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.

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.

[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.

Longitudinal MRI and neuropsychological assessment of patients with clinically isolated syndrome.

Cognitive impairment (CI) may occur in clinically isolated syndrome (CIS) patients. While the relationship between CI and magnetic resonance imaging (MRI) has been investigated extensively in multiple sclerosis (MS), MRI correlates of CI in CIS patients are unknown. To investigate the evolution of CI and to determine brain MRI structural correlates associated with CI in CIS patients. This prospective 24-month observational study examined 81 CIS patients treated with 30 µg of intramuscular interferon beta 1a once a week. MRI acquisition and neuropsychological (NP) assessment were performed at baseline, 6, 12 and 24 months. Participants were tested with Czech-validated version of Minimal Assessment of Cognitive Function in MS battery and MRI measures of lesion activity and burden, and global, tissue-specific and regional brain atrophy were performed. Over 24 months, 36 CIS patients developed clinically definite MS (CDMS). CI was observed in 10 (12.3 %) CIS patients at baseline and at the 24 months follow-up. Eight CIS patients changed their CI status over the follow-up (four improved and four worsened). No significant difference in development of CI was detected between stable CIS patients and those who developed CDMS. In multivariate regression and mixed-effect model analyses, no significant relationship was found between NP and MRI parameters. The lack of significant relationship between MRI metrics and cognition in this group of CIS patients could be attributed to several factors including the cognitive reserve, effect of disease-modifying therapy and relatively short follow-up period.

Interferon beta assessment in non-Chinese and Chinese subjects: pharmacokinetics and pharmacodynamic activity of an endogenous cytokine are not race dependent.

Interferon beta-1a (IFNß-1a) is a first-line therapy for relapsing multiple sclerosis when administered as 30 mcg intramuscularly (IM) once weekly. This endogenous cytokine displays pharmacokinetic (PK) attributes consistent with a glycoprotein of 20-kDa molecular weight that is administered IM. In this study, 24 healthy Chinese subjects (11 male, 13 female) each received 4 once-weekly 60-mcg IM doses of IFNß-1a. Serial blood samples were drawn for PK and pharmacodynamic (PD) assessments following the first and last dose of drug. Results were compared with historical data from a recent PK/PD assessment conducted in non-Chinese subjects. Noncompartmental analysis revealed that no meaningful differences in either IFNß-1a exposure or response were apparent between the Chinese and non-Chinese populations. Thus, it was concluded that no adjustment in dose regimen is warranted for future assessments of safety and efficacy in multiple sclerosis patients of Chinese origin.

Treatment satisfaction, adherence and behavioral assessment in patients de-escalating from natalizumab to interferon ß.

BACKGROUND: De-escalating natalizumab (NTZ) to interferon beta 1b (IFN B 1B) is a possible treatment option in multiple sclerosis (MS) patients interrupting NTZ because of increased risk of progressive multifocal leukoencephalopathy (PML). The aim of this study was to evaluate satisfaction and adherence to treatment, behavioral and fatigue changes in patients switched to IFN B 1B compared to continued NTZ treatment. METHODS: A 1 year, prospective, randomized, rater-blinded, parallel-group study. Nineteen relapsing remitting (RR) MS patients, randomly assigned to undergo either NTZ (n = 10) or IFN B 1B (n = 9) treatment, who had previously received NTZ for at least 12 months with disease stability and fearing or at risk for PML were included. Patients underwent behavioral and treatment assessments at baseline, after 24-week and 1 year follow-up. Behavioral assessment included measures of cognition, fatigue and quality of life. Treatment assessment included measures of satisfaction, persistence and adherence to treatment. Clinical-radiological disease activity and safety were also assessed. RESULTS: Baseline characteristics of patients were similar between groups except for Euro Quality Visual Analogue Scale, being higher in the NTZ group (p = 0.04). Within-group comparisons at the three time points, as well as interaction analysis of treatment effect over time did not show any statistically significant differences in behavioral or treatment assessments, but a coherent trend favoring NTZ over IFN B 1B. CONCLUSIONS: De-escalating NTZ to IFN B 1B is feasible and associated with overall good patient related outcome and persistently stable behavioral measures.

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.

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.

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.

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.

Narrative review of the literature on adherence to disease-modifying therapies among patients with multiple sclerosis.

