Health-Related Quality-of-Life Results From the Open-Label, Randomized, Phase III ASPIRE Trial Evaluating Carfilzomib, Lenalidomide, and Dexamethasone Versus Lenalidomide and Dexamethasone in Patients With Relapsed Multiple Myeloma.

Purpose To determine the effects of carfilzomib, lenalidomide, and dexamethasone (KRd) versus lenalidomide and dexamethasone (Rd) on health-related quality of life (HR-QoL) in the Carfilzomib, Lenalidomide, and Dexamethasone Versus Lenalidomide and Dexamethasone for the Treatment of Patients With Relapsed Multiple Myeloma (ASPIRE) trial. Methods Patients with relapsed multiple myeloma were randomly assigned to receive KRd or Rd. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and myeloma-specific module were administered at baseline; day 1 of cycles 3, 6, 12, and 18; and after treatment. The Global Health Status/Quality of Life (GHS/QoL) scale and seven subscales (fatigue, nausea and vomiting, pain, physical functioning, role functioning, disease symptoms, and adverse effects of treatment) were compared between groups using a mixed model for repeated measures. The percentages of responders with ≥ 5- or 15-point GHS/QoL improvement at each cycle were compared between groups. Results Baseline questionnaire compliance was excellent (94.1% of randomly assigned patients). KRd patients had higher GHS/QoL scores versus Rd patients over 18 treatment cycles (two-sided P < .001). The minimal important difference was met at cycle 12 (5.6 points) and approached at cycle 18 (4.8 points). There was no difference between groups for the other prespecified subscales from ASPIRE. A higher proportion of KRd patients met the GHS/QoL responder definition (≥ 5-point improvement) with statistical differences at cycle 12 (KRd v Rd patients, 25.5% v 17.4%, respectively) and 18 (KRd v Rd patients, 24.2% v 12.9%, respectively). Conclusion KRd improves GHS/QoL without negatively affecting patient-reported symptoms when compared with Rd. These data further support the benefit of KRd in patients with relapsed multiple myeloma.

Longitudinal costs of caring for people with Alzheimer's disease.

BACKGROUND: There has been an increasing interest in the relationship between severity of disease and costs in the care of people with dementia. Much of the current evidence is based on cross-sectional data, suggesting the need to examine trends over time for this important and growing cohort of the population. METHODS: This paper estimates resource use and costs of care based on longitudinal data for 72 people with dementia in Ireland. Data were collected from the Enhancing Care in Alzheimer's Disease (ECAD) study at two time points: baseline and follow-up, two years later. Patients' dependence on others was measured using the Dependence Scale (DS), while patient function was measured using the Disability Assessment for Dementia (DAD) scale. Univariate and multivariate analysis were used to explore the effects of a range of variables on formal and informal care costs. RESULTS: Total costs of formal and informal care over six months rose from €9,266 (Standard Deviation (SD): 12,947) per patient at baseline to €21,266 (SD: 26,883) at follow-up, two years later. This constituted a statistically significant (p = 0.0014) increase in costs over time, driven primarily by an increase in estimated informal care costs. In the multivariate analysis, a one-point increase in the DS score, that is a one-unit increase in patient's dependence on others, was associated with a 19% increase in total costs (p = 0.0610). CONCLUSIONS: Higher levels of dependence in people with Alzheimer's disease are significantly associated with increased costs of informal care as the disease progresses. Formal care services did not respond to increased dependence in people with dementia, leaving it to families to fill the caring gap, mainly through increased supervision with the progress of disease.

Psychometric properties of the Dependence Scale in large randomized clinical trials of patients with mild and moderate Alzheimer's disease.

OBJECTIVE: The need for assistance from others is a hallmark concern in Alzheimer's disease (AD). The psychometric properties of the Dependence Scale (DS) for measuring treatment benefit were investigated in large randomized clinical trials of patients with mild to moderate AD. METHODS: Reliability, validity, and responsiveness of the DS were examined. Path models appraised relationships and distinctiveness of key AD measures. The responder definition was empirically derived. RESULTS: Generally acceptable reliability (α ≥ .65), significant (P < .001) known-groups tests, and moderate to strong correlations (r ≥ .31) confirmed the DS psychometric properties. Path models supported relationships and distinctiveness of key AD measures. A DS change of ≤ 1 point for patients with limited home care and ≤ 2 points for patients with assisted living care best described stability of the level of dependence on caregivers. CONCLUSION: The DS is a psychometrically robust measure in mild to moderate AD. The empirically derived responder definition aids in the interpretation of DS change.

Cognition in MCI and Alzheimer's disease: baseline data from a longitudinal study of the NTB.

Baseline data are summarized from a study examining the psychometric properties of the Neuropsychological Test Battery (NTB) and its subtests, and correlating the NTB with other cognitive and functional assessments. A multicenter, longitudinal, non-interventional study included mild to moderate Alzheimer's disease (AD, n = 196), mild cognitive impairment (MCI, n = 70), or normal cognition participants (NC, n = 75). The NTB, other cognitive assessment tools, functional/behavioral questionnaires, and health outcome assessments were administered. At baseline composite NTB, NTB memory, and NTB executive function z-scores were significantly lower for participants with AD compared with MCI, and for participants with MCI compared with NC. The composite NTB z-score had high test-retest reliability between screening and baseline. The results of this study suggest that NTB exhibits good reliability in patients with mild to moderate AD and MCI.

Reliability, validity, and interpretation of the dependence scale in mild to moderately severe Alzheimer's disease.

