Curing Chronic Hepatitis C: A Cost Comparison of the Combination Simeprevir Plus Sofosbuvir vs. Protease-Inhibitor-Based Triple Therapy.

INTRODUCTION: Interferon-free, multi-direct acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection is highly effective and well tolerated, but costly. To gain perspective on the evolving economics of HCV therapy, we compared the cost per cure of a multi-DAA regimen with the prior standard of triple therapy. MATERIAL AND METHODS: Patients infected with HCV genotype 1 who were treated through the University of Colorado Hepatology Clinic between May 2011 and December 2014 comprised the study population. The multi-DAA regimen of simeprevir plus sofosbuvir (SMV/SOF) was compared to the triple therapy regimen consisting of peginterferon and ribavirin, with either boceprevir or telaprevir (TT). Sustained-virologic response (SVR) rates, total costs per treatment and adverse events were recorded. Total cost per SVR were compared for the two treatments, controlling for patient demographics and clinical characteristics. RESULTS: One hundred eighty-three patients received SMV/SOF (n = 70) or TT (n = 113). Patients receiving SMV/SOF were older, more treatment experienced, and had a higher stage of fibrosis. SVRs were 86% and 59%, average total costs per patient were $152,775 and $95,943, and average total costs per SVR were $178,237 vs. $161,813.49 for SMV/SOF and TT groups, respectively. Medication costs accounted for 98% of SMV/SOF and 85% of TT treatment costs. CONCLUSION: The high cure rate of multi-DAA treatment of HCV is offset by the high costs of the DAAs, such that the cost per cure from TT to multi-DAA therapy has been relatively constant. In order to cure more patients, either additional financial resources will need to be allocated to the treatment of HCV or drug costs will need to be reduced.

Claims analysis of hypertension occurrence, severity changes and patterns of antihypertensive use in cancer patients receiving vascular endothelial growth factor inhibitors.

BACKGROUND: Vascular endothelial growth factor inhibitors such as bevacizumab, sorafenib, and sunitinib are utilized in the treatment of multiple cancers. Although these agents are associated with hypertension, there is a lack of evidence describing patterns of antihypertensive use in patients with vascular endothelial growth factor inhibitor-associated hypertension in a non-trial, "real-world" setting. OBJECTIVE: To describe the occurrence and severity of vascular endothelial growth factor inhibitor-associated hypertension, patterns of antihypertensive use and occurrence of cardiovascular complications in a non-trial population, and to describe patterns of initial antihypertensive therapy in patients developing hypertension during treatment with a vascular endothelial growth factor inhibitor. METHODS: This retrospective cohort study utilized claims data from the Medstat MarketScan Commercial Claims and Encounter database to identify patients with claims for a vascular endothelial growth factor inhibitor and a diagnosis of cancer using International Classification of Diseases, 9th Revision, Clinical Modification codes, Healthcare Common Procedure Coding System J-codes and National Drug Codes. The study period encompassed claims from one year before the patient's first claim for a vascular endothelial growth factor inhibitor, and continued through one year after the initial vascular endothelial growth factor inhibitor claim. Patients meeting study criteria were classified into cohorts A1, patients with no hypertension throughout the study period; A2, patients without hypertension at baseline who developed hypertension after starting a vascular endothelial growth factor inhibitor; and cohort B, patients with hypertension prior to receiving a vascular endothelial growth factor inhibitor. We utilized medical and pharmacy claims data to describe the presence of hypertension, its severity, and the occurrence of cardiovascular complications throughout the study period. Initial antihypertensive use in cohort A2 was described. RESULTS: In all, 2177 patients met study criteria and were categorized into cohorts A1 (n = 708), A2 (n = 333) and B (n = 1136). Approximately 32% of patients without hypertension at baseline had claims suggestive for hypertension during the study period. Life-threatening (Grade 4) hypertension increased throughout the study period for cohorts A1, A2, and B, to 3.4%, 10.2%, and 16.4%, respectively (p < 0.001 for all). Claims suggestive of Grade 3 hypertension occurred in more patients in cohort B (45.8%) than in cohort A2 (32.7%, p < 0.001). Cardiovascular complications occurred in 4.7%, 15.6%, and 22.7% of patients in cohorts A1, A2, and B, respectively. Initial antihypertensive agent selection did not impact the occurrence of cardiovascular complications in cohort A2. CONCLUSION: Our study provides valuable insight into non-trial patterns of vascular endothelial growth factor inhibitor-associated hypertension occurrence and severity, and is consistent with prior claims analysis. Identification of optimal strategies to manage vascular endothelial growth factor inhibitor-associated hypertension remain to be clarified with the advent of more comprehensive data sets.

