Karina Hansen

Subcutaneous versus intravenous immunoglobulin in multifocal motor neuropathy: a randomized, single‐blinded cross‐over trial

Background and purpose:  For treatment of multifocal motor neuropathy (MMN), we hypothesized that (i) infusion of equivalent dosages of subcutaneous immunoglobulin (SCIG) is as effective as intravenous immunoglobulin (IVIG) and that (ii) subcutaneous infusion at home is associated with a better quality of life.

Qualify: a randomized head-to-head study of aripiprazole once-monthly and paliperidone palmitate in the treatment of schizophrenia

OBJECTIVE To directly compare aripiprazole once-monthly 400mg (AOM 400) and paliperidone palmitate once-monthly (PP) on the Heinrichs-Carpenter Quality-of-Life Scale (QLS), a validated health-related quality of life and functioning measure in schizophrenia. METHOD This 28-week, randomized, non-inferiority, open-label, rater-blinded, head-to-head study (QUALIFY) of AOM 400 and PP in adult patients (18-60 years) comprised oral conversion, initiation of AOM 400 or PP treatment, and continuation with intramuscular injections every 4weeks. The primary endpoint assessed non-inferiority and superiority on QLS total score analyzed using a mixed model for repeated measurements. RESULTS Of 295 randomized patients, 100/148 (67.6%) of AOM 400 and 83/147 (56.5%) of PP patients completed 28weeks of treatment. A statistically significant least squares mean difference in change from baseline to week 28 on QLS total score (4.67 [95%CI: 0.32;9.02], p=0.036) confirmed non-inferiority and established superiority of AOM 400 vs PP. There were also significant improvements in Clinical Global Impression - Severity scale and the Investigators Assessment Questionnaire for AOM 400 vs PP, and pre-defined sub-group analyses revealed a consistent pattern of significance favoring AOM 400 in patients ≤35years. Common treatment-emergent adverse events in the treatment continuation phase were more frequent with PP vs AOM 400, and adverse events were the most frequent reason for discontinuation (27/137 [19.7%] for PP and 16/144 [11.1%] for AOM 400). All-cause discontinuation was numerically lower with AOM 400. CONCLUSION Superior improvements on clinician-rated health-related quality of life and a favorable tolerability profile suggest greater overall effectiveness for aripiprazole once-monthly vs paliperidone palmitate. ClinicalTrials.gov identifier:NCT01795547.

A pharmacoeconomic evaluation of escitalopram, a new selective serotonin reuptake inhibitor

This study compared the cost-effectiveness of escitalopram to that of citalopram,fluoxetine, and venlafaxine in the treatment of depression in Norway.A two-path decision analytic model with a 6-month horizon was used.Patients start at the primary path and are referred to specialist care in the secondary care path. Model inputs included drugspecific probabilities from comparative trial data, literature, and a panel of experts.The main outcome measure is success (remission), and costs of treatment (total and drug costs).Treatment with escitalopram yielded lower expected cost and greater effectiveness than citalopram,fluoxetine, and venlafaxine. The expected success rate was 64.2% with escitalopram,58.7% with citalopram, 58.7% with fluoxetine, and 62.1% with venlafaxine.Average expected total costs per patient were similar with escitalopram (19,661 Norwegian crowns) and venlafaxine (20,989) and somewhat higher with citalopram (22,379) and fluoxetine (22,558).Budgetary impact estimates a decrease in total health care budget of 72 million crowns.Escitalopram is therefore the most cost-effective alternative and its use would significantly reduce health care costs for the treatment of depression in Norway.

