Poor adherence to and persistence with biologics in generalized pustular psoriasis: A claim-based study using real-world data from two large US databases.

Background: Generalized pustular psoriasis (GPP) is a rare skin disease characterized by episodes of widespread sterile pustules. Methods: A retrospective cohort study using data from the US IBM MarketScan Commercial and Optum Clinformatics Data Mart databases between October 1, 2015 and March 31, 2020 was performed to describe adherence and persistence to biologics in patients with GPP. Patients were aged ≥18 years with newly diagnosed GPP (International Classification of Diseases code L40.1) and had ≥1 inpatient or ≥2 outpatient claims. Results: Biologics were dispensed to 110 of 502 (22%) and 73 of 528 (14%) patients from MarketScan and Optum databases, respectively. The mean proportion of days covered (PDC) (range) was similar in both databases (MarketScan, 65% [8%-100%]; Optum, 59% [8%-99%]), and good adherence (≥80% PDC) was uncommon (MarketScan, 36%; Optum, 24%). Mean (standard deviation) persistence was similar in both databases (MarketScan, 287 [122] days; Optum, 261 [134] days). In Optum, the mean PDC was similar between age categories; good adherence was more common in patients aged 18 to 64 years (28%) versus ≥65 years (13%). Mean persistence was longer in patients aged 18 to 64 years (267 days) versus ≥65 years (242 days). Conclusions: Overall, adherence and persistence were generally poor and varied according to the biologic class, database, and age. Improving adherence may help improve GPP treatment outcomes.

Economic burden related to fistulas or strictures among commercially insured patients with Crohn's disease in the United States.

BACKGROUND: Crohn's disease (CD) is a chronic, progressive, immune-mediated gastrointestinal condition that can lead to fistulizing or stricturing complications. OBJECTIVE: To quantify the burden of illness related to fistulas and/or strictures in patients with CD. METHODS: Using the Optum Research Database from October 2015 to December 2019, patients with CD were classified according to 1 of 3 condition cohorts: CD with fistula (CD-F), CD with stricture (CD-S), or CD with fistula and stricture (CD-FS). Each cohort was matched to a nonfistula, nonstricture CD cohort. Postdiagnosis per patient per year (PPPY) costs and health care resource utilization were assessed, accounting for variable lengths of follow-up periods. Multivariable generalized linear models were used to estimate the adjusted mean costs in each cohort. RESULTS: The CD-F, CD-S, and CD-FS cohorts included 1,317; 4,650; and 894 patients, respectively. The mean age of patients within the CD-S and their comparator cohorts was higher than in the CD-F or CD-FS cohorts (59.9 vs 49.5 vs 49.6 years). At baseline, cardiovascular disease was the most common comorbidity across all condition and comparator cohorts. Condition cohorts had 2-4 times more inpatient visits, 5-8 times more surgical visits, and 2-3 times more endoscopies PPPY than comparator cohorts. Compared with their respective comparator cohort, patients in the 3 condition cohorts had higher medication, medical, and total health care costs. CONCLUSIONS: This study demonstrates a significant economic burden related to fistulas and/or strictures among patients with CD, highlighting the importance of prevention, early recognition, and appropriate management of CD-related complications. DISCLOSURES: Yanni Fan, Ling Zhang, Jennifer S Thompson, and Kimberly G Brodovicz are employees of Boehringer Ingelheim. Rhonda L Bohn, Monik C Jiménez, and Stephani Gray (Bohn Epidemiology, LLC) are paid consultants to Boehringer Ingelheim. Gil Y Melmed reports receiving grants from Pfizer; consulting fees from Boehringer Ingelheim, AbbVie, Arena, BMS, Celgene, Entasis, Ferring Lilly, Fresenius Kabi, Medtronic, Samsung Bioepis, Janssen, Takeda, Pfizer, Prometheus Labs, and TechLab. We conducted a retrospective study using administrative claims data from the Optum Research Database, a database of a commercially insured population in the United States. All patient data were anonymized and deidentified; therefore, informed consent was not necessary. Restrictions apply to the availability of these data because of a contract between Optum and Boehringer Ingelheim, and data are thus unavailable to the public. For enquiries on the dataset analyzed in this study, please contact Optum (https://www.optum.com).

