Real-world utilisation and switching between Janus kinase inhibitors in Australian patients with rheumatoid arthritis in the OPAL dataset.

OBJECTIVES: To describe use and treatment persistence for Janus kinase inhibitors (JAKi) in rheumatoid arthritis (RA) by line of therapy, and the mechanism of action for the drug switched to after JAKi discontinuation. METHODS: This was a retrospective, observational analysis using the OPAL dataset, a large collection of deidentified electronic medical records from 112 rheumatologists around Australia. Adult patients with RA were included if they initiated tofacitinib (TOF), baricitinib (BARI) or upadacitinib (UPA) between 1 October 2015 and 30 September 2021. Data were summarised using descriptive statistics. Kaplan-Meier survival was used to analyse treatment persistence. RESULTS: 5,900 patients initiated JAKi within the study window (TOF n=3,662, BARI n=1,875, UPA n=1,814). Median persistence was similar across JAKi within each line of therapy where there was sufficient follow-up, and almost 3 years for first-line: 34.9 months (95% CI 30.8, 40.7; n=1,408) for TOF, 33.6 months (95% CI 25.7, not reached; n=545) for BARI. While JAKi to JAKi switching occurred across all lines of therapy, switches to a tumour necrosis factor inhibitor (TNFi) were more frequent after first- or second-line JAKi. JAKi monotherapy use at baseline increased with line of therapy, and was highest at follow-up after switching to another JAKi. 'Lack of efficacy' was the most common reason for discontinuing JAKi. CONCLUSIONS: In this large analysis of Australian real-world practice separated by line of therapy, treatment persistence for JAKi was high overall subject to differential follow-up, but declined in later lines. JAKi to JAKi switching was observed across all lines of therapy.

Real-world data reveal unmet clinical needs in insulin treatment in Asian people with type 2 diabetes: the Joint Asia Diabetes Evaluation (JADE) Register.

AIMS: To explore the pattern of insulin use and glycaemic control in Asian people with type 2 diabetes, stratified by gender, young-onset diabetes (YOD; diagnosed before age 40 years), and diabetic kidney disease (DKD; estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73m2 ). MATERIALS AND METHODS: We conducted a cross-sectional analysis of 97 852 patients from 11 Asian countries/regions (2007-2017) included in the prospective Joint Asia Diabetes Evaluation (JADE) Register. RESULTS: Among 18 998 insulin users (47% women, mean ± SD age 59.2 ± 11.7 years, diabetes duration 13.2 ± 8.3 years, glycated haemoglobin [HbA1c] 72 ± 21.4 mmol/mol [8.74 ± 1.95%], median total daily insulin dose [TDD] 0.27-0.82 units/kg), 25% and 29.5% had YOD and DKD, respectively. Premixed (44%) and basal-only (42%) insulin were the most common regimens. Despite being more commonly treated with these two regimens with higher insulin dosages, patients with YOD had worse HbA1c levels than their late-onset peers (73 ± 20.5 vs. 71 ± 21.2 mmol/mol [8.82 ± 1.87% vs. 8.66 ± 1.94%]; P < 0.001). Fewer women than men attained an HbA1c level < 53 mmol/mol (7%; 15.7% vs 17.1%; P = 0.018). Adjusting for age, diabetes duration, TDD, HbA1c, eGFR, and use of oral glucose-lowering drugs at baseline, the odds of self-reported hypoglycaemia were higher in women (vs. men: adjusted odds ratio [aOR] 1.16, 95% confidence interval [CI] 1.05-1.28) and in patients with DKD treated with a premixed regimen (1.81 [95% CI 1.54-2.13] vs. 1.34 [95% CI 1.16-1.54] in non-DKD; Pinteraction < 0.001). Compared to basal-only regimens, premixed and basal-bolus regimens had similar HbA1c reductions but were independently associated with increased odds of hypoglycaemia (1.65 [95% CI 1.45-1.88] and 1.88 [95% CI 1.58-2.23], respectively). CONCLUSIONS: In this Asian population, there were varying patterns of insulin regimens with suboptimal glycaemic control, despite relatively high TDDs, which were influenced by gender, DKD, and YOD status.

Factors associated with insufficient response to acute treatment of migraine in Japan: analysis of real-world data from the Adelphi Migraine Disease Specific Programme.

