Persistence, adherence, healthcare resource utilisation and costs for interferon Beta in multiple sclerosis: a population-based study in the Campania region (southern Italy).

BACKGROUND: To differentiate five formulations of Interferon Beta for the treatment of multiple sclerosis (MS) in clinical practice, by analysing persistence, adherence, healthcare resource utilisation and costs at population level. METHODS: In this population-based study, we included individuals with MS living in the Campania Region of Italy from 2015 to 2017, on treatment with intramuscular Interferon Beta-1a (Avonex® = 618), subcutaneous pegylated Interferon Beta-1a (Plegridy® = 259), subcutaneous Interferon Beta-1a (Rebif® = 1220), and subcutaneous Interferon Beta-1b (Betaferon® = 348; and Extavia® = 69). We recorded healthcare resource utilisation from administrative databases (hospital discharges, drug prescriptions, MS-related outpatients), and derived costs from the Regional formulary. We classified hospital admissions into MS-related and non-MS-related. Persistence (time to switch to other disease modifying treatments (DMTs)), and adherence (medication possession ratio (MPR) = medication supply obtained/medication supply expected during follow-up period) were calculated. RESULTS: Patients treated with Rebif® were younger, when compared with other Interferon Beta formulations (p < 0.01). The probability of switching to other DMTs was 60% higher for Betaferon®, 90% higher for Extavia®, and 110% higher for Plegridy®, when compared with Rebif® (p < 0.01). Plegridy® presented with 7% higher adherence (p < 0.01), and Betaferon® with 3% lower adherence (p = 0.03), when compared with Rebif®. The probability of MS-related hospital admissions was 40% higher in Avonex® (p = 0.03), 400% higher in Betaferon® (p < 0.01), and 60% higher in Plegridy® (p = 0.04), resulting into higher non-DMT-related costs, when compared with Rebif®. DISCUSSION: Interferon Beta formulations presented with different prescription patterns, persistence, adherence, healthcare resource utilisation and costs, with Rebif® being used in younger patients and with less MS-related hospital admissions.

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

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-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.

A new approach to pharmaceutical pricing based on patients' willingness to pay.

OBJECTIVES: Pharmaceutical pricing is an important and contentious issue in middle- and low-income countries. The present study evaluated a value-based pricing system for estimating the price of interferon-beta (IFN-ß). METHODS: Prices were estimated through the Willingness to Pay (WTP) system using the Discrete Choice Experiment (DCE) from the viewpoint of MS patients, levels of attributes and patients' willingness to pay for these attributes. RESULTS: The results indicate that the new approach to pricing medicines leads to more integrated prices than the current system. The current prices of four brands were higher than their pharmaceutical market price; the prices of other brands were consistent with it. CONCLUSION: Application of the proposed pricing system will help pharmaceutical companies make realistic price estimates of their products while accounting for patient preferences, which may enhance patients' adherence to treatment.