Comparative effectiveness of quality improvement interventions for pressure ulcer prevention in academic medical centers in the United States.

BACKGROUND: Prevention of pressure ulcers, one of the hospital-acquired conditions (HACs) targeted by the 2008 nonpayment policy of the Centers for Medicare & Medicaid Services (CMS), is a critical issue. This study was conducted to determine the comparative effectiveness of quality improvement (QI) interventions associated with reduced hospital-acquired pressure ulcer (HAPU) rates. METHODS: In an quasi-experimental design, interrupted time series analyses were conducted to determine the correlation between HAPU incidence rates and adoption of QI interventions. Among University HealthSystem Consortium hospitals, 55 academic medical centers were surveyed from September 2007 through February 2012 for adoption patterns of QI interventions for pressure ulcer prevention, and hospital-level data for 5,208 pressure ulcer cases were analyzed. Between- and within-hospital reduction significance was tested with t-tests post-CMS policy intervention. RESULTS: Fifty-three (96%) of the 55 hospitals used QI interventions for pressure ulcer prevention. The effect size analysis identified five effective interventions that each reduced pressure ulcer rates by greater than 1 case per 1,000 patient discharges per quarter: leadership initiatives, visual tools, pressure ulcer staging, skin care, and patient nutrition. The greatest reductions in rates occurred earlier in the adoption process (p<.05). CONCLUSIONS: Five QI interventions had clinically meaningful associations with reduced stage III and IV HAPU incidence rates in 55 academic medical centers. These QI interventions can be used in support of an evidence-based prevention protocol for pressure ulcers. Hospitals can not only use these findings from this study as part of a QI bundle for preventing HAPUs.

Hospital-Acquired Pressure Ulcers at Academic Medical Centers in the United States, 2008-2012: Tracking Changes Since the CMS Nonpayment Policy.

BACKGROUND: In 2007, the Centers for Medicare & Medicaid Services (CMS) announced its intention to no longer reimburse hospitals for costs associated with hospital-acquired pressure ulcers (HAPUs) and a list of other hospital-acquired conditions (HACs), which was followed by enactment of the nonpayment policy in October 2008. This study was conducted to define changes in HAPU incidence and variance since 2008. METHODS: In a retrospective observational study, HAPU cases were identified at 210 University HealthSystem Consortium (UHC) academic medical centers in the United States. HAPU incidence rates were calculated as a ratio of HAPU cases to the total number of UHC inpatients between the first quarter of 2008 and the second quarter of 2012. HAPU cases were defined by multiple criteria: not present on admission (POA); coded for stage III or IV pressure ulcers; and a length of stay greater than four days. RESULTS: Among the UHC hospitals between 2008 and June 2012, 10,386 HAPU cases were identified among 4.08 million inpatients. The HAPU incidence rate decreased significantly from 11.8 cases per 1,000 inpatients in 2008 to 0.8 cases per 1,000 in 2012 (p < .001; 95% confidence interval: 8.39-8.56). Among HAPU cases were trends of more elderly patients, greater case-mix index, and more surgical cases. The analysis of covariance model identified CMS non-payment policy as a significant covariate of changing trends in HAPU incidence rates. CONCLUSIONS: HAPU incidence rates decreased significantly among 210 UHC AMCs after the enactment of the CMS nonpayment policy. The hospitals appeared to be reacting efficiently to economic policy incentives by improving prevention efforts.

Increased Adoption of Quality Improvement Interventions to Implement Evidence-Based Practices for Pressure Ulcer Prevention in U.S. Academic Medical Centers.