BACKGROUND: Real-world data on sufficient/insufficient response, and predictors of insufficient response, to acute treatments for migraine are limited in Japan. This study aimed to identify factors associated with insufficient response to acute treatment of migraine by exploring significant differences between people with migraine who sufficiently/insufficiently respond to prescribed acute treatment in Japan. METHODS: This was a retrospective analysis of 2014 Adelphi Migraine Disease Specific Programme cross-sectional survey data collected from physicians and their consulting adult patients with migraine in Japan. Insufficient responders to prescribed acute treatment were patients who achieved headache pain freedom within 2 h of acute treatment in no more than three of their last five migraine attacks. Factors associated with insufficient response to prescribed acute migraine treatment were identified using backward logistic regression. RESULTS: Overall, 227/538 (42.2%) patients were classified as insufficient responders to prescribed acute migraine treatment. Significantly more insufficient responders than sufficient responders had consulted a neurologist or a migraine/headache specialist, and had chronic migraine or medication-overuse or tension-type headaches (p < 0.05). More insufficient responders than sufficient responders reported taking acute treatment when/after the pain started (77.0 vs. 68.9%) than at first sign of migraine (p < 0.05). Compared with sufficient responders, insufficient responders reported a significantly higher mean ± standard deviation (SD) Migraine Disability Assessment total score (12.7 ± 23.3 vs. 5.8 ± 10.4, p < 0.001) and lower quality of life (EuroQol-5 Dimensions utility score 0.847 ± 0.19 vs. 0.883 ± 0.16, p = 0.024). Factors significantly associated with insufficient response to acute treatment included seeing a neurologist versus an internist (odds ratio [OR] 1.93; 95% confidence interval [CI] 1.29-2.88; p = 0.002), taking acute medication when/after pain started versus at first sign of migraine (OR 1.65; 95% CI 1.05-2.60; p = 0.030), a higher MIDAS total score (OR 1.04; 95% CI 1.02-1.06; p < 0.001), and presence of comorbid cardiovascular disease (OR 0.53; 95% CI 0.28-0.98; p = 0.044). CONCLUSIONS: Many people with migraine in Japan struggle to adequately treat migraine attacks with prescribed acute medication and exhibit high levels of unmet need for acute treatment. Optimized management strategies utilizing existing therapeutic options as well as additional effective therapeutic options for migraine are required to improve symptoms and quality of life.

Prevalence, burden, and clinical management of migraine in China, Japan, and South Korea: a comprehensive review of the literature.

BACKGROUND: The objective of this review was to determine the unmet needs for migraine in East Asian adults and children. METHODS: We searched MEDLINE and EMBASE (January 1, 1988 to January 14, 2019). Studies reporting the prevalence, humanistic and economic burden, and clinical management of migraine in China (including Hong Kong and Taiwan), Japan, and South Korea were included. Studies conducted before 1988 (before the International Headache Society [IHS] first edition of the International Classification of Headache Disorders) were not included. RESULTS: We retrieved 1337 publications and 41 met the inclusion criteria (28 from China, 7 from Japan, and 6 from South Korea). The 1-year prevalence of migraine (IHS criteria) among adults ranged from 6.0% to 14.3%. Peak prevalence ranged from 11% to 20% for women and 3% to 8% for men (30- to 49-year-olds). For children, prevalence of migraine increased with age. Information on the economic burden and clinical management of migraine was limited, particularly for children. When reported, migraine was significantly associated with high levels of disability and negative effects on quality of life. Studies suggested low levels of disease awareness/diagnosis within each country. Of individuals with migraine from China, 52.9% to 68.6% had consulted a physician previously, 37.2% to 52.7% diagnosed with headache had not been diagnosed with migraine previously, and 13.5% to 18% had been diagnosed with migraine previously. Of individuals with migraine from Japan, 59.4% to 71.8% had never consulted a physician previously, 1.3% to 7.3% regularly consulted physicians for their headache, and only 11.6% of individuals with migraine were aware that they had migraine. In addition, studies suggested that over-the-counter medication use was high and prescription medication use was low in each country. CONCLUSIONS: This review suggests that there are unmet needs for migraine in terms of sufficient and appropriate diagnosis, and better management and therapies for treatment of migraine in East Asia. The findings are limited by a lack of recent information and significant gaps in the literature. More recent, population-based studies assessing disease burden and clinical management of migraine are needed to confirm unmet needs for migraine across East Asia.

Real-world treatment patterns and patient-reported outcomes in episodic and chronic migraine in Japan: analysis of data from the Adelphi migraine disease specific programme.

