Calibrating Observational Health Record Data Against a Randomized Trial.

Importance: The conditions required for health record data sources to accurately assess treatment effectiveness remain unclear. Emulation of randomized clinical trials (RCTs) with health record data and subsequent calibration of the results can help elucidate this.

Objective: To pilot an emulation of the KEYNOTE-189 RCT using a commercially available electronic health record (EHR) data source.

Assessing ascertainment bias in atrial fibrillation across US minority groups.

The aim of this study is to define atrial fibrillation (AF) prevalence and incidence rates across minority groups in the United States (US), to aid in diversity enrollment target setting for randomized controlled trials. In AF, US minority groups have lower clinically detected prevalence compared to the non-Hispanic or Latino White (NHW) population. We assess the impact of ascertainment bias on AF prevalence estimates.

Enhancing site selection strategies in clinical trial recruitment using real-world data modeling.

Slow patient enrollment or failing to enroll the required number of patients is a disruptor of clinical trial timelines. To meet the planned trial recruitment, site selection strategies are used during clinical trial planning to identify research sites that are most likely to recruit a sufficiently high number of subjects within trial timelines. We developed a machine learning approach that outperforms baseline methods to rank research sites based on their expected recruitment in future studies.

Durability of Protection Post-Primary COVID-19 Vaccination in the United States.

The durability of immune responses after COVID-19 vaccination will drive long-term vaccine effectiveness across settings and may differ by vaccine type. To determine durability of protection of COVID-19 vaccines (BNT162b2, mRNA-1273, and Ad26.COV2.

Impact of Immune Checkpoint Inhibitors on COVID-19 Severity in Patients with Cancer.

Background: Amid continued uncertainty about the management of cancer patients during the pandemic, this study sought to obtain real-world data on the use of immune checkpoint inhibitors (ICIs) before COVID-19 diagnosis and its association with severity and survival outcomes in cancer patients who contracted COVID-19.

Methods: Cancer patients diagnosed with COVID-19 were identified from a large electronic health record database; those treated with ICIs before COVID-19+ diagnosis were matched in a 1:2 ratio to those not treated with ICIs, using a 2-step matching procedure. A descriptive analysis examined the difference in COVID-19 mortality (30-day and overall) and severity outcomes between the 2 cohorts, and overall survival was compared.

Association of biological antirheumatic therapy with risk for type 2 diabetes: a retrospective cohort study in incident rheumatoid arthritis.

Objective: To explore possible associations of treatment with biological disease-modifying antirheumatic drugs (bDMARDs), including T-cell-based and interleukin-6 inhibition (IL-6i)-based therapies, and the risk for type 2 diabetes mellitus (T2DM) in patients with rheumatoid arthritis (RA).

Study Design, Setting And Participants: Five treatment groups were selected from a United States Electronic Medical Records database of 283 756 patients with RA (mean follow-up, 5 years): never received bDMARD (No bDMARD, n=125 337), tumour necrosis factor inhibitors (TNFi, n=34 873), IL-6i (n=1884), T-cell inhibitors (n=5935) and IL-6i+T cell inhibitor abatacept (n=1213). Probability and risk for T2DM were estimated with adjustment for relevant confounders.

Rituximab utilization for approved and off-label nononcology indications and patients' experiences with the Patient Alert Card.

This study used retrospective chart review and survey data to evaluate: (1) off-label use of rituximab (MabThera/Rituxan) in autoimmune conditions and (2) patients' receipt and knowledge of the Patient Alert Card (PAC), a risk minimization measure for progressive multifocal leukoencephalopathy (PML) and serious infections. Anonymized patient data were collected from infusion centers in Europe from December 2015 to July 2017. Adults receiving rituximab in the same centers were provided a self-administered survey.

Characterizing Disease Manifestations and Treatment Patterns Among Adults with Systemic Sclerosis: A Retrospective Analysis of a US Healthcare Claims Population.

Introduction: Real-world use of immunomodulating therapy (IMT) in patients with systemic sclerosis (SSc) was investigated for the first time in a descriptive, retrospective cohort analysis of claims made in a healthcare insurance database to characterize treatment patterns and their alignment with SSc disease manifestations.

Methods: Treatment patterns and disease manifestations, symptoms, complications, and comorbidities were assessed in patients with SSc enrolled in a US healthcare claims database who received treatment between January 2006 and December 2013 and for whom data were available 6 months before and 12 months after SSc diagnosis.

Results: Among 7812 eligible patients, 6852 received treatments of interest for SSc and 2404 (30.

Risk of malignancy associated with use of tocilizumab versus other biologics in patients with rheumatoid arthritis: A multi-database cohort study.

Objectives: To examine the rate of incident malignancies excluding non-melanoma skin cancer (NMSC) in patients with rheumatoid arthritis (RA) newly treated with tocilizumab versus other biologic drugs.

Methods: We conducted a cohort study using data from 3 U.S.

Adverse Events in Giant Cell Arteritis and Rheumatoid Arthritis Patient Populations: Analyses of Tocilizumab Clinical Trials and Claims Data.