Patients With Stricturing or Penetrating Crohn's Disease Phenotypes Report High Disease Burden and Treatment Needs.

BACKGROUND: Crohn's disease (CD) is a chronic autoimmune disease in which inflammation can progress to complications of stricturing and/or penetrating disease. Real-world data on burden of complicated CD phenotypes are limited. METHODS: We analyzed cross-sectional data from the SPARC IBD (Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease) registry from 2016 to 2020. Four mutually exclusive phenotype cohorts were created: inflammatory CD (CD-I), complicated CD (stricturing CD, penetrating CD, and stricturing and penetrating CD [CD-SP]). Statistical analyses were performed using CD-I as the reference. RESULTS: A total of 1557 patients were identified: CD-I (n = 674, 43.3%), stricturing CD (n = 457, 29.4%), penetrating CD (n = 166, 10.7%), and CD-SP (n = 260, 16.7%). Patients with complicated phenotypes reported significantly greater use of tumor necrosis factor inhibitors (84.2%-86.7% vs 66.0%; P < .001) and corticosteroids (75.3%-82.7% vs 68.0%; P < .001). Patients with CD-SP reported significantly more aphthous ulcer (15.4% vs 10.5%; P < .05), erythema nodosum (6.5% vs 3.6%; P < .05), inflammatory bowel disease-related arthropathy (25.8% vs 17.2%; P < .01), liquid stools (24.2% vs 9.3%; P < .001), nocturnal fecal incontinence (10.8% vs 2.5%; P < .001), and CD-related surgery (77.7% vs 12.2%; P < .001). CONCLUSIONS: Patients with complicated CD phenotypes reported higher rates of active CD-related luminal and extraintestinal manifestations, and underwent more surgeries, despite being more likely to have received biologics than those with CD-I. The potential for early recognition and management of CD-I to prevent progression to complicated phenotypes should be explored in longitudinal studies.

Patients with complicated (stricturing and/or penetrating) Crohn's disease (CD) phenotypes have a higher disease burden, despite greater use of biologics, than patients with inflammatory CD. Early recognition and optimized management of CD may prevent progression to complicated phenotypes.

Healthcare Resource Utilization and Related Costs in Chronic Fibrosing Interstitial Lung Diseases with a Progressive Phenotype: A US Claims Database Analysis.

INTRODUCTION: We aimed to describe healthcare resource utilization (HCRU) patterns and costs in patients with fibrosing interstitial lung disease (ILD) and those with a progressive phenotype of fibrosing ILD in a US claims database. METHODS: Data from the IBM® MarketScan® databases (1 October 2011-30 September 2015) were used. Diagnosis codes documented on medical claims on two occasions (without any claims during the 12 months prior) identified patients with incident fibrosing ILD. Patients with chronic fibrosing ILD with a progressive phenotype were identified by proxies for progression. Patients aged ≥ 18 years with 365 days of continuous coverage before the index date were eligible for inclusion. Data were analyzed for 12 months prior to identification of fibrosing ILD/progressive phenotype (baseline) and 12 months after (follow-up). Outcomes included treatment patterns, outpatient and inpatient claims, and costs. RESULTS: We identified 23,577 patients with incident fibrosing ILD and 14,722 with the progressive phenotype. Follow-up data were available for 9986 and 5840 patients, respectively. The most frequent ILD-related medications during baseline were corticosteroids (49.4% and 56.6%). Mean (± standard deviation [SD]) annualized number of outpatient claims was 30.0 (± 26.4) and 34.1 (± 27.7) in the baseline period and 36.2 (± 28.6) and 41.9 (± 30.2) in the follow-up in fibrosing ILD and with a progressive phenotype, respectively. Mean (SD) number of all-cause hospitalizations was 0.5 (± 1.1) and 0.7 (± 1.2) during baseline and 0.6 (± 1.1) and 0.7 (± 1.2) during follow-up. Mean (SD) total costs were $40,907 (± 92,496) and $49,561 (± 98,647) during baseline and $46,157 (± 102,858) and $54,215 (± 116,833) during follow-up. Inpatient mortality during follow-up was 53.50 and 77.44 per 1000 patient-years. CONCLUSION: HCRU and costs were high in patients with chronic fibrosing ILD with a progressive phenotype, likely reflecting the disease severity and the need for close monitoring and acute care. Outpatient claims accounted for a substantial proportion of the total costs.