OBJECTIVE: In 2008, the U.S. Centers for Medicare and Medicaid Services enacted a nonpayment policy for stage III and IV hospital-acquired pressure ulcers (HAPUs), which incentivized hospitals to improve prevention efforts. In response, hospitals looked for ways to support implementation of evidence-based practices for HAPU prevention, such as adoption of quality improvement (QI) interventions. The objective of this study was to quantify adoption patterns of QI interventions for supporting evidence-based practices for HAPU prevention. METHODS: This study surveyed wound care specialists working at hospitals within the University HealthSystem Consortium. A questionnaire was used to retrospectively describe QI adoption patterns according to 25 HAPU-specific QI interventions into four domains: leadership, staff, information technology (IT), and performance and improvement. Respondents indicated QI interventions implemented between 2007 and 2012 to the nearest quarter and year. Descriptive statistics defined patterns of QI adoption. A t-test and statistical process control chart established statistically significant increase in adoption following nonpayment policy enactment in October 2008. Increase are described in terms of scope (number of QI domains employed) and scale (number of QI interventions within domains). RESULTS: Fifty-three of the 55 hospitals surveyed reported implementing QI interventions for HAPU prevention. Leadership interventions were most frequent, increasing in scope from 40% to 63% between 2008 and 2012; "annual programs to promote pressure ulcer prevention" showed the greatest increase in scale. Staff interventions increased in scope from 32% to 53%; "frequent consult driven huddles" showed the greatest increase in scale. IT interventions increased in scope from 31% to 55%. Performance and improvement interventions increased in scope from 18% to 40%, with "new skin care products . . ." increasing the most. LINKING EVIDENCE TO ACTION: Academic medical centers increased adoption of QI interventions following changes in nonpayment policy. These QI interventions supported adherence to implementation of pressure ulcer prevention protocols. Changes in payment policies for prevention are effective in QI efforts.

Dynamic medication adherence modeling in primary prevention of cardiovascular disease: a Markov microsimulation methods application.

BACKGROUND: Real-world patients' medication adherence is lower than that of clinical trial patients. Hence, the effectiveness of medications in routine practice may differ. OBJECTIVES: The study objective was to compare the outcomes of an adherence-naive versus a dynamic adherence modeling framework using the case of statins for the primary prevention of cardiovascular (CV) disease. METHODS: Statin adherence was categorized into three state-transition groups on the basis of an epidemiological cohort study. Yearly adherence transitions were incorporated into a Markov microsimulation using TreeAge software. Tracker variables were used to store adherence transitions, which were used to adjust probabilities of CV events over the patient's lifetime. Microsimulation loops "random walks" estimated the average accrued quality-adjusted life-years (QALYs) and CV events. For each 1,000-patient microsimulations, 10,000 outer loops were performed to reflect second-order uncertainty. RESULTS: The adherence-naive model estimated 0.14 CV events avoided per person, whereas the dynamic adherence model estimated 0.08 CV events avoided per person. Using the adherence-naive model, we found that statin therapy resulted in 0.40 QALYs gained over the lifetime horizon on average per person while the dynamic adherence model estimated 0.22 incremental QALYs gained. Subgroup analysis revealed that maintaining high adherence in year 2 resulted in 0.23 incremental QALYs gained as compared with 0.16 incremental QALYs gained when adherence dropped to the lowest level. CONCLUSIONS: A dynamic adherence Markov microsimulation model reveals risk reduction and effectiveness that are lower than with an adherence-naive model, and reflective of real-world practice. Such a model may highlight the value of improving or maintaining good adherence.

Frequency of Continuous Glucose Monitoring Use and Change in Hemoglobin A1C for Adults with Type 1 Diabetes in a Clinical Practice Setting.

OBJECTIVE: To estimate the frequency of continuous glucose monitoring (CGM) use and change in hemoglobin A1c (HbA1c) compared to self-monitoring of blood glucose (SMBG) alone in adults with type 1 diabetes in a clinical practice setting. METHODS: We retrospectively identified 66 adult type 1 diabetes patients at the Barbara Davis Center for Diabetes (BDC) who first initiated CGM between 2006 and 2011 and 67 controls using SMBG. The frequency of CGM use was estimated from survey recall and defined as the mean number of days/month of CGM use during a maximum follow-up of 10 months. Change in HbA1c was calculated as the difference between the baseline value and the lowest follow-up value. RESULTS: The mean change in HbA1c for CGM users was -0.48% (95% confidence interval [CI]: -0.67, -0.28) and for SMBG users was -0.37% (95% CI: -0.56, -0.18). The between-group mean difference in change in HbA1c, adjusted for patient characteristics, was -0.11% (95% CI: -0.38, 0.16), whereas the subgroup with a baseline HbA1c ≥7.0% and users of CGM ≥21 days/month was -0.36% (95% CI: -0.78, 0.05). Nearly half (n = 32, 48%) used CGM <21 days/month. The reasons for low frequency of CGM use or discontinuation included sensor costs, frequency of alarms, inaccuracy, and discomfort. CONCLUSIONS: These CGM data from clinical practice suggest a trend toward decreasing HbA1c for adults with type 1 diabetes, especially in patients with higher baseline HbA1c and higher frequency of CGM use. Future studies are needed to assess the use of CGM in larger populations of clinical practice adult type 1 diabetes patients.