INTRODUCTION: The Dependence Scale (DS) was designed to measure dependence on others among patients with Alzheimer's disease (AD). The objectives of this research were primarily to strengthen the psychometric evidence for the use of the DS in AD studies. METHODS: Patients with mild to moderately severe AD were examined in 3 study databases. Within each data set, internal consistency, validity, and responsiveness were examined, and structural equation models were fit. RESULTS: The DS has strong psychometric properties. The DS scores differed significantly across known groups and demonstrated moderate to strong correlations with measures hypothesized to be related to dependence (|r| ≥ .31). Structural equation modeling supported the validity of the DS concept. An anchor-based DS responder definition to interpret a treatment benefit over time was identified. DISCUSSION: The DS is a reliable, valid, and interpretable measure of dependence associated with AD and is shown to be related to--but provides information distinct from--cognition, functioning, and behavior.

Longitudinal changes in functional disability in Alzheimer's disease patients.

BACKGROUND: Functional impairment is a core symptom of Alzheimer's disease (AD) often measured by loss of ability to perform activities of daily living (ADL). The objective is to describe the progressive loss of specific ADL functional capabilities expressed by AD patients' cognitive ability. METHODS: Data are from ELN-AIP-901, an observational study of cognitive progression in participants aged 50-85 with AD (n = 196), mild cognitive impairment (n = 70), or cognitively normal (n = 75). Participants were evaluated using the Mini-Mental Status Exam (MMSE) and the Disability Assessment for Dementia (DAD) every six months for ≤2 years. Hierarchical regression was used to estimate annual change in DAD and MMSE; first, by individuals' rate of change using linear regression, then controlling for baseline diagnosis. RESULTS: Over a two-year period, in AD participants, a 1-point change in MMSE was associated with a 3-point change in DAD (2.79, 95% CI: 1.97-3.63); DAD items within the finance, medication, and outings subdomains were impacted earlier than other subdomains; a hierarchy of functional impairment was observed, with instrumental ADL generally impaired prior to basic ADL. CONCLUSIONS: ADL are impacted in a progressive and hierarchical manner associated with cognitive decline, but substantial variability remains among individuals, as well as in the relative order of items affected.

Changes in patient characteristics in anti-tumour necrosis factor clinical trials for rheumatoid arthritis: results of an analysis of the literature over the past 16 years.

OBJECTIVE: To evaluate changes in baseline patient characteristics and entry criteria of randomised, controlled studies of tumour necrosis factor alpha (TNFα) inhibitors in rheumatoid arthritis (RA) patients. METHODS: A systematic literature review was performed using predefined inclusion criteria to identify randomised, double-blind, controlled trials that evaluated TNFα inhibitors in adult RA patients. Entry criteria and baseline clinical characteristics were evaluated over time for methotrexate-experienced and methotrexate-naive study populations. Enrolment start date for each trial was the time metric. The anchor time was the study with the earliest identifiable enrolment start date. RESULTS: 44 primary publications (reporting the primary study endpoint) from 1993 to 2008 met the inclusion criteria. Enrolment start dates of August 1993 and May 1997 were identified as time anchors for the 37 methotrexate-experienced studies and the seven methotrexate-naive studies, respectively. In methotrexate-experienced trials, no significant change was observed over the years included in this study in any inclusion criteria (including swollen joint counts and C-reactive protein (CRP)), but a significant decrease over time was observed in the baseline swollen joint count, CRP and total Sharp or van der Heijde modified Sharp score, but not in baseline tender joint counts. In the methotrexate-naive studies, significant decreases over the years were observed in swollen joint and tender joint inclusion criteria, but not in baseline tender joint count, baseline CRP, CRP inclusion criteria or baseline total Sharp or van der Heijde modified Sharp score. CONCLUSION: Inclusion criteria and baseline characteristics of RA patients enrolled in studies of TNFα inhibitors have changed, with more recent trials enrolling cohorts with lower disease activity, especially in methotrexate-experienced trials.

Association of serum markers with improvement in clinical response measures after treatment with golimumab in patients with active rheumatoid arthritis despite receiving methotrexate: results from the GO-FORWARD study.

INTRODUCTION: The goal of this study was to identify serum markers that are modulated by treatment with golimumab with or without methotrexate (MTX) and are associated with clinical response. METHODS: Sera were collected at weeks 0 and 4 from a total of 336 patients (training dataset, n = 100; test dataset, n = 236) from the GO-FORWARD study of patients with active rheumatoid arthritis despite MTX. Patients were randomly assigned to receive placebo plus MTX; golimumab, 100 mg plus placebo; golimumab, 50 mg plus MTX; or golimumab, 100 mg plus MTX. Subcutaneous injections were administered every 4 weeks. Samples were tested for select inflammatory, bone, and cartilage markers and for protein profiling using multianalyte profiles. RESULTS: Treatment with golimumab with or without MTX resulted in significant decreases in a variety of serum proteins at week 4 as compared with placebo plus MTX. The American College of Rheumatology (ACR) 20, ACR 50, and Disease Activity Score (DAS) 28 responders showed a distinct biomarker profile compared with nonresponding patients. CONCLUSIONS: ACR 20 and ACR 50 responders among the golimumab/golimumab + MTX-treated patients had a distinct change from baseline to week 4 in serum protein profile as compared with nonresponders. Some of these changed markers were also associated with multiple clinical response measures and improvement in outcome measures in golimumab/golimumab + MTX-treated patients. Although the positive and negative predictive values of the panel of markers were modest, they were stronger than C-reactive protein alone in predicting clinical response to golimumab. TRIAL REGISTRATION: http://ClinicalTrials.gov identification number: NCT00264550.