Estimating prevalence of classical homocystinuria in the United States using Optum's de-identified market clarity data.

Background and objectives: Prevalence estimates for classical homocystinuria (HCU) are variable and likely underestimated due to underdiagnosis. Claims data represent a strong but seldom used resource to analyze prevalence of HCU. The aim of this study was to estimate a prevalence range of HCU in the US utilizing a combination of diagnosis codes, total homocysteine levels, and clinical presentations indicative of HCU. Methods: This was a non-interventional retrospective cohort study, using Optum's de-identified Market Clarity Data, with a patient identification period from January 01, 2016, through September 30, 2021. An algorithm was developed to identify 2 cohorts of patients using broad and strict definitions of HCU. The index date was the date within the identification period on which the first criterion was met for the inclusion criteria. Baseline demographics, clinical characteristics, and complications were assessed and summarized using descriptive statistics. Crude and standardized prevalence estimates were calculated. Results: There were 3880 and 633 patients that met the relevant inclusion criteria for the broad and strict cohorts, respectively. The projected US prevalence of HCU was calculated to be 17,631 and 3466 based on the broad and strict definitions, respectively. The average annual standardized prevalence across 2016-2020 was 5.29 and 1.04 per 100,000 people for the broad and strict cohorts, respectively. Conclusions: Prevalence estimates of HCU vary depending on databases or datasets used and identification criteria. Many patients with clinical presentations suggesting a diagnosis of HCU did not have an associated diagnosis, potentially indicating underdiagnosis or underreporting. Future research should study alternative methods, such as the identification algorithm in our analysis, to better diagnose and understand the true prevalence of HCU.

Cardiovascular, Kidney Failure, and All-Cause Mortality Events in Patients with Focal Segmental Glomerulosclerosis in a U.S. Real-World Database.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) leads to proteinuria and progressive decline in glomerular filtration rate which correlates with kidney failure and increased cardiovascular risk. The purpose of this study was to estimate the effects of proteinuria on kidney failure status/all-cause mortality and cardiovascular disease events/all-cause mortality, as well as the relationship between progression to kidney failure and occurrence of cardiovascular disease/mortality events among adult patients (≥18 years old) with FSGS. METHODS: This was an observational, retrospective cohort study utilizing Optum® de-identified Market Clarity Data and proprietary Natural Language Processing (NLP) data. The study period was from January 1, 2007 through March 31, 2021, with patients in the overall cohort being identified from July 1, 2007 through March 31, 2021. The index date was the first FSGS ICD-10 diagnosis code or FSGS-related NLP term within the identification period. RESULTS: Elevated proteinuria >1.5 g/g and ≥3.5 g/g increased risk for kidney failure/all-cause mortality (adjusted hazard ratio [95% CI]: 2.34 [1.99-2.74] and 2.44 [2.09-2.84], respectively) and cardiovascular disease/all-cause mortality (adjusted hazard ratio [95% CI]: 2.11 [1.38-3.22] and 2.27 [1.44-3.58], respectively). Progression to kidney failure was also associated with a higher risk of cardiovascular disease/all-cause mortality (adjusted hazard ratio [95% CI]: 3.04 [2.66-3.48]. CONCLUSIONS: A significant proportion of FSGS patients experience kidney failure and cardiovascular disease events. Elevated proteinuria and progression to kidney failure were associated with a higher risk of cardiovascular disease/all-cause mortality events, and, elevated pre-kidney failure proteinuria was associated with progression to kidney failure/all-cause mortality events. Treatments that meaningfully reduce proteinuria and slow the decline in glomerular filtration rate have the potential to reduce the risk of cardiovascular disease, kidney failure and early mortality in patients with FSGS.

Clinical Characteristics and Histopathology in Adults With Focal Segmental Glomerulosclerosis.