While no curative treatment exists for multiple sclerosis (MS), several disease-modifying therapies (DMTs) have been developed to reduce relapse rates, slow disability progression, and modify the overall disease course. However, because of the chronic nature of the disease, long-term therapy adherence can be challenging for some patients with MS. Low adherence to DMTs has been shown to be associated with higher rates of disease relapses and progression as well as with an increase in medical resource utilization. As new MS treatments are developed, a comprehensive understanding of current adherence rates and the impact of adherence on clinical and economic outcomes is of particular interest. Our objective was to conduct a review of the published literature to evaluate rates of adherence to DMTs in MS and the impact of adherence on both clinical and economic outcomes from the patient and payer perspectives. Systematic literature searches were conducted using MEDLINE, EMBASE, and the Cochrane Central Register for Controlled Trials. Studies were limited to those completed on human subjects, written in the English language, and published between May 1, 2001, and May 1, 2011. Additional inclusion criteria required that studies involve a population of patients with MS, utilize the administration of DMTs, and report a measurement of adherence. Studies reporting persistence measures (e.g., treatment discontinuation rates) or rates of switching between DMTs (with no other measure of adherence reported) were excluded if they did not also assess adherence. Among the 24 studies meeting inclusion criteria, adherence to DMTs ranged from 41% to 88%. Weighted mean adherence rates were higher for intramuscular (IM) interferon beta-1a (IFNß-1a) administered once a week (69.4%), and subcutaneous (SC) IFNß-1b administered every other day (63.8%) than for SC IFNß-1a administered 3 times a week (58.4%) and glatiramer acetate administered daily (56.8%). There was a numerically greater risk of MS relapse or disease progression among patients nonadherent to therapy versus adherent patients, with findings statistically significant in 2 of 4 studies. Additionally, 2 studies showed statistically significant reductions in inpatient or emergency room utilization and total MS-related medical costs among patients adherent to therapy compared with nonadherent patients. Higher patient out-of-pocket copayments and coinsurance were significantly associated with lower adherence to DMTs, while the use of interventional or disease therapy management programs were associated with improved adherence. Lack of medication adherence remains a problem among patients with MS. Improvements in adherence have the potential to improve patient and payer burden in terms of improved clinical outcomes and lower nonpharmacy medical resource utilization.  

Cost-effectiveness analysis of interferon beta-1b for the treatment of patients with a first clinical event suggestive of multiple sclerosis.

OBJECTIVES: To assess, from a Swedish societal perspective, the cost effectiveness of interferon ß-1b (IFNB-1b) after an initial clinical event suggestive of multiple sclerosis (MS) (ie, early treatment) compared with treatment after onset of clinically definite MS (CDMS) (ie, delayed treatment). METHODS: A Markov model was developed, using patient level data from the BENEFIT trial and published literature, to estimate health outcomes and costs associated with IFNB-1b for hypothetical cohorts of patients after an initial clinical event suggestive of MS. Health states were defined by Kurtzke Expanded Disability Status Scale (EDSS) scores. Model outcomes included quality-adjusted life years (QALYs), total costs (including both direct and indirect costs), and incremental cost-effectiveness ratios. Sensitivity analyses were performed on key model parameters to assess the robustness of model results. RESULTS: In the base case scenario, early IFNB-1b treatment was economically dominant (ie, less costly and more effective) versus delayed IFNB-1b treatment when QALYs were used as the effectiveness metric. Sensitivity analyses showed that the cost-effectiveness results were sensitive to model time horizon. Compared with the delayed treatment strategy, early treatment of MS was also associated with delayed EDSS progressions, prolonged time to CDMS diagnosis, and a reduction in frequency of relapse. CONCLUSION: Early treatment with IFNB-1b for a first clinical event suggestive of MS was found to improve patient outcomes while controlling costs.

Potential health care cost savings associated with early treatment of multiple sclerosis using disease-modifying therapy.

BACKGROUND: Clinical trials have shown that treatment with disease-modifying therapies (DMTs), such as interferon, at the time of clinically isolated syndrome can delay the onset of multiple sclerosis (MS). OBJECTIVES: The objective of this study was to assess health care utilization and expenditures associated with treating patients early with DMTs rather than delaying until patients meet the full diagnostic criteria of MS. METHODS: A retrospective study used insurance claims data (2000-2008) of enrolled patients before documented MS (1 inpatient or 2 outpatient claims with International Classification of Diseases, 9th Revision, Clinical Modification 340 coding). Treatment cohorts were early DMT (DMT claim before the first documented MS; N = 227) and delayed DMT (DMT started after documented MS; N = 3724). Comparisons during 1 year of follow-up were adjusted for confounding using multivariate methods. RESULTS: Adjusted annual per-patient expenditures (including patient out of pocket) for early versus delayed were as follows: total ($28,280 vs $29,102; P = 0.44), excluding DMT cost ($15,214 vs $17,630; P < 0.01), and MS-related ($9365 vs $13,661; P < 0.01). Hospitalizations were 10.1% versus 16.5% (adjusted odds ratio [OR] = 0.51; 95% CI, 0.32-0.81). CONCLUSIONS: Analysis indicated that early DMT treatment was associated with fewer hospitalizations than delayed treatment, and there was no statistically significant difference in annual health care expenditures. This suggests that the drug costs of early therapy were offset by savings in other medical expenditures.

