Real-world treatment patterns and outcomes of abemaciclib for the treatment of HR + , HER2- metastatic breast cancer patients in Japan.

INTRODUCTION: This study described, in routine clinical practice in Japan, the patient characteristics, treatment patterns, and outcomes of female patients with HR + /HER2- metastatic breast cancer (MBC) who started abemaciclib treatment. METHODS: Clinical charts were reviewed for patients starting abemaciclib in 12/2018-08/2021 with a minimum of 3 months follow-up data post-abemaciclib initiation regardless of abemaciclib discontinuation. Patient characteristics, treatment patterns, and tumor response were descriptively summarized. Kaplan-Meier curves estimated progression-free survival (PFS). RESULTS: 200 patients from 14 institutions were included. At abemaciclib initiation, median age was 59 years, and the Eastern Cooperative Oncology Group performance status score was 0/1/2 for 102/68/5 patients (58.3/38.9/2.9%), respectively. Most had an abemaciclib starting dose of 150 mg (92.5%). The percentage of patients receiving abemaciclib as 1st, 2nd, or 3rd line treatment was 31.5%, 25.8%, and 25.2%, respectively. The most frequent endocrine therapy drugs used with abemaciclib were fulvestrant (59%) and aromatase inhibitors (40%). Evaluation of tumor response was available for 171 patients, 30.4% of whom had complete/partial response. Median PFS was 13.0 months (95% CI 10.1-15.8 months). CONCLUSIONS: In a routine clinical practice setting in Japan, patients with HR + , HER2- MBC appear to benefit from abemaciclib treatment in terms of treatment response and median PFS, with the results broadly reflecting the evidence demonstrated in clinical trials.

Análisis retrospectivo de pacientes con cáncer gástrico localmente avanzado o metastásico en Argentina / Retrospective analysis of patients with locally advanced or metastatic gastric cancer in Argentina

OBJETIVO Describir las características clínicas, los patrones de tratamiento y los costos asociados en pacientes con cáncer gástrico localmente avanzado o metastásico en Argentina, en los sectores público y privado. MÉTODOS Una cohorte histórica de pacientes que recibieron tratamiento de quimioterapia de primera línea (análogo de platino y/o una fluoropirimidina) y fueron seguidos durante al menos tres meses después de la última administración de un agente citotóxico de primera línea fueron elegibles. Se extrajeron los datos a través de un cuestionario estructurado a partir de los registros médicos de cuatro hospitales argentinos. Las estimaciones de los costos de tratamiento también se calcularon utilizando los costos unitarios de los hospitales participantes. RESULTADOS Entre los 101 pacientes, más de tres cuartas partes (79,2%) eran hombres, 41,6% fueron diagnosticados con enfermedad metastásica en estadio IV, la edad media fue de 57,7 años y el 27,7% tenían antecedentes de tabaquismo. Antes del diagnóstico de cáncer gástrico metastásico, el 42,4% de los pacientes habían recibido gastrectomía total. El 97% de los pacientes recibió una terapia doble o triplete, de los cuales el tratamiento más frecuente fue la epirubicina en combinación con oxaliplatino y capecitabina (38%), seguida de capecitabina + oxaliplatino (29%). Alrededor del 36% de los pacientes respondieron al tratamiento de primera línea (respuesta completa y parcial). Del 76,2% de los pacientes que siguieron un tratamiento de segunda línea, al 37,7% todavía se les administró un análogo de platino y/o fluoropirimidina. Durante el período de seguimiento, el 50% de los pacientes progresó y el 32,8% tenía enfermedad estable. La terapia de apoyo consistió principalmente en visitas ambulatorias después de la última línea de quimioterapia (16,8%), radioterapia paliativa (16,8%) y cirugía (30,7%). Se observaron diferencias significativas entre los costos de los hospitales públicos y privado. CONCLUSIONES Comprender los patrones de tratamiento en pacientes con cáncer gástrico localmente avanzado o metastásico puede ayudar a abordar las necesidades médicas no satisfechas para un mejor manejo del paciente y la mejora de sus resultados clínicos en Argentina.

