Shien Guo

Responder definition of the Multiple Sclerosis Impact Scale physical impact subscale for patients with physical worsening

Background: The 29-item Multiple Sclerosis Impact Scale (MSIS-29) was developed to examine the impact of multiple sclerosis (MS) on physical and psychological functioning from a patient’s perspective. Objective: To determine the responder definition (RD) of the MSIS-29 physical impact subscale (PHYS) in a group of patients with relapsing–remitting MS (RRMS) participating in a clinical trial. Methods: Data from the SELECT trial comparing daclizumab high-yield process with placebo in patients with RRMS were used. Physical function was evaluated in SELECT using three patient-reported outcomes measures and the Expanded Disability Status Scale (EDSS). Anchor- and distribution-based methods were used to identify an RD for the MSIS-29. Results: Results across the anchor-based approach suggested MSIS-29 PHYS RD values of 6.91 (mean), 7.14 (median) and 7.50 (mode). Distribution-based RD estimates ranged from 6.24 to 10.40. An RD of 7.50 was selected as the most appropriate threshold for physical worsening based on corresponding changes in the EDSS (primary anchor of interest). Conclusion: These findings indicate that a ≥7.50 point worsening on the MSIS-29 PHYS is a reasonable and practical threshold for identifying patients with RRMS who have experienced a clinically significant change in the physical impact of MS.

Assessing the impact of multiple sclerosis disease activity and daclizumab HYP treatment on patient-reported outcomes: Results from the SELECT trial.

BACKGROUND The SELECT study demonstrated superior effects of daclizumab high-yield process (DAC HYP) to placebo in key endpoints in patients with relapsing and remitting multiple sclerosis (RRMS). OBJECTIVE To assess the impact of DAC HYP and disease activity on health-related quality of life (HRQoL) using data from this study. METHODS HRQoL was assessed at baseline, 12, 24, and 52 weeks using the Multiple Sclerosis Impact Scale (MSIS-29), the 12-items Short Form Health Survey, and the EuroQoL-5 Dimensions. An analysis of covariance model was used to compare treatment difference in change from baseline. Mixed-effects models were used to assess the impact of disability progression, relapse, treatment, and interaction between treatment and these events on HRQoL outcome. RESULTS DAC HYP 150mg resulted in significant positive impacts on HRQoL compared to placebo. It was also found to significantly reduce the adverse impact of relapse on the MSIS-29 physical scale (-12.45; p=0.0006). Relapse and disability progression were significantly associated with impaired HRQoL. CONCLUSION DAC HYP 150mg improved HRQoL in patients with RRMS compared to placebo. The treatment benefit can be partially attributed to reduction in disease activity and attenuation of the adverse impact of relapse on HRQoL.

Cost-effectiveness analysis of peginterferon beta-1a compared with interferon beta-1a and glatiramer acetate in the treatment of relapsing-remitting multiple sclerosis in the United States.

Abstract Objective Peginterferon beta-1a 125 mcg, administered subcutaneously (SC) every 2 weeks, a new disease-modifying therapy (DMT) for relapsing-remitting multiple sclerosis (RRMS), was approved by the US Food and Drug Administration in 2014. This study assesses the cost-effectiveness of peginterferon beta-1a vs interferon beta-1a (44 mcg SC 3 times per week) and glatiramer acetate (20 mg SC once-daily) in the treatment of RRMS from the perspective of a US payer over 10 years. Methods A Markov cohort economic model was developed for this analysis. The model predicts disability progression, occurrence of relapses and other adverse events and translates them into quality-adjusted life years (QALYs) and costs. Natural history data were obtained from the placebo arm of the ADVANCE trial of peginterferon beta-1a, the London Ontario (Canada) database and a large population-based MS survey. Comparative efficacy of each DMT vs placebo was obtained from a network meta-analysis. Costs (in 2014 US dollars) were sourced from public databases and literature. Clinical and economic outcomes were discounted at 3% per year. Results Over 10 years, peginterferon beta-1a was dominant (i.e., more effective and less costly), with cost-savings of

Impact of peginterferon beta-1a and disease factors on quality of life in multiple sclerosis.

22,070 and additional 0.06 QALYs when compared with interferon beta-1a 44 mcg and with cost-savings of

Cost-effectiveness of Pomalidomide, Carfilzomib, and Daratumumab for the Treatment of Patients with Heavily Pretreated Relapsed–refractory Multiple Myeloma in the United States

19,163 and 0.07 QALYs gained when compared with glatiramer acetate 20 mg. Results were most sensitive to variations in the treatment effect of each DMT, treatment acquisition costs of each DMT and the time horizon. Probabilistic sensitivity analyses indicated that peginterferon beta-1a remains dominant in >90% of 5,000 replications compared with either DMTs. Conclusion This analysis suggests that long-term treatment with peginterferon beta-1a improves clinical outcomes at reduced costs compared with interferon beta-1a 44 mcg and glatiramer acetate 20 mg and should be a valuable addition to managed care formularies for treating patients with RRMS.