Some patients with lung diseases have inflammation or scarring of the lung tissues (interstitial lung diseases, or ILDs). In some patients with lung scarring, the scarring may become progressive (i.e., it worsens over time). In this study, we looked at these patients identified in US health insurance records. We counted how many times patients visited a doctor, were admitted to hospital, or needed medications or tests. We also looked at the total cost of all this medical care. Overall, we concluded that patients with ILDs with progressive lung scarring had a high number of visits to the doctor, and the total costs of their medical care were high.

The Annual Diagnostic Prevalence of Ankylosing Spondylitis and Axial Spondyloarthritis in the United States Using Medicare and MarketScan Databases.

OBJECTIVE: The objective of this study was to investigate the diagnostic prevalence of ankylosing spondylitis (AS) and axial spondyloarthritis (axSpA) in the United States and examine treatment patterns for these diseases. METHODS: This retrospective observational cohort study drew from 2006-2014 data in the US Medicare Fee-for-Service and IBM MarketScan databases. AS and axSpA diagnoses were identified through International Classification of Diseases, Ninth Revision [ICD-9] codes. Diagnostic prevalence (per 10,000 patients) was calculated as patients with AS and axSpA with full insurance coverage in each calendar year divided by the total patients with full insurance coverage in the same year. Two diagnosis definitions were used: definition 1 (D1), one or more relevant ICD-9 codes from hospital claims or two or more relevant ICD-9 codes from outpatient claims; definition 2 (D2), one or more codes from hospital/outpatient claims. Primary analyses assessed annual AS and axSpA prevalence (D1); sensitivity analyses assessed annual (D2) and 2-year prevalence. Patterns in prevalence and treatment use were analyzed descriptively; no statistical tests were performed. RESULTS: An increase in AS prevalence (per 10,000 patients) was seen from 2006 to 2014 in primary analyses (Medicare: 2.12-3.60; MarketScan: 0.85-1.42) and sensitivity analyses. A similar trend occurred for axSpA (Medicare: 4.39-6.52; MarketScan: 1.33-2.21). For Medicare, the proportion of patients with AS (D1) using tumor necrosis factor α inhibitors (TNFis), conventional synthetic antirheumatic drugs (csARDs), nonsteroidal antiinflammatory drugs (NSAIDs), opioids, and glucocorticoids remained relatively stable; for MarketScan, TNFi-treated patients increased (51.7% to 65.7%) and NSAID-treated patients decreased (63.5% to 55.7%). CONCLUSION: AS and axSpA prevalence may have increased in the United States between 2006 and 2014. Reasons are unknown, but this may be due to increased disease awareness, among other factors.

Prevalence and Incidence of Chronic Fibrosing Interstitial Lung Diseases with a Progressive Phenotype in the United States Estimated in a Large Claims Database Analysis.