AIM To assess patient and disease characteristics, treatment patterns and associated costs in patients with locally advanced or metastatic gastric cancer in Argentina, in the public and private sectors. METHODS A historic cohort of patients who had received first-line chemotherapy treatment (platinum analog and/or a fluoropyrimidine) and were followed-up for at least three months after the last administration of a first-line cytotoxic agent were eligible. Case-report forms were prepared based on medical records from four Argentinian hospitals. Estimates of treatment costs were also calculated using the unit costs of the participating hospitals. RESULTS Of 101 patients, more than three quarters (79.2%) were male, 41.6% were diagnosed with metastatic stage IV disease (mean age, 57.7years), and 27.7 % had a smoking history. Before locally advanced or metastatic gastric cancer diagnosis, 42.4% of the patients had received total gastrectomy. Ninety-seven percent of the patients received a doublet or triplet therapy, of which epirubicin in combination with oxaliplatin and capecitabine was the most common treatment (38%), followed by capecitabine plus oxaliplatin (29%). Around 36% of the patients responded to first-line treatment (complete and partial response). Out of the 76.2% of the patients who followed a second-line treatment, 37.7% were still administered a platinum analog and/or fluoropyrimidine. During the reported follow-up period, 50% of the patients progressed, and 32.8% had stable disease. The best supportive care consisted mostly of outpatient visits after last-line therapy (16.8%), palliative radiotherapy (16.8%), and surgery (30.7%). We observed significant differences between public and private hospital costs. CONCLUSIONS Understanding treatment patterns in patients with locally advanced or metastatic gastric cancer may help address unmet medical needs for better patient management and improvement of their clinical outcome in Argentina.

Real-world comparison of health care utilization between duloxetine and pregabalin initiators with fibromyalgia.

OBJECTIVES: To compare health care utilization of duloxetine initiators and pregabalin initiators among fibromyalgia patients in a real-world setting. METHODS: A retrospective cohort study was conducted based on a US national commercial health claims database (2006-2009). Fibromyalgia patients who initiated duloxetine or pregabalin in 2008, aged 18-64 years, and who maintained continuous health insurance coverage 1 year before and 1 year after initiation were assigned to duloxetine or pregabalin cohorts on the basis of their initiated agent. Patients who had pill coverage of the agents over the course of 90 days preceding the initiation were excluded. The two comparative cohorts were constructed using propensity score greedy match methods. Descriptive analysis and paired t-test were performed to compare health care utilization rates in the postinitiation year and the changes of these rates from the preinitiation year to the postinitiation year. RESULTS: Both matched cohorts (n=1,265 pairs) had a similar mean initiation age (49-50 years), percentage of women (87%-88%), and prevalence of baseline comorbid conditions (neuropathic pain other than diabetic peripheral neuropathic pain, low back pain, cardiovascular disease, hypertension, headache or migraine, and osteoarthritis). In the preinitiation year, both cohorts had similar inpatient, outpatient, and medication utilization rates (inpatient, 15.7%-16.1%; outpatient, 100.0%; medication, 97.9%-98.7%). The utilization rates diverged in the postinitiation year, with the pregabalin cohort using more fibromyalgia-related inpatient care (3.2% versus 2.2%; P<0.05), any inpatient care (19.3% versus 16.8%; P<0.05), and fibromyalgia-related outpatient care (62.1% versus 51.8%; P<0.05). From the preinitiation period to the postinitiation period, the duloxetine cohort experienced decreases in certain utilization rates, whereas the pregabalin cohort had increases (percentage of patients with a fibromyalgia-related admission, -1.2% versus 0.4% [P<0.01]; number of fibromyalgia-related outpatient claims, -1.7 versus 4.7 [P<0.01]). CONCLUSION: Fibromyalgia patients initiating pregabalin tended to consume more fibromyalgia-related inpatient and outpatient care in the first postinitiation year, whereas fibromyalgia patients initiating duloxetine tended to have lower utilization rates of fibromyalgia-related inpatient care in the postinitiation year than in the preinitiation year.

2-Year course of bipolar disorder type I patients in outpatient care: factors associated with remission and functional recovery.

EMBLEM is a 2-year, prospective, observational study that enrolled patients initiating/changing oral treatment for an acute manic/mixed episode. This paper analysed remission and functional recovery in 1656 patients who entered the 2-year long-term phase. Cox models identified variables significantly associated with achieving remission and functional recovery at 2years. Of these patients, 64% achieved remission and 34% achieved functional recovery. Patients with a higher CGI-BP overall score at baseline, who had depressive episodes in the year before inclusion and who had poor social functioning (work or social impairment, not living independently or without a spouse/partner) were less likely to achieve remission or recovery. Prescription of typical antipsychotics and prescription of antidepressants at the first visit of the long-term treatment phase (12weeks) were independent predictors of lower remission and recovery rates. In conclusion, functional recovery occurred in approximately half of those who achieved remission. Impairment of work and social functioning was consistently associated with lower remission and recovery rates.

Assessing the infrequent oral supplementation of olanzapine long-acting injection in the treatment of schizophrenia.

