Real-world Evidence Comparing Tofacitinib and Vedolizumab in Anti-TNF-experienced Patients With Ulcerative Colitis.

BACKGROUND: Antitumor necrosis factor (anti-TNF) inhibitors are first-line treatment among patients with ulcerative colitis (UC). With time, patients tend to lose response or become intolerant, necessitating switching to small cell biologics such as tofacitinib or vedolizumab. In this real-world study of a large, geographically diverse US population of TNF-experienced patients with UC, we evaluated the effectiveness and safety of newly initiating treatment with tofacitinib vs vedolizumab. METHODS: We conducted a cohort study using secondary data from a large US insurer (Anthem, Inc.). Our cohort included patients with UC newly initiating treatment with tofacitinib or vedolizumab. Patients were required to have evidence of treatment with anti-TNF inhibitors in the 6 months prior to cohort entry. The primary outcome was treatment persistence >52 weeks. Additionally, we evaluated the following secondary outcomes as additional measures of effectiveness and safety: (1) all-cause hospitalization; (2) total abdominal colectomy; (3) hospitalization for infection; (4) hospitalization for malignancy; (5) hospitalization for cardiac events; and (6) hospitalization for thromboembolic events. We used fine stratification by propensity scores to control for confounding by demographics, clinical factors, and treatment history at baseline. RESULTS: Our primary cohort included 168 new users of tofacitinib and 568 new users of vedolizumab. Tofacitinib was associated with lower treatment persistence (adjusted risked ratio, 0.77; 95% CI, 0.60 -0.99). Differences in secondary measures of effectiveness or safety between tofacitinib initiators vs vedolizumab initiators were not statistically significant (all-cause hospitalization, adjusted hazard ratio, 1.23; 95% CI, 0.83-1.84; total abdominal colectomy, adjusted HR, 1.79; 95% CI, 0.93-3.44;and hospitalization for any infection, adjusted HR, 1.94; 95% CI, 0.83-4.52). DISCUSSION: Ulcerative colitis patients with prior anti-TNF experience initiating tofacitinib demonstrated lower treatment persistence compared with those initiating vedolizumab. This finding is in contrast to other recent studies suggesting superior effectiveness of tofacitinib. Ultimately, head-to-head randomized, controlled trials that focus on directly measured end points may be needed to best inform clinical practice.

Anti-TNF-experienced patients with UC initiating vedolizumab demonstrated higher treatment persistence compared with those initiating tofacitinib in this real-world evaluation of comparative effectiveness. Ultimately, head-to-head randomized trials that focus on directly measured end points are needed to best inform clinical practice.

Real-World Evidence Comparing Vedolizumab and Ustekinumab in Antitumor Necrosis Factor-Experienced Patients With Crohn's Disease.

INTRODUCTION: Many patients with Crohn's disease (CD) lose response or become intolerant to antitumor necrosis factor (TNF) therapy and subsequently switch out of class. We compared the effectiveness and safety of ustekinumab to vedolizumab in a large, geographically diverse US population of TNF-experienced patients with CD. METHODS: We conducted a retrospective cohort study using longitudinal claims data from a large US insurer (Anthem, Inc.). We identified patients with CD initiating vedolizumab or ustekinumab with anti-TNF treatment in the prior 6 months. Our primary outcome was treatment persistence for >52 weeks. Secondary outcomes included (i) all-cause hospitalization, (ii) hospitalization for CD with surgery, (iii) hospitalization for CD without surgery, and (iv) hospitalization for infection. Propensity score fine stratification was used to control for demographic and baseline clinical characteristics and prior treatments. RESULTS: Among 885 new users of ustekinumab and 490 new users of vedolizumab, we observed no difference in treatment persistence (adjusted risk ratio 1.09 [95% confidence interval 0.95-1.25]). Ustekinumab was associated with a lower rate of all-cause hospitalization (adjusted hazard ratio 0.73 [0.59-0.91]), nonsurgical CD hospitalization (adjusted hazard ratio 0.58 [0.40-0.83]), and hospitalization for infection (adjusted hazard ratio 0.56 [0.34-0.92]). DISCUSSION: This real-world comparative effectiveness study of anti-TNF-experienced patients with CD initiating vedolizumab or ustekinumab showed similar treatment persistence rates beyond 52 weeks, although secondary outcomes such as all-cause hospitalizations, nonsurgical CD hospitalizations, and hospitalizations for infection favored ustekinumab initiation. We, therefore, advocate for individualized decision making in this medically refractory population, considering patient preference and other factors such as cost and route of administration.

