Employment and absenteeism in working-age persons with multiple sclerosis

Aims: To better understand the impact of the clinical course of multiple sclerosis (MS) and disability on employment, absenteeism, and related factors.

Materials and methods: This study included respondents to the North American Research Committee on Multiple Sclerosis Registry spring 2015 update survey who were US or Canadian residents, aged 18–65 years and reported having relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), or primary progressive MS (PPMS). The RRMS and SPMS participants were combined to form the relapsing-onset MS (RMS) group and compared with the PPMS group regarding employment status, absenteeism, and disability. Multivariable logistic regression was used to examine the relationship between employment-related outcomes and factors that may affect these relationships.

Results: Of the 8004 survey respondents, 5887 (73.6%) were 18–65 years of age. The PPMS group (n?=?344) had a higher proportion of males and older mean age at the time of the survey and at time of diagnosis than the RMS group (n?=?4829). Female sex, age, age at diagnosis, cognitive and hand function impairment, fatigue, higher disability levels, ≥3 comorbidities, and a diagnosis of PPMS were associated with not working. After adjustment for disability, the employed PPMS sub-group reported similar levels of absenteeism to the employed RMS sub-group.

Limitations: Limitations of the study include self-report of information and the possibility that participants may not fully represent the working-age MS population.

Conclusions: In MS, employment status and absenteeism are negatively affected by disability, cognitive impairment, and fatigue. These findings underscore the need for therapies that prevent disability progression and other symptoms that negatively affect productivity in persons with MS to enable them to persist in the workforce.     

An economic evaluation attached to a single-centre,parallel group,unmasked, randomized controlled trial of a 3-day intensive social cognitive treatment (can do treatment) in patients with relapsing remitting multiple sclerosis and low disability

Abstract

Aims: This trial-based economic evaluation (EE) assesses from a societal perspective the cost-effectiveness of an intensive 3-day cognitive theory-based intervention (CDT), compared to care-as-usual, in patients with relapsing remitting multiple sclerosis (RRMS) and low disability (Expanded Disability Status Scale [EDDS] score < 4.0).

Materials and methods: The trial of the EE was registered in the Dutch Trial Register: Trial NL5158 (NTR5298). The incremental cost-effectiveness ratio (ICER) was expressed in cost on the Control sub-scale of the Multiple Sclerosis Self-Efficacy Scale (MSSES) and the incremental cost-utility ratio (ICUR) in the cost per Quality Adjusted Life Years (QALY) using the EQ-5D-5L. Bootstrap, sensitivity, and sub-group analyses were performed to determine the robustness of the findings.

Results: The two groups of 79 patients were similar in baseline characteristics. The base case ICER is situated in the northeast quadrant (€72 (40.74/€2,948)) due to a higher MSSES Control score and higher societal costs in the CDT group. The ICUR is situated in the northwest (inferior) quadrant due to losses in QALY and higher societal costs for the CDT group (?0.02/€2,948). Overall, bootstrap, sensitivity, and sub-group analyses confirm the base case findings. However, when the SF-6D is used as a study outcome, there is a high probability that the ICUR is situated in the northeast quadrant.

Limitations: The relative short follow-up time (6?months) and the unexpected increase in MSSES Control in the control group.

Conclusions: When using the EQ-5D-5L to calculate a QALY, CDT is not a cost-effective alternative in comparison to care as usual. However, when using self-efficacy or SF-6D as outcomes, there is a probability that CDT is cost-effective. Based on the current results, CDT for patients with RRMS clearly show its potential. However, an extended follow-up for the economic evaluation is warranted before a final decision on implementation can be made.     

Cost-effectiveness analysis of disease modifiying drugs (interferons and glatiramer acetate) as first line treatments in remitting-relapsing multiple sclerosis patients

Abstract

Objective:

The aim of this study was to assess cost-effectiveness of the different Disease Modifying Drugs (DMD) used as first-line treatments (interferons IM IFNβ-1a, SC IFNβ-1a, SC IFNβ-1b, and glatiramer acetate, GA) in Remitting-Relapsing Multiple Sclerosis (RRMS) in Spain.

