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

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

The cost-effectiveness of disease-modifying therapies for the treatment of relapsing-remitting multiple sclerosis

Background: The safety and efficacy of disease-modifying therapies (DMTs) for relapsing-remitting multiple sclerosis (RRMS) has been established; however, it is not clear which provides optimal value, given benefit-risk profiles and costs.

Aims: To compare the cost-effectiveness of current DMTs for patients with RRMS in the US.

Materials and methods: A Markov model predicting RRMS course following initiation of a DMT was created comparing outcomes (e.g. relapses, disease progression) and costs of natalizumab (NTZ), dimethyl fumarate (DMF), and peginterferon beta-1a (PEG) with fingolimod (FIN), glatiramer acetate (GA, 20?mg daily), and subcutaneous interferon beta-1a (IFN, 44?mcg), respectively, over 10 years. RRMS and secondary-progressive MS (SPMS) EDSS state transitions were predicted in 3-month cycles in which patients were at risk of death, relapse, or discontinuation. Upon DMT discontinuation, natural history progression and relapse rates were applied. Incremental cost-effectiveness ratios (ICERs) were estimated for the cost per relapse avoided, relapse-free years gained, progression avoided, and progression-free years gained. The impact of model parameters on outcomes was evaluated via one-way sensitivity analyses.

Results: Costs ranged from $561,177 (NTZ) to $616,251 (GA). NTZ, DMF, and PEG were dominant (less costly and more effective) compared to FIN, GA, and IFN, respectively, for all ICERs. Variability in drug costs and parameters that affected drug cost accrual (e.g. discontinuation rates and the decision to drop out after SPMS conversion) had a considerable impact on ICERs.

Limitations: Several simplifying assumptions were made that may represent potential limitations of this analysis (e.g. a constant treatment effect over time was assumed).

Conclusions: The results from this analysis suggest that the NTZ, DMF, and PEG are cost-effective DMT choices compared to FIN, GA, and IFN, respectively. The actual impact on a particular plan will vary based on drug pricing and other factors affecting drug cost accrual.     

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.     

The fiscal consequences of public health investments in disease-modifying therapies for the treatment of multiple sclerosis in Sweden

Abstract

Background and aims: The economic consequences of multiple sclerosis (MS) are broader than those observed within the health system. The progressive nature suggests that people will not be able to live a normal productive life and will gradually require public benefits to maintain living standards. This study investigates the public economic impact of MS and how investments in disease-modifying therapies (DMTs) influence the lifetime costs to government attributed to changes in lifetime tax revenue and disability benefits based on improved health status linked to delayed disease progression.

Methods: Disease progression rates from previous MS Markov cohort models were applied to interferon beta-1a, peginterferon beta-1a, dimethyl fumarate, and natalizumab using a public economic framework. The established relationship between expanded disability status scale and work-force participation, annual earnings, and disability rates for each DMT were applied. Subsequently, we assessed the effect of DMTs on discounted governmental costs consisting of health service costs, social insurance and disability costs, and changes in lifetime tax revenues.

Results: Fiscal benefits attributed to informal care and community services savings for interferon beta-1a, peginterferon beta-1a, dimethyl fumarate, and natalizumab were SEK340,387, SEK486,837, SEK257,330, and SEK958,852 compared to placebo, respectively. Tax revenue gains linked to changes in lifetime productivity for interferon beta-1a, peginterferon beta-1a, dimethyl fumarate, and natalizumab were estimated to be SEK27,474, SEK39,659, SEK21,661, and SEK75,809, with combined fiscal benefits of cost savings and tax revenue increases of SEK410,039, SEK596,592, SEK326,939, and SEK1,208,023, respectively.

Conclusion: The analysis described here illustrates the broader public economic benefits for government attributed to changes in disease status. The lifetime social insurance transfer costs were highest in non-treated patients, and lower social insurance costs were demonstrated with DMTs. These findings suggest that focusing cost-effectiveness analysis only on health costs will likely underestimate the value of DMTs.     

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 glatiramer acetate in the treatment of relapsing-remitting multiple sclerosis

SUMMARY

We have developed an economic model around the patient level data from the pivotal clinical trial for Copaxone® (glatiramer acetate), combined with published cost and natural history data, to demonstrate cost-effectiveness in relapsing-remitting multiple sclerosis (RRMS). Based upon analysis over 8 years, the cost per relapse avoided and cost per disability unit avoided was £11,000 and £8,862 respectively. To facilitate comparison with other therapies and across other disease areas we also calculated the cost per quality adjusted life year (QALY). Dependent upon the assumed utility loss associated with duration of relapse, the cost per QALY ranged between £22,586 and £64,636 over 8 years analysis. Given the nature of the disease and compared to accepted standards of cost-effectiveness in the UK, this analysis shows that glatiramer acetate is demonstrably cost-effective versus best supportive care alone.

