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Rezaul Khandker,1 Jason Shepherd,2 Farid Chekani,1 Zaina Qureshi,1 Hollie Bailey,2 Mia Berry,2 Jack Wright,2 Lucy Massey2 1Merck & Co., Inc., Kenilworth, NJ, USA; 2Adelphi Real World, Bollington, UKCorrespondence: Farid Chekani, Merck & Co., Inc., Kenilworth, NJ, USA, Tel +1-267-305-4070, Email farid.chekani@merck.comObjective: To describe and compare demographics and outcomes among patients with schizophrenia who have switched atypical treatments versus non-switchers.Methods: Data were extracted from the Adelphi Schizophrenia Disease Specific Programme™ conducted from January to May 2014 in the United States. Participating physicians provided information on their next 10 consulting schizophrenia patients aged ≥ 18 years; the same patients were invited to voluntarily complete a patient self-completion form (PSC). Patients were considered switchers (S) or non-switchers (NS) based on their physician-provided treatment history. S were patients who had switched, stopped or added an atypical treatment within the last 2 years. NS had no treatment changes within the last 2 years or were receiving their first-line treatment (for ≥ 3 months). Demographics, clinical characteristics and outcomes among S and NS were compared using both descriptive and multivariate statistics.Results: One-hundred fifty physicians provided data on 1003 patients with schizophrenia (395 S, 608 NS); 500 patients completed a PSC (170 S, 330 NS). When compared with NS, S were more likely to be unemployed (p=0.0060), have a caregiver (p< 0.0001), have greater activity impairment as assessed by Work and Productivity Activity Impairment (p=0.0031), be hospitalized for schizophrenia (p< 0.0001) and have had a greater mean number of hospitalizations in the last 12 months (p=0.0012). NS vs S were more likely to have much or very much improved illness (p< 0.0001) and less severe disease (p< 0.0001) as assessed by Clinical Global Impression.Conclusion: Despite switching drugs, some schizophrenia patients continue to have high levels of disease burden, suggesting that currently available therapies are insufficiently effective in these patients.Keywords: schizophrenia, atypical treatment, switching, compliance, outcomes, quality of life, EQ-5D, WPAI, CGI

Background: Sleep disturbances are frequent in Alzheimer’s disease (AD). Objective: To summarize the impact of sleep disturbances on AD patients and their caregivers and the effects of currently available sleep therapies. Methods: Published studies (January 1985–March 2020) assessing the burden associated with insomnia/sleep disturbances in the AD population and insomnia treatment effects were identified by searching PubMed, Embase, and Cochrane Library and screened against inclusion criteria. Results: 58 studies assessing patient and caregiver burden, institutionalization, and insomnia treatments in AD patients with sleep disturbances were identified. Sleep disturbances were associated with worse cognition, functional ability, and behavioral and neuropsychological functioning. Health status and quality of life of both patients and caregivers were reduced in the presence of sleep disturbances. Sleep disturbances were also associated with institutionalization. Although significant associations between sleep problems and clinical outcomes were apparent, there was generally no control for other influencing factors (e.g., cognitive status). Bright light and behavioral therapies as well as drugs showed some promise in AD patients, but studies were primarily small and limited data were available, particularly in regard to the effect on associated clinical burden. Conclusion: Sleep disturbances are a significant problem for AD patients and caregivers, associated with behavioral and psychological problems and cognitive decline. However, they remain poorly characterized and under-researched. As the global population is aging and AD is on thes rise, data from larger, prospective trials are required to fully understand the clinical correlates of sleep disturbances and the impact insomnia treatments can have.

Aim: Rheumatoid arthritis (RA) is an important rheumatologic disease in Asia-Pacific countries, as in other parts of the world. However, limited information is available regarding RA therapy in this region. The Asia-Pacific Study in Patients to be Treated With Etanercept or an Alternative Listed DMARD (APPEAL) compared efficacy and safety of etanercept (ETN) + methotrexate (MTX) versus usual disease-modifying anti-rheumatic drugs (DMARDs) + MTX (reflecting regional practice) in subjects with moderate to severe RA from multiple Asia-Pacific countries. Method: In this open-label, active-comparator, parallel-design, multicenter study, subjects (n = 300) in the Asia-Pacific region were randomized to ETN + MTX (n = 197) or DMARD + MTX (n = 103). The primary efficacy endpoint was the American College of Rheumatology (ACR) response (ACR-N) area under the curve (AUC) over 16 weeks. Results: Baseline characteristics were similar between groups. At Week 16, ACR-N AUC indicated a significantly greater response with ETN + MTX compared with DMARD + MTX (mean difference –145.3; P