Introduction: The safety profile of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) is well established. TCZ was approved to treat giant cell arteritis (GCA) in 2017 in the USA and Europe, and its safety profile in patients with GCA continues to be defined. The objective of this analysis was to examine incidence rates (IRs) of adverse events of special interest (AESI) occurring during the TCZ clinical development program and in healthcare claims data in patients with GCA or RA.

Risk of serious infections in tocilizumab versus other biologic drugs in patients with rheumatoid arthritis: a multidatabase cohort study.

Objective: To investigate the rate of serious bacterial, viral or opportunistic infection in patients with rheumatoid arthritis (RA) starting tocilizumab (TCZ) versus tumour necrosis factor inhibitors (TNFi) or abatacept.

Methods: Using claims data from US Medicare from 2010 to 2015, and IMS and MarketScan from 2011 to 2015, we identified adults with RA who initiated TCZ or TNFi (primary comparator)/abatacept (secondary comparator) with prior use of ≥1 different biologic drug or tofacitinib. The primary outcome was hospitalised serious infection (SI), including bacterial, viral or opportunistic infection.

Incidence and Risk of Glucocorticoid-Associated Adverse Effects in Patients With Rheumatoid Arthritis.

Objective: Using the UK Clinical Practice Research Datalink, we examined the incidence of glucocorticoid (GC)-related serious adverse events (SAEs) in rheumatoid arthritis (RA) and non-RA patients and quantified the risk of SAEs in patients with RA.

Methods: We matched incident patients with RA to an age- and sex-matched, non-RA comparison group of equal size. In a cohort analysis, we estimated incidence rates (IRs) and IR ratios (IRRs) for GC-related AEs (i.

Risk Associated with Cumulative Oral Glucocorticoid Use in Patients with Giant Cell Arteritis in Real-World Databases from the USA and UK.

Introduction: Treatment of giant cell arteritis (GCA) involves immediate initiation of high-dose glucocorticoid therapy with slow tapering of the dose over many months. Chronic exposure to glucocorticoids is associated with serious comorbidities. The objective of this analysis was to determine the glucocorticoid exposure and risk of glucocorticoid-related adverse events (AEs) in real-world patients with GCA.

Comparative effectiveness of tocilizumab versus TNF inhibitors as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis after the use of at least one biologic disease-modifying antirheumatic drug: analyses from the pan-European TOCERRA register collaboration.

Objective: To compare the effectiveness of tocilizumab (TCZ) and tumour necrosis factor (TNF) inhibitors (TNFi) as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA) after the use of at least one biologic DMARD (bDMARD).

Methods: We included patients with RA having used at least one bDMARD from 10 European registries. We compared drug retention using Kaplan-Meier and Cox models and Clinical Disease Activity Index (CDAI) change over time with mixed-effects models for longitudinal data.

No difference in cardiovascular risk of tocilizumab versus abatacept for rheumatoid arthritis: A multi-database cohort study.

Objectives: While tocilizumab may increase serum lipid levels, recent studies do not suggest a link between tocilizumab use and clinical cardiovascular risk in patients with rheumatoid arthritis (RA).

Methods: To compare cardiovascular safety of tocilizumab with abatacept, we conducted a cohort study using data from Medicare (2010-2013), IMS PharMetrics (2011-2014) and MarketScan (2011-6/2015). RA patients aged ≥18 years who newly started tocilizumab or abatacept entered the cohort on the day of their first use of tocilizumab or abatacept after a continuous enrollment period for ≥365 days.

Association Between Glucocorticoid Exposure and Healthcare Expenditures for Potential Glucocorticoid-related Adverse Events in Patients with Rheumatoid Arthritis.

Objective: Oral glucocorticoid (OGC) use for rheumatoid arthritis (RA) is debated because of the adverse event (AE) profile of OGC. We evaluated the associations between cumulative doses of OGC and potential OGC-related AE, and quantified the associated healthcare expenditures.

Methods: Using the MarketScan databases, patients ≥ 18 years old who have RA with continuous enrollment from January 1 to December 31, 2012 (baseline), and from January 1 to December 31, 2013 (evaluation period), were identified.

Effectiveness of biologic and non-biologic antirheumatic drugs on anaemia markers in 153,788 patients with rheumatoid arthritis: New evidence from real-world data.

Background: To evaluate the impact of treatment with disease-modifying antirheumatic drugs (DMARDs), including IL-6 receptor inhibitor tocilizumab (TCZ), on anaemia markers in patients with rheumatoid arthritis.

Methods: Using the Centricity Electronic Medical Records from USA, patients with rheumatoid arthritis diagnosed between January 2000 and April 2016, who initiated TCZ (n = 3732); tofacitinib (TOFA, n = 3126); other biologic DMARD (obDMARD, n = 55,964); or other non-biologic DMARD (onbDMARD, n = 91,236) were identified. Changes in haemoglobin (Hb) and haematocrit (Hct) over 2 years of treatment initiation were evaluated, adjusting and balancing for confounders.