Gold Carding Policies: Reducing the Barriers Between Payers and Providers.

A central approach to achieving high-quality neurologic care is to reduce the burden on providers in accessing services needed to achieve this level of care. Neurology-based practices across the continuum (solo, multispecialty, hospital, or health system-based) have adopted different methods to mitigate the impact of gatekeeper methods of prior authorization and related mechanisms. We discuss ways to partner with payers through innovative Gold Carding programs that reduce the burden of gatekeeper mechanisms on neurology providers, thereby allowing them to consistently focus their efforts in the provision of high-quality neurologic care.

Alternative approaches to measuring value: an update on innovative methods in the context of the United States Medicare drug price negotiation program.

INTRODUCTION: The United States has begun assessing the value of pharmaceuticals to inform negotiated prices in the Medicare program. Given strong political objections in the United States to the use of QALYs, Medicare will need to adopt an alternative approach to measuring value. AREAS COVERED: In this narrative review, we identified six alternative approaches to measuring value (equal value life-years, health years in total, generalized risk-adjusted cost-effectiveness, severity weighting based on absolute or proportional shortfall, comparative effectiveness based on conventional clinical endpoints, and comparative effectiveness based on both conventional endpoints and patient-centric value elements) and five criteria for assessing these approaches (responsiveness to concerns about discrimination, feasibility, transparency, flexibility, and the ability to incorporate factors beyond traditional value elements). EXPERT OPINION: Four of the alternatives are broadly aligned with the cost-effectiveness framework, but none fully addresses all aspects of the stated concerns that QALYs may be used to unintentionally implement discrimination. We note, however, that the extent to which these concerns lead to discrimination in practice is unknown. Finally, we recommend an approach for measuring value in terms of comparative effectiveness that combines quantitative ranking and weighting of distinct criteria (including patient-centric value elements) with deliberation.

Shifting patterns of multiple sclerosis treatment in a highly prevalent United States population.

OBJECTIVE: Our objectives were to (1) obtain the prevalence and demography of people with multiple sclerosis (MS) in a representative Colorado population, and (2) to assess the utilization of disease-modifying therapy within this prevalent cohort. METHODS: This is a retrospective, observational study of patients that had contact with the University of Colorado Health System from 2012 to 2020. We queried Health Data Compass, a data warehouse, for patient data and applied the MS Prevalence Workgroup Algorithm to generate a prevalent cohort. We calculated prevalence as of 31 December 2020, and stratified by age, sex, race, and ethnicity. Payer information and treatment exposure were obtained from linked claims from the Colorado All Payers Claim Database. Disease-modifying therapies were classified as highly effective and moderately effective based on the clinical trial, TREAT-MS (NCT03500328). RESULTS: From a population of 1,382,821 individuals, 8557 people with MS were captured. Age-adjusted prevalence of MS as of 31 December 2020 was 572.3 per 100,000 with a mean age of 47.36. Prevalence varied between demographic subgroups, with the lowest prevalence in Hispanic men (215.6) and highest in White (824.1) and Black women (820.1). Overall disease-modifying therapy exposure was 62.4%, with increased highly effective therapy use and a corresponding decrease in moderately effective therapy use on a yearly basis. INTERPRETATION: MS is highly prevalent in a representative Colorado cohort. Overall treatment and proportion of highly effective therapy exposure increased significantly during a critical period of MS therapeutic advances, indicating a shift in disease management driven sharply by the availability of on-label anti-CD20 therapy.

Examining the National Representativeness of the Axon Registry: A Neurology-Specific Patient Registry.