BACKGROUND: In Japan, detailed information on the characteristics, disease burden, and treatment patterns of people living with migraine is limited. The aim of this study was to compare clinical characteristics, disease burden, and treatment patterns in people with episodic migraine (EM) or chronic migraine (CM) using real-world data from clinical practice in Japan. METHODS: This was an analysis of data collected in 2014 by the Adelphi Migraine Disease Specific Programme, a cross-sectional survey of physicians and their consulting adult patients in Japan, using physician and patient questionnaires. We report patient demographics, prescribed treatment, work productivity, and quality-of-life data for people with CM (≥15 headache days/month) or EM (not fulfilling CM criteria). In descriptive analyses, continuous and categorical measures were assessed using t-tests and Chi-squared tests, respectively. RESULTS: Physicians provided data for 977 patients (mean age 44.5 years; 77.2% female; 94.5% with EM, 5.5% with CM). A total of 634/977 (64.9%) invited patients (600 with EM; 34 with CM) also provided data. Acute therapy was currently being prescribed in 93.7% and 100% of patients with EM and CM, respectively (p = 0.069); corresponding percentages for current preventive therapy prescriptions were 40.5% and 68.5% (p < 0.001). According to physicians who provided data, preventive therapy was used at least once by significantly fewer patients with EM than with CM (42.3% vs. 68.5%, respectively; p < 0.001). Among patients who provided physicians with information on issues with their current therapy (acute therapy: n = 668 with EM, n = 38 with CM; preventive therapy: n = 295 with EM, n = 21 with CM), lack of efficacy was the most frequently identified problem (acute therapy: EM 35.3%, CM 39.5% [p = 0.833]; preventive therapy: EM 35.3%, CM 52.4% [p = 0.131]). Moderate-to-severe headache-related disability (Migraine Disability Assessment total score ≥ 11) was reported by significantly fewer patients with EM than with CM (21.0% vs. 60.0%, respectively; p < 0.001) among patients who provided data. CONCLUSIONS: Preventive treatment patterns in people with EM versus CM differ in Japan, with both types of migraine posing notable disease burdens. Our findings demonstrate that more effective migraine therapies are required to reduce the burden of the disease.

Real-world Effectiveness of Antipsychotics for the Treatment of Negative Symptoms in Patients with Schizophrenia with Predominantly Negative Symptoms.

This study assessed the comparative effectiveness of antipsychotics in the treatment of patients with schizophrenia presenting with prominent negative symptoms and no-to-mild positive symptoms. Data were taken from a 3-year prospective, international, observational study (n=17 384). This post-hoc study focused on 3 712 patients who started antipsychotic monotherapy and had moderate-to-severe negative symptoms and no-to-mild positive symptoms (Clinical Global Impression-Severity Scale [GGI-SCH]). Patients were classified into 3 treatment cohorts: olanzapine, other atypicals and typicals. Multiple regression analyses were performed. All treatment groups experienced improvement in negative symptoms and social functioning during follow-up. The adjusted mean change in the CGI-SCH negative symptoms scores during follow-up was greater for olanzapine-treated patients by 0.220 (p<0.001) (vs. other atypicals) and by 0.453 (p<0.001) (vs. typicals). Olanzapine-treated patients were also most likely to achieve response of negative symptoms and improvement in social functioning, and to stay on the initial medication longer. Patients with schizophrenia treated with antipsychotics experienced improvement in negative symptoms and social functioning during follow-up. Olanzapine appeared to be more effective compared with other antipsychotics.

Relationship of insight with medication adherence and the impact on outcomes in patients with schizophrenia and bipolar disorder: results from a 1-year European outpatient observational study.

BACKGROUND: Many patients with schizophrenia and bipolar disorder have impaired insight and low medication adherence. The aim of this post hoc analysis was to explore the relationship between insight and medication adherence. METHODS: We included 903 patients with schizophrenia or bipolar disorder who participated in an observational study conducted in Europe on the outcomes of patients treated with two oral formulations of olanzapine over a 1-year period. Evaluations included Clinical Global Impression (CGI), Global Assessment of Functioning (GAF), insight (Scale to Assess Unawareness of Mental Disorder, SUMD) medication adherence (Medication Adherence Rating Scale, MARS), and therapeutic alliance (Working Alliance Inventory, WAI). RESULTS: Medication adherence was higher in bipolar patients (mean MARS score (SD) 6.5 (2.8) versus 5.8 (2.7) in schizophrenia; p < 0.001). Patients with schizophrenia had lower insight (i.e., SUMD item 1, unawareness of mental disorder, mean (SD) of 2.5 (1.3) in schizophrenia versus 1.9 (1.2) in bipolar, p < 0.001). Better insight was associated with higher adherence (Spearman Correlation Coefficient, SCC, ranging from 0.39 to 0.49 for the three SUMD general items, p < 0.0001 in all cases). Higher insight was related to a stronger therapeutic alliance (SCC ranging from 0.38 to 0.48, p < 0.0001). A path analysis revealed a positive impact of insight on adherence and alliance and that stronger alliance was related to lower clinical severity (lower CGI score). CONCLUSION: Insight and adherence were found to be closely related. Insight impacts on the therapeutic alliance with mental health professionals. These factors are associated to treatment outcomes.

