database during the index period (October 1, 2015, to August 31, 2017). Patients had continuous health plan enrollment for 12 months or more before and after the index date (first OAG or OHT diagnosis during index period) and were stratified by baseline disease severity based on diagnosis code. Annual eye-related outpatient healthcare use and costs were estimated on a per-user basis. A generalized linear model was used to estimate adjusted mean costs by severity and to evaluate the impact of observed disease worsening on costs. A multivariate logistic regression analysis evaluated the relationship between severity and odds of falls or fractures. MAIN OUTCOME MEASURES: Total eye-related outpatient costs and odds of falls or fractures. RESULTS: One hundred seventy-seven thousand three hundred fifty-two OHT and OAG patients were identified (67.8% with OAG). Open-angle glaucoma patients showed higher eye-related outpatient costs than OHT patients (median, $516 [interquartile range (IQR), $323-$898] vs. $344 [IQR, $197-$617], respectively). Patients with severe OAG showed higher eye-related outpatient costs than moderate and mild OAG patients (median, $639 [IQR, $381-$1264] vs. $546 [IQR, $345-$950] vs. $476 [IQR, $304-$765], respectively; P < 0.0001), as well as higher glaucoma-related pharmacy costs (median, $493 [IQR, $122-$1457] vs. $244 [IQR, $84-$1113] vs. $139 [IQR, $66-$818], respectively; P < 0.0001). In adjusted analyses, disease worsening was associated with at least 2-fold higher annual eye-related outpatient costs (P < 0.0001). Severe OAG patients had significantly higher odds of fall or fracture compared with OHT patients (odds ratio, 1.34; 95% confidence interval, 1.13-1.59). CONCLUSIONS: Updated estimates showed highest eye-related costs for those with severe disease and disease progression among patients with OAG and OHT. Severe OAG was associated with increased risk of falls or fractures compared with patients with OHT. Therapies that delay disease progression may provide clinical and economic benefits.

Economic and Clinical Burden Associated With Intensification of Glaucoma Topical Therapy: A US Claims-based Analysis.

PRECIS: Incremental addition of intraocular pressure-lowering topical drops is associated with shorter-lasting benefit and higher health-related costs with each additional agent, suggesting a need for new treatment options to improve disease control and reduce treatment burden. PURPOSE: The purpose of this study was to evaluate treatment intensification as a driver of clinical and economic burden in patients receiving topical glaucoma medications for open-angle glaucoma/ocular hypertension. METHODS: This retrospective analysis of administrative claims data (January 2011 to July 2017) from the IQVIA PharMetrics Plus database included diagnosed patients who initiated or intensified treatment with 1 to 4 topical glaucoma medications of a different drug class between January 2012 and July 2015 (index date being the first such event during this period). Patients with prior open-angle glaucoma surgery or an equal or greater number of topical glaucoma medication classes during the preindex period were excluded. Treatment intensification rates and eye-related outpatient costs were assessed over 24 months postindex. RESULTS: Of 48,402 patients (mean age: 61.4 y), 22,874 (47.3%), 16,214 (33.5%), 7137 (14.7%), and 2177 (4.5%) received a first, second, third, or fourth medication class, respectively, as their first observed initial or intensified regimen. Among cohorts receiving 1, 2, 3, or 4 medication classes, 7.8%, 12.2%, 17.2%, and 22.6% of patients and 12.6%, 18.5%, 25.9%, and 33.7% of patients had subsequent treatment augmentation (class addition or glaucoma procedure, laser or surgical) within 12 and 24 months postindex, respectively. Eye-related outpatient costs over 24 months increased with each additional topical glaucoma medication class at index [mean (SD): $1610 ($3460), $2418 ($4863), $2872 ($5110), and $3751 ($6608) in the 1, 2, 3, or 4 class cohorts, respectively]. CONCLUSION: Multiple-drop therapies yielded shorter-lasting benefits with each additional agent and were associated with the increased clinical and economic burden.

Management and Outcomes for Neovascular Age-Related Macular Degeneration: Analysis of United States Electronic Health Records.

