Dataset Information

Cost-effectiveness and budget impact analysis of siponimod in the treatment of secondary progressive multiple sclerosis in Italy.

ABSTRACT:

Background

Siponimod is an effective treatment for patients with secondary progressive multiple sclerosis (SPMS), with active disease evidenced by relapses or imaging features characteristic of multiple sclerosis inflammatory activity, however there is a need to evaluate its economic value and sustainability compared to other disease modifying-therapies (DMTs).

Objective

To estimate the siponimod cost-effectiveness profile and its relative budget impact compared with other DMTs, by using the Italian National Healthcare System perspective.

Methods

We performed: 1) a cost-effectiveness analysis (CEA) vs interferon beta-1b using an analytical Markov model and a life time-horizon, and 2) a budget impact analysis by using 3-years time-horizon. The results were reported as incremental cost-effectiveness ratio (ICER) and net-monetary benefit (NMB) for CEA, using a willingness to pay threshold of €40,000 per QALY gained, and as difference in the overall budget (Euro) between the scenario with and without siponimod for budget impact.

Results

In the base case scenario siponimod resulted cost-effective compared with interferon beta-1b 28,891€ per QALY. Overall, the market access of siponimod was associated to an increased budget of about 3€ millions (+0.9%) in the next 3 years simulated.

Conclusion

Compared to interferon beta-1b, siponimod seems to be cost-effective in SPMS patients and sustainable, with less than 1% overall budget increased in the next 3 years. Future studies need to confirm our results in the real word setting and in other countries.

SUBMITTER: Cortesi PA

PROVIDER: S-EPMC8903273 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Cost-effectiveness and budget impact analysis of siponimod in the treatment of secondary progressive multiple sclerosis in Italy.

Cortesi Paolo Angelo PA Antonazzo Ippazio Cosimo IC Gasperini Claudio C Nica Mihaela M Ritrovato Daniela D Mantovani Lorenzo Giovanni LG

PloS one 20220308 3

<h4>Background</h4>Siponimod is an effective treatment for patients with secondary progressive multiple sclerosis (SPMS), with active disease evidenced by relapses or imaging features characteristic of multiple sclerosis inflammatory activity, however there is a need to evaluate its economic value and sustainability compared to other disease modifying-therapies (DMTs).<h4>Objective</h4>To estimate the siponimod cost-effectiveness profile and its relative budget impact compared with other DMTs, b ...[more]

PMID: 35259168

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Project description:ObjectiveThe study aim was to evaluate the cost effectiveness and budget impact of siponimod compared to interferon beta-1a for adult patients with secondary progressive multiple sclerosis (SPMS) with active disease, from a Swiss health insurance perspective.MethodsWe conducted an analysis using a Markov cohort model with a cycle length of 1 year, life-long time horizon, and discount rate of 3% for cost and health outcomes. We used a matching-adjusted indirect comparison to estimate clinical outcomes using data from the EXPAND randomised controlled trial of siponimod vs placebo and the Nordic SPMS randomised controlled trial of interferon beta-1a vs placebo as the basis for estimates of disability progression and relapse outcomes. We used 6-month confirmed disability progression results to estimate disability progression in the base-case analysis. We calculated quality-adjusted life-years (QALYs) based on an external study that administered the EQ-5D-3L questionnaire to European patients with multiple sclerosis. We included costs (Swiss Franc (CHF), year 2020) of drug acquisition/administration, adverse events and disease management. We also performed a budget impact analysis to estimate the cost over the first 3 years of introducing siponimod.ResultsFor the base case, siponimod resulted in mean incremental costs of CHF 84,901 (siponimod: CHF 567,838, interferon beta-1a: CHF 482,937) and mean incremental QALYs of 1.591 (siponimod: 7.495, interferon beta-1a: 5.905), leading to an incremental cost-effectiveness ratio of CHF 53,364 per QALY gained. In the probabilistic sensitivity analysis, the probability of the cost effectiveness of siponimod assuming a willingness-to-pay threshold of CHF 100,000 per QALY gained was 90%. Siponimod was projected to result in drug administration costs for siponimod of CHF 23,817,856 in the first 3 years after introduction, accompanied by large cost offsets in drug acquisition of other multiple sclerosis drugs. Considering drug administration, monitoring and adverse event management costs, it was estimated to result in additional healthcare costs in Switzerland of CHF 2,177,021.ConclusionsIn the base-case analysis, we found that siponimod may be cost effective for treating Swiss adult patients with SPMS with active disease. The results of the cost-effectiveness analyses are valid under the assumption that the efficacy of siponimod and the comparators on disability progression for the overall SPMS population would be the same in the active SPMS population.Clinical trial identifierNCT01665144. This economic evaluation was based on the EXPAND trial.