Rationale & Objective: Few data are available regarding histological features at the time of focal segmental glomerulosclerosis (FSGS) diagnosis among diverse real-world populations. This study describes clinical and histological characteristics and correlates of histological disease severity in adults with FSGS who underwent a clinical kidney biopsy. Study Design: Real-world cohort study with data derived from health records. Setting & Participants: Adults with FSGS by kidney biopsies from Arkana Laboratories from January 1, 2016 to May 31, 2020. Exposure: Race, chronic kidney disease stage, nephrotic proteinuria, age, sex, and hypertension. Outcomes: Severe histological disease, defined as global glomerulosclerosis in >50% of glomeruli and >25% interstitial fibrosis and tubular atrophy (IFTA). Analytical Approach: Demographic, clinical, and histological characteristics were compared between race groups. Correlates of severe disease were analyzed using multiple logistic regression. Results: Among 2,011 patients with FSGS, 40.6% were White, and 23.6% Black. White patients were older (52.8 vs 45.5 years, P < 0.001) with a higher estimated glomerular filtration rate (eGFR) than Black patients (53.5 vs 43.1 mL/min/1.73 m2, P < 0.001). A higher proportion of Black patients had global glomerulosclerosis ≥50% (32.1% vs 14.6%, P < 0.001) or IFTA >50% (34.6% vs 14.7%, P < 0.001). Severe histological disease was more likely in Black patients (OR, 2.46; 95% CI, 1.59-3.79; P < 0.001). A higher proportion of patients with nephrotic than nonnephrotic proteinuria exhibited diffuse foot process effacement. Limitations: Unequal representation across United States regions, missing demographic and clinical data, and lack of data on primary versus secondary FSGS, treatments, or outcomes. Conclusions: Black patients were more frequently diagnosed at younger age with lower eGFR and more severe histological disease compared with White patients. Timelier identification of FSGS could increase the opportunity for therapeutic intervention, especially for high-risk patients, to mitigate disease progression and complications. Plain-Language Summary: Focal segmental glomerulosclerosis (FSGS) accounts for around one-quarter of diagnoses derived from clinical kidney biopsies in the United States. Limited data are available regarding the classes and distribution of histological features at FSGS diagnosis among diverse real-world populations. Analyzing data from US patients who underwent kidney biopsy and were diagnosed with FSGS, we showed that up to half of patients had features of severe histological disease. Of this overall population, Black patients were more frequently diagnosed at a younger age but with more severe histological disease than White patients. The work highlights the need for timelier diagnosis of FSGS to enable intervention at an earlier disease stage.

Corrigendum to "Clinicopathological Characteristics of Adult IgA Nephropathy in the United States" [Kidney International Reports Volume 8, Issue 9, September 2023, Pages 1792-1800].

[This corrects the article DOI: 10.1016/j.ekir.2023.06.016.].

Clinicopathological Characteristics of Adult IgA Nephropathy in the United States.

Introduction: IgA nephropathy (IgAN) is a progressive autoimmune kidney disease and a leading cause of glomerular disease that can result in kidney failure (KF). The median age at diagnosis is 35 to 37 years and approximately 50% of patients will progress to KF within 20 years. We aimed to enhance the understanding of renal histology and chronic kidney disease (CKD) stage at the time of IgAN diagnosis using a large real-world biopsy cohort. Methods: This retrospective cohort study evaluated biopsy data and clinical characteristics from adult patients within the US who were diagnosed with IgAN between January 1, 2016 to May 31, 2020. Descriptive statistics were summarized and relationship(s) between each Oxford Classification (MEST-C) component score with 24-hour proteinuria or CKD stage were examined using regression analysis. Results: A total of 4375 patients (mean age 47.7 years, 62.7% male) met eligibility criteria. Mild to moderate mesangial hypercellularity (47.3%), segmental sclerosis (65.0%), tubular atrophy ≥25% (57.4%), and crescents (18.5%) were identified; and 74.6% of patients were at CKD stage ≥3. Proteinuria ≥1 g/d was associated with higher MEST-C scores, and the odds of mesangial hypercellularity, segmental sclerosis, tubular atrophy, and crescents increased with CKD stage. Conclusion: Most patients with IgAN in our US cohort were diagnosed at CKD stage ≥3 and had high MEST-C scores and proteinuria that are suggestive of significant disease burden at the time of kidney biopsy. Strategies are required to raise awareness and promote earlier detection of asymptomatic urinary abnormalities before extensive irreversible kidney damage has occurred.