Patient characteristics associated with treatment initiation among paediatric patients with Attention-Deficit/Hyperactivity Disorder symptoms in a naturalistic setting in Central Europe and East Asia.

BACKGROUND: Cultural views of Attention-Deficit/Hyperactivity Disorder (ADHD), differing healthcare systems and funding mechanisms, and the availability of mental health services can greatly influence the perceptions, diagnosis, and treatment of ADHD. There is, however, lack of information about treatment practice and the treatment decision-making process for ADHD, particularly in non-Western countries. Our study compared characteristics of paediatric patients newly diagnosed with ADHD symptoms who did and who did not initiate treatment, and also examined whether any differences varied by region in Central Europe and East Asia. METHODS: Data were taken from a 1-year prospective, observational study that included 1,068 paediatric patients newly diagnosed with ADHD symptoms. Clinical severity was measured using the Clinical Global Impression-ADHD-Severity (CGI-ADHD-S) scale and the Child Symptom Inventory-4 (CSI-4) checklist. Logistic regression was used to explore patient characteristics associated with treatment initiation (pharmacotherapy and/or psychotherapy) at baseline for each region. RESULTS: A total of 74.3% of patients initiated treatment at baseline (78.3% in Central Europe and 69.9% in East Asia). Of these, 48.8% started with both pharmacotherapy and psychotherapy in Central Europe, and only 17.1% did so in East Asia. The level of clinical severity was highest in the combination treatment group in Central Europe, but was highest in the psychotherapy only group in East Asia. In East Asia, treatment initiation was associated with being older, being male, and having a higher CGI-ADHD-S score. In Central Europe, treatment initiation was associated with parental psychological distress, having a higher CSI-4 score, and not being involved in bullying. CONCLUSIONS: Although factors associated with treatment initiation differed to some extent between Central Europe and East Asia, clinical severity appeared to be one of the most important determinants of treatment initiation in both regions. However, the choice between pharmacotherapy and psychotherapy, either alone or in combination, varied substantially across the regions.

Real-world evidence for ixekizumab in the treatment of psoriasis and psoriatic arthritis: literature review 2016-2021.

OBJECTIVES: To describe the results of a structured literature review of real-world outcomes with ixekizumab in patients with psoriasis (PsO) and/or psoriatic arthritis (PsA). METHODS: Literature databases, conference proceedings and additional sources were searched for relevant publications. Real-world studies of ≥25 ixekizumab-treated patients with PsO and/or PsA were included. Data on clinical effectiveness, treatment persistence/patterns, economic outcomes, patient-reported outcomes (PROs) and safety were extracted. RESULTS: Fifty-one publications were included. Most studies focused on patients with PsO, and the number of publications with a focus on PROs was low. Studies of treatment patterns found that in general, ixekizumab had similar or better persistence versus other biologics, and rates or risk of switching similar to or less than comparator drugs. Adherence to ixekizumab was high, and patients were less likely to discontinue ixekizumab than other biologics. Ixekizumab was effective in the real world, with a safety profile consistent with that reported in clinical trials. CONCLUSIONS: Real-world use of ixekizumab in PsO and PsA is effective and safe, with generally high treatment persistence and adherence. Further work is required to determine the impact of ixekizumab on PROs in PsO, and to gather more data on real-world use of ixekizumab in PsA.

Systematic Literature Review of Real-World Evidence on Baricitinib for the Treatment of Rheumatoid Arthritis.