Escitalopram and Duloxetine in Major Depressive Disorder: A Pharmacoeconomic Comparison Using UK Cost Data

AbstractBackground: Selective serotonin reuptake inhibitors (SSRIs) and serotoninnoradrenaline reuptake inhibitors (SNRIs) are approved for the treatment of major depressive disorder (MDD). The allosteric SSRI escitalopram has been shown to be at least as clinically effective as the SNRIs venlafaxine and duloxetine in MDD, with a better tolerability profile. In addition, escitalopram has been shown to be cost saving compared with venlafaxine.Objective: To evaluate the cost effectiveness of escitalopram versus duloxetine in the treatment of MDD, and to identify key cost drivers.Methods: The pharmacoeconomic evaluation was conducted alongside a 24-week, double-blind, multinational randomized study (escitalopram 20 mg/day and duloxetine 60 mg/day) in outpatients with MDD, aged 18–65 years, with Montgomery-Åsberg Depression Rating Scale (MADRS) score ≥26 and Clinical Global Impression Severity (CGI-S) score ≥4, and baseline duration of the current depressive episode of 12 weeks to 1 year.The analysis was conducted on the full analysis set (FAS), which included all patients with ≥1 valid post-baseline health economic assessment. Effectiveness outcomes of the cost-effectiveness analyses (CEA) included the change in Sheehan Disability Scale (SDS) score (primary CEA), treatment response (MADRS score decrease ≥50%) and remission (MADRS score ≤12) rates at week 24. Cost outcomes were assessed from the societal perspective. Healthcare resource use and sick leave were evaluated using a health economic assessment questionnaire. Unit costs of healthcare services were obtained from standard UK sources (£, year 2006 values).Results: Over the total 24-week study period, escitalopram was associated with significant cost savings compared with duloxetine (total per-patient monthly cost £188 vs £334, respectively). In the primary CEA, escitalopram dominated duloxetine (i.e. was more effective on the disability scale and less costly). Treatment with escitalopram resulted in significantly lower mean sick leave duration per patient over 24 weeks than duloxetine (30.7 days vs 62.2 days).In multivariate analyses, escitalopram as a treatment choice was associated with a 54% reduction in sick leave duration (p < 0.001). Treatment with escitalopram also resulted in 49% lower total costs than treatment with duloxetine (p = 0.002). Absenteeism accounted for about two-thirds of the overall cost. Early clinical improvement (mean change in MADRS total score, response and remission) had an independent significant impact on the sick leave duration, after controlling for key co-variates.Conclusions: Escitalopram was associated with significantly lower duration of sick leave and significant savings in the total cost compared with duloxetine; it dominated duloxetine when effectiveness was assessed on the SDS scale. Indirect costs due to sick leave accounted for the most substantial portion of the total cost and should, therefore, be an important consideration when pharmacoeconomic comparisons between treatments are made from the societal perspective. The link between decrease in absenteeism and early (8-week) clinical improvement suggested in the additional analyses may explain the reduced sick leave observed with escitalopram, given its superior short-term efficacy compared with duloxetine (demonstrated in the underlying clinical trial).

The 6-month persistence on SSRIs and associated economic burden.

Abstract Objectives: To assess persistence on SSRIs (most prescribed antidepressants) and associated healthcare costs in a naturalistic setting. Methods: For this retrospective cohort study based on a US reimbursement claims database, all adults with a claim for a SSRI (citalopram, escitalopram, fluoxetine, paroxetine or sertraline) related to a diagnosis of depression were included. Patients should have had no previous reimbursement for any antidepressant within the previous 6 months. Non-persistence was defined as failing to renew prescription within 30 days in the 6-month period after the index date. Results: In the 45,481 patients included, persistence decreased from 95.5% at 1 month, to 52.6% at 2 months, 37.6% at 3 months and 18.9% at 6 months. Among factors associated with higher 6-month persistence were age 18–34 years, physician’s specialty, treatment with escitalopram, absence of abuse history and psychotropic prescription history. During the 6-month after index date, healthcare costs tended to be higher in non-persistent than in persistent patients although not significantly (RR = 1.05, adjusted p = 0.055). Conclusion: Despite some limitations associated with the use of computerized administrative claims data (residual unmeasured confounding), these results highlight a generally low persistence rate at 6 months. Special attention should be given to persistence on treatment, with consideration of potential antidepressant impact.

