Cost effectiveness of fingolimod, teriflunomide, dimethyl fumarate and intramuscular interferon-ß1a in relapsing-remitting multiple sclerosis.

OBJECTIVE: The aim of the study was to compare the cost effectiveness of fingolimod, teriflunomide, dimethyl fumarate, and intramuscular (IM) interferon (IFN)-ß(1a) as first-line therapies in the treatment of patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: A Markov model was developed to evaluate the cost effectiveness of disease-modifying drugs (DMDs) from a US societal perspective. The time horizon in the base case was 5 years. The primary outcome was incremental net monetary benefit (INMB), and the secondary outcome was incremental cost-effectiveness ratio (ICER). The base case INMB willingness-to-pay (WTP) threshold was assumed to be US$150,000 per quality-adjusted life year (QALY), and the costs were in 2012 US dollars. One-way sensitivity analyses and probabilistic sensitivity analysis were conducted to test the robustness of the model results. RESULTS: Dimethyl fumarate dominated all other therapies over the range of WTPs, from US$0 to US$180,000. Compared with IM IFN-ß(1a), at a WTP of US$150,000, INMBs were estimated at US$36,567, US$49,780, and US$80,611 for fingolimod, teriflunomide, and dimethyl fumarate, respectively. The ICER of fingolimod versus teriflunomide was US$3,201,672. One-way sensitivity analyses demonstrated the model results were sensitive to the acquisition costs of DMDs and the time horizon, but in most scenarios, cost-effectiveness rankings remained stable. Probabilistic sensitivity analysis showed that for more than 90% of the simulations, dimethyl fumarate was the optimal therapy across all WTP values. CONCLUSION: The three oral therapies were favored in the cost-effectiveness analysis. Of the four DMDs, dimethyl fumarate was a dominant therapy to manage RRMS. Apart from dimethyl fumarate, teriflunomide was the most cost-effective therapy compared with IM IFN-ß(1a), with an ICER of US$7,115.

Frequency and economic impact of comorbid cardiac conditions with multiple sclerosis.

BACKGROUND: Fingolimod, an oral immunomodulatory therapy approved to treat multiple sclerosis (MS) is contraindicated in patients with certain cardiac conditions, yet the frequency of these conditions in patients with MS is not known. This study assessed the frequency and economic impact of cardiac conditions among hospitalizations of patients with MS. OBJECTIVE: To determine the frequency and economic impact of selected comorbid cardiac conditions among hospitalizations of patients with a diagnosis of MS. METHODS: This was a retrospective, discharge-level cohort study of hospital discharge data from 2006-2010. The frequencies of cardiac conditions of interest (based on contraindications to fingolimod in the prescribing information) were reported among all discharges with a diagnosis of MS. Two cohorts were defined: (1) MS with cardiac condition of interest and (2) MS with no cardiac condition of interest. The mean adjusted cost per discharge and incremental cost per hospital day were reported. RESULTS: Among 136,542 discharges with a diagnosis of MS, 9.2% (n = 12,504) had a comorbid cardiac condition of interest based on contraindications to fingolimod in the prescribing information. Heart failure (59.4%), myocardial infarction (17.2%), and occlusion of cerebral arteries (12.4%) were the most common cardiac conditions. The mean adjusted cost per discharge was significantly higher for the MS with cardiac condition cohort compared with the MS with no cardiac condition cohort ($17,623 vs. $11,663, P less than 0.0001). The incremental cost per hospital day was $6,479 for the MS with cardiac condition cohort.  CONCLUSIONS: The presence of comorbid cardiac conditions among hospital discharges in patients with MS is substantial and associated with higher hospitalization costs. Health plans should give consideration to the overlapping presence of these diseases when determining coverage criteria for immunomodulatory therapies and designing clinical programs for MS.

Cost minimisation analysis of fingolimod vs natalizumab as a second line of treatment for relapsing-remitting multiple sclerosis.