Cost-Effectiveness of Peginterferon Beta-1a and Alemtuzumab in Relapsing-Remitting Multiple Sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system, affecting 2.5 million people globally and 400,000 people in the United States. While no cure exists for MS, the goal is to manage the disease using disease-modifying therapies (DMTs), which have been shown to slow disease progression and prevent relapses. Relapsing-remitting MS (RRMS) is the most common form of MS at the time of diagnosis. Peginterferon beta-1a (PEG) and alemtuzumab (ALT) were recently approved and have demonstrated good clinical outcomes, including reduced relapse rates in clinical trials. High costs associated with these DMTs necessitates cost-effectiveness analyses to understand their overall value in RRMS management. OBJECTIVES: To assess the cost-effectiveness of (a) Model 1: PEG relative to intramuscular interferon beta-1a (IM IFN), subcutaneous interferon beta-1b (SC IFN), glatiramer acetate 20 mg per mL (GA), fingolimod (FIN), natalizumab (NAT), and dimethyl fumarate (DMF), and (b) Model 2: ALT relative to subcutaneous interferon beta-1a 44 µg (IFN beta-1a 44 µg). Both analyses were conducted from a U.S. third-party payer perspective. METHODS: Two static decision models were used to compare the cost-effectiveness of PEG and ALT over a 1-year and a 2-year time horizon, respectively. Model inputs were drug acquisition costs (wholesale acquisition cost from RED BOOK); drug administration and monitoring costs (package inserts and Centers for Medicare & Medicaid Services 2015 Physician Fee Schedule); relapse rates and relapse rate reduction (clinical trials); and cost of managing relapses (published literature). All costs were adjusted to 2015 U.S. dollars using the medical care component of the Consumer Price Index. Outcomes measured were total cost of therapy per patient, cost per relapse avoided, and incremental cost-effectiveness ratios (ICERs) calculated as cost per relapse avoided. Sensitivity analysis was conducted to test model robustness given the uncertainty of model inputs and study assumptions. RESULTS: Model 1 results showed that PEG dominated IM IFN and GA, compared with SC IFN; PEG had an ICER of $1,978,000 per relapse avoided. Compared with FIN, NAT, and DMF, PEG was less expensive and less effective. Model 2 showed that ALT had an ICER of $25,276 per relapse avoided relative to IFN beta-1a 44 µg. CONCLUSIONS: In patients with RRMS, PEG is a viable alternative when compared with the DMTs in our model. Deciding whether to choose PEG over other DMTs would depend on multiple factors. On the other hand, ALT had an ICER of $25,276 cost per relapse avoided relative to IFN beta-1a 44 µg. The study results will assist payers in evaluating different medication choices for effective therapy. DISCLOSURES: No outside funding supported this study. Kamal has received research funding from Novartis Pharmaceuticals and the College of Psychiatric and Neurologic Pharmacists and also serves as a consultant for the Lynx Group. Dashputre and Pawar report no conflicts of interest. Study concept and design were primarily contributed by Dashputre, along with Kamal and Pawar. Dashputre took the lead in data collection, along with Kamal, and data analysis was performed by Dashputre, Kamal, and Pawar. The manuscript was written and revised primarily by Dashputre, along with Kamal and Pawar.

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

AIMS: Peginterferon beta-1a 125 mcg administered subcutaneously every 2 weeks, a new disease-modifying therapy (DMT) for relapsing-remitting multiple sclerosis (RRMS), was approved in January 2015 by the Scottish Medicines Consortium. This study assesses long-term clinical and economic outcomes of peginterferon beta-1a compared with other self-injectable DMTs (interferon beta-1a [22 mcg, 30 mcg, and 44 mcg], interferon beta-1b, and glatiramer acetate 20 mg) in the treatment of RRMS, from the National Health Service and Personal Social Services perspective in Scotland. METHODS: A previously published, validated Markov cohort model was adapted for this analysis. The model estimates changes in patient disability, occurrence of relapses, and other adverse events, and translates them into quality-adjusted life years and costs. Natural history data came from the ADVANCE trial of peginterferon beta-1a, the London Ontario (Canada) database, and a large population-based MS survey in the UK. The comparative efficacy of each DMT vs placebo was obtained from a network meta-analysis. Costs (2015 British Pounds) were obtained from public databases and literature. Clinical and economic outcomes were projected over 30 years and discounted at 3.5% per year. RESULTS: Over 30 years, peginterferon beta-1a was dominant compared with interferon beta-1a (22, 30, and 44 mcg), and interferon beta-1b, and cost-effective compared with glatiramer acetate 20 mg. Results were most sensitive to variations in each DMT's efficacy and acquisition costs. Deterministic and probabilistic sensitivity analyses confirmed the robustness of the results. LIMITATIONS: The impact of improved adherence with peginterferon beta-1a on clinical and economic outcomes and the impact of subsequent DMTs after treatment discontinuation were not considered. Oral and infused DMTs were not included as comparators. Conclusion Long-term treatment with peginterferon beta-1a improves clinical outcomes, while its cost profile makes it either dominant or cost-effective compared with other self-injectable DMTs for the treatment of RRMS in Scotland.

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.

New FDA-Approved Disease-Modifying Therapies for Multiple Sclerosis.