INTRODUCTION: Many fibrosing interstitial lung diseases (ILDs) develop a chronic progressive phenotype. While idiopathic pulmonary fibrosis, which is always progressive, is well characterized with established treatment options, the epidemiology of other chronic fibrosing ILDs with a progressive phenotype has not been widely investigated. Treatment options are limited, with a high unmet need. This claims database study estimates the incidence and prevalence of these diseases in the USA. METHODS: Diagnosis, procedure and resource utilization codes from insurance claims were used to identify patients with fibrosing ILD and those with a chronic progressive phenotype among 37,565,644 adult patients in the IBM® MarketScan® Research Database 2012-2015. Two eligible ILD claims were required for a fibrosing ILD diagnosis. Progression was defined using a novel algorithm constituted by criteria considered proxies for progression. Patients were defined as having incident (new) or existing diagnoses based on claims during a 365-day period before study entry. RESULTS: The estimated age- and sex-adjusted prevalence per 100,000 persons of fibrosing ILD (95% confidence interval) was 117.82 (116.56, 119.08) and of chronic fibrosing ILDs with a progressive phenotype was 70.30 (69.32, 71.27). The estimated adjusted incidence per 100,000 patient-years of fibrosing ILD was 51.56 (50.88, 52.24) and of chronic fibrosing ILDs with a progressive phenotype was 32.55 (32.01, 33.09). Among incident fibrosing ILD patients, 57.3% experienced progression over a median of 117 days (interquartile range 63-224), with largely comparable rates of progression among different diseases. CONCLUSIONS: Chronic fibrosing ILDs with a progressive phenotype comprise a relatively new disease construct requiring varied approaches to obtain reliable estimates of prevalence and incidence. This is the first large claims database study using real-world data to provide estimates of the prevalence and incidence of these diseases among a very large segment of the US population and could form the groundwork for future studies.

Progressive lung fibrosis occurs in idiopathic pulmonary fibrosis; however, interstitial lung fibrosis may occur in other diseases such as rheumatoid arthritis, chronic hypersensitivity pneumonitis and sarcoidosis, and may or may not be progressive in these diseases. Little is known about the frequency of lung fibrosis among patients with these diseases or how often such fibrosis is progressive. This study used information from a large insurance claims database (IBM^® MarketScan^®) to estimate the frequency and progression of lung fibrosis associated with different diseases.

Risk of interstitial lung disease in patients treated for atrial fibrillation with dronedarone versus other antiarrhythmics.

PURPOSE: To compare risks of interstitial lung disease (ILD) between patients treated with dronedarone versus other antiarrhythmics. METHODS: Parallel retrospective cohort studies were conducted in the United States Department of Defense Military Health System database (DoD) and the HealthCore Integrated Research Database (HIRD). Study patients were treated for atrial fibrillation (AF) with dronedarone, amiodarone, sotalol, or flecainide. Propensity score matching was employed to create analysis cohorts balanced on baseline variables considered potential confounders of treatment decisions. The study period of July 20, 2008 through September 30, 2014 included a 1-year baseline and minimum 6 months of follow-up, for patients with drugs dispensed between July 20, 2009 and March 31, 2014. Suspect ILD outcomes were reviewed by independent adjudicators. Cox proportional hazards regression compared risk of confirmed ILD between dronedarone and each comparator cohort. A sensitivity analysis examined the effect of broadening the outcome definition. RESULTS: A total 72 ILD cases (52 DoD; 20 HIRD) were confirmed among 27 892 patients. ILD risk was significantly higher among amiodarone than dronedarone initiators in DoD (HR = 2.5; 95% CI = 1.1-5.3, p = 0.02). No difference was detected in HIRD (HR = 1.0; 95% CI = 0.4-2.4). Corresponding risks in sotalol and flecainide exposure groups did not differ significantly from dronedarone in either database. CONCLUSIONS: ILD risk among AF patients initiated on dronedarone therapy was comparable to or lower than that of amiodarone initiators, and similar to that of new sotalol or flecainide users. This finding suggests that elevated ILD risk associated with amiodarone does not necessarily extend to dronedarone or other antiarrhythmic drugs.