INTRODUCTION: Baricitinib, an orally available small-molecule inhibitor of Janus kinase (JAK)1 and JAK2, is indicated to treat active moderate-to-severe rheumatoid arthritis (RA). OBJECTIVE: This systematic review described the real-world clinical characteristics of baricitinib-treated patients with RA, prescription patterns, effectiveness, drug persistence, patient-reported outcomes (PROs; physical function, pain, health-related quality of life [HRQoL]), patient global assessment (PGA), and safety of baricitinib. METHODS: A PRISMA systematic review of real-world studies was conducted to identify relevant literature published between January 2016 and September 2022 using MEDLINE®, EMBASE®, and evidence-based medicine review databases. Websites or online repositories of the American College of Rheumatology and the European Alliance of Associations for Rheumatology were searched manually to include relevant abstracts from conferences held between January 2016 and November 2022. RESULTS: A total of 11,472 records were identified by searching online databases. Seventy studies were included in the study, of which 40 were abstracts. Most patients were older (51-71 years), female, and with mean RA duration of 4-19 years. Baricitinib was mostly used after the failure of one or more bDMARDs, and 4 mg dosing was prevalent in patients with RA (range 22-100%). Clinical effectiveness of baricitinib was reported in real-world settings regardless of prior biologic/targeted synthetic disease-modifying antirheumatic drug (DMARD) use and concomitant conventional synthetic DMARD use. Achievement of Clinical Disease Activity Index (CDAI) remission was reported in 8.7-60% of patients at week 12 and CDAI low disease activity (LDA) in 20.2-81.6% at week 24. The proportion of patients attaining Simple Disease Activity Index (SDAI) remission was reported in 12% at week 4 to 45.4% at 24 weeks. Drug persistence was high, similar, or equal to anti-tumor necrosis factor drugs. No new safety signals were identified. CONCLUSION: Baricitinib demonstrated effectiveness in the real-world setting with a consistent safety profile observed in clinical studies. Better persistence rates for baricitinib compared to bDMARDs with improvement in PROs were reported, although baricitinib-treated patients had RA with poor prognostic characteristics.

Comparative Effectiveness of First-Line Baricitinib in Patients With Rheumatoid Arthritis in the Australian OPAL Data Set.

OBJECTIVE: To analyze comparative treatment persistence for first-line baricitinib (BARI) versus first-line tumor necrosis factor inhibitor (TNFi) in patients with rheumatoid arthritis (RA) and for first-line BARI initiated as monotherapy versus first-line BARI initiated with at least one conventional synthetic disease-modifying antirheumatic drug (csDMARD). METHODS: Patients with RA who initiated BARI or TNFi as first-line biologic or targeted synthetic DMARD from October 1, 2015, to September 30, 2021, were identified in the OPAL data set. Drug survival times to 6, 12, and 24 months were analyzed using restricted mean survival time (RMST). Multiple imputation and inverse probability of treatment weighting were used to address missing data and nonrandom treatment assignment. RESULTS: A total of 545 patients initiated first-line BARI, including 118 as monotherapy and 427 as csDMARD combination therapy. Three thousand five hundred patients initiated first-line TNFi. There was no difference in drug survival to 6 or 12 months for BARI compared with TNFi; differences in RMST were 0.02 months (95% CI: -0.08 to 0.013; P = 0.65) and 0.31 months (95% CI: -0.02 to 0.63; P = 0.06), respectively. Patients in the BARI group had 1.00 month (95% CI: 0.14 to 1.86; P = 0.02) longer drug survival to 24 months. There was no difference in drug survival for BARI monotherapy compared with combination therapy, with differences in RMST to 6, 12, and 24 months of -0.19 months (95% CI: -0.50 to 0.12; P = 0.12), -0.35 months (95% CI: -1.17 to 0.42; P = 0.41), and -0.56 months (95% CI: -2.66 to 1.54; P = 0.60), respectively. CONCLUSION: In this comparative analysis, treatment persistence up to 24 months was significantly longer for first-line BARI compared with TNFi, but the effect size of 1.00 month is not clinically meaningful. There was no difference in persistence for BARI monotherapy versus combination therapy.

Patient Characteristics, Treatment Patterns, Healthcare Resource Utilization, and Costs of Targeted Therapy-Eligible Atopic Dermatitis Patients in Taiwan-A Real-World Study.

