Real-world clinical outcomes and healthcare costs in patients with Crohn's disease treated with vedolizumab versus ustekinumab in the United States.

OBJECTIVE: To compare real-world treatment persistence, dose escalation, rates of opportunistic or serious infections, and healthcare costs in patients with Crohn's disease (CD) receiving vedolizumab (VDZ) vs ustekinumab (UST) in the United States. METHODS: A retrospective observational study in adults with CD initiated on VDZ or UST on/after 26 September 2016, was performed using the IBM Truven Health MarketScan databases (1 January 2009-30 September 2018). Rates of treatment persistence, dose escalation, opportunistic or serious infection-related encounters, and healthcare costs per patient per month (PPPM) were evaluated. Entropy balancing was used to balance patient characteristics between cohorts. Event rates were assessed using weighted Kaplan-Meier analyses and compared between cohorts using log-rank tests. Healthcare costs were compared between cohorts using weighted 2-part models. RESULTS: 589 VDZ and 599 UST patients were included (172 [29.2%] and 117 [19.5%] were bio-naïve, respectively). After weighting, baseline characteristics were comparable between cohorts. No significant difference in rates of treatment persistence (12-month: VDZ, 76.5%; UST, 82.1%; p = .17), dose escalation (12-month: VDZ, 29.3%; UST, 32.7%; p = .97), or opportunistic or serious infection-related encounters were observed between VDZ and UST. Total mean healthcare costs were significantly lower for patients treated with VDZ vs UST (mean cost difference = -$5051 PPPM; p < .01). Findings were consistent in bio-naïve patients. CONCLUSIONS: In this real-world study, similar treatment persistence, dose escalation, and rates of opportunistic or serious infections were observed with VDZ- and UST-treated patients with CD. However, VDZ was associated with a significantly lower cost outlay for healthcare systems.

Crohn's disease (CD) causes inflammation in the digestive system. Vedolizumab (VDZ) and ustekinumab (UST) are therapies for patients with CD. Little is known about the clinical outcomes and healthcare costs of VDZ versus UST in the real world in the United States. We used health claims data and found that VDZ and UST had comparable real-world clinical outcomes. After 12 months of treatment, the proportions of patients with CD who stayed on treatment and those who needed to increase therapy dose were similar with VDZ and UST. The rate of infection was also similar between the two groups of patients. However, the monthly healthcare costs were $5051 less for patients treated with VDZ than with UST. This was mainly due to the lower cost of VDZ, which was almost half of that of UST. The lower treatment costs with VDZ may provide substantial savings for the healthcare system and patients specifically. Future cost-effectiveness studies on VDZ and UST are needed to aid treatment selection for patients with CD.

Pharmacokinetics, pharmacodynamics and safety assessment of multiple doses of soticlestat in healthy volunteers.

AIMS: Soticlestat, a first-in-class inhibitor of cholesterol 24-hydroxylase (also known as cytochrome P450 46A1), is currently in development for the treatment of developmental and epileptic encephalopathies. Here, we report safety, tolerability, pharmacokinetic and pharmacodynamic outcomes from a phase I, randomized, double-blind, placebo-controlled, multiple-rising-dose study of soticlestat in healthy adults. METHODS: Five cohorts of healthy subjects (n = 8 each, randomized 6:2 soticlestat:placebo) received oral soticlestat 100-600 mg once daily (QD) or 300 mg twice daily (BID) for 10-14 days. Serial blood and urine samples were obtained on days 1, 7 (blood only) and 14. RESULTS: Soticlestat in the dose range 100-400 mg/day for up to 14 days was generally well tolerated. In total, 45 treatment-emergent adverse events (TEAEs) were reported; most (91%) were transient and mild in intensity. Two subjects experienced TEAEs leading to discontinuation: one receiving soticlestat 600 mg QD reported a severe event of acute psychosis; another receiving 300 mg BID reported a mild event of confusional state. Steady-state exposure to soticlestat increased in a slightly greater than dose-proportional manner across the dose range 100-400 mg QD. Peak plasma concentrations were reached within 0.33-0.5 hour, and soticlestat elimination half-life was approximately 4 hours. Renal excretion of soticlestat was negligible. Soticlestat 100-400 mg QD reduced 24S-hydroxycholesterol levels by 46.8 (coefficient of variation [CV%] -9.2) to -62.7% (CV% -7.3) at steady state; values of enzymatic inhibition were compatible with antiepileptic effects observed in preclinical models. CONCLUSION: The pharmacokinetic and pharmacodynamic profiles of soticlestat characterized here provided a data-driven rationale for clinical trial dose selection.