BACKGROUND AND OBJECTIVES: The objective of this study was to determine the external validity of the Axon Registry by comparing the 2019 calendar year data with 2 nationally representative, publicly available data sources, specifically the National Ambulatory Medical Care Survey (NAMCS) and the Medical Expenditure Panel Survey (MEPS). The Axon Registry is the American Academy of Neurology's neurology-focused qualified clinical data registry that reports and analyzes electronic health record data from participating US neurology providers. Its key function is to support quality improvement within ambulatory neurology practices while also promoting high-quality evidence-based care in clinical neurology. We compared demographics of patients who had an outpatient or office visit with a neurologist along with prevalence of selected neurologic conditions and neurologic procedures across the 3 data sets. METHODS: We performed a cross-sectional, retrospective comparison of 3 data sets: NAMCS (2012-2016), MEPS (2013-2017, 2019), and Axon Registry (2019). We obtained patient demographics (age, birth sex, race, ethnicity), patient neurologic conditions (headache, epilepsy, cerebrovascular disease, multiple sclerosis, parkinsonism, dementia, spinal pain, and polyneuropathy), provider location, and neurologic procedures (neurology visits, MR/CT neuroimaging studies and EEG/EMG neurophysiologic studies). Parameter estimates from the pooled 5-year samples of the 2 public data sets, calculated at the visit level, were compared descriptively with those of the Axon Registry. We calculated Cohen h and performed Wald tests (α = 0.05) to conduct person-level statistical comparisons between MEPS 2019 and Axon Registry 2019 data. RESULTS: The Axon Registry recorded 1.3 M annual neurology visits (NAMCS, 11 M; MEPS, 22 M) and 645 K people with neurologic conditions (MEPS, 10 M). Compared with the pooled national surveys, the Axon Registry has similar patient demographics, neurologic condition prevalence, neuroimaging and neurophysiologic utilization, and provider location. In direct comparison with MEPS 2019, the Axon Registry 2019 had fewer children (2% vs 7%), more elderly persons (21% vs 16%), fewer non-Black and non-White race persons (5% vs 8%), less number of patients with epilepsy (10% vs 13%), more patients with dementia (8% vs 6%), more patients with cerebrovascular disease (11% vs 8%), and a greater predominance of neurology providers in the Midwest (25% vs 20%). The only difference with a non-negligible effect size was the proportion of people younger than 15 years (Cohen h = 0.25). DISCUSSION: The Axon Registry demonstrates high concordance with 2 nationally representative surveys. Recruiting more and diverse neurology providers will further improve the volume, representativeness, and value of the Axon Registry.

Framework for Patient Experience Value Elements in Rare Disease: A Case Study Demonstrating the Applicability of Combined Qualitative and Quantitative Methods.

BACKGROUND AND OBJECTIVE: Several novel methods have been suggested to extend a conventional value assessment to capture a more comprehensive perspective of value from a patient perspective. The objective of this research was to demonstrate a framework for implementing a combined qualitative and quantitative method to elicit and prioritize patient experience value elements in rare diseases. Neuromyelitis optica spectrum disorder was used as a case study. METHODS: The method for eliciting and prioritizing patient experience value elements involved a three-step process: (1) collecting potential patient experience value elements from existing literature sources followed by deliberation by a multi-stakeholder research team; (2) a pre-workshop webinar and survey to identify additional patient-reported value elements; and (3) a workshop to discuss, prioritize the value elements using a swing weighting method. Outcomes were prioritized value elements with normalized weights for patients considering a treatment for neuromyelitis optica spectrum disorder. RESULTS: A literature review and deliberation resulted in the following initial value elements: ability to reach important personal milestones, patient's financial burden, value of hope/balance or timing of risks and benefits, Uncertainty about long-term benefits and safety of the treatment, Patient empowerment through therapeutic advancement and technology, Caregiver/family's financial burden, patient experience related to treatment regimen, Therapeutic options, and Caregiver/family's quality of life. Eight patients with neuromyelitis optica spectrum disorder participated in the case study. In the online survey, participants found the nine proposed patient experience value elements both understandable and important with no additions. During the workshop, 'Uncertainty about long-term benefits and safety,' 'Patient experience related to treatment regimen,' and 'Patient's financial burden' were found to be the most important patient experience value elements, with a respective weight of 25%, 19.2%, and 14.4% (out of total 100%). CONCLUSIONS: This case study provides a framework for eliciting and prioritizing patient experience value elements using direct patient input. Although elements/weights may differ by disease, and even in neuromyelitis optica spectrum disorder, additional research is needed, value frameworks, researchers, and manufacturers can use this practical method to generate patient experience value elements and evaluate their impact on treatment selection.

Real-world cost of care and site of care in patients with multiple sclerosis initiating infused disease-modifying therapies.