PURPOSE: Interferon injectables and glatiramer acetate have served as the primary disease-modifying treatments for multiple sclerosis (MS) since their introduction in the 1990s and are first-line treatments for relapsing-remitting forms of MS (RRMS). Many new drug therapies were launched since early 2010, expanding the drug treatment options considerably in a disease state that once had a limited treatment portfolio. The purpose of this review is to critically evaluate the safety profile and efficacy data of disease-modifying agents for MS approved by the US Food and Drug Administration (FDA) from 2010 to the present and provide cost and available pharmacoeconomic data about each new treatment. METHODS: Peer-reviewed clinical trials, pharmacoeconomic studies, and relevant pharmacokinetic/pharmacologic studies were identified from MEDLINE (January 2000-December 2014) by using the search terms multiple sclerosis, fingolimod, teriflunomide, alemtuzumab, dimethyl fumarate, pegylated interferon, peginterferon beta-1a, glatiramer 3 times weekly, and pharmacoeconomics. Citations from available articles were also reviewed for additional references. The databases publically available at www.clinicaltrials.gov and www.fda.gov were searched for unpublished studies or studies currently in progress. FINDINGS: A total of 5 new agents and 1 new dosage formulation were approved by the FDA for the treatment of RRMS since 2010. Peginterferon beta-1a and high-dose glatiramer acetate represent 2 new effective injectable options for MS that reduce burden of administration seen with traditional interferon and low-dose glatiramer acetate. Fingolimod, teriflunomide, and dimethyl fumarate represent new oral agents available for MS, and their efficacy in reducing annualized relapse rates is 48% to 55%, 22% to 36.3%, and 44% to 53%, respectively, compared with placebo. Alemtuzumab is a biologic given over a 2-year span that reduced annualized relapse rates by 55% in treatment-naive patients and by 49% in patients relapsing on prior disease-modifying agents. Treatment emergent adverse effects were common with all new drug treatments. The cost of treating MS remains high, because MS therapies accounted for the highest spending growth of any specialty drug class in 2013. Most therapies cost, on average, US $6000/mo based on wholesale acquisition cost, and few cost-benefit studies are available for new treatments. IMPLICATIONS: With expansion of new treatments, patients and providers now have multiple options and improved flexibility in managing MS. The relative place in therapy of new treatments is unknown, and treatment decisions are largely based on patient preference, efficacy, and risk potential. The cost of treating MS continues to be high, even with more treatment options available.

Effectiveness and cost-effectiveness of interferon beta and glatiramer acetate in the UK Multiple Sclerosis Risk Sharing Scheme at 6 years: a clinical cohort study with natural history comparator.

BACKGROUND: In 2002, the UK's National Institute for Clinical Excellence (NICE) concluded that interferon beta and glatiramer acetate would be cost effective as disease-modifying therapies (DMTs) for multiple sclerosis only if the short-term disability benefits reported in clinical trials were maintained. The UK Multiple Sclerosis Risk Sharing Scheme (RSS) was established to assess whether disability progression was consistent with a cost-effectiveness target of £36 000 per quality-adjusted life-year projected over 20 years. We aimed to evaluate the long-term effectiveness and cost-effectiveness of these DMTs by comparing a cohort of patients with relapsing-remitting multiple sclerosis enrolled in the UK RSS with a natural history cohort from British Columbia, Canada. METHODS: In our clinical cohort we included patients starting a DMT who were enrolled in the UK RSS who had relapsing multiple sclerosis at baseline and had at least one further clinical assessment. In our control cohort we included patients in the British Columbia multiple sclerosis database (BCMS; data collection 1980-96) who met the same eligibility criteria as for the RSS cohort. We compared disability progression at 6 years for RSS patients with untreated progression modelled from BCMS patients using continuous Markov and multilevel models. The primary outcomes were the progression ratio (treated vs untreated) measured both in Expanded Disability Status Scale (EDSS) score and utility. A ratio of less than 100% for EDSS implied slower than expected progression on treatment compared with off treatment; a utility ratio of 62% or less implied that the DMTs were cost effective. FINDINGS: 5610 patients starting a DMT were enrolled in the UK RSS between Jan 14, 2002, and July 13, 2005 (72 sites), of whom 4137 were included in our clinical cohort. We included 898 BCMS patients in the control cohort who met the RSS inclusion criteria and had at least one EDSS score after baseline. RSS patients had a mean follow-up of 5·1 years (SD 1·4). Both models showed slower EDSS progression than predicted for untreated controls (Markov model, 75·8% [95% CI 71·4-80·2]; multilevel model, 60·0% [56·6-63·4]). Utility ratios were consistent with cost-effectiveness (Markov model, 58·5% [95% CI 54·2-62·8]; multilevel model, 57·1% [53·0-61·2]). INTERPRETATION: Findings from this large observational study of treatment with interferon beta or glatiramer acetate provide evidence that their effects on disability in patients with relapsing-remitting multiple sclerosis are maintained and cost effective over 6 years. Similar modelling approaches could be applied to other chronic diseases for which long-term controlled trials are not feasible. FUNDING: Health Departments of England, Wales, Scotland, and Northern Ireland, Biogen Idec, Merck Serono, Bayer Schering Pharmaceuticals, Teva Pharmaceuticals Industries, UK National Institute of Health Research's Health Technology Assessment Programme.