INTRODUCTION: The objective of this study was to conduct a retrospective analysis to understand the patient profile, treatment patterns, healthcare resource utilization, and cost of atopic dermatitis (AD) of patients eligible for targeted therapy in Taiwan. METHODS: A retrospective, claims-based analysis was undertaken using Taiwan's National Health Insurance Research Database from 01 January 2014 to 31 December 2017. Patients aged ≥ 2 years and with at least one diagnosis code for AD during 2015 were identified. Patients with comorbid autoimmune diseases were excluded. Enrolled AD patients were categorized using claims-based treatment algorithms by disease severity and their eligibility for targeted therapy treatment. A cohort of targeted therapy-eligible patients was formed, and a matched cohort using patients not eligible for targeted therapy was derived using propensity score matching based on age, gender, and the Charlson Comorbidity Index (CCI). Treatment patterns, resource utilization, and costs were measured during a 1-year follow-up period. RESULTS: A total of 377,423 patients with AD were identified for this study. Most patients had mild AD (84.5%; n = 318,830) with 11.9% (n = 45,035) having moderate AD, and 3.6% (n = 13,558) having severe AD. Within the 58,593 moderate-to-severe AD patients, 1.5% (n = 897) were included in the targeted therapy-eligible cohort. The matched cohort consisted of 3558 patients. During the 1-year follow-up period, targeted therapy-eligible patients utilized antihistamines (85.5%), topical treatments (80.8%), and systemic anti-inflammatories (91.6%) including systemic corticosteroids (51.4%) and azathioprine (59.1%). During the first year of follow-up, targeted therapy-eligible patients (70.5%; 7.01 [SD = 8.84] visits) had higher resource utilization rates and frequency of AD-related outpatient visits compared with the matched cohort (40.80%; 1.85 [SD = 4.71] visits). Average all-cause direct costs during 1-year follow-up were $2850 (SD = 3629) and $1841 (SD = 6434) for the eligible targeted therapy and matched cohorts, respectively. AD-related costs were 17.7% ($506) of total costs for the targeted therapy eligible cohort and 2.2% ($41) for the matched cohort. CONCLUSIONS: AD patients eligible for targeted therapy in Taiwan experienced high resource and economic burden compared with their non-targeted-therapy-eligible counterparts.

Weight Gain Risk Factor assessment checklist: overview and recommendation for use.

OBJECTIVES: Patients with mental illness are at risk for weight gain. Evidence-based risk assessment checklists have the potential to identify patients at risk early in treatment and improve patient outcomes. METHODS: The 16-item Weight Gain Risk Factor (WGRF-16) checklist has been developed as a simple brief assessment of key weight gain risk factors during antipsychotic treatment. It consists of factors that were collected on the basis of published research on predictors to be assessed at initiation of, and early in treatment with antipsychotics. RESULTS: The factors in the WGRF-16 checklist included age, sex, body mass index, race, appetite, energy intake, a diagnosis of undifferentiated schizophrenia, early clinical response, comorbiditites, social activity, patient insight, housing conditions, weight satisfaction, eating habits, and physical activity level. The WGRF-16 is designed to be repeated 2-3 weeks after initiation of treatment to help to predict an individual's risk of clinically significant weight gain (>7%) during long-term treatment. Further research is required to assess the predictive validity of the checklist. CONCLUSIONS: The WGRF-16 checklist is not intended to replace other required monitoring of patients with severe mental disorders but is a facilitator of weight monitoring in conjunction with clinical guidelines.

Costs and resource use of community-dwelling patients with Alzheimer's disease in Japan: 18-month results from the GERAS-J study.

OBJECTIVE: To determine the longitudinal societal costs and burden of community-dwelling patients with Alzheimer's disease (AD) and their caregivers in Japan. METHODS: GERAS-J was an 18-month, prospective, longitudinal, observational study. Using the Mini-Mental State Examination (MMSE), patients routinely visiting memory clinics were stratified into groups based on AD severity at baseline (mild, moderate, and moderately severe/severe [MS/S]). Healthcare resource utilization and caregiver burden were assessed using the Resource Utilization in Dementia and Zarit "Caregiver" Burden Interview questionnaires, respectively. Total monthly societal costs were estimated using Japan-specific unit costs of services and products (patient direct healthcare use, patient social care use, and informal caregiving time). RESULTS: Overall, 553 patients (156 mild; 209 moderate; 188 MS/S) were enrolled. MMSE scores declined (1.73, 1.38, and 0.95 points for the mild, moderate, and MS/S AD groups, respectively) and caregiver burden and resource utilization increased over 18 months in each of the AD severity groups. Cumulative total societal costs per patient over 18 months were 3.1, 3.8, and 5.3 million Japanese yen (29,006, 35,662, and 49,725 USD) for mild, moderate, and MS/S AD, respectively. Both patient social care costs and caregiver informal care costs increased with baseline disease severity, with >50% of total costs due to caregiver informal care in each disease severity subgroup. CONCLUSIONS: Total treatment costs increased with AD severity over 18 months due to increases in both patient social care costs and caregiver informal care costs. Our data suggest current social care services in Japan are insufficient to alleviate the negative impact of AD on caregiver burden.

Unmet Needs in Japanese Patients Who Report Insufficient Efficacy with Triptans for Acute Treatment of Migraine: Retrospective Analysis of Real-World Data.