Health Care Costs and Resource Utilization Among Patients With Crohn's Disease With and Without Perianal Fistula.

BACKGROUND: Perianal fistula (PAF), a complication of Crohn's disease (CD), is associated with substantial economic costs and poor prognosis. We determined prevalence of PAF CD in the United States and compared costs and health care resource utilization (HRU) of PAF CD patients with matched non-PAF CD patients. METHODS: This was a retrospective cohort study of claims data from the IBM MarketScan Commercial Database from October 1, 2015, to September 30, 2018. Eligible patients were aged 18 to 89 years with ≥2 CD diagnoses. Patients with PAF CD had ≥1 PAF diagnosis or procedure code and were matched with non-PAF CD patients. Cumulative prevalence of PAF CD in the US population was calculated across total patients in MarketScan. All-cause and gastrointestinal (GI)-related costs and HRU were compared between groups using a generalized linear model (GLM). RESULTS: Cumulative 3-year prevalence of PAF was 7.70% of patients with CD (N = 81,862) and 0.01% of the US population. Among PAF CD (n = 1218) and matched non-PAF CD (n = 4095) patients, most all-cause costs and HRU were GI-related. Mean total all-cause and GI-related health care costs per patient and per year for PAF CD were $85,233 and $71,612, respectively, vs $40,526 and $29,458 for non-PAF CD (P < .0001). Among PAF CD vs non-PAF CD patients, GLM-adjusted proportions of patients with GI-related inpatient, outpatient, or pharmacy visits, mean GI-related inpatient length of stay, and mean GI-related surgeries were higher (P < .0001 for all comparisons). CONCLUSIONS: Costs and HRU are significantly higher for patients with PAF CD vs non-PAF CD patients, highlighting the economic burden of the disease.

Collaborative Cohort of Cohorts for COVID-19 Research (C4R) Study: Study Design.

The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults at risk for coronavirus disease 2019 (COVID-19) comprising 14 established United States (US) prospective cohort studies. For decades, C4R cohorts have collected extensive data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R will link this pre-COVID phenotyping to information on SARS-CoV-2 infection and acute and post-acute COVID-related illness. C4R is largely population-based, has an age range of 18-108 years, and broadly reflects the racial, ethnic, socioeconomic, and geographic diversity of the US. C4R is ascertaining severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 illness using standardized questionnaires, ascertainment of COVID-related hospitalizations and deaths, and a SARS-CoV-2 serosurvey via dried blood spots. Master protocols leverage existing robust retention rates for telephone and in-person examinations, and high-quality events surveillance. Extensive pre-pandemic data minimize referral, survival, and recall bias. Data are being harmonized with research-quality phenotyping unmatched by clinical and survey-based studies; these will be pooled and shared widely to expedite collaboration and scientific findings. This unique resource will allow evaluation of risk and resilience factors for COVID-19 severity and outcomes, including post-acute sequelae, and assessment of the social and behavioral impact of the pandemic on long-term trajectories of health and aging.

Banning Asbestos in New Zealand, 1936-2016, an 80-Year Long Saga.

The banning by the New Zealand Government of the import and export of asbestos-containing products resulted from the interplay of a number of factors. At a personal level, there were the actions of the asbestos sufferers, their families and support groups. At the political level, there were the activities of progressive trade union groups representing the hazardous trades, such as labourers, construction workers and demolition workers, and at a Government level, there was a positive response to these public health pressures. The Prohibition Order 2016 concerning Imports and Exports (asbestos-containing products) was the outcome of this 80-year long saga.

Identifying Gaps in Respiratory Syncytial Virus Disease Epidemiology in the United States Prior to the Introduction of Vaccines.

Respiratory syncytial virus (RSV) causes lower respiratory tract illness frequently. No effective antivirals or vaccines for RSV are approved for use in the United States; however, there are at least 50 vaccines and monoclonal antibody products in development, with those targeting older adults and pregnant women (to protect young infants) in phase 2 and 3 clinical trials. Unanswered questions regarding RSV epidemiology need to be identified and addressed prior to RSV vaccine introduction to guide the measurement of impact and future recommendations. The Centers for Disease Control and Prevention (CDC) convened a technical consultation to gather input from external subject matter experts on their individual perspectives regarding evidence gaps in current RSV epidemiology in the United States, potential studies and surveillance platforms needed to fill these gaps, and prioritizing efforts. Participants articulated their individual views, and CDC staff synthesized individuals' input into this report.