Sujata Sarda

Efficacy and safety of BG-12 (dimethyl fumarate) and other disease-modifying therapies for the treatment of relapsing–remitting multiple sclerosis: a systematic review and mixed treatment comparison

Abstract Objective: Currently, direct comparative evidence or head-to-head data between BG-12 (dimethyl fumarate) and other disease-modifying treatments (DMTs) is limited. This study is a systematic review and data synthesis of published randomized clinical trials comparing the efficacy and safety of existing DMTs to BG-12 for relapsing–remitting multiple sclerosis (RRMS). Methods: A systematic review was conducted by searching MEDLINE, EMBASE, and the Cochrane Library for English-language publications from 1 January 1960 to 15 November 2012. Clinicaltrials.gov, metaRegister of Controlled Trials, and conference proceedings from relevant annual symposia were also hand searched. Two independent reviewers collected and extracted data, with discrepancies reconciled by a third reviewer. Included studies were randomized controlled trials (RCTs) of DMTs (interferon [IFN] beta-1a, IFN beta-1b, glatiramer acetate [GA], BG-12, fingolimod, natalizumab, and teriflunomide) in adults with RRMS. Mixed treatment comparisons were conducted to derive the relative effect size for the included treatments. Annualized relapse rate (ARR), disability progression, and safety outcomes were assessed. Results: BG-12 240 mg twice a day (BID) significantly reduces ARR compared to placebo (rate ratio: 0.529 [95% CI: 0.451–0.620]), IFNs (0.76 [95% CI: 0.639–0.904]), GA (0.795 [95% CI: 0.668–0.947]), and teriflunomide 7 mg and 14 mg (0.769 [95% CI: 0.610–0.970] and 0.775 [95% CI: 0.614–0.979]), and does not show a significant difference when compared to fingolimod. Only natalizumab was significantly superior to BG-12 in reducing ARR. BG-12 also demonstrated favorable results for disability and safety outcomes. Conclusion: Based on indirect comparison, BG-12 offers an effective oral treatment option for patients with RRMS with an overall promising efficacy and safety profile compared to currently approved DMTs. Key limitations of the systematic review were the large heterogeneity in patients enrolled and the variability in the definition of outcomes in included trials.

Quality of life outcomes with BG-12 (dimethyl fumarate) in patients with relapsing–remitting multiple sclerosis: The DEFINE study:

Background: Oral BG-12 (dimethyl fumarate), approved for the treatment of the relapsing forms of MS, has demonstrated clinical efficacy with an acceptable safety profile in the Phase III “Determination of the Efficacy and Safety of Oral Fumarate in Relapsing–Remitting Multiple Sclerosis (RRMS)” (DEFINE) and “Comparator and an Oral Fumarate in RRMS” (CONFIRM) studies. Objectives: To evaluate the health-related quality of life (HRQoL) impairment that is associated with RRMS and to assess the effects of BG-12 on HRQoL in the DEFINE study. Methods: Patients with RRMS were randomized to BG-12 240 mg twice (BID) or three times (TID) daily, or placebo, for 2 years. HRQoL was assessed by the Short Form-36 (SF-36), global assessment of well-being visual analog scale and the EuroQol-5D. Results: In the 1237 patients from DEFINE, HRQoL impairment was greatest in patients who had higher disability scores and in those who had experienced relapse. Change in SF-36 physical component summary scores during 2 years’ treatment significantly favored BG-12 over placebo (both doses: p < 0.001). We saw similar benefits in other measures of functioning and general well-being as early as Week 24. These benefits were maintained during the study. Conclusions: Our results add to evidence for a negative impact of RRMS on HRQoL and they demonstrate the benefits of BG-12 on HRQoL measures, which coupled with significant clinical efficacy, further support its use as a new treatment for RRMS.