PURPOSE: To assess anti-vascular endothelial growth factor (VEGF) management patterns and anatomic and visual acuity (VA) outcomes among patients with neovascular age-related macular degeneration (nAMD) in United States clinical practice. DESIGN: Retrospective observational cohort study. PARTICIPANTS: Patients (N = 30 106) initiating intravitreal anti-VEGF treatment for nAMD between October 2009 and November 2016. METHODS: Analysis of longitudinal electronic health records from USRetina. MAIN OUTCOME MEASURES: Number of intravitreal injections, OCT examinations, and fluorescein angiography (FA) examinations per study eye during the first 12 months; corrected VA and central retinal thickness (CRT) at 12 months; and number of ophthalmologist visits, stratified by index anti-VEGF agent. RESULTS: Over the first 12 months, patients made a mean of 8.1 (range, 1-39) ophthalmologist visits, received a mean of 6.0 (range, 1-27) anti-VEGF injections, and underwent 7.2 OCT and 5.3 FA examinations per study eye. For eyes with paired baseline and 12-month readings, mean CRT declined from 320 to 271 µm (mean change, -48 µm), and mean VA increased from 60.3 to 61.0 approximate Early Treatment Diabetic Retinopathy Study (ETDRS) letters (mean change, +0.6 letters). Twelve months after initiating index treatment with bevacizumab, ranibizumab, and aflibercept, 19.3%, 15.8%, and 15.5% of eyes, respectively, showed greater than 10-letter gain, whereas 13.2%, 14.7%, and 14.4% of eyes, respectively, showed greater than 10-letter loss. Mean change from baseline VA at 12 months increased linearly with cumulative anti-VEGF injection count: +1.79 versus -0.95 approximate ETDRS letters for eyes receiving 7 or more injections versus fewer than 7 injections. Similarly, the magnitude of the reduction from baseline CRT at 12 months tended to increase linearly with increasing number of anti-VEGF injections. Multivariate linear regression analysis, adjusted for covariates, indicated a significant association between cumulative number of anti-VEGF injections and change from baseline in VA at 12 months, with each unit increase producing an estimated gain of 0.37 approximate ETDRS letters. CONCLUSIONS: This analysis of combined morphologic and functional outcomes of anti-VEGF therapy, the largest conducted to date in nAMD, identified relatively low anti-VEGF injection frequencies, coupled with moderate anatomic and limited VA improvements, in United States clinical practice.

Direct Costs Incurred Among Women Undergoing Surgical Procedures to Treat Uterine Fibroids.