Project description:BACKGROUNDSiponimod (BAF312) is a selective sphingosine-1-phosphate receptor 1 and 5 (S1PR1, S1PR5) modulator recently approved for active secondary progressive multiple sclerosis (SPMS). The immunomodulatory effects of siponimod in SPMS have not been previously described.METHODSWe conducted a multicentered, randomized, double-blind, placebo-controlled AMS04 mechanistic study with 36 SPMS participants enrolled in the EXPAND trial. Gene expression profiles were analyzed using RNA derived from whole blood with Affymetrix Human Gene ST 2.1 microarray technology. We performed flow cytometry-based assays to analyze the immune cell composition and microarray gene expression analysis on peripheral blood from siponimod-treated participants with SPMS relative to baseline and placebo during the first-year randomization phase.RESULTSMicroarray analysis showed that immune-associated genes involved in T and B cell activation and receptor signaling were largely decreased by siponimod, which is consistent with the reduction in CD4+ T cells, CD8+ T cells, and B cells. Flow cytometric analysis showed that within the remaining lymphocyte subsets there was a reduction in the frequencies of CD4+ and CD8+ naive T cells and central memory cells, while T effector memory cells, antiinflammatory Th2, and T regulatory cells (Tregs) were enriched. Transitional regulatory B cells (CD24hiCD38hi) and B1 cell subsets (CD43+CD27+) were enriched, shifting the balance in favor of regulatory B cells over memory B cells. The proregulatory shift driven by siponimod treatment included a higher proliferative potential of Tregs compared with non-Tregs, and upregulated expression of PD-1 on Tregs. Additionally, a positive correlation was found between Tregs and regulatory B cells in siponimod-treated participants.CONCLUSIONThe shift toward an antiinflammatory and suppressive homeostatic immune system may contribute to the clinical efficacy of siponimod in SPMS.TRIAL REGISTRATIONNCT02330965.

Project description:BackgroundTherapeutic options targeting inflammation in multiple sclerosis (MS) have evolved rapidly for relapsing-remitting MS, whereas few therapies are available for progressive forms of MS, in particular secondary progressive MS (SPMS). The approval of siponimod for SPMS has allowed for optimism in the otherwise discouraging therapeutic landscape.MethodsWe conducted a retrospective, multicenter, non-interventional study analyzing the efficacy and safety of siponimod under real-world conditions in 227 SPMS patients. According to the retrospective study framework, data was acquired at prespecified time points. Clinical readouts were assessed every three months. Disease progression was determined as increase in expanded disability status scale (EDSS), radiological progression, or the occurrence of new relapses under treatment. For safety analyses, adverse events (AE) and reasons for discontinuation were documented. The collected data points were analyzed at baseline and after 6, 12 and 18 months. However, data were predominately collected at the 6- and 12-month time points as many patients were lost to follow-up. In a group consisting of 41 patients, a more detailed investigation regarding disease progression was conducted, including data from measurement of cognitive and motoric functions.ResultsUnder siponimod therapy, 64.8% of patients experienced sustained clinical disease stability at 12 months. Out of the stable patients 21.4% of patients improved. Of the remaining patients, 31.5% experienced EDSS progression, 3.7% worsened without meeting the threshold for progression. Relapses occurred in 7.4%. Radiological disease activity was detected in 24.1% of patients after six months of treatment and in 29.6% of patients at 12 months follow-up. The in-depth cohort consisting of 41 patients demonstrated no substantial changes in cognitive abilities measured by Paced Auditory Serial Addition Test and Symbol Digit Modalities Test or motoric functions measured with Timed 25-Foot Walk, 100-m timed test, and 9-Hole Peg Test throughout the 12-month study period. Radiological assessment showed a stable volume of white and grey matter, as well as a stable lesion count at 12 months follow-up. AE were observed in nearly half of the included patients, with lymphopenia being the most common. Due to disease progression or AE, 31.2% of patients discontinued therapy.ConclusionTreatment with siponimod had an overall stabilizing effect regarding clinical and radiological outcome measures. However, there is a need for more intensive treatment management and monitoring to identify disease progression and AE.