Antibiotics prior to age 2 years have limited association with preschool growth trajectory.

BACKGROUND: Prior studies of early antibiotic use and growth have shown mixed results, primarily on cross-sectional outcomes. This study examined the effect of oral antibiotics before age 24 months on growth trajectory at age 2-5 years. METHODS: We captured oral antibiotic prescriptions and anthropometrics from electronic health records through PCORnet, for children with ≥1 height and weight at 0-12 months of age, ≥1 at 12-30 months, and ≥2 between 25 and 72 months. Prescriptions were grouped into episodes by time and by antimicrobial spectrum. Longitudinal rate regression was used to assess differences in growth rate from 25 to 72 months of age. Models were adjusted for sex, race/ethnicity, steroid use, diagnosed asthma, complex chronic conditions, and infections. RESULTS: 430,376 children from 29 health U.S. systems were included, with 58% receiving antibiotics before 24 months. Exposure to any antibiotic was associated with an average 0.7% (95% CI 0.5, 0.9, p < 0.0001) greater rate of weight gain, corresponding to 0.05 kg additional weight. The estimated effect was slightly greater for narrow-spectrum (0.8% [0.6, 1.1]) than broad-spectrum (0.6% [0.3, 0.8], p < 0.0001) drugs. There was a small dose response relationship between the number of antibiotic episodes and weight gain. CONCLUSION: Oral antibiotic use prior to 24 months of age was associated with very small changes in average growth rate at ages 2-5 years. The small effect size is unlikely to affect individual prescribing decisions, though it may reflect a biologic effect that can combine with others.

Use of a mobile app to capture supplemental health information during pregnancy: Implications for clinical research.

PURPOSE: Mobile applications ("apps") may be efficient tools for improving the quality of clinical research among pregnant women, but evidence is sparse. We assess the feasibility and generalizability of a mobile app for capturing supplemental data during pregnancy. METHODS: In 2017, we conducted a pilot study of the FDA MyStudies mobile app within a pregnant population identified through Kaiser Permanente Washington (KPWA), an integrated healthcare delivery system. We ascertained health conditions, medications, and substance use through app-based questionnaires. In a post-hoc analysis, we utilized electronic health records (EHR) to summarize sociodemographic and health characteristics of pilot participants and, for comparison, a pregnant population identified using similar methods. RESULTS: Six percent (64/1070) of contacted women enrolled in the pilot study. Nearly half (23/53) reported taking medication for headaches and one-fourth for constipation (13/53) and nausea (12/53) each. Few instances (2/92) of over-the-counter medication use were identified in electronic dispensing records. One-quarter to one-third of participants with depression and anxiety/panic, respectively, reported recently discontinuing medications for these conditions. Eighty-eight percent of pilot participants reported White race (95%CI: 81-95%), versus 67% of the comparison population (N = 2065). More pilot participants filled ≥1 prescription for antianxiety medication (22% [95%CI: 13-35%]) and antidepressants (19% [95%CI 10-31%]) pre-pregnancy than the comparison population (10 and 9%, respectively). CONCLUSIONS: Mobile apps may be a feasible tool for capturing health data not routinely available in EHR. Pregnant women willing to use a mobile app for research may differ from the general pregnant population, but confirmation is needed.

Identifying prescribing cascades in Alzheimer's disease and related dementias: The calcium channel blocker-diuretic prescribing cascade.