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.

[Pharmacoeconomic analysis of the efficacy of natalizumab in relapsing-remitting multiple sclerosis].

OBJECTIVE: To perform pharmacoeconomic assessment of interferone-1a for intramuscular and subcortical infusions, interferon-beta-1b, glatiramer acetate and natalizumab in the treatment of relapsing-remitting multiple sclerosis (RRMS). MATERIAL AND METHODS: Modeling and "cost-effectiveness" analysis as well as evaluation of "disease cost" were performed. A model was based on the data on the efficacy of the drugs, summarized in the meta-analysis of G.Filippini et al, and treatment costs in the Russian health care system. To compare the efficacy, we used a criteria of "reduction of the risk of 1 and more relapses during 2 years of treatment compared to placebo". The analysis of treatment costs of patients with RRMS included direct treatment costs during the remission, medical care costs and costs of disease-modifying drugs (DMD). The analysis of direct costs was performed using standards of treatment of patients with multiple sclerosis. The duration of the study was 2 years. RESULTS AND CONCLUSION: Based on the meta analysis, we calculated the relative decrease of the risk of 1 and more relapses during 2 years of treatment as 3,6 % for interferon-beta-1b for intramuscular infusions (avonex), 15,2% for interferon-beta-1b for subcortical infusions (rebif), 10,5% for interferon-beta-1b for (betaferon), 21,6% for glatiramer acetate (copaxone), 42,8% for natalizumab (tisabri). For 2 years, total management costs per patient were 1567082,98 rub for avonex, 1563369,38 rub for rebif, 1322 635,80 for betaferon, 1 459 976,15 rub. for copaxone and 2 694 699,35 rub. for tisabri. The minimal cost/effectiveness ratio (62 960,27 rub.) was calculated for natalizumab. This drug was most preferable in terms of economic effectiveness.

[The cost-effectiveness of interferon beta treatment in patients with a clinically isolated syndrome in Colombia]. / Costo-efectividad del tratamiento con interferón beta en pacientes con síndrome clínico aislado de alto riesgo en Colombia.

INTRODUCTION: Approximately 85% of patients with multiple sclerosis have an initial demyelinating event. Treatment with interferon beta delays the progression of multiple sclerosis for nearly two years in patients with a clinically isolated syndrome. In Colombia, interferon is very expensive when compared to other countries. OBJECTIVE: We sought to determine the cost-effectiveness of a two-year interferon beta treatment within Colombia in patients with a clinically isolated syndrome. MATERIALS AND METHODS: Based on patient and society perspectives, a cost-effectiveness analysis was conducted using a decision tree. A variety of probabilities were defined after a systematic review of the available literature. The disease costs were calculated by reviewing medical charts at the Hospital San Ignacio University and surveys completed by multiple sclerosis patients. To control for uncertainty in these data, analysis of approximately one-thousand patients was performed using Monte Carlo methods. RESULTS: The two-year treatment cost per patient exceeds Col$ 95,000,000 (US$ 50,000). Approximately 80 % of this cost corresponds to medications (US$ 40,500). The price of relapse and indirect costs totals Col$ 41,632,149 (US$ 21,744) and Col$ 11,656,389 (US$ 6,088), respectively. Treatment represents an increase of 0.06 quality-adjusted life years (QALY). The incremental cost-effectiveness ratio exceeds the threshold, regardless of the use of Monte Carlo methods for analysis. CONCLUSION: Administering interferon beta over the course of two years to high-risk patients with a clinically isolated syndrome is not cost-effective within Colombia.