BACKGROUND: Uterine fibroids (UF) affect up to 70%-80% of women by 50 years of age and represent a substantial economic burden on patients and society. Despite the high costs associated with UF, recent studies on the costs of UF-related surgical treatments remain limited. OBJECTIVE: To describe the health care resource utilization (HCRU) and all-cause costs among women diagnosed with UF who underwent UF-related surgery. METHODS: Data from the IBM MarketScan Commercial Claims and Encounters database and Medicaid Multi-State database were independently, retrospectively analyzed from January 1, 2009, to December 31, 2015. Women aged 18-64 years with ≥ 1 UF claim from January 1, 2010, to December 31, 2014, a claim for a UF-related surgery (hysterectomy, myomectomy, uterine artery embolization [UAE], or ablation) from January 1, 2010, to November 30, 2015, and continuous enrollment for ≥ 1 year presurgery and ≥ 30 days postsurgery qualified for study inclusion. A 1-year period before the date of the first UF-related surgical claim after the first UF diagnosis was used to report baseline demographic and clinical characteristics. Surgery characteristics were reported. All-cause HCRU and costs (adjusted to 2017 U.S. dollars) were described by the 14 days pre-, peri-, and 30 days postoperative periods, and independently by the inpatient or outpatient setting. RESULTS: Overall, 113,091 patients were included in this study: commercial database, n = 103,814; Medicaid database, n = 9,277. Median time from the initial UF diagnosis to first UF-related surgical procedure was 33 days for the commercial population and 47 days for the Medicaid population. Hysterectomy was the most common UF-related surgery received after UF diagnosis (commercial, 68% [n = 70,235]; Medicaid, 75% [n = 6,928]). In both populations, 97% of patients had ≥ 1 outpatient visit from 14 days presurgery to 30 days postsurgery (commercial, n = 100,402; Medicaid, n = 9,023), and the majority of all UF-related surgeries occurred in the outpatient setting (commercial, 64% [n = 66,228]; Medicaid, 66% [n = 6,090]). Mean total all-cause costs for patients with UF who underwent any UF-related surgery were $15,813 (SD $13,804) in the commercial population (n = 95,433) and $11,493 (SD $26,724) in the Medicaid population (n = 4,785). Mean total all-cause costs for UF-related surgeries for the commercial/Medicaid populations were $17,450 (SD $13,483)/$12,273 (SD $19,637) for hysterectomy, $14,216 (SD $16,382)/$11,764 (SD $15,478) for myomectomy, $17,163 (SD $13,527)/$12,543 (SD $23,777) for UAE, $8,757 (SD $9,369)/$7,622 (SD $50,750) for ablation, and $12,281 (SD $10,080)/$5,989 (SD $5,617) for myomectomy and ablation. Mean total all-cause costs for any UF-related surgery performed in the outpatient setting in the commercial and Medicaid populations were $14,396 (SD $11,466) and $6,720 (SD $10,374), respectively, whereas costs in the inpatient setting were $18,345 (SD $16,910) and $21,805 (SD $43,244), respectively. CONCLUSIONS: This retrospective analysis indicated that surgical treatment options for UF continue to represent a substantial financial burden. This underscores the need for alternative, cost-effective treatments for the management of UF. DISCLOSURES: This study was sponsored by Allergan, Dublin, Ireland. Allergan played a role in the conduct, analysis, interpretation, writing of the report, and decision to publish this study. Harrington and Ye are employees of Allergan. Stafkey-Mailey, Fuldeore, and Yue are employees of Xcenda. Ta was a contractor at Allergan at the time the study was conducted and is currently supported by a training grant from Allergan. Bonine, Shih, and Gillard are employees of Allergan and have stock, stock options, and/or restricted stock units as employees of Allergan. Banks has no disclosures to report. This study was presented as a poster at Academy of Managed Care Pharmacy Nexus 2017; October 16-19, 2017; Dallas, TX.

Relationship between duration and extent of oedema and visual acuity outcome with ranibizumab in diabetic macular oedema: A post hoc analysis of Protocol I data.

BACKGROUND/OBJECTIVES: This post hoc analysis explores the relationship between residual oedema exposure after ranibizumab treatment initiation and long-term visual acuity outcome in eyes with centre-involved diabetic macular oedema (DMO). SUBJECTS/METHODS: Eyes randomised to the ranibizumab + prompt or deferred laser treatment arms in the Protocol I trial and with observed central retinal thickness (CRT) readings at baseline and ≥1 follow-up visits (n = 367) were stratified by 1) oedema duration (number of study visits with CRT ≥ 250 µm during the first 52 weeks of ranibizumab treatment); and 2) oedema extent (amount of excess CRT [≥ 250 µm] at each study visit, averaged over the first 52 weeks). Associations between measures of residual oedema and best-corrected visual acuity (BCVA) were assessed in multiple regression analyses. RESULTS: Oedema duration and oedema extent during the first 52 weeks of ranibizumab treatment showed significant negative associations with BCVA improvement at weeks 52, 104 and 156. Eyes with the most persistent oedema gained (mean) 4.4 (95% CI 0.1─8.7) fewer Early Treatment Diabetic Retinopathy Study (ETDRS) letters at week 156 than eyes with the least persistent oedema (P = 0.044). Eyes with the greatest amount of oedema gained (mean) 9.3 (95% CI 4.0─14.5) fewer ETDRS letters at week 156 than eyes with the least amount of oedema (P < 0.001). CONCLUSIONS: Macular oedema exposure over the first 52 weeks of ranibizumab treatment is a negative prognostic factor for long-term visual acuity improvement in centre-involved DMO.

Healthcare resource utilization and costs among women diagnosed with uterine fibroids compared to women without uterine fibroids.

