Cost-effectiveness analysis of escalating to natalizumab or switching among immunomodulators in relapsing-remitting multiple sclerosis in Italy.

BACKGROUND: Published literature suggests that early treatment with natalizumab ("escalation strategy") is more effective than switch within the same class of immunomodulators (interferons/glatiramer acetate, "switching strategy") in relapsing-remitting multiple sclerosis (RRMS) patients who failed first-line self-injectable disease-modifying treatment (DMT). The present analysis aims to evaluate the cost-effectiveness profile of escalation strategy vs. switching strategy, adopting the Italian societal perspective. METHODS: A lifetime horizon Markov model was developed to compare early escalation to natalizumab vs. switching among immunomodulators, followed by subsequent escalation to natalizumab. The two compared treatment algorithms were: a) early escalation until progression to Expanded Disability Status Scale (EDSS) = 7.0 vs. b) switching until EDSS = 4.0, followed by escalation until EDSS = 7.0. The model analyzed social costs, quality-adjusted survival and effects of therapies in prolonging time without disability progression and burden of relapses. Clinical data were mainly extracted from a published observational study. RESULTS: Lifetime costs of early escalation to natalizumab and switching among immunomodulators amounted to €699,700 and €718,600 per patient, respectively. Early escalation was associated with prolonged quality-adjusted survival (11.19 vs. 9.67 QALYs, + 15.8%). A slight overall survival increase was also observed (20.10 vs. 19.67 life years). Both deterministic and probabilistic sensitivity analyses confirmed the robustness of findings. CONCLUSIONS: Adopting the Italian social perspective, early escalation to natalizumab is dominant vs. switching among immunomodulators, in RRMS patients who do not respond adequately to conventional immunomodulators.

Intravenous or subcutaneous natalizumab in patients with relapsing-remitting multiple sclerosis: investigation on efficiency and savings-the EASIER study.

INTRODUCTION: EASIER is a multicenter, observational, cross-sectional study investigating the consumption of healthcare resources, including healthcare professional (HCP) active working time, the costs associated with the current natalizumab intravenous (IV) administration, and the potential impact of the adoption of subcutaneous (SC) route. METHODS: The EASIER study has three parts: (1) time and motion study to measure healthcare resources and working time needed for natalizumab IV administration using a digital data collection tool operated directly by HCPs; (2) HCP structured questionnaire-based estimation of the potential impact of natalizumab SC vs. IV administration; and (3) patient survey on the burden of natalizumab administration. RESULTS: Nine Italian multiple sclerosis (MS) centers measured 404 IV natalizumab administration procedures and administered 26 HCP questionnaires and 297 patient questionnaires. Patients had a mean of 52 (range 1-176) previous IV administrations and spent a mean (median, IQR) of 152 (130, 94-184) minutes in the center per each IV procedure, with IV infusion covering 50% of the total. Including patient travel time, an average of 5 h was dedicated to each IV administration. Active working time by HCP amounted to 29 min per IV administration procedure, 70% of which by nursing staff. With adoption of the SC route, HCPs estimated a 50% reduction in patient procedure time and 55% lower HCP active working time. This translated into a 63% cost reduction for the MS center per natalizumab administration procedure. CONCLUSIONS: SC natalizumab administration will consistently reduce consumption of patient and HCP times per procedure and associated costs.

The cost of first-ever stroke in Valle d'Aosta, Italy: linking clinical registries and administrative data.

BACKGROUND: Stroke is one of the most relevant reasons of death and disability worldwide. Many cost of illness studies have been performed to evaluate direct and indirect costs of ischaemic stroke, especially within the first year after the acute episode, using different methodologies. METHODS: We conducted a longitudinal, retrospective, bottom-up cost of illness study, to evaluate clinical and economic outcomes of a cohort of patients affected by a first cerebrovascular event, including subjects with ischaemic, haemorrhagic or transient episodes. The analysis intended to detect direct costs, within 1, 2 and 3 years from the index event. Clinical patient data collected in regional disease registry were integrated and linked to regional administrative databases to perform the analysis. RESULTS: The analysis of costs within the first year from the index event included 800 patients. The majority of patients (71.5%) were affected by ischaemic stroke. Overall, per patient costs were €7,079. Overall costs significantly differ according to the type of stroke, with costs for haemorrhagic stroke and ischaemic stroke amounting to €9,044 and €7,289. Hospital costs, including inpatient rehabilitation, were driver of expenditure, accounting for 89.5% of total costs. The multiple regression model showed that sex, level of physical disability and level of neurological deficit predict direct healthcare costs within 1 year. The analysis at 2 and 3 years (per patient costs: €7,901 and €8,874, respectively) showed that majority of costs are concentrated in the first months after the acute event. CONCLUSIONS: This cost analysis highlights the importance to set up significant prevention programs to reduce the economic burden of stroke, which is mostly attributable to hospital and inpatient rehabilitation costs immediately after the acute episode. Although some limitation typical of retrospective analyses the approach of linking clinical and administrative database is a power tool to obtain useful information for healthcare planning.