Costo-efectividad del tratamiento con interferón beta en pacientes con síndrome clínico aislado de alto riesgo en Colombia / The cost-effectiveness of interferon beta treatment in patients with a clinically isolated syndrome in Colombia

Introducción. En 85 % de los pacientes con esclerosis múltiple se presenta como manifestación inicial un primer evento desmielinizante o síndrome clínico aislado. En estos casos, el tratamiento con interferón beta retrasa hasta dos años la progresión a esclerosis múltiple. Sin embargo, en Colombia este medicamento es costoso. Objetivo. Determinar si el tratamiento del síndrome clínico aislado con interferón beta es costo-efectivo al retrasar la esclerosis múltiple en dos años. Materiales y métodos. Se realizó un análisis de costo-efectividad empleando un árbol de decisiones basado en la perspectiva del paciente y la sociedad. A partir de una revisión sistemática de la literatura y de conceptos de expertos se definieron las diversas probabilidades. Los costos de la enfermedad se calcularon por medio de la revisión de historias y la aplicación de encuestas a los pacientes atendidos en el Hospital Universitario San Ignacio. Para controlar la incertidumbre se realizó un análisis de sensibilidad mediante una simulación de Monte Carlo con mil pacientes. Resultados. El costo del tratamiento con interferón sobrepasa los Col$ 95´000.000 (US$ 50.000) por paciente durante los dos años. Aproximadamente, 80 % corresponde a los costos del medicamento. El costo de la recaída se acerca a Col$ 39´139.200 (US$ 21.744), y los costos indirectos corresponden a Col$ 10´958.400 (US$ 6.088). La tasa representativa del mercado fue de Col$ 1.800. Con el tratamiento se ganan sólo 0,06 años de vida ajustados por discapacidad (AVAD) adicionales. La razón de costo-efectividad ‘incremental´ (sic.) supera el umbral, incluso en el análisis de sensibilidad. Conclusión. La administración de interferón beta en pacientes con síndrome clínico aislado de alto riesgo en los primeros dos años no es costo-efectiva en Colombia.

Introduction: Approximately 85% of patients with multiple sclerosis have an initial demyelinating event. Treatment with interferon beta delays the progression of multiple sclerosis for nearly two years in patients with a clinically isolated syndrome. In Colombia, interferon is very expensive when compared to other countries. Objective: We sought to determine the cost-effectiveness of a two-year interferon beta treatment within Colombia in patients with a clinically isolated syndrome. Materials and methods: Based on patient and society perspectives, a cost-effectiveness analysis was conducted using a decision tree. A variety of probabilities were defined after a systematic review of the available literature. The disease costs were calculated by reviewing medical charts at the Hospital San Ignacio University and surveys completed by multiple sclerosis patients. To control for uncertainty in these data, analysis of approximately one-thousand patients was performed using Monte Carlo methods. Results: The two-year treatment cost per patient exceeds Col$ 95,000,000 (US$ 50,000). Approximately 80 % of this cost corresponds to medications (US$ 40,500). The price of relapse and indirect costs totals Col$ 41,632,149 (US$ 21,744) and Col$ 11,656,389 (US$ 6,088), respectively. Treatment represents an increase of 0.06 quality-adjusted life years (QALY). The incremental cost-effectiveness ratio exceeds the threshold, regardless of the use of Monte Carlo methods for analysis. Conclusion: Administering interferon beta over the course of two years to high-risk patients with a clinically isolated syndrome is not cost-effective within Colombia.

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 of injectable disease-modifying therapies for the treatment of relapsing forms of multiple sclerosis in Spain.