INTRODUCTION: At present, there is a lack of economic assessments of second-line treatments for relapsing-recurring multiple sclerosis. The aim of this study was to compare the efficiency between fingolimod and natalizumab in Spain. METHODS: A cost minimisation analysis model was developed for a 2-year horizon. The same relapse rate was applied to both treatment arms and the cost of resources was calculated using Spain's stipulated rates for 2012 in euros. The analysis was conducted from the perspective of Spain's national health system and an annual discount rate of 3% was applied to future costs. A sensitivity analysis was performed to validate the robustness of the model. RESULTS: Indirect comparison of fingolimod with natalizumab revealed no significant differences (hazard ratio between 0.82 and 1.07). The total direct cost, considering a 2-year analytical horizon, a 7.5% discount stipulated by Royal Decree, and a mean annual relapse rate of 0.22, was € 40914.72 for fingolimod and € 45890.53 for natalizumab. Of the total direct costs that were analysed, the maximum cost savings derived from prescribing fingolimod prescription was € 4363.63, corresponding to lower administration and treatment maintenance costs. Based on the sensitivity analysis performed, fingolimod use was associated with average savings of 11% (range 3.1%-18.7%). CONCLUSIONS: Fingolimod is more efficient than natalizumab as a second-line treatment option for relapsing-remitting multiple sclerosis and it generates savings for the Spanish national health system.

Heading for an economic industrial upgrading of crude glycerol from biodiesel production to 1,3-propanediol by Lactobacillus diolivorans.

Lactobacillus diolivorans was evaluated as a potential organism for production of 1,3-propanediol under industrially relevant conditions. Crude glycerol of different origins has been tested and showed no inhibitory effects on growth or production. Using crude glycerol from biodiesel production from palm oil 85 g/l 1,3-propanediol have been obtained with a productivity of 0.45 g/lh in a fed-batch cultivation. Sugar necessary for the formation of biomass was replaced with a hydrolysate from lignocellulosic material resulting in 75 g/l 1,3-propanediol and a productivity of 0.36 g/lh. Lignocellulosic hydrolysate contained the potential inhibitors furfural and 5-hydroxymethylfurfural at concentrations of 0.7 and 0.3 g/l, respectively. Addition of furfural and 5-hydroxymethylfurfural to batch cultures in said concentrations did not show inhibitory effects on growth or 1,3-propanediol production.

Cost-minimization analysis of fingolimod compared with natalizumab for the treatment of relapsing-remitting multiple sclerosis in Sweden.

BACKGROUND: Fingolimod and natalizumab have the same European Union licence for the treatment of relapsing multiple sclerosis, and are considered by the Committee for Medicinal Products for Human Use (CHMP) to have broadly similar efficacy. OBJECTIVE: A cost-minimization analysis was performed to compare differences in treatment costs between fingolimod and natalizumab from a societal perspective in Sweden. METHODS: This analysis included costs associated with initiating and following treatment (physician visits and monitoring), continuing therapy (drugs and administration), and lost patient productivity and leisure time. Unit costs (in Swedish krona [SEK]) were based on regional data (median prices for physician visits and monitoring sessions). Natalizumab infusion costs were obtained from the national cost-per-patient database. Drug costs for both therapies were 15,651 SEK/28 days. RESULTS: After 3 years, fingolimod use was associated with savings of 124,823 SEK/patient compared with natalizumab (total cost/patient: 566,718 SEK vs 691,542 SEK). Cost savings with fingolimod were 40,402 SEK/patient after 1 year and 301,730 SEK/patient after 10 years. Treatment with natalizumab was 18% more expensive than fingolimod therapy after 1 year and 23% more expensive after 10 years. LIMITATIONS: Based on the CHMP assessment, it was assumed that fingolimod and natalizumab have similar efficacy. The analysis was conducted for Sweden, and caution is needed in extrapolating the results to other countries. CONCLUSION: Fingolimod is cost-saving compared with natalizumab for the treatment of relapsing-remitting multiple sclerosis in Sweden.

Cost-effectiveness of early initiation of fingolimod versus delayed initiation after 1 year of intramuscular interferon beta-1a in patients with multiple sclerosis.

BACKGROUND: Fingolimod is a once-daily orally administered disease-modifying therapy (DMT) indicated for treatment of relapsing forms of multiple sclerosis (MS) to reduce the frequency of clinical relapses and delay accumulation of physical disability. In the randomized, double-blind, phase 3 TRANSFORMS trial, 0.5 mg/d oral fingolimod substantially reduced relapse frequency when compared with IM interferon-ß1a (IFN-ß1a) at 12-months. In a 12-month, double-blind, extension phase of the TRANSFORMS study, patients assigned to receive fingolimod continued to receive the same dosage, whereas patients who originally received IM IFN-ß1a were randomized to receive either 0.5 or 1.25 mg/d fingolimod. OBJECTIVE: To investigate the cost-effectiveness of initiating fingolimod therapy early versus after 1 year of IFN-ß1a therapy using TRANSFORMS study extension data. METHODS: A Microsoft Excel-based model was used to calculate the cost per relapse avoided for 2 years with continuous treatment with fingolimod compared with first-year treatment with IM IFN-ß1a and second-year treatment with fingolimod. One-way sensitivity analyses were conducted on key input variables to assess their effect on cost per relapse avoided. RESULTS: The 2-year relapse rate in the early fingolimod arm was 0.23, and in the delayed fingolimod arm was 0.53. The cost per relapse avoided was $83,125 in the early fingolimod arm versus $103,624 in the delayed fingolimod arm. Results of the sensitivity analyses showed an effect of drug acquisition cost and number of relapses in patients who received no treatment. CONCLUSION: Continuous treatment with fingolimod for 2 years resulted in a lower cost per relapse avoided compared with treatment with IM IFN-ß1a for the first year and then switching to fingolimod therapy. Thus, delaying fingolimod therapy does not seem to be cost effective.