Copaxone is a registered trademark of Teva Pharmaceutical Industries, Israel     

Glatiramer acetate and interferon beta-1a for intramuscular administration: a study of outcomes among multiple sclerosis intent-to-treat and persistent-use cohorts

Abstract

Objective:

To study outcomes of multiple sclerosis (MS) patients treated with either glatiramer acetate (Copaxone) or interferon beta-1a for once-weekly, intramuscular administration (Avonex).

Methods:

An ‘intent-to-treat’ (ITT) cohort (n?=?1282) was established, consisting of patients diagnosed with MS who began therapy on either glatiramer acetate (GA) or intramuscular interferon beta-1a (IFN beta-1a-IM) and had continuous insurance coverage from 6 months before to 24 months after the date when they began taking the medication. A ‘persistent use’ (PU) cohort (n?=?639) was also constructed, consisting of individuals who, in addition to the criteria listed above, had a claim for GA or IFN beta-1a-IM within 28 days of the end of the 2-year post-period. Data were obtained from the i3 InVision Data Mart Database from July 2001 to June 2006. Multivariate regressions were used to examine both the 2-year total direct medical costs and the likelihood of relapse associated with the use of each of these alternative MS medications. A relapse was defined as either being hospitalized with a principal diagnosis of MS or having an outpatient visit with a MS diagnosis followed within 7 days by a claim for a corticosteroid. All regressions controlled a wide range of factors that may potentially affect outcomes.

Results:

In the ITT cohort, patients who started therapy on GA had a significantly lower 2-year risk of relapse (10.01 vs. 5.18%; p?=?0.0034) as well as significantly lower 2-year total medical costs ($44,201 vs. $41,121; p?=?0.0294). In the PU cohort, patients who used GA also had a significantly lower 2-year risk of relapse (7.25 vs. 2.16%; p?=?0.0048) as well as significantly lower total medical costs ($67,744 vs. 63,714; p?=?0.0445).

Limitations:

The analyses relies on an administrative claims database of an insured population and hence, may not be generalizeable to other populations. In addition, such a database precludes measurement of lost work time, unemployment, caregiver burden or other costs associated with MS.

Conclusions:

Results from this study indicate that the use of GA is associated with significantly lower probability of relapse as well as significantly lower 2-year total direct medical costs than IFN beta-1a-IM.     

A cost utility model of interferon beta-1b in the treatment of relapsing-remitting multiple sclerosis

SUMMARY

This study estimates the long-term cost effectiveness of Betaferon®, (interferon beta-1b) in the treatment of relapsing-remitting multiple sclerosis (RRMS). Clinical trial data, natural disease history information, and costs and quality of life (EQ-5D) data, are linked using disease severity levels, via a model that accounts for the number, severity and duration of relapses, and the probability and speed of disease progression. Previous attempts at modeling the cost effectiveness of beta interferon have produced very estimates of costs per QALY gained (CQG). Increasing data availability enables the modification or replacement of many of the assumptions underlying these models. In particular, longer term modeling and the consideration of wider societal costs is appropriate in the context of this chronic disease. The evidence presented here provides much lower, and more precise, estimates of CQG. The base case 20-year model estimates a CQG of £8,100. These new estimates are in line with other recent estimates and demonstrate the cost effectiveness of beta interferon.     

Costs and effectiveness of fingolimod versus alemtuzumab in the treatment of highly active relapsing-remitting multiple sclerosis in the UK: re-treatment,discount, and disutility

Objective: Patients with relapsing-remitting multiple sclerosis (RRMS) treated with disease modifying therapies (DMTs) who continue to experience disease activity may be considered for escalation therapies such as fingolimod, or may be considered for alemtuzumab. Previous economic modeling used Markov models; applying one alternative technique, discrete event simulation (DES) modeling, allows re-treatment and long-term adverse events (AEs) to be included in the analysis.

