A Threshold of Meaning for Work Disability Improvement in Psoriatic Arthritis Measured by the Work Productivity and Activity Impairment Questionnaire.

INTRODUCTION: The Work Productivity and Activity Impairment Specific Health Problem Questionnaire (WPAI:SHP) is used to assess the impact of an intervention on work productivity in patients with psoriatic arthritis (PsA). Unfortunately, studies reporting changes or improvements in domains of WPAI:SHP by patients with PsA have a limited threshold of meaning due to the absence of published minimal clinically important differences (MCIDs). Our objective was to determine the MCIDs for improvement in WPAI:SHP in patients with active PsA. METHODS: MCIDs for WPAI:SHP domains (presenteeism, work productivity loss, and activity impairment) were derived for patients with active PsA who were biologic naïve or TNF inhibitor (TNFi) experienced using 24-week results from two phase 3 trials (SPIRIT-P1 and SPIRIT-P2). MCIDs were derived using the anchor-based method supplemented by the distribution-based method. Anchors included achievement of the American College of Rheumatology 20 responder index (ACR20), the minimal disease activity (MDA), and the Health Assessment Questionnaire and Disability Index (HAQ-DI) MCID (improvement ≥ 0.35). Anchor validity was assessed by biserial correlation and analysis of covariance modeling against the domains. MCIDs were triangulated using the receiver operating characteristic (ROC) method supplemented by the distribution-based method. RESULTS: The analyses included 417 biologic-naïve and 363 TNFi-experienced patients. ACR20, MDA, and HAQ-DI were valid anchors. Significant differences in WPAI:SHP domain scores were observed between patients achieving ACR20, MDA, or HAQ-DI compared to patients not achieving these clinical thresholds (all P < 0.001). ROC analyses suggested that a ≥ 20% improvement in presenteeism, a 15% improvement in work productivity loss, and a 20% improvement in activity impairment represented clinically meaningful improvements in both populations. The distribution-based method supported the results. CONCLUSION: MCIDs for the presenteeism, work productivity loss, and activity impairment domains were estimated to be 20%, 15%, and 20%, respectively, in biologic-naïve or TNFi-experienced PsA populations. These results will help improve the meaningfulness of WPAI:SHP improvements reported by PsA patients. TRIAL REGISTRATION: SPIRIT-P1: NCT01695239, SPIRIT-P2: NCT02349295. FUNDING: Eli Lilly and Company.

Treatment patterns, adherence, and persistence among psoriasis patients treated with biologics in a real-world setting, overall and by disease severity.

PURPOSE: Describe treatment patterns by disease severity among biologic-treated psoriasis patients. MATERIALS AND METHODS: We selected our study cohort in the IQVIA PharMetrics Plus adjudicated claims database linked to Electronic Health Record data from Modernizing Medicine Data Services. Patients were classified as having mild, moderate, or severe psoriasis based on a hierarchy of available severity measures. Patients were followed for 360 days to assess combination therapy, therapy switching and restarting, adherence and persistence. RESULTS: The cohort comprised 2130 biologic-treated patients (mean age: 47.6 years; 45.4% female); 447 (21%) had available disease severity measures. Compared to patients with mild (N = 282) psoriasis, more patients with moderate (N = 116) or severe (N = 49) disease used combination therapy (21.3% vs. 34.5% and 32.7%, respectively), switched therapies (12.1% vs. 19.8% and 22.4%), and discontinued biologics (18.4% vs. 27.6% and 36.7%). Mean adherence was <75% by Medication Possession Ratio (MPR) (73.9%) and Proportion of Days Covered (PDC) (70.2%). Overall, 52.2% had a mean MPR >80%. Mean persistence to biologics was 297.6 days. Persistence and adherence decreased with increasing disease severity. CONCLUSIONS: Biologic-treated psoriasis patients had inadequate adherence (i.e., MPR <80%) and modest persistence to biologics, with moderate and severe patients demonstrating lower adherence and persistence than mild patients.

Analysis of inpatient use of fresh frozen plasma and other therapies and associated outcomes in patients with major bleeds from vitamin K antagonism.

OBJECTIVE: We conducted an observational study of outcomes and costs associated with fresh frozen plasma (FFP) use in patients receiving warfarin with intracerebral, gastrointestinal, or musculoskeletal bleeding. METHODS: Patients who had at least 1 International Classification of Diseases, Ninth Revision code indicative of anticoagulation history, received ≥ 1 unit FFP, and had patient costs >$0 were identified from a database of >600 US hospitals. The main outcome was transfusion of additional blood products (eg, cryoprecipitate, red blood cells, or platelets) or vitamin K. Further outcomes included administration of other bleeding-related therapies (eg, recombinant activated factor VII, albumin, or crystalloids), incidence of fluid overload, days in the intensive care unit, discharge status, and total hospital costs. RESULTS: The most frequently administered products were vitamin K and red blood cells, given to 55.6% to 61.0% and 19.2% to 29.3% of patients, respectively. The number of FFP units transfused correlated highly with fluid overload (r > 0.91) and was associated with inpatient mortality, nonhome discharge, and intensive care unit admittance. For both inpatient mortality and nonhome discharge, the odds ratio was significant when ≥ 4 units FFP were transfused (P < 0.05). A dose of >2 units FFP was associated with an increased probability of an intensive care unit stay (P < 0.05). Total costs were greater among patients receiving >2 units FFP compared with patients who received 1 unit FFP (P < 0.001), with a substantial increase in costs incurred when ≥ 4 units FFP were transfused. CONCLUSIONS: In patients with warfarin-related bleeding, inpatient mortality, nonhome discharge, intensive care unit admission, and hospital costs were associated with the number of units of FFP transfused.