AIM: Evaluate the real-world costs over two years and costs by site of care for ocrelizumab (OCR), natalizumab (NTZ), and alemtuzumab (ATZ) in patients with multiple sclerosis (MS). METHODS: This retrospective study used HealthCore Integrated Research Database and included continuously enrolled adults with MS initiating OCR, NTZ, and ATZ between April 2017 and July 2019 (i.e. patient identification period). Annual total cost of care (pharmacy and medical costs) was evaluated for the first- and second-year of follow-up, further stratified by site of care. Costs were measured using health plan allowed amount and adjusted to 2019 US dollars. Sensitivity analyses were conducted in patients who completed yearly dosing schedule according to Food and Drug Administration approved prescribing information. RESULTS: Overall, 1,058, 166, and 46 patients were included in OCR, NTZ, and ATZ cohorts, respectively. Mean (standard deviation [SD]) total cost of care during first- and second-year follow-up were $125,597 ($72,274) and $109,618 ($75,085) for OCR, $117,033 ($57,102) and $106,626 ($54,872) for NTZ, and $179,809 ($97,530) and $108,636 ($77,973) for ATZ. Infusible drug cost was the main driver in all three cohorts accounting for >78% of the total costs. Annual total cost of care increased substantially after patients started/switched to infusible DMTs. Across site of care, hospital outpatient infusion was common (OCR 58%, NTZ 37%, ATZ 49%) and expensive followed by physician office infusion (OCR 28%, NTZ 40%, ATZ 16%); home infusion was the least common (<10%) and least expensive. LIMITATIONS: The results were limited to commercially insured patients (specifically those with Anthem-affiliated health plans). CONCLUSIONS: Real-world costs increased after patients started/switched to infusible DMTs. Drug cost is the main driver for the total costs, which varied substantially by site of care. Controlling drug cost markups and using home setting for infusion can reduce costs in the treatment of MS patients.

Ocrelizumab (OCR), natalizumab (NTZ), and alemtuzumab (ATZ) are infusible drugs to treat patients with multiple sclerosis (MS). We did a study to understand the costs of these infusible MS drugs in real-world settings by analyzing a patients' pharmacy and medical claims database. A total of 1,058 patients were included. We found that the annual total costs increased substantially after patients started to use these infusible MS drugs. Specifically, the average first- and second-year total costs for patients were $125,597 and $109,618 for OCR, $117,033 and $106,626 for NTZ, and $179,809 and $108,636 for ATZ, respectively. We also found that the cost of the drug itself is the main driver for the overall healthcare spending, accounting for >78% of the total costs. Additionally, we found that the cost varies depending on where patients receive these infusible MS drugs, and generally speaking, infusions received from hospital outpatient settings would be more expensive than received from home settings. In summary, this study showed that the real-world costs of these infusible MS drugs are very high. Shifting patients away from more costly hospital outpatient departments or using MS drugs that do not require infusion resources (e.g. oral/self-injectable) may help reduce the overall healthcare spending on MS.

Safety and patient experience with at-home infusion of ocrelizumab for multiple sclerosis.

OBJECTIVE: This study aimed to evaluate safety (infusion-related reactions [IRRs]) and patient satisfaction (patient-reported outcomes [PROs]) for at-home ocrelizumab administration for patients with multiple sclerosis (MS). METHODS: This open-label study included adult patients with an MS diagnosis who had completed a ≥ 600-mg ocrelizumab dose, had a patient-determined disease steps score of 0 to 6 and had completed PROs. Eligible patients received a 600-mg ocrelizumab home-based infusion over 2 h, followed by 24-h and 2-week post-infusion follow-up calls. IRRs and adverse events (AEs) were documented during infusions and follow-up calls. PROs were completed before and 2 weeks post infusion. RESULTS: Overall, 99 of 100 expected patients were included (mean [SD] age, 42.3 [7.7] years; 72.7% female; 91.9% White). The mean (SD) infusion time was 2.5 (0.6) hours, and 75.8% of patients completed their ocrelizumab infusion between 2 to 2.5 h. The IRR incidence rate was 25.3% (95% CI: 16.7%, 33.8%)-similar to other shorter ocrelizumab infusion studies-and all AEs were mild/moderate. In total, 66.7% of patients experienced AEs, including itch, fatigue, and grogginess. Patients reported significantly increased satisfaction with the at-home infusion process and confidence in the care provided. Patients also reported a significant preference for at-home infusion compared with prior infusion center experiences. INTERPRETATION: IRRs and AEs occurred at acceptable rates during in-home infusions of ocrelizumab over a shorter infusion time. Patients reported increased confidence and comfort with the home infusion process. Findings from this study provide evidence of the safety and feasibility of home-based ocrelizumab infusion over a shorter infusion period.

Comparison of patient characteristics and gout-related health-care resource utilization and costs in patients with frequent versus infrequent gouty arthritis attacks.