Methods: A DES was adapted to model relapse-triggered re-treatment with alemtuzumab and the effect of including ongoing quality-adjusted life year (QALY) decrements for AEs that extend beyond previous 1-year Markov cycles. As the price to the NHS of fingolimod in the UK is unknown, due to a confidential patient access scheme (PAS), a variety of possible discounts were tested. The interaction of re-treatment assumptions for alemtuzumab with the possible discounts for fingolimod was tested to determine which DMT resulted in lower lifetime costs. The lifetime QALY results were derived from modeled treatment effect and short- and long-term AEs.

Results: Most permutations of fingolimod PAS discount and alemtuzumab re-treatment rate resulted in fingolimod being less costly than alemtuzumab. As the percentage of patients who are re-treated with alemtuzumab due to experiencing a relapse approaches 100% of those who relapse whilst on treatment, the discount required for fingolimod to be less costly drops below 5%. Consideration of treatment effect alone found alemtuzumab generated 0.2 more QALYs/patient; the inclusion of AEs up to a duration of 1 year reduced this advantage to only 0.14 QALYs/patient. Modeling AEs with a lifetime QALY decrement found that both DMTs generated very similar QALYs with the difference only 0.04 QALYs/patient.

Conclusions: When the model captured alemtuzumab re-treatment and long-term AE decrements, it was found that fingolimod is cost-effective compared to alemtuzumab, assuming application of only a modest level of confidential PAS discount.     

Cost-effectiveness of cladribine tablets,alemtuzumab, and natalizumab in the treatment of relapsing-remitting multiple sclerosis with high disease activity in England

Aims: Cladribine tablets were the first oral short-course treatment approved for highly active relapsing multiple sclerosis (MS). The Association of British Neurologists guidelines currently recommend two infusion therapies, alemtuzumab and natalizumab, to treat high disease activity relapsing remitting MS (HDA-RRMS). This analysis assessed the cost-effectiveness of cladribine tablets in HDA-RRMS compared with alemtuzumab and natalizumab, from the perspective of the National Health Service (NHS) in England.

Materials and methods: A cohort-based Markov model with 11 health states (10 Expanded Disability Status Scale [EDSS] plus death) was developed. Transition matrices from the British Columbia registry were used to model the natural history of EDSS. The treatment effect on EDSS was modelled using hazard ratios for 6-month confirmed disability progression from an indirect treatment comparison (ITC). Relapses and drug-related adverse events were modeled via annualized relapse rates and event probabilities, with associated costs and quality-adjusted life year (QALY) losses. Utilities were derived from trials and the literature, and costs from NHS and literature sources. Uncertainty was assessed via probabilistic and deterministic sensitivity analyses.

Results: Cladribine tablets were dominant (i.e., less costly and more effective) vs alemtuzumab and natalizumab in pairwise comparisons, and the dominant strategy in fully incremental analyses. Incremental cost was driven largely by drug acquisition and administration costs, and incremental QALY gain largely by differences in delayed EDSS progression. Cladribine tablets had a 93% probability of being cost-effective at a threshold of GBP 30,000 per QALY gained, and remained dominant across the scenario analyses tested. The greatest influence on results was the treatment effect on disability progression derived from the ITC.

Limitations: Uncertainty over the efficacy of DMT beyond trial durations. In line with other comparative effectiveness analyses, the network meta-analysis informing this cost-effectiveness analysis was associated with a degree of uncertainty. No treatment switching analyses were undertaken.

Conclusions: Cladribine tablets are a cost-effective alternative to alemtuzumab and natalizumab in the treatment of HDA-RRMS from the perspective of the NHS in England.     

Estimating the rates of disability progression in people with active relapsing-remitting multiple sclerosis

SUMMARY

Estimated progression rates for people with active relapsing-remitting multiple sclerosis (RRMS) are essential for resource management but are poorly quantified according to disability severity. In this study data from the placebo arm of the AFFIRM study were used to estimate rates for a population of active RRMS patients and for a rapidly evolving severe (RES) subgroup of RRMS patients. A multistate Markov model was fitted to the data to derive a matrix of annual transition probabilities between disability states. The average progression over 2 years was estimated to be 0.27 Expanded Stability Status (EDSS) points (95% confidence interval (CI) 0.11-0.43) for active RRMS patients and 0.46 EDSS points (95% CI 0.16-0.79) for the RES subgroup. When similar baseline characteristics were used, progression in the RES subgroup was approximately 0.06-0.08 EDSS points faster per year than active RRMS patients. These results may be used for long-term forecasts of progression of these patient groups when used in conjunction with transition rates from RRMS to secondary progressive multiple sclerosis, and between secondary progressive multiple sclerosis EDSS states.     