Clinical outcomes following bone marrow transplantation in patients with sickle cell disease: A cohort study of US Medicaid enrollees.

OBJECTIVES: Bone marrow transplantation (BMT) is currently the only curative therapy available for patients with sickle cell disease (SCD), but clinical outcomes in routine care are not well understood. We describe the rates of vaso-occlusive crises (VOCs), transplant complications, and mortality in SCD patients after BMT. METHODS: A cohort study of SCD patients who underwent BMT was designed using US Medicaid claims data (2000-2013). RESULTS: A total of 204 SCD patients undergoing BMT were identified with a mean (SD) age of 10.6 (7.3) years, with 52.9% male and 67.6% African American. The overall VOC rate was 0.99 per person-year (95% CI: 0.91-1.07) over a median follow-up time of 2.1 years (IQR: 0.8-4.3 years). A total of 138 (67.6%) remained free of VOCs. The mortality rate was 1.7 (95% CI: 0.9-3.1) per 100 person-years, transplant-related complications occurred among 113 (55.4%) patients with an incidence rate of 38.2 (95% CI: 31.7-45.9) per 100 person-years, while 47 (23%) patients had GvHD with an incidence rate of 8.0 (95% CI: 6.0-10.7) per 100 person-years. CONCLUSION: Two thirds of the BMT recipients remained VOC-free over 2 years of follow-up, but transplant-related complications, including GvHD occurred with high frequency. This highlights a continuing unmet need for alternative curative interventions in SCD.

Clinical outcomes and healthcare utilization in patients with sickle cell disease: a nationwide cohort study of Medicaid beneficiaries.

To add to the limited existing evidence on clinical outcomes and healthcare use in sickle cell disease (SCD) among beneficiaries of the US Medicaid program, we conducted a cohort study using nationwide Medicaid claims data (2000-2013). Patients were included based on HbSS SCD diagnosis and followed until Medicaid disenrollment, death, bone marrow transplant, or end of data availability to assess vasoocclusive crises (VOC), emergency room (ER) visits, hospitalizations, outpatient visits, and blood transfusions. Annualized event rates (with 95% confidence intervals [CI]) were reported. The impact of VOCs on the risk of mortality was analyzed using a multivariable Cox model with VOC modeled as time-varying and updated annually. In a total of 44,033 SCD patients included with a mean (SD) age of 15.7 (13.6) years, the VOC rate (95% CI) was 3.71 (3.70-3.72) per person-year, with highest rate among patients 19-35 years who had ≥ 5 VOCs at baseline (13.20 [13.15-13.26]). Event rates (95% CI) per person per year for other outcomes were 2.97 (2.97-2.98) ER visits, 2.39 (2.38-2.40) hospitalizations, 5.80 (5.79-5.81) outpatient visits, and 0.91 (0.90-0.91) blood transfusions. A higher VOC burden in the preceding year was associated with an increased risk of mortality, with a hazard ratio (95% CI) of 1.26 (1.14-1.40) for 2-4 VOC vs. < 2 and 1.57 (1.41-1.74) for ≥ 5 VOC vs < 2. In conclusion, we documented a substantial burden of SCD in US Medicaid enrollees, especially during early adulthood and noted that ongoing burden of VOC is associated with mortality in these patients.

Outcomes Associated with Dronedarone Use in Patients with Atrial Fibrillation.