Clinical and economic impact of vagus nerve stimulation therapy in patients with drug-resistant epilepsy☆

We evaluated long-term medical and economic benefits of vagus nerve stimulation (VNS) therapy in drug-resistant epilepsy. A pre-post analysis was conducted using multistate Medicaid data (January 1997-June 2009). One thousand six hundred fifty-five patients with one or more neurologist visits with epilepsy diagnoses (ICD-9 345.xx, 780.3, or 780.39), one or more procedures for vagus nerve stimulator implantation, one or more antiepileptic drugs (AEDs), and 6 or more months of continuous Medicaid enrollment pre- and post-VNS were selected. The pre-VNS period was 6 months. The post-VNS period extended from implantation to device removal, death, Medicaid disenrollment, or study end (up to 3 years). Incidence rate ratios (IRRs) and cost differences (

Effects of BG-12 (dimethyl fumarate) on health-related quality of life in patients with relapsing–remitting multiple sclerosis: findings from the CONFIRM study

2009) were estimated. Mean age was 29.4 years. Hospitalizations decreased post-VNS compared with pre-VNS (adjusted IRR=0.59, P<0.001). Grand mal status events decreased post-VNS compared with pre-VNS (adjusted IRR=0.79, P<0.001). Average total health care costs were lower post-VNS than pre-VNS (

Cost Burden and Treatment Patterns Associated with Management of Heavy Menstrual Bleeding

18,550 vs

Effects of Delayed-Release Dimethyl Fumarate (DMF) on Health-Related Quality of Life in Patients With Relapsing-Remitting Multiple Sclerosis: An Integrated Analysis of the Phase 3 DEFINE and CONFIRM Studies

19,945 quarterly, P<0.001). VNS is associated with decreased resource utilization and epilepsy-related clinical events and net cost savings after 1.5 years.

Impact of increasing adherence to disease-modifying therapies on healthcare resource utilization and direct medical and indirect work loss costs for patients with multiple sclerosis.

Multiple sclerosis (MS) has a significant impact on health-related quality of life (HRQoL) with symptoms adversely affecting many aspects of everyday living. BG-12 (dimethyl fumarate) demonstrated significant efficacy in the phase III studies DEFINE and CONFIRM in patients with relapsing–remitting MS. In CONFIRM, HRQoL was worse in patients with greater disability at baseline, and who relapsed during the study, and improved with BG-12 treatment. Mean Short Form-36 Physical Component Summary scores for BG-12 increased over 2 years and scores for placebo decreased. Coupled with clinical and neuroradiological benefits, these HRQoL results further support BG-12 as an effective oral treatment for relapsing MS.

Costs associated with angiogenesis inhibitor therapies for metastatic renal cell carcinoma in clinical practice: Results from a medical chart review study

OBJECTIVES This study evaluated the healthcare resource use, work productivity loss, costs, and treatment patterns associated with newly diagnosed idiopathic heavy menstrual bleeding (HMB) using a large employer database. METHODS Medical and pharmacy claims (1998-2009) from 55 self-insured U.S. companies were analyzed. Women aged 18-52 years with ≥2 HMB claims (ICD-9 626.2, 627.0) and continuously enrolled for ≥6 months before the first claim were matched 1:1 with controls. Exclusion criteria were cancer, pregnancy, and infertility; HMB-related uterine conditions; endometrial ablation; hysterectomy; anticoagulant medications; and other known HMB causes. All-cause healthcare resource use and costs were compared between the HMB and control cohorts using statistical methods accounting for matched study design. Treatment patterns were examined for HMB subjects. RESULTS HMB and control cohorts (n=29,842 in both) were matched and balanced in baseline characteristics and costs. During follow-up, HMB subjects had significantly higher all-cause resource use than did control subjects: hospitalization incidence rate ratio (IRR)=2.70 (95% confidence interval [CI] 2.62-2.79); emergency room visits IRR=1.35 (95% CI 1.31-1.38); outpatient visits IRR=1.29 (95% CI 1.29-1.30). Average annualized all-cause costs were also higher for HMB subjects than controls (mean difference

Cost-effectiveness of delayed-release dimethyl fumarate for the treatment of relapsing forms of multiple sclerosis in the United States

2,607, p<0.001). Costs associated with HMB claims represented 50% (

The cost-effectiveness of delayed-release dimethyl fumarate for the treatment of relapsing-remitting multiple sclerosis in Canada

1,313) of the all-cause cost difference. Of HMB subjects, 63.2% underwent surgical treatment as initial therapy. CONCLUSIONS In this large matched-cohort study, an idiopathic diagnosis of HMB was associated with high rates of surgical intervention and increased healthcare resource use and costs.