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

Background: Multiple sclerosis (MS) causes significant disability and diminished quality-of-life. Delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) is a new oral treatment for relapsing-remitting MS (RRMS) approved in the US, Australia, Canada, and Europe. Objectives: A cost-effectiveness model was developed to compare the health economic impact of DMF against other disease-modifying therapies (DMTs) as first-line RRMS treatment from a Canadian Ministry of Health perspective. Methods: A Markov cohort model was developed to simulate patients’ progression through health states based on the Kurtzke Expanded Disability Status Scale (EDSS) over a life-time horizon. Patients entered the model based on a distribution of baseline EDSS scores, from which they could progress to higher or regress to lower EDSS state, or remain in the same state. Relapses could occur at any EDSS score. Results from a mixed-treatment comparison were used to inform model inputs for disease progression and relapse rates per treatment. Costs included direct medical costs stratified by EDSS score. Utilities were accrued based on time spent in each EDSS state. Results: Compared with glatiramer acetate, DMF yielded 0.528 incremental quality-adjusted life-years (QALYs) at an incremental cost of $23 338 Canadian dollars (CAD), resulting in an incremental cost-effectiveness ratio (ICER) of CAD $44 118/QALY. The ICER for DMF compared with Rebif 44?mcg was CAD $10 672. Results were consistent across a wide range of one-way and probabilistic sensitivity analyses. Conclusions: Based on traditional cost-effectiveness thresholds in Canada (CAD $50 000–60 000), DMF can be considered a cost-effective option compared to other first-line DMTs.     

A discrete event simulation to model the cost-utility of fingolimod and natalizumab in rapidly evolving severe relapsing-remitting multiple sclerosis in the UK

Objective: Two disease-modifying therapies are licensed in the EU for use in rapidly-evolving severe (RES) relapsing-remitting multiple sclerosis (RRMS), fingolimod and natalizumab. Here a discrete event simulation (DES) model to analyze the cost-effectiveness of natalizumab and fingolimod in the RES population, from the perspective of the National Health Service (NHS) in the UK, is reported.

Methods: A DES model was developed to track individual RES patients, based on Expanded Disability Status Scale scores. Individual patient characteristics were taken from the RES sub-groups of the pivotal trials for fingolimod. Utility data were in line with previous models. Published costs were inflated to NHS cost year 2015. Owing to the confidential patient access scheme (PAS) discount applied to fingolimod in the UK, a range of discount levels were applied to the fingolimod list price, to capture the likelihood of natalizumab being cost-effective in a real-world setting.

Results: At the lower National Institute of Health and Care Excellence (NICE) threshold of £20,000/quality-adjusted life year (QALY), fingolimod only required a discount greater than 0.8% of list price to be cost-effective. At the upper threshold of £30,000/QALY employed by the NICE, fingolimod was cost-effective if the confidential discount is greater than 2.5%. Sensitivity analyses conducted using fingolimod list-price showed the model to be most sensitive to changes in the cost of each drug, particularly fingolimod.

Conclusions: The DES model shows that only a modest discount to the UK fingolimod list-price is required to make fingolimod a more cost-effective option than natalizumab in RES RRMS.     

Cost-effectiveness of alemtuzumab and natalizumab for relapsing-remitting multiple sclerosis treatment in Iran: decision analysis based on an indirect comparison

Background: Alemtuzumab and natalizumab are approved as second-line therapies for relapsing-remitting multiple sclerosis (RRMS) patients in Iran who have shown an inadequate response to other disease-modifying therapy (DMT). In the absence of head-to-head trials, evaluations based on decision analytic modeling may be a suitable alternative to compare alemtuzumab and natalizumab in RRMS.

Purpose: To evaluate the cost-effectiveness of alemtuzumab compared with natalizumab in RRMS in Iran, based on an indirect comparison of clinical trial data.

Methods: A cost-utility analysis was conducted using a cohort-based Markov model to analyze cost-utility in a cohort of 1,000 RRMS patients treated with alemtuzumab or natalizumab who had failed at least one previous DMT. Costs were measured in 2018?US Dollars, and were estimated from both the societal and National Healthcare Service (NHS) perspective over a 20-year time horizon in Iran. One-way deterministic sensitivity analyses were carried out to investigate the impact of individual variables on model results.