OBJECTIVE: To examine the association between frequent gouty arthritis and the presence of absolute/relative contraindications to gout therapies, and health-care expenditure associated with frequent gouty arthritis. METHODS: This retrospective study used administrative claims to identify patients with gouty arthritis between 1 July 2005 and 30 June 2010. Patients with ≥3 yearly gouty arthritis attacks (frequent gout) were matched 1:2 to patients with <3 yearly attacks (infrequent gout). Absolute and relative contraindications to gout medications were evaluated based on product labelling. Negative binomial regression and generalized linear models with logarithmic transformation were used for multivariate analysis of overall and gout-related health-care use and cost. RESULTS: Mean patient age was 58 years (n = 15 669) and 77% were men. Compared with patients with infrequent gout, those with frequent gout had higher rates of absolute/relative contraindications to NSAIDs (91.5% vs 78.7%, P < 0.0001), corticosteroids (96.4% vs 87.3%, P < 0.0001), allopurinol (51.0% vs 41.2%, P < 0.0001) and probenecid (13.4% vs 9.4%, P < 0.0001). Mean gout-related costs were $889 for frequent gout vs $210 for infrequent gout (P < 0.0001) and all-cause direct costs were $10 913 for frequent vs $10 685 for infrequent gout (P = ns). Mean all-cause outpatient visits among patients with comorbidities compared with those without were 25.8 vs 11.8 among frequent and 19.7 vs 9.0 among infrequent (both P < 0.001) groups. Gout-related costs were higher among frequent gout patients with comorbidities than those without comorbidities ($886 vs $513, P = 0.03). CONCLUSION: Patients with frequent gouty arthritis are likely to have absolute and/or relative contraindications to gout medications and higher gout-related treatment costs.

Role of the Bruton tyrosine kinase pathway in multiple sclerosis.

Multiple sclerosis (MS) is a chronic, immune-mediated, neurodegenerative condition that results in progressive accumulation of disability over the course of the disease. MS presents heterogeneously, and, as the disease progresses, patients develop a range of physical and neurologic problems that include reduced mobility, cognitive impairment, weakness, fatigue, pain, and defects in speech or vision. Economically, MS is costly, including both direct costs stemming from clinical care and medications and the indirect costs of productivity losses. These costs pose a substantial burden to patients, families, caregivers, employers, and society. There are 21 approved disease-modifying therapies for MS across several drug classes. The importance of early MS treatment has been confirmed, and progress has been made in the treatment of relapsing-remitting MS, although this progress has not been replicated for progressive presentations of the disease. Ongoing research continues to elucidate the exact mechanisms of disease in MS as well as potential new treatment strategies that may better address current gaps, such as disability progression in secondary progressive MS without activity. One of the novel pathways under investigation is the inhibition of Bruton tyrosine kinase, a cytoplasmic tyrosine kinase, which is expressed in B cells and other potentially targetable hematopoietic lineage cells. This review examines emerging hypotheses that targeting both B cells and myeloid cells within the periphery and central nervous system could yield clinical effects in key areas of MS pathophysiology that are currently unaddressed.

Practical Considerations in the Administration of Aducanumab for the Neurologist.

Aducanumab (Aduhelm), developed by the biotechnology firm Biogen in Cambridge, MA, was approved using the less common accelerated approval pathway by the Federal Drug Administration (FDA) reserved for treatments that fill a significant unmet need.1 Its approval on June 7, 2021, has been met with an outpouring of opinions from prescribers, insurers, advocacy groups, and hospital systems regarding its risk-benefit profile.2-4 Originally approved for all forms of Alzheimer disease (AD), the FDA updated aducanumab's labeling on July 8, 2021, for "treatment in patients with mild cognitive impairment (MCI) or mild dementia stage of disease, the population in which treatment was initiated in clinical trials."5 With 6 million people nationally in the United States who suffer from AD and an anticipated one-third of those who may now fulfill the criteria under the revised labeling, the implications of aducanumab's approval continue to generate national interest.6.

Tolerability and Safety of Switching from Rituximab to Ocrelizumab: Evaluating Factors Associated with Infusion Related Reactions.