The antiarrhythmic drug dronedarone was designed to reduce the extra-cardiac adverse effects associated with amiodarone use in treatment of patients with atrial fibrillation / atrial flutter (AF/AFL). This epidemiological study used a retrospective cohort design to compare risk of cardiovascular-related hospitalizations and death in AF/AFL patients treated with dronedarone versus other antiarrhythmic drugs (AADs). AF/AFL patients with incident dronedarone fills were matched by propensity score (PS) to incident users of other AADs. The primary study outcome was hospitalization for cardiovascular (CV) causes within 24 months after the first study drug fill. A secondary composite outcome comprised hospitalization for CV causes or all-cause mortality during follow-up. In the AF/AFL patient cohort meeting eligibility criteria, 6,964 incident users of dronedarone and 25 607 incident users of other AADs were identified. The PS-matched cohort comprised 6,349 Dronedarone users (91.2% of all eligible) and 12,698 other AAD users. Dronedarone patients had a significantly lower risk of hospitalization for a CV event compared to Other AAD users (hazard ratio = 0.87; 95% confidence interval = 0.79 to 0.96). This was consistent with results for the composite outcome (hazard ratio=0.86; 95% confidence interval = 0.78 to 0.95). In conclusion, AF/AFL patients initiated on dronedarone versus other AADs had significantly lower risk of CV hospitalizations as well as the composite CV hospitalization / death from any cause.

The clinical, humanistic, and economic burden of palmoplantar pustulosis: a structured review.

Introduction: Palmoplantar pustulosis (PPP) is a chronic, relapsing and refractory disease characterized by sterile pustules appearing on the palms and/or soles, accompanied by erythema, blistering, scales and/or keratinization. The overall burden of PPP in terms of its clinical impact, effect on patients and families, and economic consequences has not previously been investigated in a structured manner.Areas covered: A structured search focused on identification of studies in PPP using specific search terms in PubMed and EMBASE® from 2005 onwards, with additional back-referencing and pragmatic searches. Outcomes of interest included clinical burden, humanistic burden, and economic burden.Expert opinion: In cross-sectional studies, approximately 75% of all PPP patients suffer from active disease, with risk of relapse remaining constant over time. Patients' health-related quality of life is significantly impaired, as expected for a disease affecting hands and feet. Tools have been described that assess the clinical as well as patient-reported burden of PPP; their performance in larger cohorts and/or clinical trials remains to be investigated. The key data limitations identified include inconsistent definitions for characterizing remission/relapse, and limited humanistic and economic burden data; future studies are required to address these evidence gaps.

The clinical, humanistic, and economic burden of generalized pustular psoriasis: a structured review.

Introduction: Generalized pustular psoriasis (GPP) is characterized by widespread erythema and edema, superficial sterile coalescing pustules, and lakes of pus. Although the impact of GPP is thought to be substantial, emerging literature on its clinical, humanistic, and economic burden has not previously been described in a structured way.Areas covered: A structured search focused on the identification of studies in GPP using specific search terms in PubMed and EMBASE® from 2005 onwards, with additional back-referencing and pragmatic searches. Outcomes of interest included clinical, humanistic, and economic burden.Expert opinion: Despite its significant clinical, humanistic, and economic burden, GPP is poorly classified and inadequately studied. A recent European (ERASPEN) consensus classifies GPP into relapsing and persistent disease and classifies patients on the presence or absence of psoriasis vulgaris. Classification of GPP lesions involving >30% body surface area or use of hospitalization as a surrogate may be a way to identify significant flares. Given the frequency of flares, the impaired quality of life during the post-flare period, and safety/tolerability issues, it is clear that current treatment options are not sufficient. Long-term studies utilizing the European consensus statement with subclassifiers are required to supplement our current understanding of the burden of GPP.

Incidence and prevalence of axial spondyloarthritis: methodologic challenges and gaps in the literature.