Results: Alemtuzumab dominated natalizumab in both NHS and societal perspective analyses. From the NHS perspective, the total discounted costs per patient were estimated at $147,417 and $150,579 for alemtuzumab and natalizumab, respectively, over 20 years. The discounted quality-adjusted life years were estimated to be 7.07 and 6.05, respectively. Results were similar for the societal perspective analysis. Results were most sensitive to acquisition costs and the time horizon, while no sensitivity was observed for Expanded Disability Status Scale (EDSS) health-states utility, relapse relative risk, adverse event or EDSS-related costs, and laboratory/monitoring costs.

Conclusion: Alemtuzumab was dominant in the treatment of RRMS compared with natalizumab due to lower total cost, greater efficacy and slowing of disease progression, and lower rate of relapses over a 20-year time horizon in Iran. Comparative head-to-head trials and long-term follow-up are needed to confirm these results.     

Fingolimod versus natalizumab in patients with relapsing remitting multiple sclerosis: a cost-effectiveness and cost-utility study in Iran

Aims: Multiple sclerosis (MS) is a chronic, autoimmune, and inflammatory disease. If the first-line medicines are not effective enough, specialists will prescribe second-line medicines, such as natalizumab and fingolimod. This study aimed to compare the cost-effectiveness and cost-utility of fingolimod with those of natalizumab in patients with relapsing-remitting multiple sclerosis (RRMS) in Iran, Fars province in 2016.

Materials and methods: This study was a cost-effectiveness and cost-utility study in which a Markov model was used. The study used the census method to evaluate 81 patients with MS in Iran, Fars province who were being treated with fingolimod and natalizumab. In this study, costs were collected from the societal perspective, and the outcomes were the mean of relapse avoided rate and QALY. The cost data collection form, Kurtzke Expanded Disability Status Scale, and EQ-5D-3L questionnaire were used to collect the required data.

Results: The results showed that, compared to natalizumab, patients who used fingolimod had decreased costs (58,087 vs 201,707), increased QALYs (8.09 vs 7.37), and a better relapse avoided rate (6.27 vs 5.83) per patient over the lifetime. The results of the sensitivity analysis showed that the results of the study were robust. Also, the results of the scatter plots showed that fingolimod was more cost-effective based on the QALY and relapse avoided rate in 62% and 56%, respectively, of the simulations for the thresholds below $15,657 for the studied patients.

Conclusions: According to the results of this study, the cost-effectiveness and cost-utility of fingolimod were higher than those of natalizumab. Therefore, it is recommended that treatment with fingolimod be the first priority of second-line treatment for MS patients, and policy-makers and health managers are encouraged to make efforts in order to increase insurance coverage and reduce the out-of-pocket payments of these patients.     

Cost-utility analysis of alemtuzumab in comparison with interferon beta,fingolimod, and natalizumab treatment for relapsing-remitting multiple sclerosis in Austria

Background: Multiple sclerosis (MS), a chronic progressive, demyelinating, inflammatory disease, affects 2.5 million people worldwide. Approximately 63% of cases are classified as relapsing–remitting MS (RRMS) at the time of diagnosis. The aim of this cost-utility analysis is to evaluate alemtuzumab vs interferon beta (intramuscular [IM] interferon beta-1a, subcutaneous [SC] interferon beta-1a, SC interferon beta-1b, and SC pegylated interferon beta-1a) in previously treated, and vs SC interferon beta-1a, fingolimod, and natalizumab in untreated RRMS patients to determine the incremental cost-effectiveness ratio among the treatment alternatives as prices, the route, and the frequency of administration of considered products vary significantly.

Methods: The primary outcome was the modeled incremental cost-effectiveness ratio (ICER; €/quality-adjusted life-year [QALY] gained). Markov modeling with a 10-year time horizon was carried out. During each 3-month cycle, patients maintained the Expanded Disability Status Scale (EDSS) score or experienced progression, developed secondary progressive MS (SPMS), or showed EDSS progression in SPMS; experienced relapses; suffered from an adverse event (AE); changed treatment; or died. A published network meta-analysis (NMA) was used for indirect comparison. The possibility of a therapy switch was considered. Clinical input data and resource utilization data were derived from the literature. Costs were extracted from price lists published in Austria and were calculated from the payer’s perspective.

Results: In treatment naïve patients, alemtuzumab is associated with costs of €132,663 and 5.25 QALYs in a 10-year time horizon. Costs for SC interferon beta amount to €164,159 and generate 4.85 QALYs. Also, in the pre-treated patients, alemtuzumab dominated comparators by accumulating higher total QALYs (4.88) and lower total costs (€137.409) compared to interferon beta-1a (€200.133), fingolimod (€240.903), and natalizumab (€247.758).