INTRODUCTION: Migraine attacks notably impact people's daily lives, health-related quality of life (HRQoL), and ability to work. Triptans are widely used as acute medication for a migraine attack but are ineffective, poorly tolerated, or contraindicated in some patients. HRQoL and work productivity are therefore likely to pose particular problems for patients whose migraine attacks do not respond sufficiently to triptan acute treatment. This real-world study aimed to determine whether migraine-related HRQoL, disability, and work productivity differed between triptan insufficient responders (TIRs) and sufficient responders (TSRs) receiving this acute treatment for migraine in Japan. METHODS: This was a retrospective analysis of 2017 Adelphi Migraine Disease Specific Programme cross-sectional survey data collected from physicians and their consulting patients with migraine in Japan. Patients had to be receiving a triptan as their sole acute prescribed medication for migraine. TIRs were defined as patients who achieved headache pain freedom within 2 h of taking triptan acute treatment in no more than three of five migraine attacks. Differences in outcomes between TIRs and TSRs were examined in adjusted analyses using a multivariable general linear model. RESULTS: Of 200 patients receiving a triptan as their sole prescribed acute treatment for migraine, 88 (44.0%) were classed as TIRs. Migraine-Specific Quality of Life Questionnaire scores were significantly lower-indicating poorer HRQoL-among TIRs than TSRs, as were mean EuroQol 5-dimension utility and visual analog scale scores (p < 0.05 for comparisons). TIRs also reported significantly (p ≤ 0.003) greater impairment than TSRs across all Work Productivity and Activity Impairment domains, with the exception of work time missed. Migraine disability was higher among TIRs than TSRs. CONCLUSION: Migraine attacks had a negative impact on the HRQoL, disability, and work productivity of people with migraine in Japan reporting insufficient efficacy with acute triptan treatment, highlighting the need for more effective acute treatment options.

The potential role of appetite in predicting weight changes during treatment with olanzapine.

BACKGROUND: Clinically significant weight gain has been reported during treatment with atypical antipsychotics. It has been suggested that weight changes in patients treated with olanzapine may be associated with increased appetite. METHODS: Data were used from adult patients for whom both appetite and weight data were available from 4 prospective, 12- to 24-week clinical trials. Patients' appetites were assessed with Eating Behavior Assessment (EBA, Study 1), Platypus Appetite Rating Scale (PARS, Study 2), Eating Inventory (EI, Study 3), Food Craving Inventory (FCI, Study 3), and Eating Attitude Scale (EAS, Study 4). RESULTS: In Studies 1 (EBA) and 4 (EAS), patients who reported overall score increases on appetite scales, indicating an increase in appetite, experienced the greatest overall weight gains. However, in Studies 2 (PARS) and 3 (EI, FCI), patients who reported overall score increases on appetite scales did not experience greater weight changes than patients not reporting score increases. Early weight changes (2-4 weeks) were more positively correlated with overall weight changes than early or overall score changes on any utilized appetite assessment scale. No additional information was gained by adding early appetite change to early weight change in correlation to overall weight change. CONCLUSIONS: Early weight changes may be a more useful predictor for long-term weight changes than early score changes on appetite assessment scales. CLINICAL TRIALS REGISTRATION: This report represents secondary analyses of 4 clinical studies. Studies 1, 2, and 3 were registered at http://clinicaltrials.gov/ct2/home, under NCT00190749, NCT00303602, and NCT00401973, respectively. Study 4 predates the registration requirements for observational studies that are not classified as category 1 observational studies.

Cross-sectional survey in patients with type 1 and type 2 diabetes to understand mealtime insulin unmet needs in Japan: The MINUTES-J study.

AIMS: This study was conducted to evaluate existing burden and unmet needs related to mealtime insulin (MTI) injection timing among adult Japanese patients with type 1 (T1D) and type 2 (T2D) diabetes. It also aimed to evaluate if a novel MTI could reduce this burden. METHODS: This study comprised of a qualitative pilot study facilitating development of an online survey; followed by an online quantitative survey involving T1D, young T2D (yT2D) and elderly T2D (eT2D) patients to assess burden of current MTI timings in Japan. RESULTS: Overall, 38% patients (amongst T1D, yT2D and eT2D groups) reported injecting MTI just before start or during meal in the past month. Experiencing lower glucose level/hypoglycemic condition before the meal and forgetting were the main reasons for injecting during/after meal in T1D and T2D patients respectively. Patients reported moderate-to-severe burden in multiple aspects of their lives, associated with current MTI timing. Most patients perceived that this burden would remain the same if a faster acting MTI was available. CONCLUSIONS: Substantial burden reported by Japanese patients regarding the current MTI timings suggests the need for new MTI products that could achieve optimal post-prandial glucose control at different timings to meet patients' needs in Japan.