Fluid overload is associated with increases in length of stay and hospital costs: pooled analysis of data from more than 600 US hospitals.

BACKGROUND: Fluid overload, including transfusion-associated circulatory overload (TACO), is a serious complication of fresh frozen plasma (FFP) transfusion. The incidence of fluid overload is underreported and its economic impact is unknown. An evaluation of fluid overload cases in US hospitals was performed to assess the impact of fluid overload on length and cost of hospital stay. STUDY DESIGN AND METHODS: Retrospective analysis was performed using a clinical and economic database covering >600 US hospitals. Data were collected for all inpatients discharged during 2010 who received ≥1 unit FFP during hospitalization. Incidence of fluid overload was determined through International Classification of Diagnosis (ICD-9) codes. Multivariate regression analysis was performed for primary outcome measures: hospital length of stay (LOS) and total hospital costs. RESULTS: Data were analyzed for 129,839 FFP-transfused patients, of whom 4,138 (3.2%) experienced fluid overload (including TACO). Multivariate analysis, adjusting for baseline characteristics, found that increased LOS and hospital costs were independently associated with fluid overload. Patients diagnosed with fluid overload had longer mean LOS (12.9 days versus 10.0 days; P < 0.001) and higher mean hospital cost per visit ($46,644 versus $32,582; P < 0.001) compared with patients without fluid overload. CONCLUSION: For a population of US inpatients who received FFP during hospitalization, fluid overload was associated with a 29% increase in LOS and a $14,062 increase in hospital costs per visit. These findings suggest that the incidence of fluid overload in the general population is greater than historically reported. A substantial economic burden may be associated with fluid overload in the US.

Preference-based quality of life in patients with Alzheimer's disease.

BACKGROUND: This study was developed to evaluate the feasibility, reliability, and validity of use of patients' ratings of health preference measures as outcomes for cost-effectiveness analyses in persons with very mild to moderate Alzheimer's disease (AD). METHODS: Patients and caregivers completed ratings of the EuroQol-5D system (EQ-5D) and the Health Utilities Index Mark 2 (HUI2) and instruments that assess cognition, mood, insight, AD-specific and generic health-related quality of life (QOL) and activities of daily living. RESULTS: Patients' HUI2 scores were reliable. EQ-5D scores were somewhat less so. Patients rated their utility high, with overall EQ-5D and HUI2 scores greater than 0.8. Neither the EQ-5D nor the HUI2 scores had a relationship with severity of cognitive impairment. Both the EQ-5D and the HUI2 had expected relationships with patient-rated measures of QOL, function, mood, and specific subscales we hypothesized should be associated with patient preferences. Patient insight into functional and cognitive impairments had little association with their health preference scores. CONCLUSIONS: AD patients' scores on the EQ-5D and the HUI2 have many of the characteristics of valid preference measures. However, the proportions of persons who do not perceive any disability, the lack of association with the caregivers' ratings of activities of daily living, limited associations with insight, and no association with their Mini-Mental State Exam scores suggest that patients' reports of disability might reflect legitimate self-perceptions of mood and function that are associated with comorbidities rather than with AD.

Caregivers' assessments of preference-based quality of life in Alzheimer's disease.

BACKGROUND: This study was designed to evaluate the feasibility, reliability, and validity of use of caregivers' ratings of two health preference measures as outcomes for cost-effectiveness analyses in persons with very mild to moderate Alzheimer's disease (AD). METHODS: Caregivers completed ratings of preference for AD patients' health by use of the EuroQol-5D system (EQ-5D) and the Health Utilities Index Mark 2 (HUI2). They also rated patients' cognition, mood, burden, AD-specific and generic health-related quality of life (QOL), and activities of daily living. RESULTS: Caregivers' HUI2 scores were reliable. Neither the caregiver ratings of the patients' health by use of the EQ-5D nor the HUI2 had a relationship with severity of cognitive impairment. Both the EQ-5D and the HUI2 had expected relationships with caregivers' assessments of patients' function, AD-specific QOL, and physical and mental health and selected subscales of the measures of AD-specific QOL and overall health. In addition, caregiver scores showed relationships with patient self-rated function, mood, and physical health but not AD-specific QOL. Caregiver burden was associated with caregivers' scores. CONCLUSIONS: Caregiver-completed ratings of preference for patients' health made by use of the EQ-5D and the HUI2 have many of the characteristics of valid preference measures. However, the lack of association with patient Mini-Mental Status Exam scores and patient self-rated AD-specific QOL and the associations with caregiver subjective burden might present limitations to their use as proxy measures for cost-effectiveness analyses.