Healthcare resource utilization and costs for extended interval dosing of natalizumab in multiple sclerosis.

Aims: Natalizumab is approved as an infusion every 4 weeks (standard-interval dosing [SID]) in relapsing-remitting multiple sclerosis (MS). Extended-interval dosing (EID) reduces risk of progressive multifocal leukoencephalopathy (PML) compared with SID, but the impact on healthcare resources and costs remains unknown. Methods: In this population-based study, we included 208 natalizumab-treated MS patients who were classified into EID (≤15 infusions in the previous 18 months; n = 51; age = 33.7 ± 11.1 years; female = 72.5%) and SID (>15 infusions in the previous 18 months; n = 157; age = 36.5 ± 10.8 years; female = 68.1%) groups. Results: Natalizumab EID had fewer MS outpatient visits (p = 0.01) and related costs (p = 0.03), and lower natalizumab costs (p < 0.01) compared with SID, without changes in other healthcare resources and costs. Conclusion: Natalizumab EID is associated with reduced direct treatment costs, apparently without additional healthcare burden.

The Cost of Relapsing-Remitting Multiple Sclerosis Patients Who Develop Neutralizing Antibodies during Interferon Beta Therapy.

BACKGROUND: Relapsing Remitting Multiple Sclerosis (RRMS) patients treated with interferon beta (IFN beta) can develop neutralizing antibodies (NAbs) that reduce treatment efficacy. Several clinical studies explored the association of NAb+ status with increased disease activity. OBJECTIVE: The aim of this study was to estimate the cost of RRMS patients who develop NAbs while treated with IFN beta by the Italian National Healthcare Service (NHS) and the Italian Society perspectives. METHODS: The clinical data derived from a published observational study on 567 RRMS Italian patients treated with IFN beta. The management cost data derived from the published literature. Cost data were inflated to Euro 2014. RESULTS: The annual direct cost to treat a patient was estimated in €15,428 in the NAb+ cohort and €14,317 in the NAb- cohort. The annual societal cost was estimated in €33,890 and €30,790 in NAb+ and NAb- patients, respectively. The cost increase related to the NAb+ status was €3,100 in the Italian societal perspective and €1,111 in the Italian NHS perspective. CONCLUSION: The results of this economic evaluation suggest the presence of an association between NAb+ status and increased costs for the management of RRMS in Italy. Further pharmacoeconomic research will be needed to confirm this first result.

An economic evaluation based on a randomized placebo-controlled trial of varenicline in smokers with cardiovascular disease: results for Belgium, Spain, Portugal, and Italy.

BACKGROUND: An estimated 17.2% of patients continue to smoke following diagnosis of cardiovascular disease (CVD). To reduce the risk of further morbidity or mortality in cardiovascular patients, smoking cessation has been shown to reduce the risk of mortality by 36% and myocardial infarction by 32%. The objective of this study was to evaluate the long-term health and economic consequences of smoking cessation in patients with CVD. DESIGN AND METHODS: Results of a randomized clinical trial comparing varenicline plus counselling vs. placebo plus counselling were extrapolated using a Markov model to simulate the lifetime costs and health consequences of smoking cessation in patients with stable CVD. For the base case, we considered a payer's perspective including direct costs attributed to the healthcare provider, measuring cumulative life years (LY) and quality adjusted life (QALY) years as outcome measures. Secondary analyses were conducted from a societal perspective, evaluating lost productivity due to premature mortality. Sensitivity and subgroup analyses were also undertaken. Results were analysed for Belgium, Spain, Portugal, and Italy. RESULTS: Varenicline plus counselling was associated with a gain in LY and QALY across all countries; relative to placebo plus counselling. From a payer's perspective, incremental cost effectiveness ratios were € 6120 (Belgium), € 5151 (Spain), € 5357 (Portugal), and € 5433 (Italy) per QALY gained. From a societal perspective, varenicline in addition to counselling was less costly than placebo and counselling in all cases. Sensitivity analyses showed little sensitivity in outcomes to model assumptions or uncertainty in model parameters. CONCLUSIONS: Varenicline in addition to counselling is cost-effective compared to placebo and counselling in smokers with CVD.