OBJECTIVE: Adding another antipsychotic to a treatment regimen was previously used in evaluating the medication's efficacy. Supplementation of depot antipsychotics with oral antipsychotics is particularly meaningful because depot formulations are typically chosen for patients struggling with adherence to oral antipsychotics. This post-hoc analysis assessed supplementation of olanzapine long-acting injection (olanzapine-LAI) with oral olanzapine. SUBJECTS AND METHODS: We used 12 months of data from an open-label, single-arm extension study of patients with schizophrenia or schizoaffective disorder (N=931) treated with olanzapine-LAI. The prevalence, duration, time to first supplementation, and best predictors of oral supplementation were assessed. RESULTS: Oral supplementation occurred in 21% of patients for a median of 31 days with mean modal dose of 10.8 mg/day. Mean time to first supplementation was shorter for patients who were at least moderately ill at baseline compared to less ill patients (47 vs. 97 days, p<0.001). Best predictors of oral supplementation included a more severe illness profile at baseline, lower olanzapine-LAI dose prior to oral supplementation, supervised living arrangements, and being African-American. CONCLUSION: Supplementation of olanzapine-LAI appears to be infrequent, of relatively short duration, and reserved for more severely ill patients who may require a targeted rescue medication due to signs of impending relapse.

Assessment of medication adherence in a cohort of patients with bipolar disorder.

INTRODUCTION: This study aimed to identify factors associated with medication adherence in bipolar disorder (BPD) patients. METHODS: EMBLEM is a 2-year, prospective, observational study on the outcomes of BPD patients initiating or changing treatment for a manic/mixed episode. Data were collected at baseline, during the first 12 weeks of treatment (acute phase) and up to 24 months of follow-up (maintenance phase). Adherence was assessed by investigators at every visit. Repeated measures logistic regression analyses identified variables associated with adherence. RESULTS: Of 1,831 patients included in the analysis, 76.6% were adherent and 23.4% were non-adherent with their BPD medication during the maintenance phase. Patients were more likely to be adherent if they had insight into their illness at week 12. Patients were less likely to be adherent if they had cannabis abuse/dependence during the acute phase, work impairment or higher CGI hallucinations/delusions at baseline DISCUSSION: Psychotic symptoms, poor insight, cannabis abuse/dependence and work impairment are negatively related to medication adherence during maintenance therapy of bipolar disorder. Patients with these characteristics may need a different therapeutic approach.

The number needed to treat for all-cause medication discontinuation in the treatment of schizophrenia: consistency across world geographies and study designs.

INTRODUCTION: The number needed to treat (NNT) for all-cause medication discontinuation in large, industry-sponsored, non-randomized, observational studies conducted across world geographies was compared with NNTs from CATIE, an 18-month, NIMH-sponsored, randomized study. METHODS: NNTs (with 95% confidence intervals) were calculated using data from 3 large Lilly-sponsored, non-randomized, observational studies (EU-SOHO, IC-SOHO, and US-SCAP, n=20 957). Group differences at medication initiation were adjusted by Cox regression modeling. These NNTs were compared with published NNTs for CATIE (phase 1). RESULTS: NNTs for olanzapine vs. risperidone and for olanzapine vs. quetiapine were similar across the observational studies and similar to those of CATIE. The NNTs for olanzapine vs. oral typical antipsychotics were similar across the observational studies but demonstrated a somewhat stronger effect size than the NNT reported for olanzapine vs. perphenazine in CATIE. DISCUSSION: NNTs for all-cause treatment discontinuation (a proxy measure of a medication's effectiveness from patients' and clinicians' perspectives) appear to be consistent across study designs (non-interventional, observational vs. RCT), study sponsorship (industry vs. independent), and across world geographies, suggesting that antipsychotics differ in this measure.

Worldwide-Schizophrenia Outpatient Health Outcomes (W-SOHO): baseline characteristics of pan-regional observational data from more than 17,000 patients.