Effects of cohort selection on the results of cost-effectiveness analysis of disease-modifying drugs for relapsing-remitting multiple sclerosis.

BACKGROUND: Decision-analytic cost-effectiveness models are used to determine the most cost-effective treatment option on the basis of the best available data. Guidelines for pharmacoeconomic model development indicate that models should be updated as new evidence becomes available. OBJECTIVE: To evaluate the appropriateness of the clinical data that were selected for Goldberg et al.'s 2009 model of cost-effectiveness in multiple sclerosis and calculate results based on a revised cohort selection method for intramuscular (IM) interferon (IFN) beta-1a. METHODS: The original model compared cost per relapse avoided for IM IFN beta-1a, subcutaneous (SC) IFN beta-1a, IFN beta-1b, and glatiramer acetate (GA) based on intent-to-treat (ITT) results from clinical trials. However, due to lower-than-expected subject dropout rates, the IM IFN beta-1a trial had sufficient statistical power to be terminated early and was subsequently found to have met its primary endpoint, time to sustained 1.0-point Expanded Disability Status Scale progression. Within the "all-patient"(ITT) cohort (n=301), approximately 43% of patients were followed for less than 2 years; 172 patients were followed for 2 years or more. In contrast, the proportions of patients followed for at least 2 years in the clinical trials of IFN beta-1b, SC IFN beta-1a, and GA were 92%, 90%, and 86%, respectively. To test the impact of data selection on the cost-effectiveness model results, we recreated the original model using both the all-patient and 2-year cohorts from the IM IFN beta-1a pivotal trial. We then compared our results with those of the original model. RESULTS: In the original model, costs per relapse avoided were $141,721 for IM IFN beta-1a, $80,589 for SC IFN beta-1a, $87,061 for SC IFN beta-1b, and $88,310 for GA. In the reanalysis using the 2-year completer data for IM IFN beta-1a, costs per relapse avoided were $77,980 for IM IFN beta-1a, $80,121 for SC IFN beta-1a, $86,572 for IFN beta-1b, and $87,767 for GA. The cost per relapse avoided for IM IFN beta-1a was approximately 45% lower than in the original analysis, whereas the recreated results for the other 3 therapies differed from the original results by less than 1%. Sensitivity analyses showed that the recreated model was robust and that the rank order of cost-effectiveness results was unaffected by changes to any univariate parameter. CONCLUSIONS: The current study highlights the importance of data selection in cost-effectiveness analyses. After limiting the pivotal trial data for IM IFN beta-1a to patients followed for at least 2 years, we found that IM IFN beta-1a was more cost-effective than in the original analysis, while results for the other first-line disease-modifying drugs remained stable.

Assessment of new application system in Portuguese patients with relapsing-remitting multiple sclerosis.

OBJECTIVE: To evaluate the satisfaction level of multiple sclerosis (MS) patients treated with interferon beta-1b (IFNbeta-1b, Betaferon*) using a newly developed application system compared to their currently used application system. METHODS: A survey was conducted in Portugal in patients treated with IFNbeta-1b for relapsing-remitting MS with the Betaject or Betaject Lite autoinjector. Nurses demonstrated the new application system and supervised the first injection. Patients rated their overall satisfaction retrospectively with their current application system and prospectively after the first, the seventh and the 15th injection with the newly developed application system. Additionally, the ease of use was evaluated for both application systems using a questionnaire consisting of 13 questions. Responses were compiled and descriptive analyses performed. RESULTS: A total of 249 patients evaluated the current and the new system after the first, 235 after the seventh and 174 after the 15th injection. The satisfaction level was high with the current system (70.3%, 'satisfied' or 'very satisfied'). However, compared with the current system, more patients were either 'satisfied' or 'very satisfied' (98%) with the new system after first injection. Only a minority of patients rated 'somewhat satisfied': 2.0% after the first, 8.6% after the seventh, and 4.4% after the 15th injection. Increased overall satisfaction level ('satisfied' or 'very satisfied') with the newly developed system was maintained over time (98% - first, 90.5% - seventh, 93.8% - 15th injection). The thinner, pre-attached 30-gauge needle and the visual signalling of injection completion were among the changes considered as strong improvements to the new system by up to 80.3% of patients. LIMITATION: Retrospective analysis of current system. CONCLUSIONS: This survey documented patient satisfaction with different application systems of IFNbeta-1b. The increased satisfaction with the new application system indicates an improvement to the currently used injection system, which may contribute to further advancement in adherence and consequently higher clinical efficacy of treatment.