OBJECTIVES: The incidence and prevalence of axial spondyloarthritis (axSpA), including ankylosing spondylitis (AS) and non-radiographic (nr-)axSpA, have been investigated in multiple populations, though there is a paucity of population-level data. Here, we identify population-based studies in AS and nr-axSpA, and describe the methodologic challenges in conducting these, outlining potential reasons for disparate incidence and prevalence estimates. METHODS: PubMed and Embase were searched for population-based studies providing incidence and prevalence rates, published in English from 1 Jan 2000-30 Jun 2015. Extracted information included incidence/prevalence rates, geographical population, study design, data source, case definition, age/gender, and classification criteria used. RESULTS: Of 2,148 articles identified, 19, from 15 countries, fulfilled eligibility criteria. Incidence rates per 100,000 patient-years were reported in 4 AS studies and varied from 0.4 (Iceland) to 15.0 (Canada). Reported AS prevalence rates per 100,000 persons also showed considerable variation (16 studies: 6.5 [Japan] to 540.0 [Turkey]). Only 3 axSpA and no nr-axSpA prevalence rates were reported. Considerable variation was seen in the methodology used to estimate incidence and prevalence rates, e.g. screening method, study design, and classification criteria. Although the prevalence of AS is known to vary by HLA-B27 status, only 4 studies reported this genetic marker. CONCLUSIONS: There is an unmet need for future studies to use consistent methodology, capture all relevant information (including HLA-B27 positivity), and investigate under-reported populations (e.g. nr-axSpA; southern hemisphere countries) to estimate the population burden of axSpA. Future studies should aim to address data gaps to provide accurate incidence/prevalence estimates for the global axSpA population.

Use of Bypassing Agents and Risk of Thromboembolic Events in Patients with Haemophilia and Inhibitors.

Patients with haemophilia and inhibitors to factors VIII or IX require bypassing therapy. The primary safety concern of bypassing agents is thromboembolism; however, the incidence of thromboembolic adverse events (TAEs) in haemophilia patients with inhibitors remains poorly characterized. The aim of this study was to assess the incidence of TAEs following exposure to bypassing agents in patients with haemophilia. Using U.S. Medicaid database (2000­2010), we identified a cohort of 719 males (mean age: 10 years at cohort entry) with haemophilia A or B and use of either recombinant factor VIIa (rFVIIa) or activated prothrombin complex concentrate (aPCC). Patients were followed up until loss of insurance eligibility, end of study period, or the first occurrence of TAE. Exposure was assessed on as-treated basis, and outcomes were adjudicated through review of healthcare claims. During the observation of a total of 2,823 person-years (py; mean follow-up: 3.9 years), 22 TAEs were identified, leading to incidence rates of 4.2 events (95% confidence interval [CI]: 1.8­8.3) per 1,000 unexposed py; 15.4 events (95% CI: 6.7­30.3) per 1,000 aPCC-exposed py; 18.2 events (95% CI: 8.3­34.6) per 1,000 rFVIIa-exposed py; and 29.7 events (95% CI: 6.1­86.7) per 1,000 py of concomitant exposure to both agents. The results were consistent across sensitivity analyses. In conclusion, we found no difference in the rate of TAEs across agents, but the data are compatible with a possibly increased rate associated with a combination therapy, highlighting the need for continuing safety monitoring through prospective registries or observational data.

Near-real-time monitoring of new drugs: an application comparing prasugrel versus clopidogrel.

BACKGROUND: Methods for near-real-time monitoring of new drugs in electronic healthcare data are needed. OBJECTIVE: In a novel application, we prospectively monitored ischemic, bleeding, and mortality outcomes among patients initiating prasugrel versus clopidogrel in routine care during the first 2 years following the approval of prasugrel. METHODS: Using the HealthCore Integrated Research Database, we conducted a prospective cohort study comparing prasugrel and clopidogrel initiators in the 6 months following the introduction of prasugrel and every 2 months thereafter. We identified patients who initiated antiplatelets within 14 days following discharge from hospitalizations for myocardial infarction (MI) or acute coronary syndrome. We matched patients using high-dimensional propensity scores (hd-PSs) and followed them for ischemic (i.e., MI and ischemic stroke) events, bleed (i.e., hemorrhagic stroke and gastrointestinal bleed) events, and all-cause mortality. For each outcome, we applied sequential alerting algorithms. RESULTS: We identified 1,282 eligible new users of prasugrel and 8,263 eligible new users of clopidogrel between September 2009 and August 2011. In hd-PS matched cohorts, the overall MI rate difference (RD) comparing prasugrel with clopidogrel was -23.1 (95 % confidence interval [CI] -62.8-16.7) events per 1,000 person-years and RDs were -0.5 (-12.9-11.9) and -2.8 (-13.2-7.6) for a composite bleed event outcome and death from any cause, respectively. No algorithms generated alerts for any outcomes. CONCLUSIONS: Near-real-time monitoring was feasible and, in contrast to the key pre-marketing trial that demonstrated the efficacy of prasugrel, did not suggest that prasugrel compared with clopidogrel was associated with an increased risk of gastrointestinal and intracranial bleeding.