Conclusion: The analysis shows that alemtuzumab is a cost-saving alternative to treat RRMS in pre-treated and therapy naïve patients. From the patient perspective, alemtuzumab improves quality-of-life.     

Cost-minimization analysis of alemtuzumab compared to fingolimod and natalizumab for the treatment of active relapsing-remitting multiple sclerosis in the Netherlands

Aim: In active relapsing remitting multiple sclerosis (RRMS) patients requiring second-line treatment, the Dutch National Health Care Institute (ZiN) has not stated a preference for either alemtuzumab, fingolimod, or natalizumab. The aim was to give healthcare decision-makers insight into the differences in cost accumulation over time between alemtuzumab—with a unique, non-continuous treatment schedule—and fingolimod and natalizumab for second-line treatment of active RRMS patients in the Netherlands.

Methods: In line with ZiN’s assessment, a cost-minimization analysis was performed from a Dutch healthcare perspective over a 5-year time horizon. Resource use was derived from hospital protocols and summaries of product characteristics, and validated by two MS specialists. Unit costs were based on national tariffs and guidelines. Robustness of the base case results was verified with multiple sensitivity and scenario analyses.

Results: Alemtuzumab results in cost savings compared to fingolimod and natalizumab from, respectively, 3.3 and 2.8 years since treatment initiation onwards. At 5 years, total discounted costs per patient of alemtuzumab were €79,717, followed by fingolimod with €110,044 and natalizumab with €122,238, resulting in cost savings of €30,327 and €42,522 for alemtuzumab compared to fingolimod and natalizumab, respectively. Key drivers of the model are drug acquisition costs and the proportions of patients that do not require further alemtuzumab treatment after either two, three, or four courses.

Limitations: No treatment discontinuation and associated switching between treatments were incorporated. Consequences of JC virus seropositivity while continuing natalizumab treatment (e.g. additional monitoring) were omitted from the base case.

Conclusion: The current cost-minimization analysis demonstrates that, from the Dutch healthcare perspective, treating active RRMS patients with alemtuzumab results in cost savings compared to second-line alternatives fingolimod and natalizumab from ～3 years since treatment initiation onwards. After 5 years, alemtuzumab’s cost savings are estimated at €30k compared to fingolimod and €43k compared to natalizumab.     

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.     

A cost-effectiveness analysis of subcutaneous interferon beta-1a 44mcg 3-times a week vs no treatment for patients with clinically isolated syndrome in Sweden

Abstract

Objective:

To assess the cost-effectiveness of subcutaneous interferon (sc IFN) beta-1a 44?mcg 3-times weekly (tiw) vs no treatment at reducing the risk of conversion to multiple sclerosis (MS) in patients with clinically isolated syndrome (CIS) in Sweden.

Methods:

A Markov model was constructed to simulate the clinical course of patients with CIS treated with sc IFN beta-1a 44?mcg tiw or no treatment over a 40-year time horizon. Costs were estimated from a societal perspective in 2012 Swedish kronor (SEK). Treatment efficacy data were derived from the REFLEX trial; resource use and quality-of-life (QoL) data were obtained from the literature. Costs and outcomes were discounted at 3%. Sensitivity analyses explored whether results were robust to changes in input values and use of Poser criteria.

Results:

Using McDonald criteria sc IFN beta-1a was cost-saving and more effective (i.e., dominant) vs no treatment. Gains in progression free life years (PFLYs) and quality-adjusted life-years (QALYs) were 1.63 and 0.53, respectively. Projected cost savings were 270,263 SEK. For Poser criteria cost savings of 823,459 SEK were estimated, with PFLY and QALY gains of 4.12 and 1.38, respectively. Subcutaneous IFN beta-1a remained dominant from a payer perspective. Results were insensitive to key input variation. Probabilistic sensitivity analysis estimated a 99.9% likelihood of cost-effectiveness at a willingness-to-pay threshold of 500,000 SEK/QALY.

Conclusion:

Subcutaneous IFN beta-1a is a cost-effective option for the treatment of patients at high risk of MS conversion. It is associated with lower costs, greater QALY gains, and more time free of MS.

Limitations:

The risk of conversion from CIS to MS was extrapolated from 2-year trial data. Treatment benefit was assumed to persist over the model duration, although long-term data to support this are unavailable. Cost and QoL data from MS patients were assumed applicable to CIS patients.