PURPOSE: Prescribing cascades occur when a physician prescribes a new drug to address the side-effect of another drug. Persons with Alzheimer's disease and related dementias (ADRD) are at increased risk for prescribing cascades. Our objective was to develop an approach to estimating the proportion of calcium channel blocker-diuretic (CCB-diuretic) prescribing cascades among persons with ADRD in two U.S. health plans. METHODS: We identified patients aged ≥50 on January 1, 2017, dispensed a drug to treat ADRD in the 365-days prior to/on cohort entry date. Patients had medical/pharmacy coverage for 1 year before and through cohort entry. We excluded individuals with an institutional stay encounter in the 45 days prior to cohort entry and censored patients based on: disenrollment from coverage, death, or end of data. We identified incident and prevalent CCB use in the 183-days following cohort entry, and identified subsequent incident diuretic use among incident and prevalent CCB-users within 365-days from cohort entry. RESULTS: There were 121 538 eligible patients. Approximately 62% were female, with a mean age of 79.5 (SD ±8.6). Overall 2.1% of the cohort experienced a prevalent CCB-diuretic prescribing cascade with 1586 incident diuretic-users among 36 462 prevalent CCB-users (4.3%, 95% CI 4.1-4.6%]); and there were161 incident diuretic-users among 3304 incident CCB-users (4.9%, 95% CI 4.2-5.7%) (incident CCB-diuretic cascade). CONCLUSIONS: We describe an approach to identify prescribing cascades in persons with ADRD, which can be used to assess the proportion of prescribing cascades in large cohorts. We determined the proportion of CCB-diuretic prescribing cascades was low.

Antidopaminergic-Antiparkinsonian Medication Prescribing Cascade in Persons with Alzheimer's Disease.

OBJECTIVES: Persons living with Alzheimer's disease (AD) may be at increased risk for prescribing cascades due to greater multimorbidity, polypharmacy, and the need for more complex care. Our objective was to assess the proportion of the antidopaminergic-antiparkinsonian medication prescribing cascades among persons living with Alzheimer's disease. SETTING: Two large administrative claims databases in the United States. PARTICIPANTS: We identified patients aged ≥50 on January 1, 2017, who were dispensed a drug used to treat Alzheimer's disease for at least 1 day in the 365 days prior to or on cohort entry date and who had medical and pharmacy coverage in the 365 days prior to the cohort entry date. We excluded individuals with a recent institutional stay. We identified incident antidopaminergic (antipsychotic/metoclopramide) use in the 183 days following cohort entry and identified subsequent incident antiparkinsonian drug use within 8 to 365 days. RESULTS: There were 121,538 patients with Alzheimer's disease eligible for inclusion. Approximately 62% were women with a mean age of 79.5 (SD ± 8.6). The mean number of drugs dispensed was 9.2 (SD ± 4.9). There were 36 incident antiparkinsonian users among 4,534 incident antipsychotic/metoclopramide users (0.8%). CONCLUSION: We determined that the proportion of antidopaminergic-antiparkinsonian medication prescribing cascades, widely considered as high-priority, was low. Our approach can be used to assess the proportion of prescribing cascades in populations considered to be at high risk and to prioritize system-level interventional efforts to improve medication safety in these patients.

Early Life Antibiotic Prescriptions and Weight Outcomes in Children 10 Years of Age.

OBJECTIVE: We previously found that antibiotic use at <24 months of age was associated with slightly higher body weight at 5 years of age. In this study, we examine associations of early life antibiotic prescriptions with weight outcomes at 108 to 132 months of age ("10 years"). METHODS: We used electronic health record data from 2009 through 2016 from 10 health systems in PCORnet, a national distributed clinical research network. We examined associations of any (vs no) antibiotics at <24 months of age with body mass index z-score (BMI-z) at 10 years adjusted for confounders selected a priori. We further examined dose response (number of antibiotic episodes) and antibiotic spectrum (narrow and broad). RESULTS: Among 56,727 included children, 57% received any antibiotics at <24 months; at 10 years, mean (standard deviation) BMI-z was 0.54 (1.14), and 36% had overweight or obesity. Any versus no antibiotic use at <24 months was associated with a slightly higher BMI-z at 10 years among children without a complex chronic condition (ß 0.03; 95% confidence interval [CI] 0.01, 0.05) or with a complex chronic condition (ß 0.09; 95% CI 0.03, 0.15). Any versus no antibiotic use was not associated with odds of overweight or obesity at 10 years among children without (odds ratio 1.02; 95% CI 0.97, 1.07) or with a complex chronic condition (odds ratio 1.07; 95% CI 0.96, 1.19). CONCLUSIONS: The small and likely clinically insignificant associations in this study are consistent with our previous 5-year follow-up results, suggesting that, if this relationship is indeed causal, early increases in weight are small but maintained over time.

