Relative performance of brivaracetam as adjunctive treatment of focal seizures in adults: a network meta-analysis.

Objective: To estimate the relative efficacy, safety and tolerability of adjunctive brivaracetam and other antiepileptic drugs (AEDs) using a Bayesian network meta-analysis (NMA) approach. Methods: A systematic literature review (SLR) identified randomized controlled trials of AEDs treating focal (partial-onset) seizures for ≥8 weeks and assessed them for inclusion in the NMA. Bayesian random-effects NMA was performed for several outcomes. All interventions within the licensed dose range were included in the network of evidence. Results: The SLR identified 82 studies; 65 were included in the NMA. These studies had baseline mean age 33.1-38.0 years, mean duration of epilepsy 18.7-23.0 years and median seizure frequency/28 days 8.1-11.8. All AEDs had significantly higher odds than placebo of achieving ≥50% responder rates (odds ratios 1.83-3.58) and all AEDs had a trend of higher odds than placebo of achieving seizure freedom (odds ratios 1.36-5.73), most being statistically significant. Tolerability outcomes were comparable between AEDs; most AEDs had higher odds than placebo of treatment-emergent adverse events leading to discontinuation, serious AEs, nausea, fatigue, dizziness and somnolence. Conclusions: This NMA would appear to show relative equivalence in efficacy, safety and tolerability outcomes of the included AEDs. However, patient heterogeneity within trials and in clinical practice should be considered when interpreting these results. While NMAs are based on the best available evidence the authors suggest that, due to the inability of NMAs to capture unmeasured confounding factors and population heterogeneity, NMAs must not be the sole basis for comparative treatment recommendations.

First-line therapy for non-transplant eligible patients with multiple myeloma: direct and adjusted indirect comparison of treatment regimens on the existing market in Germany.

OBJECTIVES: The purpose of this study was to compare approved first-line therapies for patients with multiple myeloma. METHODS: A systematic literature search for phase III randomized controlled trials (RCTs) comparing first-line chemotherapies approved in Germany and recommended by guidelines at the time of study design was conducted. Random-effects meta-analysis (MA) was used for direct and the Bucher method for adjusted indirect treatment comparison. RESULTS: One RCT comparing melphalan and prednisone plus bortezomib (VMP) vs. melphalan and prednisone (MP) and six RCTs comparing MP plus thalidomide (MPT) vs. MP were analysed. For MPT vs. MP, an individual patient data (IPD) MA was used for sensitivity analyses. VMP and MPT were superior to MP regarding efficacy endpoints (VMP vs. MP, overall survival (OS): hazard ratio (HR) 0.70, 95 % confidence interval (CI) 0.57-0.86; progression-free survival (PFS): HR 0.56, 0.39-0.79; complete response (CR), risk-ratio (RR) for non-response: 0.70, 0.65-0.75; MPT vs. MP, OS: HR 0.83, 0.66-1.03; PFS: HR 0.67, 0.56-0.81; CR, RR for non-response 0.92, 0.88-0.95); but had a higher risk of developing any grade 3-4 adverse events (AEs) (VMP vs. MP: RR 1.13, 1.06-1.20; MPT vs. MP: RR 2.06, 1.43-2.98). The indirect comparison of VMP vs. MPT via MP showed a statistically not significant advantage for VMP regarding survival outcomes (OS: HR 0.85, 0.63-1.14; PFS: HR 0.83, 0.56-1.23) and a significant advantage regarding CR (RR for non-response 0.76, 0.70-0.83) and AEs (RR 0.55, 0.38-0.80). Treatment comparisons using results of IPD MA yielded similar effect sizes. CONCLUSIONS: VMP and MPT seem more effective than MP, VMP was superior to MPT regarding response criteria and AEs. Our results may best be confirmed by a head-to-head trial of VMP vs. MPT.

Systematic review of humanistic and economic burden of symptomatic chronic obstructive pulmonary disease.

BACKGROUND: An understanding of the humanistic and economic burden of individuals with symptomatic chronic obstructive pulmonary disease (COPD) is required to inform payers and healthcare professionals about the disease burden. OBJECTIVES: The aim of this systematic review was to identify and present humanistic [health-related quality of life (HRQoL)] and economic burdens of symptomatic COPD. METHODS: A comprehensive search of online databases (reimbursement or claims databases/other databases), abstracts from conference proceedings, published literature, clinical trials, medical records, health ministries, financial reports, registries, and other sources was conducted. Adult patients of any race or gender with symptomatic COPD were included. Humanistic and economic burdens included studies evaluating HRQoL and cost and resource use, respectively, associated with symptomatic COPD. RESULTS: Thirty-two studies reporting humanistic burden and 74 economic studies were identified. Symptomatic COPD led to impairment in the health state of patients, as assessed by HRQoL instruments. It was also associated with high economic burden across all countries. The overall, direct, and indirect costs per patient increased with an increase in symptoms, dyspnoea severity, and duration of disease. Across countries, the annual societal costs associated with symptomatic COPD were higher among patients with comorbidities. CONCLUSIONS: Symptomatic COPD is associated with a substantial economic burden. The HRQoL of patients with symptomatic COPD is, in general, low and influenced by dyspnoea.

Impact of reducing dosing frequency on adherence to oral therapies: a literature review and meta-analysis.

OBJECTIVES: To assess the impact of reduced frequency of oral therapies from multiple-dosing schedules to a once-daily (OD) dosing schedule on adherence, compliance, persistence, and associated economic impact. METHODS: A meta-analysis was performed based on relevant articles identified from a comprehensive literature review using MEDLINE® and Embase®. The review included studies assessing adherence with OD, twice-daily (BID), thrice-daily (TID), and four-times daily (QID) dosing schedules and costs associated with optimal/suboptimal adherence among patients with acute and chronic diseases. Effect estimates across studies were pooled and analyzed using the DerSimonian and Laird random-effect model. RESULTS: Forty-three studies met inclusion criteria, and meta-analyzable data were available from 13 studies. The overall results indicated that OD schedules were associated with higher adherence rates (odds ratio [OR] 3.07, 95% confidence interval [CI] 1.80-5.23; P < 0.001 for OD versus > OD dosing) and compliance rates (OR 3.50, 95% CI 1.73-7.08; P < 0.001 for OD versus > OD dosing); persistence rates showed the same direction but were not statistically significant (OR 1.43, 95% CI 0.62-3.29; P = 0.405 for OD versus BID dosing). Results for each of the conditions were consistent with those observed overall with respect to showing the benefits of less frequent dosing. From a health economic perspective, higher adherence rates with OD relative to multiple dosing in a number of conditions were consistently associated with corresponding lower costs of health care resources utilization. CONCLUSION: Current meta-analyses suggested that across acute and chronic disease states, reducing dosage frequency from multiple dosing to OD dosing may improve adherence to therapies among patients. Improving adherence may result in subsequent decreases in health care costs.