OBJECTIVE: To describe the Worldwide-Schizophrenia Outpatient Health Outcomes (W-SOHO) patient population at study entry, focusing on illness burden and prescribing practices across regions. METHODS: The SOHO study was a 3-year, prospective, observational study designed to assess costs and outcomes associated with antipsychotic use in outpatients initiating or changing antipsychotic (with an emphasis on olanzapine compared with other antipsychotics). SOHO was conducted in 10 European countries and 27 other countries as Intercontinental SOHO (IC-SOHO). Data from all countries have been pooled to produce the W-SOHO dataset. MAIN OUTCOMES MEASURES: Clinical Global Impression-Schizophrenia (CGI-SCH) severity scores, psychotropic medication use, adverse events, social interaction, housing and employment status, self-perceived health state (EuroQoL EQ-5D scale and Visual Analogue Scale, EQ-VAS), and reasons for initiation/change of antipsychotic. RESULTS: The W-SOHO database comprises 17,384 patients from six regions; East Asia (n = 1223), Central and Eastern Europe (n = 2175), Northern Europe (n = 4291), Southern Europe (n = 5788), Latin America (n = 2566), North Africa and the Middle East (n = 1341). Overall, patients were 38 +/- 13 years old (mean +/- SD), moderately ill (mean CGI-SCH overall score of 4.4 +/- 1.0) with a median duration of illness of 7 years (interquartile range 1-16 years); 43% were female, 10% were receiving antipsychotic medication for the first time. Adverse events were prevalent across all regions; on average, 50% (range 41-59%) of patients taking antipsychotics exhibited extrapyramidal symptoms at baseline, and 62% (34-67%) of patients reported sexual dysfunction in the previous month. On average, only 19% (16-23%) of patients were in paid employment and as many as 69% were living in dependent housing. CONCLUSIONS: Despite inherent diversity in these patients and the health care systems supporting them, there are striking cross-regional similarities in baseline characteristics for most measures. Not all countries are represented; regional comparisons may not be valid outside of the countries studied.

Reasons and outcomes of olanzapine dose adjustments in the outpatient treatment of schizophrenia.

INTRODUCTION: Antipsychotic treatment dose adjustments may influence treatment outcomes in patients with schizophrenia. METHODS: We analysed data from 4,247 outpatients with schizophrenia who started olanzapine monotherapy in the 3-year, prospective, observational SOHO study to determine factors associated with olanzapine dose adjustments and how these impact on treatment effectiveness and tolerability. RESULTS: Regression analyses showed an association between changes in the Clinical Global Impression (CGI) and olanzapine dose changes: patients with a lack of effectiveness were more likely to have their dose increased, whereas patients with good treatment response were more likely to have a dose decrease. Improvement in tardive dyskinesia was associated with dose increase or no change (p=0.034) and worsening of sexual problems was associated with dose decrease (p=0.001). Conversely, an increase in olanzapine dose was associated with subsequent clinical improvement (CGI), but dose adjustment had no significant effects on tolerability outcomes. DISCUSSION: These results indicate that psychiatrists tend to modify olanzapine dose according to treatment response. Dose increases seem to be associated with a better response to treatment and not with a worsening of side-effects.

Translation of randomised controlled trial findings into clinical practice: comparison of olanzapine and valproate in the EMBLEM study.

OBJECTIVES: The aim of this study was to compare the outcomes of olanzapine- and valproate-treated patients in an observational study of acute mania with the results of a randomised controlled trial (RCT) assessing the same treatments. METHODS: EMBLEM (European Mania in Bipolar Evaluation of Medication) was a 2-year, prospective, observational study of health outcomes associated with the treatment of mania. Severity of mania and depression were assessed at baseline and 6 weeks using the YMRS and the 5-item version of the HAMD, respectively. RESULTS: 621 patients were analysed (n=107 valproate, n=514 olanzapine). Both groups improved from baseline to 6 weeks in mean YMRS and HAMD-5 total scores, with greater mean improvements in the olanzapine compared with the valproate group. Olanzapine was associated with more weight gain and less gastrointestinal difficulties than valproate. DISCUSSION: The EMBLEM results support those of the RCT, which suggest that olanzapine monotherapy seems to be more effective than valproate monotherapy in the treatment of acute mania.

Interleukin-18 binding protein in the sera of patients with Wegener's granulomatosis.

INTRODUCTION: In the present study, we examined the levels of the pro-inflammatory cytokine IL-18 and its natural inhibitor, the IL-18 binding protein (IL-18BP), in sera of Wegener's granulomatosis (WG) patients at various stages of the disease. PATIENTS AND METHODS: Sera from eight consecutive biopsy-proven systemic WG patients (four men and four women; age at diagnosis 58.4 +/- 13.8 years) were obtained longitudinally with a follow-up period of 55.2 +/- 30 months. Sera obtained from 50 healthy subjects were used as controls. RESULTS AND DISCUSSION: Serum levels of IL-18, IL-18BP, and free IL-18 obtained during an active phase of the disease (Birmingham Vasculitis Activity Score, BVAS > 10) were more than twofold higher than levels in the same patients during inactive disease stages (BVAS < 5; P < 0.002; P < 0.006, and P < 0.03 for IL-18, IL-18BP, and free IL-18, respectively). During inactive stages, the levels of these markers were comparable to those of healthy controls. The elevated levels of IL-18 and IL-18BP in sera during active stages of disease suggest a possible role in the pathogenesis and course of the WG. CONCLUSION: Despite the elevated IL-18BP levels during active disease, free IL-18 remained higher than in the inactive disease stages, suggesting a potential benefit of administration of exogenous IL-18BP as a novel therapeutic approach for active WG.