Impact of Proteinuria and Kidney Function Decline on Health Care Costs and Resource Utilization in Adults With IgA Nephropathy in the United States: A Retrospective Analysis.

Rationale & Objective: Among patients with IgA nephropathy (IgAN), proteinuria and decline in kidney function may be associated with increased economic burden. This study aimed to provide current information on the epidemiology and economic burden of IgAN in the United States. Study Design: Retrospective cohort study. Setting & Study Population: Overall, 9,984 patients in the Optum's Market Clarity database identified by the presence of at least 2 natural language processing-derived IgAN signs and disease and symptoms terms; 813 with linked claims data included in a health care resource utilization/cost subcohort. Predictor: High-risk proteinuria (≥1 g/d), chronic kidney disease (CKD) stage. Outcomes: Standardized prevalence, health care resource utilization, costs. Analytical Approach: Descriptive statistics for categorical and continuous variables. Direct standardization for prevalence estimation. Generalized linear models for health care resource utilization/costs, reported as per-patient-per-month (PPPM) costs in 2020 US dollars. Results: The estimated standardized US prevalence of IgAN (2016-2020) was 329.0 per 1,000,000 persons. High-risk proteinuria (≥1 vs <1 g/d) was associated with a higher mean PPPM number of outpatient visits (3.49 vs 1.74; P = 0.01) and pharmacy claims (3.79 vs 2.41; P = 0.01), contributing to higher mean total costs PPPM ($3,732 vs $1,457; P = 0.01). Furthermore, higher CKD stage was also associated with higher health care resource utilization (number of outpatient visits PPPM, number of pharmacy claims PPPM, proportion of patients with inpatient visits and emergency department visits; P < 0.001) and mean total cost PPPM (from $2,111 CKD stage 1 to $10,703 CKD stage 5/kidney failure; P < 0.001). Limitations: Generalizability outside of the catchment group for the database, missing data/errors inherent in retrospective database studies, relatively small sample size, use of Optum Market Clarity standardized pricing algorithms, exclusion of out-of-pocket costs. Conclusions: Health care resource utilization and costs were higher for IgAN patients with high-risk proteinuria and worsening kidney function. Treatments that reduce proteinuria and slow CKD disease progression may reduce the economic burden associated with IgAN. Plain-Language Summary: Immunoglobulin A nephropathy (IgAN) is a rare kidney disease. Over time, the kidneys may leak protein into the urine (proteinuria). IgAN can lead to kidney failure. Because IgAN is rare, it is hard to know how many people have it. This study used electronic health records to estimate the number of patients with IgAN in the United States, describe the characteristics of patients, and understand their treatments and the costs. The number of patients with IgAN increased between 2016 and 2020. The researchers think this is because doctors learned more about IgAN. Patients with severe disease used more health care resources and had higher costs. The authors believe treatments that slow kidney damage may reduce the cost of treating IgAN.

Medication Utilization Patterns 90 Days Before Initiation of Treatment with Repository Corticotropin Injection in Patients with Infantile Spasms.

INTRODUCTION: Infantile spasms (IS) is a rare and devastating form of early childhood epilepsy. Two drugs are approved in the United States for treatment of IS, H.P. Acthar® Gel (repository corticotropin injection, RCI) and Sabril® (vigabatrin). Given real-world variation in treatment of patients with IS, this study characterized treatment patterns with IS medications and determined all-cause health care resource utilization (HCRU) during the 90 days before initiating therapy with RCI in patients with IS. MATERIALS AND METHODS: Truven Health MarketScan® Research Databases were used to identify commercially insured US patients <2 years of age at RCI initiation with an IS diagnosis, per label use, from 1/1/07 to 12/31/15; presence of an electroencephalogram following diagnosis was required to assure diagnosis. Diagnosis codes and dispensed IS treatments of interest (drug classes including corticosteroids, vigabatrin, and other antiepileptic drugs [AEDs] excluding vigabatrin) before RCI initiation were evaluated. RESULTS: The 5 most common diagnoses other than IS observed in the study cohort (n=422) were "other convulsions," "acute upper respiratory infection," "esophageal reflux," "epilepsy, unspecified," and "abnormal involuntary muscle movements." Among the study cohort, 51.7% received RCI first; 38.9% received 1 drug class and 9.5% received >1 drug class before RCI initiation. Other AEDs were dispensed most often, either alone (31.3%) or with other drug classes (9.3%). Mean HCRU included 11.8 all-cause outpatient visits and 4.5 medications dispensed. Patients who received RCI or corticosteroids as their initial IS treatment had the lowest and second-lowest HCRU. CONCLUSION: In the 90 days before initiating RCI, patients with IS received multiple diagnoses and treatments, characterized by frequent HCRU. Use of RCI first (no prior IS medications) and AEDs first were associated with the lowest and highest HCRU, respectively, across all categories (all-cause outpatient visits, emergency department visits, hospital admissions, prescription medications).