BACKGROUND: Ocrelizumab and rituximab are frequently used treatments for multiple sclerosis (MS). Data on switching from rituximab to ocrelizumab is limited. OBJECTIVES: To assess the frequency, severity, and factors of infusion related reactions (IRRs) in patients with MS who switch from rituximab to ocrelizumab, compared to those who stay on rituximab. METHODS: Prospective study on MS patients aged 18-65, on rituximab for at least 2 cycles, who either switched to ocrelizumab (switch group) or stayed on rituximab (comparator group) (n = 100 each). Participants were followed for IRRs, safety, and tolerability over 12 months. RESULTS: The proportion of IRRs in patients who continue on rituximab (14%) were similar to those who switched to ocrelizumab on Day 1 (14%; p = 1.000) and Week 24 (12%; p = 0.647) but higher than at Day 15 (4%; 0.005). The risk of IRRs for the switch group was associated with the presence of B cells (CD19 and/or CD20 counts ≥1%) increasing by 5.01 (1.49, 16.82) times on Day 1 (p = 0.007). Antidrug antibodies to ocrelizumab were not associated with IRRs. No other safety concerns were identified in switching to ocrelizumab. CONCLUSION: IRRs are similar between both groups, which suggests that it is safe to switch from rituximab to ocrelizumab.

Prevalence of multiple sclerosis and treatment utilization in a large, highly diverse population.

BACKGROUND: Despite advances in algorithms for identifying people with MS (PwMS) in large data sets, limited data exists on regional prevalence, or prevalence and care in minority populations. OBJECTIVES: To report the 7-year (01/01/2012-12/31/2018) prevalence and demographics of MS and disease-modifying therapy (DMT) utilization in a large, diverse population. METHODS: This retrospective analysis used the OneFlorida Data Trust, which captures health data from >15 million Floridians across 10 constituent organizations. A validated algorithm identified subjects with MS. DMTs were identified using RxNorm concept unique identifiers and National Drug Codes. Results were stratified across age, sex, race-ethnicity, and location. RESULTS: Of 6,638,649 adults in the database, the algorithm identified 9681 PwMS. Overall prevalence per 100,000 was 145.83. MS prevalence was considerable in women of all races and ethnicities ranging from 138.86 to 253.76 per 100,000. 52.6% of PwMS had one or more DMT prescription. DMT prescription was more likely in Hispanic PwMS. CONCLUSION: Prevalence analysis of the OneFlorida Data Trust revealed a substantial burden of disease in women of all races and ethnicities. Variation in treatment utilization among demographic subgroups underscores the need for additional studies to assess health care disparities in MS at the population level.

Evaluation of Plasma Neurofilament Light Chain Levels as a Biomarker of Neuronal Injury in the Active and Chronic Phases of Autoimmune Neurologic Disorders.

Objective: To evaluate plasma neurofilament light (NfL) levels in autoimmune neurologic disorders (AINDs) and autoimmune encephalitis (AE). Background: Each particular neural autoantibody syndrome has a different clinical phenotype, making one unifying clinical outcome measure difficult to assess. While this is a heterogeneous group of disorders, the final common pathway is likely CNS damage and inflammation. Defining a biomarker of CNS injury that is easily obtainable through a blood sample and reflects a positive treatment response would be highly advantageous in future therapeutic trials. Measurement of blood concentration of neurofilament light (NfL) chain, however, may provide a biomarker of central nervous system (CNS) injury in AE and other AINDs. Here we provide an initial evaluation of plasma NfL levels in AE as well as other AINDs during active and chronic phases of disease and demonstrate its potential utility as a minimally-invasive biomarker for AE and AINDs. Design/Methods: Patients were retrospectively identified who were enrolled in the biorepository at the Rocky Mountain MS Center at the University of Colorado, or were prospectively enrolled after initial presentation. Patients had a well-defined AIND and were followed between 2014 and 2021. NfL was tested using the Single Molecule Array (SIMOA) technology. Patients with headaches but without other significant neurologic disease were included as controls. Results: Twenty-six plasma and 14 CSF samples of patients with AINDs, and 20 plasma control samples stored in the biorepository were evaluated. A positive correlation was found between plasma and CSF NfL levels for patients with an AIND (R 2 = 0.83, p < 0.001). Elevated plasma levels of NfL were seen in patients with active AE compared to controls [geometric mean (GM) 51.4 vs. 6.4 pg/ml, p = 0.002]. Patients with chronic symptoms (>6 months since new or worsening symptoms) of AE or cerebellar ataxia (CA) showed a trend toward lower plasma NfL levels (GM 15.1 pg/ml) compared to active AE or CA. Six patients with longitudinal, prospective sampling available demonstrated a trend in decreased plasma NfL levels over time. Conclusions: Our findings support the use of plasma NfL as a potential minimally-invasive biomarker of CNS injury.