To assess the association between clinical remission in RA and patient-reported outcomes (PROs), including depression/anxiety symptoms, in adults with moderate-to-severe active early RA.Patients from the COmbination of Methotrexate and ETanercept in Active Early Rheumatoid Arthritis (COMET) trial (104 weeks) with measures on the Hospital Anxiety and Depression Scale at baseline and subsequent visits (n = 389) were included. PROs investigated were the HAQ disability index, pain and fatigue visual analogue scales (VASs), EuroQoL health status VAS and the Medical Outcomes Short Form-36 physical and mental component summaries. The impact of clinical remission as measured by 28-joint DAS (DAS-28) on depression/anxiety symptoms at Week 104 was assessed using logistic regression. Least square means for PRO improvements from baseline were estimated by analysis of covariance. Missing data were imputed using the last observation carried forward method.When depression/anxiety symptoms were absent at baseline, significantly more patients achieved clinical remission, low disease activity and normal functioning at Week 104. Reciprocally, patients who achieved clinical remission were less likely to maintain symptoms of depression or anxiety compared with non-remitters [depression odds ratio (OR): 0.35, P = 0.0233; anxiety OR: 0.48, P = 0.0371]. Fatigue and pain had a significant impact on changes in depression status, but did not influence anxiety status. Finally, clinical remission was significantly associated with improvements in all PRO measures (P 0.001); conversely, depression/anxiety symptoms reduced PRO improvements.Among moderate-to-severe active early RA patients, clinical remission reduces symptoms of depression/anxiety, and independently improves PROs, thereby suppressing the negative impact of depression/anxiety on these measures.

Objective.To examine resource utilization and direct healthcare cost associated with comorbid cardiovascular disease (CVD) and depression among patients with prevalent rheumatoid arthritis (RA) based on analyses of retrospective healthcare claims data.Methods.The index date was set as the first observed claim with an RA diagnosis. Patients were required to be ≥ 18 years of age, to have received RA-related treatment during the pre-index period, and to have 12-month pre- and post-index data. Based on pre-index utilization, patients were classified into 4 diagnosis groups: RA alone, RA + CVD, RA + depression, and RA + CVD + depression. Analyses focused on annual differences in costs between patients with RA alone and those with CVD and/or depression. A generalized linear model was applied to control for demographic and clinical characteristics and to estimate cohort-specific adjusted mean annual healthcare cost.Results.Of 10,298 patients, 8,916 had RA alone (86.6%), 608 had RA + CVD (5.9%), 716 had RA + depression (7.0%), and 58 had RA + CVD + depression (0.5%). All patients with CVD and/or depression incurred significantly higher followup costs compared with patients with RA alone. Adjusted annual mean healthcare costs were highest for RA + CVD (US$14,145), followed by RA + CVD + depression ($13,513), RA + depression ($12,225), and RA alone ($11,404). Although patients with CVD and/or depression had a greater rate of RA-related hospitalization, adjusted RA-related healthcare costs did not reflect any statistically significant differences as compared to the RA-alone cohort.Conclusion.A significant proportion (13.4%) of patients with prevalent RA have comorbid CVD and/or depression. The presence of these conditions significantly affects annual healthcare costs as well as specific RA-related utilization patterns.

Background Patient reported outcomes (PROs) are especially useful in assessing treatments for rheumatoid arthritis (RA) since they measure dimensions of health-related quality of life that cannot be captured using strictly objective physiological measures. The aim of this study was to compare the effects of combination etanercept and methotrexate (ETN + MTX) versus combination synthetic disease modifying antirheumatic drugs (DMARDs) and methotrexate (DMARD + MTX) on PRO measures among RA patients from the Asia-Pacific region, a population not widely studied to date. Patients with established moderate to severe rheumatoid arthritis who had an inadequate response to methotrexate were studied. Methods Patients were randomized to either ETN + MTX (N = 197) or DMARD + MTX (N = 103) in an open-label, active-comparator, multicenter study, with PRO measures designed as prospective secondary endpoints. The Health Assessment Questionnaire (HAQ), Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-Fatigue), Medical Outcomes Short Form-36 Health Survey (SF-36), Hospital Anxiety and Depression Scale (HADS) and the Work Productivity and Activity Impairment Questionnaire: General Health (WPAI:GH) were used. Results Significantly greater improvements were noted for the ETN + MTX group at week16 for HAQ mean scores and for proportion of patients achieving HAQ score ≤ 0.5, compared to patients in the DMARD + MTX group. SF-36 Summary Scores for physical and mental components and for 6 of 8 health domains showed significantly greater improvements at week16 for the ETN + MTX group; only scores for physical functioning and role-emotional domains did not differ significantly between the two treatment arms. Greater improvements at week16 were noted for the ETN + MTX group for FACIT-Fatigue, HADS, and WPAI:GH mean scores. Conclusion Combination therapy using ETN + MTX demonstrated superior improvements using a comprehensive set of PRO measures, compared to combination therapy with usual standard of care DMARDs plus MTX in patients with established rheumatoid arthritis from the Asia-Pacific region. Trial registration clintrials.gov # NCT00422227