Cardiovascular Safety of Tocilizumab Versus Tumor Necrosis Factor Inhibitors in Patients With Rheumatoid Arthritis: A Multi-Database Cohort Study.

Objective: While tocilizumab (TCZ) is known to increase low-density lipoprotein (LDL) cholesterol levels, it is unclear whether TCZ increases cardiovascular risk in patients with rheumatoid arthritis (RA). This study was undertaken to compare the cardiovascular risk associated with receiving TCZ versus tumor necrosis factor inhibitors (TNFi).

Methods: To examine comparative cardiovascular safety, we conducted a cohort study of RA patients who newly started TCZ or TNFi using claims data from Medicare, IMS PharMetrics, and MarketScan.

Serious adverse effects associated with glucocorticoid therapy in patients with giant cell arteritis (GCA): A nested case-control analysis.

Objective: Giant cell arteritis (GCA) is an inflammatory vasculitis preferentially affecting large and medium-sized arteries. High-dose oral glucocorticoids (GCs) are the mainstay of GCA therapy. Using data from the UK Clinical Practice Research Datalink (CPRD), we examined the risk of oral GC-related serious adverse events (SAEs) in a UK population of patients with giant cell arteritis (GCA).

Incidence of outcomes potentially associated with corticosteroid therapy in patients with giant cell arteritis.

Objective: Giant cell arteritis (GCA) is an inflammatory disorder of blood vessels that preferentially affects large- and medium-sized arteries. High-dose oral corticosteroids (CS) are the mainstay of GCA therapy. Using data from the UK Clinical Practice Research Datalink, we quantified and compared the incidence of selected potentially CS-associated adverse outcomes in patients with and without GCA.

Incidence of Gastrointestinal Perforations in Patients with Rheumatoid Arthritis Treated with Tocilizumab from Clinical Trial, Postmarketing, and Real-World Data Sources.

Introduction: The aim of this study was to use multiple data sources to update information on gastrointestinal perforations (GIPs) during tocilizumab (TCZ) treatment in patients with rheumatoid arthritis (RA).

Methods: Reporting rates of GIP events were estimated from three distinct patient data sets: a TCZ-IV RA clinical trial all-exposure population, a global TCZ postmarketing safety database population, and a US healthcare claims database population of patients with RA, including patients who received TCZ, anti-tumor necrosis factor (aTNF) agents, or abatacept.

Results: The clinical trial, global postmarketing, and healthcare claims populations provided 17,906, 382,621, and 3268 patient-years (PYs) of TCZ exposure, respectively.

The influence of caregivers and behavioral and psychological symptoms on nursing home placement of persons with Alzheimer's disease: A matched case-control study.

Objectives: Behavioral and psychological symptoms of dementia in individuals with Alzheimer's disease and caregiver characteristics may influence the decision to provide care at home or in a nursing home, though few studies examine this association near the actual time of nursing home placement. Using a matched case-control design, this study investigates the association between (1) total Neuropsychiatric Inventory score, (2) the Neuropsychiatric Inventory-4 (an agitation/aggression subscale), and (3) individual domains of the Neuropsychiatric Inventory and nursing home placement.

Methods: Data from the South Carolina Alzheimer's disease Registry provides an opportunity to expand the literature by looking at cases at the time of nursing home care eligibility/placement and allowing for propensity-score-matched controls.

Corticosteroid-related adverse events in patients with giant cell arteritis: A claims-based analysis.

Objective: Corticosteroids (CS) are standard treatment for giant cell arteritis (GCA), but concerns persist over toxicities associated with long-term use. In this retrospective study of medical claims data, we estimated risks for adverse events (AEs) in CS-treated GCA patients.

Methods: Cox regression analyses with CS use as a time-dependent variable were conducted on data from the 2003 to 2012 Truven Health Analytics MarketScan Database.

Incidence and complications of interstitial lung disease in users of tocilizumab, rituximab, abatacept and anti-tumor necrosis factor α agents, a retrospective cohort study.

Introduction: Interstitial lung disease (ILD) is a common extra-articular condition in rheumatoid arthritis (RA), but few studies have systematically investigated its incidence and risk factors in patients receiving anti-tumor necrosis factor-alpha (anti-TNFα) agents or alternate mechanisms of action (MOAs) (e.g., T-cell, B-cell, and interleukin-6 inhibitors).

Diagnostic Pathways to Alzheimer Disease: Costs Incurred in a Medicare Population.

Despite its implications on the personal and policy level, little is currently known about the specific diagnostic pathways that patients with cognitive impairment (CI) pass through before being diagnosed with Alzheimer disease (AD). Four major diagnostic pathways were identified in the Medicare claims records for 2001 to 2006: AD as initial diagnosis, cognitive disturbance followed by AD; dementia with suspected etiologies followed by AD; dementia without known cause followed by AD; and 1 triple pathway, cognitive disturbance followed by dementia without known cause followed by AD. For all of these pathways, previously low medical costs peaked during patients' month of initial diagnosis and then declined to a level substantially higher than before.