The Sertindole Safety Survey: A retrospective analysis under a named patient use programme in Europe

BackgroundAfter sertindoles suspension, health authorities established a specific named-patient use (NPU) programme in order to supply sertindole to patients who did not respond to or did not tolerate alternative treatments. This programme provided the possibility of prospectively following an exhaustive cohort of patients treated with sertindole after its suspension. A survey was performed to assess sertindoles modalities of prescription, assess and document any serious adverse events (SAEs), and assess the mortality rate within the NPU cohort.MethodsThe study comprised a survey of sertindole-treated patients in eleven European countries. All patients treated with sertindole within the NPU programme were eligible for the study.Results1,432 patients were included in the study. The reason for sertindole prescription was lack of efficacy (approximately 50%) or adverse events (approximately 20%) of other antipsychotic treatments. The mean sertindole dose was 13.4 mg daily. Lack of efficacy and adverse events were reported as reasons for sertindole discontinuation.A total of 97 SAEs were recorded, including ten fatal outcomes, which occurred during the study period or within thirty days after sertindole discontinuation. The all-cause mortality rate was 0.51 per 100 Person-Years of Exposure (95% Poisson confidence interval: 0.23–0.97). QTc prolongation was reported in 15 patients (1.05% of total patients), being a rate of 0.85 per 100 Person-Years of Exposure [95% CI: 0.48–1.41].ConclusionAlthough prescribing and supplying sertindole were subject to administrative constraints, a significant number of patients were treated with sertindole, thus supporting the need for sertindole in specific cases.Trial registration numberNot applicable.

Cost-effectiveness of asenapine in the treatment of bipolar I disorder patients with mixed episodes

Abstract Objective: Around one-third of patients with bipolar I disorder (BD-I) experience mixed episodes, characterized by both mania and depression, which tend to be more difficult and costly to treat. Atypical antipsychotics are recommended for the treatment of mixed episodes, although evidence of their efficacy, tolerability, and cost in these patients is limited. This study evaluates, from a UK National Health Service perspective, the cost-effectiveness of asenapine vs olanzapine in BD-I patients with mixed episodes. Methods: Cost-effectiveness was assessed using a Markov model. Efficacy was informed by a post-hoc analysis of two short-term clinical trials, with response measured as a composite Young Mania Rating Score and Montgomery-Åsberg Depression Rating Scale end-point. Probabilities of discontinuation and relapse to manic, mixed, and depressive episodes were sourced from published meta-analyses. Direct costs (2012–2013 values) included drug acquisition, monitoring, and resource use related to bipolar disorder as well as selected adverse events. Benefits were measured as quality-adjusted life years (QALYs). Results: For treating mixed episodes, asenapine generated 0.0187 more QALYs for an additional cost of £24 compared to olanzapine over a 5-year period, corresponding to a £1302 incremental cost-effectiveness ratio. The higher acquisition cost of asenapine was roughly offset by the healthcare savings conferred through its greater efficacy in treating these patients. The model shows that benefits were driven by earlier response to asenapine during acute treatment and were maintained during longer-term follow-up. Results were sensitive to changes in key parameters including short and longer-term efficacy, unit cost, and utilities, but conclusions remained relatively robust. Conclusions: Results suggest that asenapine is a cost-effective alternative to olanzapine in mixed episode BD-I patients, and may have specific advantages in this population, potentially leading to healthcare sector savings and improved outcomes. Limitations of the analysis stem from gaps in clinical and economic evidence for these patients and should be addressed by future clinical trials.

