Predicting time to relapse in patients with schizophrenia according to patients' relapse history: a historical cohort study using real-world data in Sweden.

BACKGROUND: For patients with schizophrenia, relapse is a recurring feature of disease progression, often resulting in substantial negative impacts for the individual. Although a patient's relapse history (specifically the number of prior relapses) has been identified as a strong risk factor for future relapse, this relationship has not yet been meticulously quantified. The objective of this study was to use real-world data from Sweden to quantify the relationship of time to relapse in schizophrenia with a patient's history of prior relapses. METHODS: Data from the Swedish National Patient Register and Swedish Prescribed Drug Register were used to study relapse in patients with schizophrenia with a first diagnosis recorded from 2006-2015, using proxy definitions of relapse. The primary proxy defined relapse as a psychiatric hospitalisation of ≥7 days' duration. Hazard ratios (HRs) were calculated for risk of each subsequent relapse, and Aalen-Johansen estimators were used to estimate time to next relapse. RESULTS: 2,994 patients were included, and 5,820 relapse episodes were identified using the primary proxy. As the number of previous relapses increased, there was a general trend of decreasing estimated time between relapses. Within 1.52 years of follow-up, 50% of patients with no history of relapse were estimated to have suffered their first relapse episode. 50% of patients with one prior relapse were estimated to have a second relapse within 1.23 years (HR: 1.84 [1.71-1.99]) and time to next relapse further decreased to 0.89 years (HR: 2.77 [2.53-3.03]) and 0.22 years (HR: 18.65 [15.42-22.56]) for 50% of patients with two or ten prior relapses, respectively. Supplementary analyses using different inclusion/exclusion criteria for the study population and redefined proxies of relapse reflected the pattern observed with the primary analyses of a higher number of prior relapses linked with increased risk of/reduced estimated time to the next relapse. CONCLUSIONS: The results suggested a trend of accelerating disease progression in schizophrenia, each relapse episode predisposing an individual to the next within a shorter time period. These results emphasise the importance of providing early, effective, and tolerable treatments that better meet a patient's individual needs.

A Noninterventional Cohort Study Assessing Time to All-Cause Treatment Discontinuation After Initiation of Aripiprazole Once Monthly or Daily Oral Atypical Antipsychotic Treatment in Patients With Recent-Onset Schizophrenia.

Introduction: Aripiprazole once-monthly 400 mg (extended-release injectable suspension) is effective in long-term maintenance treatment of schizophrenia based on clinical studies. As study results may not reflect clinical practice, we compared treatment persistence with aripiprazole once-monthly 400 mg versus daily oral atypical antipsychotics in a naturalistic setting.Methods: This was an observational, noninterventional study of patients (aged 18-35 years) with recent-onset schizophrenia (< 5 years post diagnosis) who initiated maintenance treatment with aripiprazole once-monthly 400 mg or any daily oral atypical antipsychotic during a schizophrenia-related hospitalization or within 3 months post hospital discharge (timeframe: July 13, 2017-July 31, 2019). Data were from patient files/obtained during routine visits. Patients were followed for ≤ 12 months or until all-cause treatment discontinuation (including lost to follow-up), whichever came first. Data were analyzed using a sample constructed with inverse probability of treatment weighting (IPTW).Results: Among 357 patients (aripiprazole once-monthly 400 mg: 215, oral atypical antipsychotics: 142), all-cause treatment discontinuation occurred in 87 (41%) of aripiprazole once-monthly 400 mg, 68 (48%) of oral atypical antipsychotic patients over 52 weeks. In the IPTW sample, time to all-cause discontinuation was significantly different between both groups in favor of aripiprazole once-monthly 400 mg (hazard ratio = 1.46; 95% CI, 1.05-2.03; P = .023). Generalizability of results to the overall population with schizophrenia was limited due to incomplete overlap of patient characteristics between cohorts. The primary reason for treatment discontinuation in both groups was voluntary discontinuation by subject (aripiprazole once-monthly 400 mg: 11%; oral atypical antipsychotics: 8%).Conclusions: In a naturalistic setting, younger patients with recent-onset schizophrenia treated with aripiprazole once-monthly 400 mg after hospitalization tended to discontinue treatment later than patients treated with daily oral atypical antipsychotics.Trial Registration: ClinicalTrials.gov identifier: NCT03130465.

Real-World, Non-Interventional, Retrospective Study (SAMPLE) of Tolvaptan in Patients with Hyponatraemia Secondary to the Syndrome of Inappropriate Antidiuretic Hormone Secretion.

INTRODUCTION: The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most common cause of hyponatraemia in hospital inpatients. We present data on treatment setting, patient characteristics, and outcomes for patients treated with tolvaptan for SIADH across a range of real-world settings in Germany and Spain. METHODS: This was a non-interventional, observational, retrospective chart review study. Management was at the discretion of the treating physician, with tolvaptan prescribed according to local clinical practice. Hospital notes and/or medical charts were reviewed from treatment initiation for 6 weeks. Follow-up data were collected when patients were discharged early. Patients were eligible for inclusion if they were ≥ 18 years of age and had been treated with ≥ 2 doses of tolvaptan for one episode of hyponatraemia secondary to SIADH in 2014. RESULTS: The Full Analysis Set comprised 100 patients from 8 centres. The mean age of patients was 73.9 years. The primary endpoint of the mean increase in serum sodium level from baseline to hospital discharge, or to final available measurement, was 10.3 mmol/L (SD 6.4; 95% CI 9.0, 11.6), from 123.0 mmol/L (SD 6.0) to 133.3 mmol/L (SD 4.9). Seventy-seven patients (77.0%) achieved sodium normalisation within 6 weeks of tolvaptan initiation. Mean daily dose of tolvaptan was 12.7 mg (SD 9.2), and mean treatment duration 28.0 days (SD 16.5). Tolvaptan at off-label doses (< 15 mg/day) was prescribed to 72 patients at some point. A favourable safety and tolerability profile was reported. CONCLUSIONS: Tolvaptan was well tolerated and effectively corrected sodium levels in hospitalised adults with hyponatraemia secondary to SIADH in real-world settings. CLINICALTRIALS. GOV IDENTIFIER: NCT02545101.