Costs and Resource Use Associated with Community-Dwelling Patients with Alzheimer's Disease in Japan: Baseline Results from the Prospective Observational GERAS-J Study.

BACKGROUND: As the Japanese population ages, caring for people with Alzheimer's disease (AD) dementia is becoming a major socioeconomic issue. OBJECTIVE: To determine the contribution of patient and caregiver costs to total societal costs associated with AD dementia. METHODS: Baseline data was used from the longitudinal, observational GERAS-J study. Using the Mini-Mental State Examination (MMSE) score, patients routinely visiting memory clinics were stratified into three groups based on AD severity. Health care resource utilizationwas recorded using the Resource Utilization in Dementia questionnaire. Total monthly societal costs were estimated using Japan-specific unit costs of services and products (patient direct health care use, patient social care use, and informal caregiving time). Uncertainty around mean costs was estimated using bootstrapping methods. RESULTS: Overall, 553 community-dwelling patients withADdementia (28.3% mild[MMSE21-26], 37.8% moderate[MMSE 15-20], and 34.0% moderately severe/severe [MMSE < 14]) and their caregivers were enrolled. Patient characteristics were: mean age 80.3 years, 72.7% female, and 13.6% living alone. Caregiver characteristics were: mean age 62.1 years, 70.7% female, 78.8% living with patient, 49.0% child of patient, and 39.2% sole caregiver. Total monthly societal costs of AD dementia (Japanese yen) were: 158,454 (mild), 211,301 (moderate), and 294,224 (moderately severe/severe). Informal caregiving costs comprised over 50% of total costs. CONCLUSION: Baseline results of GERAS-J showed that total monthly societal costs associated with AD dementia increased with AD severity. Caregiver-related costs were the largest cost component. Interventions are needed to decrease informal costs and decrease caregiver burden.

Intramuscular olanzapine versus short-acting typical intramuscular antipsychotics: comparison of real-life effectiveness in the treatment of agitation.

OBJECTIVE: To compare the effectiveness of intramuscular (IM) olanzapine and typical IM antipsychotics in naturalistically treated acutely agitated patients with schizophrenia or acute mania. METHODS: During the acute phase, 2011 inpatients (including emergency settings) were assessed at 2, 24 and 72 h, and 7 days following initial injection and on oral antipsychotic transition. Mean change in agitation was assessed via Positive and Negative Symptom Scale-Excited Component (PANSS-EC) and Clinical Global Impressions-Severity (CGI-S) scores. Response (> or = 40% reduction in baseline PANSS-EC score) was analysed using logistic regression. RESULTS: Significantly greater decreases in PANSS-EC and CGI-S scores were observed in patients receiving IM olanzapine (n = 1294) as their first injection compared with patients receiving other IM antipsychotics (n = 717) (P<0.05; 2 h: effect size 0.1); IM haloperidol treatment (all assessments, P<0.05); and IM zuclopenthixol treatment (2 h, P<0.001). Higher response rates were observed with IM olanzapine compared with other IM antipsychotics at 24 and 72 h, and 7 days (P<0.05). IM olanzapine was associated with fewer extrapyramidal side effects compared with other assessed IM antipsychotics. CONCLUSIONS: IM olanzapine provided somewhat more effective control of acute agitation than other assessed IM antipsychotics.

Patterns and trends in insulin initiation and intensification among patients with Type 2 diabetes mellitus in the Middle East and North Africa region.

AIM: Current and future estimates of the burden of diabetes in the Middle East and North Africa (MENA) region are among the highest in the world. VISION, an 18-month observational study, explored patterns of insulin initiation and intensification in T2DM patients in the MENA region. METHODS: 1192 patients aged ≥18 years were enrolled from Algeria, Egypt, Saudi Arabia and the UAE. Treating physicians recorded participants' data. Patient-reported outcomes (PROs) were assessed using questionnaires completed by participants. RESULTS: 67.6% patients had HbA1c ≥9% at insulin initiation, with a mean HbA1c of 9.9%, despite 68.3% patients being on ≥2 oral anti-diabetics, indicating a significant delay in insulin initiation. Basal insulin was initiated in 50.6% and premixed insulin in 46.3% patients. After 18 months, changes in insulin therapy were observed in 33.7% patients, while 39.6% patients achieved HbA1c levels of <7.5%. The proportion of patients completely satisfied with their insulin treatment, and the QoL increased over the study course. CONCLUSION: Results support that timely initiation and early intensification of insulin therapy are necessary in the region to achieve adequate and timely glycemic control and to prevent diabetic complications.