Methods:

A Markov model was developed to simulate the progression of a cohort of patients with RRMS, during a period of 10 years. Seven health states, defined by the Expanded Disability Status Scale (EDSS), were considered in the model. Patients with an EDSS score less than 6.0 were assumed to be treated with one of the DMD. In addition, all patients were assumed to receive symptomatic treatment. The monthly transition probabilities of the model were obtained from the literature. The analysis was performed from the societal perspective, in which both direct and indirect (losses in productivity) healthcare costs (€, 2010) were included. A discount rate of 3% was applied to both costs and efficacy results.

Results:

GA was the less costly strategy (€322,510), followed by IM IFNβ-1a (€329,595), SC IFNβ-1b (€ 333,925), and SC IFNβ-1a (€348,208). IM IFNβ-1a has shown the best efficacy results, with 4.176 quality-adjusted life years (QALY), followed by SC IFNβ-1a (4.158 QALY), SC IFNβ-1b (4.157 QALY), and GA (4.117 QALY). Incremental costs per QALY gained with IM IFNβ-1a were €?1,005,194/QALY, €?223,397/QALY, and €117,914/QALY in comparison to SC IFNβ-1a, SC IFNβ-1b, and GA, respectively.

Conclusions:

First-line treatment with GA is the less costly strategy for the treatment of patients with RRMS. Treatment with IM IFNβ-1a is a dominant strategy (lower cost and higher QALY) compared with SC IFNβ-1a and SC IFNβ-1b. However, IM IFNβ-1a is not a cost-effective strategy vs GA, because incremental cost per QALY gained with IM IFNβ-1a exceeds the €30,000 per QALY threshold commonly used in Spain.

Limitations:

The highly-restrictive inclusion criteria of clinical trials limits generalization of the results on efficacy to all patients with multiple sclerosis. Availability of data for head-to-head comparisons is associated with the use of information from clinical trials.     

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

Abstract

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.     

出口业务中以D／P方式成交的前提与风险防范

D／P，即付款交单，是国际贸易中重要的付款方式之一。与信用证相比，它对进出口双方都有许多有利和不利的特点。作为出口商，在实际业务中，应了解以D／P方式成交的前提和采取各种风险防范措施．达到安全收汇的目的。     

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

Abstract

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 glatiramer acetate and interferon beta-1a for relapsing-remitting multiple sclerosis,based on the CombiRx study

Background:

To assess the cost-effectiveness of the Disease Modifying Treatments (DMT), Glatiramer Acetate (GA) and Interferon beta-1a (IFN) in monotherapy alone and in combination for the prevention of relapses among Spanish patients aged between 18–60 years old with established Relapsing–Remitting Multiple Sclerosis (RRMS).

Methods:

A Markov model was developed to represent the transition of a cohort of patients over a 10 year period using the perspective of the Spanish National Health Service (NHS). The model considered five different health states with 1-year cycles including without relapse, patients with suspect, non-protocol defined and protocol defined exacerbations, as well as a category information lost. Efficacy data was obtained from the 3-year CombiRx Study. Costs were reported in 2013 Euros and a 3% discount rate was applied for health and benefits. Deterministic results were presented as the annual treatment cost for the number of relapses. A probabilistic sensitivity analysis was performed to test the robustness of the model.

Results:

Deterministic results showed that the expected annual cost per patient was lower when treated with GA (€13,843) compared with IFN (€15,589) and the combined treatment with IFN?+?GA (€21,539). The annual number of relapses were lower in the GA cohort with 3.81 vs 4.18 in the IFN cohort and 4.08 in the cohort treated with IFN?+?GA. Results from probabilistic sensitivity analysis showed that GA has a higher probability of being cost-effective than treatment with IFN or IFN?+?GA for threshold values from €28,000 onwards, independent of the maximum that the Spanish NHS is willing to pay for avoiding relapses.

Conclusion:

GA was shown to be a cost-effective treatment option for the prevention of relapses in Spanish patients diagnosed with RRMS. When GA in monotherapy is compared with INF in monotherapy and IFN?+?GA combined, it may be concluded that the first is the dominant strategy.     