A prospective study of health care resource utilisation and selected costs of schizophrenia in France

BackgroundSchizophrenia is among the most burdensome and costly illnesses worldwide. To estimate the cost of schizophrenia in France, a longitudinal study was carried out between 1998 and 2002. The main objective of this study was to describe and update the cost of schizophrenia in a longitudinal, representative sample of French patients. The second objective was to identify cost drivers in the treatment of schizophrenia.MethodsBased on a cohort of 288 French schizophrenic patients during 2 years of prospective follow-up, this study collected clinical, patient reported outcomes, quality of life, functioning, patient management, care giver involvement and resource utilisation data every 6 months. For each service, information was collected on the type of service, the frequency of attendance and type of intervention provided to the patient. Unit costs were based on available French databases. Mean service use and costs over the five time points were estimated using between-effects regression models.ResultsIn the total sample of 288 patients aged 18-64 years, the mean total cost (€ 3 534) was mainly accounted for by the cost of inpatient treatment (€ 1 390) and day care (€ 1 331). The estimate of the annual cost for direct medical health care for all French schizophrenic patients was € 1 581 million, including € 621 million for inpatient treatment and € 595 million for day care (77%). The costs for medication accounted for 16.1% of total annual costs. The remaining costs (6.9%) included visits to psychiatrists, general practitioners, other physicians and psychologists. The direct resource allocation showed inpatient treatment as the main direct cost. Unemployment was identified as a major indirect cost of schizophrenia treatment. Positive and depressive schizophrenia symptoms at baseline and relapse occurrence during the follow-up period were associated with a higher cost of treatment. Health satisfaction or negative symptoms of schizophrenia at baseline were associated with lower costs.ConclusionSeveral cost drivers were identified. Based on the results obtained in France, we suggest further analysis of mechanisms that influence the service-specific costs for schizophrenia in other areas of the world.

A pharmacoeconomic analysis of sertindole in the treatment of schizophrenia in Sweden

Background: Atypical antipsychotics have similar clinical efficacy in the treatment of schizophrenia; variability in their tolerability represents the discerning factor in treatment choices. Sertindole has a relatively good tolerability profile that favours long-term patient adherence and, therefore, is associated with lower rates of relapse and rehospitalization. Aim: A model was developed to compare the cost-effectiveness of a 5-year treatment strategy starting with sertindole versus olanzapine, risperidone, aripiprazole or the typical antipsychotic agent, haloperidol. Methods: The model was based on published trials and local clinical practice, and considered costs from the perspective of the Swedish National Health Insurance Board. Results: All atypical agents were clinically superior and more cost-effective than haloperidol with a cost per quality-adjusted life year gained of approximately 490,000 Swedish kroner. Sertindole was associated with the lowest direct and indirect medical costs, driven by its tolerability profile. Conclusions: Sertindole represents a useful alternative to the current treatment options available in Sweden. Clinical implications: The relatively good tolerability profile of sertindole translates into lower costs of schizophrenia management, primarily driven by substantially lower direct and indirect costs. Sertindole appears to be a clinically and cost-effective alternative in the management of patients with schizophrenia in Sweden.

Defining the minimal clinically important difference (MCID) of the Heinrichs–carpenter quality of life scale (QLS)

To determine the Minimal Clinically Important Difference (MCID) of the Heinrichs–Carpenter Quality of Life Scale (QLS). Data from the “Schizophrenia Trial of Aripiprazole” (STAR) study were used in this analysis. The MCID value of the QLS total score was estimated using the anchor‐based method. These findings were substantiated/validated by comparing the MCID estimate to other measurements collected in the study. Half of the patients (49%) showed improvement in Clinical Global Impressions of Severity (CGI‐S) during the trial. The estimated MCID of the QLS total score was 5.30 (standard error: 2.60; 95% confidence interval: [0.16; 10.43]; p < 0.05). Patients were divided into two groups: “QLS improvers” (QLS total score increased ≥ six points) and “non‐improvers”. The QLS improvers had significantly better effectiveness and reported significantly higher levels of preference for their current medications. There was a statistically significant difference between the two groups in the change in two of the four domains of QLS; “Interpersonal relations” and “Intrapsychic foundations” domains during the study. These findings support the value of the estimated MCID for the QLS and may be a useful tool in evaluating antipsychotic treatment effects and improving long‐term patient outcomes in schizophrenia. Copyright