OBJECTIVE: To compare the cost-effectiveness of injectable disease-modifying therapies (DMTs) for the first-line treatment of relapsing-remitting multiple sclerosis (RRMS) in Spain. METHODS: A Markov model was developed to estimate the cost-effectiveness of intramuscular interferon beta-1a (IM IFNß-1a), subcutaneous interferon beta-1a (SC IFNß-1a), interferon beta-1b (IFNß-1b) and glatiramer acetate (GA) relative to best supportive care in a hypothetical cohort of 1,000 RRMS patients in Spain. The model was developed from a societal perspective with a time horizon of 30 years. Natural history and clinical trial data were used to model relapse rates and disease progression. Cost and utility data were obtained from a published survey of multiple sclerosis patients in Spain. The primary outcome measure was cost per quality-adjusted life year (QALY) gained. Univariate and probabilistic sensitivity analyses were performed. RESULTS: Compared to best supportive care, the base case cost-effectiveness was 168,629 per QALY gained for IM IFNß-1a, 231,853 per QALY gained for IFNß-1b, 295,638 per QALY gained for SC IFNß-1a, and 318,818 per QALY gained for GA. Results were most sensitive to changes in DMT cost, utility values and treatment effect. CONCLUSIONS: In our cost-effectiveness analysis of first-line injectable DMTs in Spain, we found IM IFNß-1a to be more cost-effective than SC IFNß-1a, IFNß-1b or GA. Sensitivity analyses confirmed the robustness of these results.

Cost effectiveness analysis of Avonex and CinnoVex in Relapsing Remitting MS.

INTRODUCTION: Multiple sclerosis is a chronic and degenerative neurological disease characterized by loss of myelin sheath of some neurons in brain and spinal cord. It is associated with high economic burden due to premature deaths and high occurrence of disabilities. The aim of the current study was to determine cost effectiveness of two major products of interferon 1a in patients with relapsing-remitting multiple sclerosis. METHOD AND MATERIALS: Altogether, 140 patients who have consumed Avonex and CinnoVex in Relapsing Remitting MS for at least two years were randomly selected (70 patients in each group). Health-related quality of life (HRQoL) was assessed using the adopted MSQoL-54 instrument. Costs were measured and valued from Ministry of Health and Medical Education (MOHME) perspective. Two-way sensitivity analysis was used to check robustness of the results. RESULTS: Patients in CinnoVex group reported significantly higher scores in both physical (69.5 vs. 50.9, P<0.001) and mental (63.3 vs. 56.6, P=0.03) aspects of HRQoL than Avonex group. On the other hand, annual cost of CinnoVex and Avonex were 2410 US$ and 4515US$ per patient, respectively (P<0.001). CONCLUSIONS: The results showed that CinnoVex was dominant option over the study period. It is suggested that results of the current study should be considered in allocating resources to MS treatments in Iran. Of course, our findings should be interpreted with caution duo to short term horizon and lack of HRQoL scores at baseline (before the intervention).

Socio-economic aspects of the testing for antibodies in MS-patients under interferon therapy in Austria: a cost of illness study.

BACKGROUND: According to EU-guidelines testing patients on interferon-beta (IFNb) for the presence of neutralising antibodies (NAb) is recommended; IFNb treatment efficacy of NAb-positive patients equals that of placebo-treated patients. Economic impact of NAb testing in MS patients has not been explored yet. The aim of this analysis is to estimate the impact of NAb testing in RRMS-patients on Austria׳s health-care-system. METHODS: A decision-analytic model over 5 years was performed. The cost effectiveness of NAb testing versus no testing was evaluated. The model considers switching after relapse and withdrawal. All direct costs are based on Austrian data from 2013 and were discounted at 5% per year. The efficacy outcome measure was "relapse free". Clinical data and resource use were determined by literature. RESULTS: Total costs for all Austrian MS-patients on IFNb-therapy with testing amount to 187,554,021€ over 5 years; without testing is 175,091,300 €. Costs per relapse avoided over 5 years were 90,075€ in the NAb testing arm, and 99,535€ in the no NAb test arm, resulting in a difference of 9460€ in favour of routine NAb testing. Considering all 3590 IFNb-treated patients 2082 relapses can be avoided in the NAb testing arm versus 1759 in the no-testing arm within 5 years. Testing for NAb leads to costs per relapse avoided of 18,015€ per year versus 19,907€ when no tests are done. CONCLUSION: The results suggest that NAb testing reduces relapses and associated costs.

Upregulation of innate antiviral restricting factor expression in the cord blood and decidual tissue of HIV-infected mothers.