Rates and predictors of remission and recovery during 3 years in 392 never-treated patients with schizophrenia.

OBJECTIVE: Few studies have prospectively examined remission and recovery as well as their predictors in schizophrenia simultaneously. Aims of the study were to identify remission and recovery rates as well as their predictors in schizophrenia. METHOD: 392 never-treated patients with schizophrenia were assessed over 3 years. Combined remission and recovery required concurrent achievement of symptomatic and functional remission as well as adequate quality of life for at least 6 and 24 months respectively. Predictors were analysed using stepwise logistic regression models. RESULTS: At 3 years, remission rates for symptoms, functioning and subjective wellbeing were 60.3%, 45.4% and 57.0%; recovery rates were 51.7%, 35.0% and 44.3%. Of those, 28.1% were in combined remission and 17.1% in combined recovery. Predictors mainly included the baseline functional status and early remission within the first 3 months. CONCLUSION: The proportion of patients who met combined remission or recovery criteria is low. Early treatment adaptations in case of early non-remission are mandatory.

Remisión y recaída en el tratamiento ambulatorio de los pacientes con esquizofrenia. Resultados a 3 años / Remission and relapse in the outpatient treatment of patients with schizophrenia. Outcomes at 3 years

Introducción. Los datos del seguimiento de 3 años realizado para el estudio SOHO en España se han empleado para evaluar los resultados del tratamiento antipsicótico en términos de incidencia y factores asociados a la remisión y la recaída. Métodos. El SOHO es un estudio observacional, prospectivo, longitudinal realizado en 10 países europeos sobre los resultados del tratamiento de la esquizofrenia en pacientes ambulatorios que inician o modifican su farmacoterapia antipsicótica con el objetivo particular de comparar olanzapina con los demás antipsicóticos. El presente artículo presenta la incidencia y los factores asociados a la remisión y recaída clínicas de la esquizofrenia (definidas según los criterios internacionales al uso) en la muestra española. Resultados. En España se reclutaron 2.020 pacientes. Casi dos tercios (60,1%) cumplieron los criterios de remisión clínica. Se identificaron varios factores relacionados con la probabilidad de remisión, tales como el sexo, el estado clínico y/o funcional basal, el tiempo de evolución desde el primer tratamiento para esquizofrenia, el tratamiento con olanzapina frente a antipsicóticos típicos orales y la prescripción concomitante de fármacos ansiolíticos. El 18,7% de los pacientes presentó alguna recaída. El tratamiento con quetiapina y el uso concomitante de anticolinérgicos se asociaron con un mayor riesgo de recaída. Conclusiones. Los resultados de este estudio señalan algunos factores asociados a la evaluación de la esquizofrenia y subrayan la importancia de una correcta elección del fármaco antipsicótico y su mantenimiento para lograr un resultado clínico favorable a largo plazo en la práctica clínica habitual (AU)

Introduction. Three year data collected in the frame of the SOHO study within Spain were used to evaluate antipsychotic treatment outcomes by analyzing remission and relapse as well as the factors influencing them. Methods. The SOHO was a prospective, long-term, observational study of the outcomes of schizophrenia treatment in ambulatory who initiated therapy or who changed to a new antipsychotic drug performed in10 European countries, with a focus on olanzapine. This article reports the attainment of international schizophrenia clinical remission and relapse criteria and the associated correlates in these patients. Results and conclusions. A total of 2,020 patients were recruited in Spain. Almost 2/3 (60.1%) of the patients met the criteria for clinical remission. Factors that influence the likelihood of remission were identified, such as gender, baseline clinical and/or functional status, time since treatment initiation, treatment with olanzapine versus oral typical antipsychotics, duration of treatment, gender or the need for concomitant anxiolytics. Relapse occurred in 18.7 % of patients. Treatment with quetiapine or the prescription of anticholinergics was associated with a greater risk of relapse. Conclusions. These results highlight some prognostic factors of the course of schizophrenia and underscore the importance of the antipsychotic choice and its maintenance to achieve favorable long-term clinical outcomes in routine practice (AU)