Cost-effectiveness analysis of ocrelizumab versus subcutaneous interferon beta-1a for the treatment of relapsing multiple sclerosis

Aim: To conduct a cost-effectiveness analysis to compare ocrelizumab vs subcutaneous (SC) interferon beta-1a for the treatment of relapsing multiple sclerosis (RMS).

Methods: A Markov cohort model with a 20-year horizon was developed to compare ocrelizumab with SC interferon beta-1a from a US payer perspective. A cohort of patients with relapsing-remitting MS (RRMS) and Expanded Disability Status Scale (EDSS) scores of 0–6, who initiated treatment with ocrelizumab or SC interferon beta-1a, were entered into the model. The model considered 21 health states: EDSS 0–9 in RRMS, EDSS 0–9 in secondary-progressive multiple sclerosis (SPMS), and death. Patients with RRMS could transition across EDSS scores, progress to SPMS, experience relapses, or die. Transition probabilities within RRMS while patients received ocrelizumab or SC interferon beta-1a were based on data from the two SC interferon beta-1a-controlled Phase III OPERA I and OPERA II trials of ocrelizumab in RMS. Transitions within RRMS when off-treatment, RRMS-to-SPMS transitions, transitions within SPMS, and transitions to death were based on the literature. Utilities of health states, disutilities of relapses, costs of therapies, and medical costs associated with health states, relapse, and adverse events were from the literature and publicly available data sources. The model estimated per-patient total costs, incremental cost per life year (LY) gained, and incremental cost per quality-adjusted LY (QALY) gained. Deterministic sensitivity analyses (DSA) and probabilistic sensitivity analysis (PSA) were conducted to evaluate the robustness of the model results.

Results: Ocrelizumab was associated with a cost savings of $63,822 and longer LYs (Δ?=?0.046) and QALYs (Δ?=?0.556) over a 20-year time horizon. The results of the model were robust in the DSA and PSA.

Limitations: The model did not consider subsequent treatments and their impact on disease progression.

Conclusions: The results suggest that ocrelizumab is more cost-effective than SC interferon beta-1a for the treatment of RMS.     

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

Objective:

To assess the cost-effectiveness of delayed-release dimethyl fumarate (DMF, also known as gastro-resistant DMF), an effective therapy for relapsing forms of multiple sclerosis (MS), compared with glatiramer acetate and fingolimod, commonly used treatments in the US.

Methods:

A Markov model was developed comparing delayed-release DMF to glatiramer acetate and fingolimod using a US payer perspective and 20-year time horizon. A cohort of patients, mean age 38 years, with relapsing-remitting MS and Kurtzke Expanded Disability Status Scale (EDSS) scores between 0–6 entered the model. Efficacy and safety were estimated by mixed-treatment comparison of data from the DEFINE and CONFIRM trials and clinical trials of other disease-modifying therapies. Data from published studies were used to derive resource use, cost, and utility inputs. Key outcomes included costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. Alternative scenarios tested in a sensitivity analysis included drug efficacy, EDSS-related or relapse-related costs, alternative perspectives, drug acquisition costs, and utility.

Results:

Base-case results with a 20-year time horizon indicated that delayed-release DMF increased QALYs +0.450 or +0.359 compared with glatiramer acetate or fingolimod, respectively. Reductions in 20-year costs with delayed-release DMF were ?$70,644 compared with once-daily glatiramer acetate and ?$32,958 compared with fingolimod. In an analysis comparing delayed-release DMF to three-times-weekly glatiramer acetate and assuming similar efficacy and safety to the once-daily formulation, 20-year costs with delayed-release DMF were increased by $15,806 and cost per QALY gained was $35,142. The differences in costs were most sensitive to acquisition cost and inclusion of informal care costs and productivity losses. The differences in QALYs were most sensitive to the impact of delayed-release DMF on disease progression and the EDSS utility weights.

Conclusion:

Delayed-release DMF is likely to increase QALYs for patients with relapsing forms of MS and be cost-effective compared with fingolimod and glatiramer acetate.