Programs for the prevention of mother-to-child transmission of HIV have reduced the transmission rate of perinatal HIV infection and have thereby increased the number of HIV-exposed uninfected (HEU) infants. Natural immunity to HIV-1 infection in both mothers and newborns needs to be further explored. In this study, we compared the expression of antiviral restricting factors in HIV-infected pregnant mothers treated with antiretroviral therapy (ART) in pregnancy (n=23) and in cord blood (CB) (n=16), placental tissues (n=10-13) and colostrum (n=5-6) samples and compared them to expression in samples from uninfected (UN) pregnant mothers (n=21). Mononuclear cells (MNCs) were prepared from maternal and CB samples following deliveries by cesarean section. Maternal (decidua) and fetal (chorionic villus) placental tissues were obtained, and colostrum was collected 24 h after delivery. The mRNA and protein expression levels of antiviral factors were then evaluated. We observed a significant increase in the mRNA expression levels of antiviral factors in MNCs from HIV-infected mothers and CB, including the apolipoprotein B mRNA-editing enzyme 3G (A3G), A3F, tripartite motif family-5α (TRIM-5α), TRIM-22, myxovirus resistance protein A (MxA), stimulator of interferon (IFN) genes (STING) and IFN-ß, compared with the levels detected in uninfected (UN) mother-CB pairs. Moreover, A3G transcript and protein levels and α-defensin transcript levels were decreased in the decidua of HIV-infected mothers. Decreased TRIM-5α protein levels in the villi and increased STING mRNA expression in both placental tissues were also observed in HIV-infected mothers compared with uninfected (UN) mothers. Additionally, colostrum cells from infected mothers showed increased tetherin and IFN-ß mRNA levels and CXCL9 protein levels. The data presented here indicate that antiviral restricting factor expression can be induced in utero in HIV-infected mothers. Future studies are warranted to determine whether this upregulation of antiviral factors during the perinatal period has a protective effect against HIV-1 infection.

Using observational analysis of multiple sclerosis relapse to design outcomes-based contracts for disease-modifying drugs: a feasibility assessment.

OBJECTIVE: To assess predictors and costs of multiple sclerosis (MS) relapse, a potential outcome measure in payer-manufacturer risk-sharing agreements for disease-modifying drugs (DMDs). METHODS: A retrospective cohort analysis of medical/pharmacy claims was used. Study patients had ≥1 DMD (interferon beta, glatiramer, natalizumab) claim, without DMD claims in a 6-month pre-period before DMD initiation; were aged 18-64 years and continuously enrolled from the pre-period through a 24-month post-period; and had ≥2 MS medical claims during the 30-month study period. Post-period relapse cohorts included: (1) severe (hospitalization with MS diagnosis); (2) moderate (outpatient services including intravenous methylprednisolone); and (3) none. Poisson regression modeled severe relapse frequency, logistic regression modeled ≥1 severe relapse, and generalized linear modeling predicted healthcare costs. Tested predictors included demographics, insurance type, index DMD, pre-period health status, and DMD medication possession ratio (MPR). RESULTS: Severe relapse was experienced by 14.5% and moderate relapse by 13.8% of 2291 patients. In logistic regression, severe relapse was predicted by plan type; age (odds ratio [OR] = 1.018, 95% confidence interval [CI] = 1.005-1.031); pre-period Charlson Comorbidity Index (OR = 1.307, 95% CI = 1.166-1.464); pre-period proxy measure indicating impaired activities of daily living (OR = 1.470, 95% CI = 1.134-1.905); pre-period MS hospitalization (OR = 2.174, 95% CI = 1.537-3.074); and DMD non-adherence (MPR OR = 0.101, 95% CI = 0.068-0.151). Poisson regression results were similar. Predicted mean [standard deviation] all-cause healthcare expenditures were tripled for patients with severe compared with moderate relapse ($48,173 [$8665] and $13,334 [$1929], respectively). LIMITATIONS: Commercially insured patients from a single payer; use may have been inconsistent with approved indications; proxy relapse measure may have misclassified patients. CONCLUSIONS: Severe MS relapses requiring hospitalization, although affecting less than 15% of patients initiating DMD treatment, are associated with high medical costs. The only actionable predictor of severe relapse identified in observational analysis was MPR, raising questions about the feasibility of using observational data to guide outcomes-based contracting.