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

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.

Comparing the cost-effectiveness of disease-modifying drugs for the first-line treatment of relapsing-remitting multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an inflammatory autoimmune disorder of the central nervous system that primarily afflicts young adults. Approximately 400,000 people in the United States are affected by MS. Although several forms of MS exist, the most common course is known as relapsing-remitting MS (RRMS), which affects about 85% of MS patients. This form of MS is characterized by relapses of neurologic symptoms followed by periods of recovery. Progression of disease can lead to increasingly severe disability. Since the introduction of immunomodulatory biologic agents, such as interferon betas and glatiramer acetate, treatment has helped to change the course of the disease. Under budgetary constraints, health services payers are challenged to differentiate the economic value of these agents for formulary selection and/or placement. OBJECTIVE: The primary objective of this analysis was to evaluate the 2-year cost-effectiveness of 4 disease modifying drugs (DMDs) used as first-line treatment of RRMS: glatiramer acetate, interferon (IFN) Beta-1a IM injection, IFN Beta-1a SC injection, and IFN Beta-1b SC injection. METHODS: An Excel-based model was developed to compare the relative effectiveness and cost components of relapses, disability progression, and DMDs in the treatment of RRMS over a 2-year time horizon. The relative risk reduction (RRR) method was used to compare reduction in relapse rates and disease progression data from pivotal randomized double-blind placebo-controlled clinical trials of the DMDs. RRRs for relapses and disability progression, respectively, were calculated as the relative difference (treatment vs. placebo) in relapse rates and disease progression rates from placebo-controlled clinical trials. These RRRs were applied to the weighted average rates of relapse and number of disability progression steps seen in the placebo arms of the pivotal studies. The evaluation was conducted from the perspective of a U.S. health care payer (only direct medical costs considered). Medical savings were calculated as costs saved due to relapses avoided and prevention in disability progression steps. In the base case analysis, we assumed 89.4% persistence, a cost per relapse of $4,682, and a cost per disability progression step of $1,788. Monthly cost of therapy was defined as wholesale acquisition cost ($0 contractual discounts and $25 patient copayment assumed in the base case analysis) plus routine monitoring costs as assessed by an expert panel. The primary economic endpoint was cost per relapse avoided. Costs and outcomes occurring in the second year were discounted 3% to bring to 2008 present values. Oneway and multiway probabilistic (Monte Carlo) sensitivity analyses were conducted on key input variables to assess their impact on cost per relapse avoided. RESULTS: Without DMD treatment, patients were predicted to experience 2.55 relapses and 0.44 disability progression steps over a 2-year period (discounted values). The 2-year reductions in clinical relapses for treatment with glatiramer acetate, IFN Beta-1a IM injection, IFN Beta-1a SC injection, and IFN Beta-1b were 0.66, 0.42, 0.74, and 0.70, respectively. The 2-year reductions in disability progression steps for treatment with glatiramer acetate, IFN Beta-1a IM injection, IFN Beta-1a SC injection, and IFN Beta-1b were 0.05, 0.15, 0.12, and 0.11, respectively. In the base case analysis, IFN Beta-1a SC injection, IFN Beta-1b SC injection, and glatiramer acetate had the most favorable costs per relapse avoided ($80,589; $87,061; and $88,310; respectively) and IFN Beta-1a IM injection had the least favorable cost-effectiveness ratio ($141,721 per relapse avoided). Sensitivity analyses showed that these results were robust to changes in key input parameters, such as the number of relapses and disease progression steps in untreated patients, the RRR in clinical relapse and progression rates, the rate of persistence, the average cost of relapse, and the average cost of a disease progression step. CONCLUSION: This evaluation suggests that IFN Beta-1a SC injection, IFN Beta-1b SC injection, and glatiramer acetate represent the most cost-effective DMDs for the treatment of RRMS, where cost-effectiveness is defined as cost per relapse avoided, assuming that (a) the RRR in relapses and disease progression steps calculated from multiple DMD placebo-controlled clinical trials reflect real differences among DMDs over 2 years; and (b) resource unit costs derived from published sources reflect economic consequences of relapses and disease progression.