Peginterferon beta-1a versus other self-injectable disease-modifying therapies in the treatment of relapsing-remitting multiple sclerosis in Scotland: a cost-effectiveness analysis.

BACKGROUND The Phase III ADVANCE study has shown clinical benefits for peginterferon beta-1a 125 µg dosed every 2 weeks versus placebo at 1 year in patients with relapsing-remitting multiple sclerosis (MS). This study assessed the impact of peginterferon beta-1a and disease factors on health-related quality of life (HRQoL) using data from ADVANCE. METHODS HRQoL was assessed at baseline and 12, 24, and 48 weeks using the 29-item Multiple Sclerosis Impact Scale (MSIS-29) and other generic HRQoL measures. Changes in scores from baseline within each group and differences in mean change from baseline between groups were evaluated. Post-hoc mixed-effects repeated measures analyses were performed to assess the impact of confirmed disability progression and relapses, and the interactions of treatment and these MS events on HRQoL. Predictors with p≥0.1 were excluded from the final models, unless they were clinically meaningful. RESULTS Relapses and confirmed disability progression were major drivers of HRQoL. When comparing week 48 to baseline, in placebo-treated patients (n=500), confirmed disability progression was associated with a 6.0-point worsening (p<0.0001) of MSIS-29 physical scores, relative to a 1.9-point worsening (p=0.044) with peginterferon beta-1a every 2 weeks (n=512). Such findings were observed consistently with other generic HRQoL measures. Additionally, having a recent relapse (≤29 days before the HRQoL assessment) was associated with a 10.0-point worsening (p<0.0001) of MSIS-29 psychological scores in placebo-treated patients, compared with a 3.5-point (p=0.031) worsening with peginterferon beta-1a every 2 weeks. CONCLUSION Treatment with peginterferon beta-1a could help to improve or maintain HRQoL in addition to clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov: NCT00906399.

The Effect of Lenalidomide on Health-Related Quality of Life in Patients With Lower-Risk non-del(5q) Myelodysplastic Syndromes: Results From the MDS-005 Study

PURPOSE Pomalidomide plus low-dose dexamethasone (POM-d), daratumumab monotherapy (DARA), and carfilzomib monotherapy (CAR) have been approved for use in the treatment of patients with heavily pretreated relapsed-refractory multiple myeloma (RRMM) in the US, based on findings from the MM-002, SIRIUS, and PX-171-003-A1 studies, respectively. The objective of this study was to assess the cost-effectiveness of POM-d, DARA, and CAR in this patient population from a US payers perspective. METHODS A cost-effectiveness model was developed to estimate the cost and health outcomes over a 3-year time horizon in 3 health states: progression-free, post-progression, and death. The main efficacy data source was a matching-adjusted indirect comparison using data from the aforementioned studies. Direct medical costs were considered, including: treatment acquisition and administration (initial line and subsequent line), pre- and post-medication, prophylaxis treatment, adverse event management, and health care resource utilization. Sensitivity analyses were conducted. A scenario analysis that assumed equal efficacy across all 3 treatments was conducted. Costs, life-years, and quality-adjusted life-years were estimated and discounted at 3% per annum. FINDINGS Over 3 years, the use of POM-d was associated with similar life-years and quality-adjusted life-years gained compared with DARA and CAR (incremental: life-years, +0.02 and +0.07, respectively; quality-adjusted life-years, +0.01 and +0.05), and with a cost less than that of DARA (-

Cost-Effectiveness Analysis of Peginterferon Beta-1a In The Treatment of Relapsing-Remitting Multiple Sclerosis In Ireland.

8,919) and similar to that of CAR (-

Clinical and Cost Consequences of Metabolic Effects of Lurasidone VersusOther Atypical Antipsychotics in Schizophrenia

195). Sensitivity analyses illustrated that the results were sensitive to progression-free survival, treatment duration, and drug costs. An equal efficacy scenario resulted in cost-savings relative to those of both DARA and CAR (-

Matching-Adjusted Indirect Comparison of Relative Efficacies Is Feasible and Useful in the Multiple Myeloma Therapy Landscape: A Comparison of Pomalidomide Plus Low-Dose Dexamethasone Versus Daratumumab

11,779 and -