Project description:BackgroundCirculating immune cells play a pathogenic role in multiple sclerosis (MS). However, the role of specific lymphocyte subpopulations is not unveiled yet, especially in progressive stages. We aimed to investigate lymphocyte changes during siponimod treatment in active secondary progressive MS (aSPMS) and their associations with clinical outcomes.MethodsWe enrolled 46 aSPMS patients starting on siponimod treatment with at least 6 months of follow-up and two visits within the scheduled timeframes and 14 sex- and age-matched healthy controls (HCs). Clinical and laboratory data were collected retrospectively at baseline, 3rd, 6th, 12th, and 24th month for MS patients, and at baseline for HCs.ResultsAt baseline SPMS patients presented with increased naïve regulatory T lymphocytes (p = 0.02) vs. HCs. Over time, SPMS patients showed decreased T CD4+ (coeff. range = -24/-17, 95% CI range = -31.60 to -10.40), B lymphocyte (coeff. range = -3.77/-2.54, 95% CI range = -6.02 to -0.35), memory regulatory B cells (coeff. range = -0.78/-0.57, 95% CI range = -1.24 to -0.17) and CD4/CD8 ratio (coeff. range = -4.44/-0.67, 95% CI range = -1.61 to -0.17) from month 3 thereafter vs. baseline, and reduced CD3+CD20+ lymphocytes from month 12 thereafter (coeff. range = -0.32/-0.24, 95% CI range = -0.59 to -0.03). Patients not experiencing disability progression while on siponimod treatment showed B lymphocyte reduction from month 3 (coeff. range = -4.23/-2.32, 95% CI range = -7.53 to -0.15) and CD3+CD20+ lymphocyte reduction from month 12 (coeff. range = -0.32/-0.24, 95% CI range = -0.59 to -0.03) vs. patients experiencing progression.ConclusionsPatients treated with siponimod showed a T and B lymphocyte reduction, especially CD4+, CD3+CD20+ and naïve regulatory T cells and memory regulatory B cells. Disability progression while on siponimod treatment was associated with a less pronounced effect on B and CD3+CD20+ lymphocytes.

Project description:BACKGROUND:Conversion to secondary progressive multiple sclerosis (SPMS) is associated with a relatively poor prognosis, and SPMS is responsible for the majority of the social and economic costs associated with MS. Managing the Transition to SPMS (ManTra) is a mixed methods project conducted in Italy and Germany aimed to set up a user-led resource to empower and improve the quality of life of newly diagnosed SPMS patients. AIMS:To assess the experiences and the needs of Italian people who recently converted to SPMS, patient significant others (SOs), neurologists and other health professionals (HPs). METHODS:We conducted 15 personal semistructured interviews (PSIs) with SPMS patients who transitioned up to five years, and three focus group meetings (FGMs), one of SPMS SOs, one of neurologists, and one of other HPs. Participants were purposely selected from the three geographic areas of Italy, and varied in terms of gender, education and (for patients) disease severity. PSIs and FGMs were audiorecorded, transcribed and analyzed by two researchers using the framework analysis. RESULTS:One hundred sub-categories were identified, grouped into 13 categories and four themes: 'awareness of the transition', 'communication of the transition', 'dealing with symptoms worsening', and 'needs'. The major unmet needs were collected in four dimensions 'organization and management; 'empowerment training'; 'information'; and 'policies'. CONCLUSIONS:Two are the main findings: first, the widespread lack of awareness around the transition; second, the need to improve the quality of the care pathway in the Italian context. It was particularly stressed the need for a holistic and multidisciplinary approach (with patients and SOs as members of the team), the development of an ad hoc plan of follow up visits with easy access to MS specialists' consultation/treatment; specialized training for each stakeholders; more information on SPMS, daily management and changes at policy level.

Dataset Information

Cost-effectiveness and budget impact analysis of siponimod in the treatment of secondary progressive multiple sclerosis in Italy.

Background

Objective

Methods

Results

Conclusion

Publications

Cost-effectiveness and budget impact analysis of siponimod in the treatment of secondary progressive multiple sclerosis in Italy.

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