Risk of ischemic cerebrovascular and coronary events in adult users of anticonvulsant medications in routine care settings.

BACKGROUND: Older-generation anticonvulsants that highly induce cytochrome P450 enzyme system activity produce metabolic abnormalities that may increase cardiovascular risk. The objective of this study was to evaluate the risk of ischemic cerebrovascular and coronary events in adult new users of anticonvulsants that highly induce cytochrome P450 activity compared with other anticonvulsant agents, as observed in a routine care setting. METHODS AND RESULTS: This was a cohort study of patients 40 to 64 years old from the HealthCore Integrated Research Database who had initiated an anticonvulsant medication between 2001 and 2006 and had no recorded major coronary or cerebrovascular condition in the 6 months before treatment initiation. Propensity score (PS) matching was used to evaluate ischemic cerebrovascular and coronary risk among anticonvulsant new users. High-dimensional propensity score (hdPS)-matched analyses were used to confirm adjusted findings. The study identified 913 events in 166 031 unmatched new treatment episodes with anticonvulsant drugs. In a PS-matched population of 22 864 treatment episodes, the rate ratio (RR) for ischemic coronary or cerebrovascular events associated with highly inducing agents versus other agents was 1.22 (95% CI, 0.90-1.65). The RR moved to 0.99 (95% CI, 0.73-1.33) with adjustment for hdPS matching (RR, 1.47; 95% CI, 0.95-2.28 for cerebrovascular events; RR, 0.70; 95% CI, 0.47-1.05 for coronary events). CONCLUSIONS: In this exploratory analysis, there was no evidence of a consistent and statistically significant effect of initiating anticonvulsants that highly induce cytochrome P450 activity on ischemic coronary or cerebrovascular outcomes compared with other agents, given routine care utilization patterns.

Risk of Guillain-Barré syndrome after meningococcal conjugate vaccination.

PURPOSE: A new meningococcal conjugate vaccine (MCV4) was introduced in 2005. Shortly after, case reports of Guillain-Barré syndrome (GBS), a serious demyelinating disease, began to be reported to the Vaccine Adverse Event Reporting System. In 2006, the Centers for Disease Control and Prevention and the Food and Drug Administration requested the evaluation of GBS risk after MCV4 vaccination. We conducted a study to assess the risk of GBS after MCV4 vaccination using health plan administrative and claims data together with the review of primary medical records of potential cases. METHODS: Retrospective cohort study among 12.6 million 11- to 21-year-old members of five US health plans with a total membership of 50 million. Automated enrollment and medical claims data from March 2005 through August 2008 were used to identify the population, the vaccinations administered, and the medical services associated with possible GBS. Medical records were reviewed and adjudicated by a neurologist panel to confirm cases of GBS. The study used distributed data analysis methods that minimized sharing of protected health information. RESULTS: We confirmed 99 GBS cases during 18,322,800 person-years (5.4/1,000,000 person-years). More than 1.4 million MCV4 vaccinations were observed. No confirmed cases of GBS occurred within 6 weeks after vaccination. The upper 95% CI for the attributable risk of GBS associated with MCV4 is estimated as 1.5 cases per 1,000,000 doses. CONCLUSIONS: Among members of five US health plans, MCV4 vaccination was not associated with increased GBS risk.