Objective: To perform a retrospective, matched-cohort, longitudinal evaluation of annual pre- and post-diagnosis costs incurred among women with uterine fibroids (UF) (cases) compared to controls without UF. Methods: Data were derived from the IBM Watson Health MarketScan Commercial Claims and Encounters and Medicaid Multi-State databases. Women aged 18-64 years with ≥1 inpatient or outpatient medical claim with an initial UF diagnosis (index date) from 1 January 2010 to 31 December 2014 were included. Healthcare resource utilization (HCRU) data including pharmacy, outpatient and inpatient hospital claims were collected for 1 year pre-index and ≤5 years post-index. All-cause costs (adjusted to 2017 $US) were compared between cases and controls using multivariable regression models. Results: Analysis included 205,098 (Commercial) and 24,755 (Medicaid) case-control pairs. HCRU and total all-cause healthcare costs were higher for cases versus controls during the pre-index year and all years post-index. Total unadjusted mean all-cause costs were $1197 higher (p < .0001; Commercial) and $2813 higher (standardized difference 0.08; Medicaid) for cases during the pre-index year. Total adjusted mean all-cause costs in the first year post-index were $14,917 for cases versus $5717 for controls in the Commercial population, and $20,244 versus $10,544, respectively, in the Medicaid population. In Years 2-5 post-index, incremental mean adjusted total costs decreased, but remained significantly higher for cases versus controls at all time points in both populations (all p < .05). Conclusions: Costs were higher for women with UF compared to women without UF during the pre-index year and over 5 years post-index; differences were greatest in the first year post-index.

ASSOCIATION BETWEEN EARLY ANATOMIC RESPONSE TO ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY AND LONG-TERM OUTCOME IN DIABETIC MACULAR EDEMA: An Independent Analysis of Protocol i Study Data.

PURPOSE: This post hoc analysis explores the relationship between early retinal anatomical response and long-term anatomical and visual outcomes with ranibizumab in center-involved diabetic macular edema. METHODS: Eyes randomized to the ranibizumab plus prompt laser and ranibizumab plus deferred laser treatment arms in the Protocol I study were categorized according to their proportional reduction (<20 vs. ≥20%) in central retinal thickness (CRT) after 12 weeks. Adjusted and unadjusted analyses assessed the association between early (Week 12) anatomical response and long-term (Weeks 52 and 156) anatomical and best-corrected visual acuity outcomes. RESULTS: Of 335 study eyes, 118 showed limited (<20%) and 217 showed strong (≥20%) CRT reduction at Week 12. In unadjusted and adjusted analyses, limited early CRT response was negatively and significantly associated with strong CRT response at Weeks 52 and 156. Sensitivity analyses indicated that this association was robust and unrelated to any "floor effect." In unadjusted analyses, a strong early CRT response was associated with greater long-term improvement in best-corrected visual acuity; after controlling for confounders, the association lost statistical significance. CONCLUSION: Early CRT response to ranibizumab is a significant prognostic indicator of medium- to long-term anatomical outcome in center-involved diabetic macular edema.

Targeted Therapies Compared to Dacarbazine for Treatment of BRAF(V600E) Metastatic Melanoma: A Cost-Effectiveness Analysis.

Purpose. Two BRAF(V600E) targeted therapies, dabrafenib and vemurafenib, have received US approval for treatment of metastatic melanoma in BRAF(V600E) patients, a mutation that affects ~50% of patients. We evaluated the cost-effectiveness of BRAF inhibitors and traditional chemotherapy for treatment of metastatic melanoma. Methods. A Markov model was developed using a societal perspective. Transition probabilities were derived from two Phase III registration trials comparing each BRAF inhibitor against dacarbazine. Costs were obtained from literature, national databases, and Medicare fee schedules. Utilities were obtained from published literature. Deterministic and probabilistic sensitivity analyses were run to test the impact of uncertainties. Results. The incremental cost-effectiveness ratio of dabrafenib was $149,035/QALY compared to dacarbazine. Vemurafenib was dominated by dabrafenib. Probabilistic sensitivity analysis showed that, at a willingness-to-pay (WTP) threshold of ≤$100,000/QALY, dacarbazine was the optimal treatment in ~85% of simulations. At a WTP threshold of ≥$150,000/QALY, dabrafenib was the optimal treatment. Conclusion. Compared with dacarbazine, dabrafenib and vemurafenib were not cost-effective at a willingness-to-pay threshold of $100,000/QALY. Dabrafenib is more efficient compared to vemurafenib. With few treatment options, dabrafenib is an option for qualifying patients if the overall cost of dabrafenib is reduced to $30,000-$31,000 or a WTP threshold of ≥$150,000/QALY is considered. More comparative data is needed.