The FDA MyStudies app: a reusable platform for distributed clinical trials and real-world evidence studies.

We developed a mobile application and secure patient data storage platform, FDA MyStudies, to address privacy, engagement, and extensibility challenges in mobile clinical research. The system extends the capabilities of the mobile frameworks Apple ResearchKit and ResearchStack through an intuitive front-end application and secure storage environment that can support health research studies. The platform supports single or multisite studies via role-based access and can be implemented within highly secure data environments. As a proof-of-concept, pregnant women participated in a descriptive study via the app in which data not routinely captured in electronic health records (EHR) were collected and linked with existing patient data to provide a more wholistic view of the patient and illustrate how patient data combined with EHR data could be used to support public health research.

Early Antibiotic Exposure and Weight Outcomes in Young Children.

: media-1vid110.1542/5839981580001PEDS-VA_2018-0290Video Abstract OBJECTIVES: To determine the association of antibiotic use with weight outcomes in a large cohort of children. METHODS: Health care data were available from 2009 to 2016 for 35 institutions participating in the National Patient-Centered Clinical Research Network. Participant inclusion required same-day height and weight measurements at 0 to <12, 12 to <30, and 48 to <72 months of age. We assessed the association between any antibiotic use at <24 months of age with BMI z score and overweight or obesity prevalence at 48 to <72 months (5 years) of age, with secondary assessments of antibiotic spectrum and age-period exposures. We included children with and without complex chronic conditions. RESULTS: Among 1 792 849 children with a same-day height and weight measurement at <12 months of age, 362 550 were eligible for the cohort. One-half of children (52%) were boys, 27% were African American, 18% were Hispanic, and 58% received ≥1 antibiotic prescription at <24 months of age. At 5 years, the mean BMI z score was 0.40 (SD 1.19), and 28% of children had overweight or obesity. In adjusted models for children without a complex chronic condition at 5 years, we estimated a higher mean BMI z score by 0.04 (95% confidence interval [CI] 0.03 to 0.05) and higher odds of overweight or obesity (odds ratio 1.05; 95% CI 1.03 to 1.07) associated with obtaining any (versus no) antibiotics at <24 months. CONCLUSIONS: Antibiotic use at <24 months of age was associated with a slightly higher body weight at 5 years of age.

PCORnet Antibiotics and Childhood Growth Study: Process for Cohort Creation and Cohort Description.

OBJECTIVES: The National Patient-Centered Clinical Research Network (PCORnet) supports observational and clinical research using health care data. The PCORnet Antibiotics and Childhood Growth Study is one of PCORnet's inaugural observational studies. We sought to describe the processes used to integrate and analyze data from children across 35 participating institutions, the cohort characteristics, and prevalence of antibiotic use. METHODS: We included children in the cohort if they had at least one same-day height and weight measured in each of 3 age periods: 1) before 12 months, 2) 12 to 30 months, and 3) after 24 months. We distributed statistical queries that each institution ran on its local version of the PCORnet Common Data Model, with aggregate data returned for analysis. We defined overweight or obesity as age- and sex-specific body mass index ≥85th percentile, obesity ≥95th percentile, and severe obesity ≥120% of the 95th percentile. RESULTS: A total of 681,739 children met the cohort inclusion criteria, and participants were racially/ethnically diverse (24.9% black, 17.5% Hispanic). Before 24 months of age, 55.2% of children received at least one antibiotic prescription; 21.3% received a single antibiotic prescription; 14.3% received 4 or more; and 33.3% received a broad-spectrum antibiotic. Overweight and obesity prevalence was 27.6% at age 4 to <6 years (n = 362,044) and 36.2% at 9 to <11 years (n = 58,344). CONCLUSIONS: The PCORnet Antibiotics and Childhood Growth Study is a large national longitudinal observational study in a diverse population that will examine the relationship between early antibiotic use and subsequent growth patterns in children.