Relapse prevalence, symptoms, and health care engagement: patient insights from the Multiple Sclerosis in America 2017 survey.

BACKGROUND: Underestimation of relapse in multiple sclerosis (MS) is detrimental to the patient as well as to their relationship with their MS healthcare professional (HCP). OBJECTIVE: To obtain direct insight into relapse prevalence, symptoms, and HCP engagement from patients with MS who responded to the Multiple Sclerosis in America (MSIA) 2017 survey. METHODS: Information on patient demographics, health insurance coverage, symptoms, disability, relapses, and related HCP interactions were captured. Descriptive analyses were conducted and relapses were annualized. Chi-square tests were used to evaluate frequency of patient engagement, i.e. speaking with or seeing their HCP during relapse with annualized relapse frequency and topics discussed. RESULTS: Of the 5,311 patient-respondents, the mean age was 51.2 years (84.3% female, 89.3% Caucasian); 40.1% were on disability, and 96.8% had health insurance coverage. A total of 72.2% of patients were diagnosed with relapsing-remitting MS (RRMS); 74.8% of patients not reporting a diagnosis of primary progressive MS (PPMS) (n = 4819) were using disease-modifying therapy. In the 2 years preceding the survey, 73.1% experienced a relapse for a median number of 2 relapses; this corresponded to an annualized relapse distribution among all patients of 44.1% with < 1 relapse, 35.5% with 1-2 relapses, and 20.2% with > 2 relapses. In patients reporting relapses, 62.5% cited an average relapse duration of < 1 month, 10.9% cited 1-2 months, and 13.6% cited > 2 months (12.9% were unsure/didn't recall). Leading symptoms experienced with MS relapse were fatigue (77.4%), numbness/tingling (70.0%), and walking or balance issues (68.8%). With respect to HCP engagement during relapse, 46.9% of patients reported doing so always/often, vs. sometimes (27.3%), rarely (18.5%), and never (7.3%). The most common reasons cited for not engaging an HCP were that the relapse was not severe enough (57.9%), the HCP was unhelpful or didn't specifically tell the patient to contact them (30.9%), the treatment didn't work well or wasn't tolerated (25.6%), or the preference to manage alone (24.4%). A higher percentage of patients with 1 relapse coincided with the highest frequency of HCP engagement during relapse, and the highest percentage of patients with ≥ 5 relapses coincided with the lowest frequency of HCP engagement during relapse. Key relapse-related and MS-related topics were discussed more by patients who always/often engage their HCP during relapse. HCP follow-up after relapse was variable, with 35.0% of patients reporting follow-up within 1 month of first contact, 50.3% reporting follow-up at the next office visit, and 14.7% reporting no follow-up. CONCLUSION: MS relapse remains particularly challenging for certain patients; some experience > 2 relapses in 1 year, relapse durations > 1 month, and relapse symptoms that interfere with daily functioning (e.g. walking/balance by 68.8%). Approximately 25% of patients reported rarely or never engaging their HCP during relapse. Common reasons for not engaging, like HCP helpfulness and treatment effectiveness/tolerance, warrant further exploration. Results indicating the benefits of timely touchpoints on both the part of the patient and HCP during relapse include the relationship between higher frequency of engagement with lower relapse frequency and more discussion of both relapse-related and MS-related discussion topics. Survey limitations apply.