Fingolimod reduces direct medical costs compared to natalizumab in patients with relapsing-remitting multiple sclerosis in The Netherlands.

OBJECTIVE: To assess the costs of oral treatment with Gilenya® (fingolimod) compared to intravenous infusion of Tysabri® (natalizumab) in patients with relapsing-remitting multiple sclerosis (RRMS) in The Netherlands. METHODS: A cost-minimization analysis was used to compare both treatments. The following cost categories were distinguished: drug acquisition costs, administration costs, and monitoring costs. Costs were discounted at 4%, and incremental model results were presented over a 1, 2, 5, and 10 year time horizon. The robustness of the results was determined by means of a number of deterministic univariate sensitivity analyses. Additionally, a break-even analysis was carried out to determine at which natalizumab infusion costs a cost-neutral outcome would be obtained. RESULTS: Comparing fingolimod to natalizumab, the model predicted discounted incremental costs of -€2966 (95% CI: -€4209; -€1801), -€6240 (95% CI: -€8800; -€3879), -€15,328 (95% CI: -€21,539; -€9692), and -€28,287 (95% CI: -€39,661; -€17,955) over a 1, 2, 5, and 10-year time horizon, respectively. These predictions were most sensitive to changes in the costs of natalizumab infusion. Changing these costs of €255 within a range from €165-364 per infusion resulted in cost savings varying from €4031 to €8923 after 2 years. The additional break-even analysis showed that infusion costs-including aseptic preparation of the natalizumab solution-needed to be as low as the respective costs of €94 and €80 to obtain a cost neutral result after 2 and 10 years. LIMITATIONS: Neither treatment discontinuation and subsequent re-initiation nor patient compliance were taken into account. As a consequence of the applied cost-minimization technique, only direct medical costs were included. CONCLUSION: The present analysis showed that treatment with fingolimod resulted in considerable cost savings compared to natalizumab: starting at €2966 in the first year, increasing to a total of €28,287 after 10 years per RRMS patient in the Netherlands.

Cost-effectiveness of fingolimod versus interferon beta-1a for relapsing remitting multiple sclerosis in the United States.

OBJECTIVE: Fingolimod has been shown to be more efficacious than interferon (IFN) beta-1a, but at a higher drug acquisition cost. The aim of this study was to assess the cost-effectiveness of fingolimod compared to IFN beta-1a in patients diagnosed with relapsing-remitting multiple sclerosis (RRMS) in the US. METHODS: A Markov model comparing fingolimod to intramuscular IFN beta-1a using a US societal perspective and a 10-year time horizon was developed. A cohort of 37-year-old patients with RRMS and a Kurtzke Expanded Disability Status Scale score of 0-2.5 were assumed. Data sources included the Trial Assessing Injectable Interferon vs FTY720 Oral in Relapsing-Remitting Multiple Sclerosis (TRANSFORMS) and other published studies of MS. Outcomes included costs in 2011 US dollars, quality-adjusted life years (QALYs), number of relapses avoided, and incremental cost-effectiveness ratios (ICERs). RESULTS: Compared to IFN beta-1a, fingolimod was associated with fewer relapses (0.41 vs 0.73 per patient per year) and more QALYs gained (6.7663 vs 5.9503), but at a higher cost ($565,598 vs $505,234). This resulted in an ICER of $73,975 per QALY. Results were most sensitive to changes in drug costs and the disutility of receiving IFN beta-1a. Monte Carlo simulation demonstrated fingolimod was cost-effective in 35% and 70% of 10,000 iterations, assuming willingness-to-pay thresholds of $50,000 and $100,000 per QALY, respectively. LIMITATIONS: Event rates were primarily derived from a single randomized clinical trial with 1-year duration of follow-up and extrapolated to a 10-year time horizon. Comparison was made to only one disease-modifying drug-intramuscular IFN beta-1a. CONCLUSION: Fingolimod use is not likely to be cost-effective compared to IFN beta-1a unless fingolimod cost falls below $3476 per month or a higher than normal willingness-to-pay threshold is accepted by decision-makers.