Rheumatoid arthritis (RA) is an important rheumatologic disease in Asia-Pacific countries, as in other parts of the world. However, limited information is available regarding RA therapy in this region. The Asia-Pacific Study in Patients to be Treated With Etanercept or an Alternative Listed DMARD (APPEAL) compared efficacy and safety of etanercept (ETN) + methotrexate (MTX) versus usual disease-modifying anti-rheumatic drugs (DMARDs) + MTX (reflecting regional practice) in subjects with moderate to severe RA from multiple Asia-Pacific countries.In this open-label, active-comparator, parallel-design, multicenter study, subjects (n = 300) in the Asia-Pacific region were randomized to ETN + MTX (n = 197) or DMARD + MTX (n = 103). The primary efficacy endpoint was the American College of Rheumatology (ACR) response (ACR-N) area under the curve (AUC) over 16 weeks.Baseline characteristics were similar between groups. At Week 16, ACR-N AUC indicated a significantly greater response with ETN + MTX compared with DMARD + MTX (mean difference -145.3; P0.001). Significantly greater proportions of subjects achieved ACR 20, 50 and 70 responses with ETN + MTX versus DMARD + MTX at Week 16 (P0.05). Low Disease Activity Score based on a 28-joint count (DAS283.2) was also achieved by significantly more subjects in the ETN + MTX group versus the DMARD + MTX group (P0.001). Greater improvements were shown for DAS28, pain visual analogue scale, health assessment questionnaire, and physician and patient global assessments (P0.05) for ETN + MTX versus DMARD + MTX. No new safety signals were found.In this Asia-Pacific population of subjects with moderate to severe RA, ETN + MTX showed superior efficacy versus usual DMARD + MTX regimens, with similar safety profiles.

To evaluate the impact of uncontrolled asthma on the absenteeism and health-related quality of life (HRQOL) of adults and children with asthma and the caregivers of pediatric patients.Patient information was obtained from datasets maintained by National Jewish Health for this cross-sectional study. Participants in the study were 12 years of age or older. Participants younger than 18 years had their information provided by caregivers. Caregivers also provided 6 months of absenteeism and QOL data. Participants were classified as having uncontrolled asthma based on a treatment and symptom guideline-based algorithm. Absenteeism was assessed from the self-reported number of work or school days missed due to asthma during the previous 6 months. HRQOL among adults was measured using the validated Marks Asthma Quality of Life Questionnaire (Marks-AQLQ) and among caregivers using the validated Pediatric Asthma Caregivers Quality of Life Questionnaire (PACQLQ). To account for the positive skew in absenteeism data, a zero-inflated Poisson regression model was used to compare group differences. HRQOL was analyzed for adults and caregivers using the Wilcoxon-Mann-Whitney test.A total of 15,149 patients met the inclusion criteria for the study and were included in the analysis. Adults with uncontrolled asthma and caregivers of children with uncontrolled asthma reported significantly higher absenteeism than their controlled counterparts: 43% vs 24% adults reported missing days of work, with a median 6 days vs 3 days missed; 31% vs 16% of caregivers reported missing days of work, with 4 days vs 2 days missed; and caregivers reported that more than 70% vs 45% pediatric patients missed school, with a median of 6 days vs 4 days missed (uncontrolled vs controlled asthma, respectively). Adult uncontrolled asthmatics and caregivers of uncontrolled pediatric patients had significantly lower HRQOL as indicated by the Marks-AQLQ (scores 1.5 points higher, p0.001) and PACQLQ (scores0.5 points lower, p0.001), respectively.Uncontrolled asthma has far-reaching impact on the productivity and quality of life of asthma patients and their caregivers. Proper assessment, treatment, and disease management to improve asthma control may reduce the impact of uncontrolled asthma on asthmatic adults, children, and the caretakers of pediatric asthmatic patients.

International audience; Rationale: An efficacious medical therapy for idiopathic pulmonary fibrosis (IPF) remains elusive. Objectives: To explore the efficacy and safety of etanercept in the treatment of IPF. Methods: This was a randomized, prospective, double-blind, placebo-controlled, multicenter exploratory trial in subjects with clinically progressive IPF. Primary endpoints included changes in the percentage of predicted FVC and lung cliff using capacity for carbon monoxide corrected for hemoglobin (D-LCOHB) and change in the alveolar to arterial oxygen pressure difference P(A-a)(O2) at rest from baseline over 48 weeks. Measurements and Main Results: Eighty-eight subjects received subcutaneous etanercept (25 mg) or placebo twice weekly as their sole treatment for IPF. No differences in baseline demographics and disease status were detected between treatment groups; the mean time from first diagnosis was 13.6 months and mean FVC was 63.9% of predicted. At 48 weeks, no significant differences in efficacy end points were observed between the groups. A nonsignificant reduction in disease progression was seen in several physiologic, functional, and quality-of-life endpoints among subjects receiving etanercept. There was no difference in adverse events between treatment groups. Conclusions: In this exploratory study in patients with clinically progressive IPF, etanercept was well tolerated. Although there were no differences in the predefined endpoints, a decreased rate of disease progression was observed on several measures. Further evaluation of TNF antagonists in the treatment of IPF may be warranted.