Fingolimod for multiple sclerosis.

Fingolimod (Gilenya--Novartis) is a new treatment for patients with highly active relapsing-remitting multiple sclerosis. It is the first oral disease-modifying drug for the treatment of patients with multiple sclerosis. Here we assess the place of this drug.

Cost-effectiveness of natalizumab versus fingolimod for the treatment of relapsing multiple sclerosis.

BACKGROUND: With the addition of new agents for the treatment of multiple sclerosis (MS) (e.g., fingolimod), there is a need to evaluate the relative value of newer therapies in terms of cost and effectiveness, given healthcare resource constraints in the United States. OBJECTIVE: To assess the cost-effectiveness of natalizumab vs fingolimod in patients with relapsing MS. METHODS: A decision analytic model was developed to estimate the incremental cost per relapse avoided of natalizumab and fingolimod from a US managed care payer perspective. Two-year costs of treating patients with MS included drug acquisition costs, administration and monitoring costs, and costs of treating MS relapses. Effectiveness was measured in terms of MS relapses avoided (data from AFFIRM and FREEDOMS trials). One-way and probabilistic sensitivity analyses were conducted to assess uncertainty. RESULTS: Mean 2-year estimated treatment costs were $86,461 (natalizumab) and $98,748 (fingolimod). Patients receiving natalizumab had a mean of 0.74 relapses avoided per 2 years vs 0.59 for fingolimod. Natalizumab dominated fingolimod in the incremental cost-effectiveness analysis, as it was less costly and more effective in reducing relapses. One-way sensitivity analysis showed the results of the model were robust to changes in drug acquisition costs, administration costs, and costs of treating MS relapses. Probabilistic sensitivity analysis showed natalizumab was cost-effective 95.1% of the time, at a willingness-to-pay (WTP) threshold of $0 per relapse avoided, increasing to 96.3% of the time at a WTP threshold of $50,000 per relapse avoided. LIMITATIONS: Absence of data from direct head-to-head studies comparing natalizumab and fingolimod, use of relapse rate reduction rather than sustained disability progression as primary model outcome, assumption of 100% adherence to MS treatment, and not capturing adverse event costs in the model. CONCLUSIONS: Natalizumab dominates fingolimod in terms of incremental cost per relapse avoided, as it is less costly and more effective.

Today's and tomorrow's bio-based bulk chemicals from white biotechnology: a techno-economic analysis.

Little information is yet available on the economic viability of the production of bio-based bulk chemicals and intermediates from white biotechnology (WB). This paper details a methodology to systematically evaluate the techno-economic prospects of present and future production routes of bio-based bulk chemicals produced with WB. Current and future technology routes are evaluated for 15 products assuming prices of fermentable sugar between 70 euro/t and 400 euro/t and crude oil prices of US $25/barrel and US $50/barrel. The results are compared to current technology routes of petrochemical equivalents. For current state-of-the-art WB processes and a crude oil price of US $25/barrel, WB-based ethanol, 1,3-propanediol, polytrimethylene terephthalate and succinic acid are economically viable. Only three WB products are economically not viable for future technology: acetic acid, ethylene and PLA. Future-technology ethylene and PLA become economically viable for a higher crude oil price (US $50/barrel). Production costs plus profits of WB products decrease by 20-50% when changing from current to future technology for a crude oil price of US $25 per barrel and across all sugar prices. Technological progress in WB can thus contribute significantly to improved economic viability of WB products. A large-scale introduction of WB-based production of economically viable bulk chemicals would therefore be desirable if the environmental impacts are smaller than those of current petrochemical production routes.

The impact of new pharmaceutical agents on the cost of neurologic care.

Since the emergence of the specialty, neurologists have worked with a rather restricted list of relatively inexpensive pharmacologic agents. This is rapidly changing with the development of new agents for the treatment of migraine, multiple sclerosis, Parkinson's disease, Alzheimer's disease, and epilepsy, accelerated in part by designation of the 1990s as the "Decade of the Brain." Exciting as these developments are, they are very costly when applied to the large number of patients who may benefit, perhaps exceeding $6.4 billion. Since this cost exceeds the $1.5 billion income of all practicing neurologists, it enhances the value of the neurologic consultation, which can provide more accurate diagnosis and more expertly directed therapy. Our relationships with the drug manufacturers are changing as our prescribing habits become a more likely determinant of profits.