Evaluation of the efficacy and cost-effectiveness of safinamide versus rasagiline: a systematic review

The present study adheres to established guidelines and has been structured in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement [13].

To our knowledge, this is the first study that compares the efficacy, safety and costs of safinamide versus rasagiline for the treatment of PD, as no other meta-analyses or systematic reviews have been published on this subject. Taking into account the considered parameters, the analysis revealed that safinamide consistently surpassed rasagiline across efficacy and safety metrics, including NNT, NNH and the LHH. Moreover, when evaluating the combined measures of efficacy and safety (NNT-NEAR), safinamide also demonstrated superior performance. In terms of cost-efficacy, safinamide outperformed rasagiline with respect to both NNT and NNT-NEAR. Additionally, safinamide presented lower costs per NNT for both On time and Off time. Although rasagiline could potentially treat a larger number of patients within a predefined pharmacy budget, safinamide showcased a more favorable responder to nonresponder ratio in all evaluated scenarios, emphasizing its superior efficacy and cost-efficiency. This comprehensive analysis underscores safinamide as a potentially more advantageous choice for the management of PD, considering both clinical outcomes and economic feasibility.

Given the financial strain on many healthcare systems, there is a critical need for treatment decisions that consider not only efficacy and safety but also economic impact [31]. Comprehensive evaluations can support clinicians, pharmacists and health managers in selecting cost-effective options. This is especially vital in PD, where increasing prevalence and treatment costs heighten the need for strategic, evidence-based therapy choices [32,33].

Previous studies have explored the efficacy, safety and cost-effectiveness of MAO-B inhibitors for PD, though with differing methodologies. In contrast, our study applies a comprehensive framework using NNT, NNH, LHH and NEAR to evaluate clinical outcomes, alongside a robust pharmacoeconomic analysis incorporating CEA, ICER and budget impact. These metrics – particularly NNT and NNH – help balance benefit and risk, and are widely recognized, including by the Spanish Society of Hospital Pharmacy [34–37]. Favorable profile of safinamide is supported by its dual mechanism of action – enhancing dopaminergic transmission and modulating glutamate – along with its reversibility, selectivity and superior bioavailability, distinguishing it among MAO-B inhibitors [38,39].

In healthcare management, the efficacy and safety of a drug, while crucial, are insufficient in isolation and must be complemented by favorable pharmacoeconomics [40]. Consequently, we have incorporated several analyses including CEA, ICER and assessments of the number of patients treatable within a fixed pharmacy budget of €100,000/year. CEA is fundamental as it evaluates the economic value of a drug by comparing the costs incurred to achieve specified health outcomes, thereby aiding decisions on drug coverage and patient access [41]. ICER plays a pivotal role in this context by providing a ratio that juxtaposes the additional cost of a drug against its health benefits relative to alternatives [42]. At last, assessing how many patients can be treated within a predetermined budget provides a tangible measure of the financial implications of drug selection. Our findings indicate that safinamide is more cost-effective, particularly evident in the ‘Off time’ and ‘On time’ metrics, where it demonstrates lower NNTs and costs per NNT compared with rasagiline. Furthermore, safinamide tends to yield a more favorable response ratio under fixed budget constraints in critical treatment areas. Although the cost per NNT may be marginally higher in some instances, the overall advantages in terms of treatment outcomes and enhanced capability to manage severe symptoms could justify the additional expenditure. In this regard, it is also important to consider broader economic impacts and health service metrics when analyzing the cost and effectiveness of any drug. The quality-adjusted life year (QALY) has served as the benchmark metric in these analyses worldwide for more than three decades, offering a standardized measure to assess how various medical interventions extend and improve the quality of patient life [43]. Within the framework of the Spanish National Health Service, a comprehensive study utilizing data from 17 regional health services established that the average cost per QALY ranges between €22,000 and €25,000 [44,45]. In the present study, QALY was not calculated because current controversies regarding QALYs impede their application in clinical decision-making [46]. For this reason, NNT, a standard clinical decision-making metric, was used [47]. The data collected showed that the incremental cost of treating with safinamide over rasagiline ranges from €1409.27 to €8171.36 in the efficacy parameters studied. Therefore, all the metrics studied indicated that the cost of improving the efficacy of the treatment in a patient by changing from rasagiline to safinamide is at least two-times lower than the established QALY threshold in Spain. This data should be taken into consideration when underscoring the economic viability of opting for safinamide, given its higher cost-effectiveness.

Concerning the economic analysis, it is also to be highlighted that this study focused solely on the monetary value of each treatment, yet the full economic impact of PD encompasses a broader array of costs directly affecting patients, their families and caretakers. A recent multinational, real-world, cost-of-illness study reported that only 9–32% of the total expenditures related to PD management in European countries correspond to drug treatments [33]. In contrast, these costs reach up to 62% and 68% in Japan and the US, respectively [33]. Therefore, it is important to note that other costs should also be considered in the comprehensive picture of PD management. While the literature lacks comprehensive analyses of the impact of safinamide and rasagiline on the overall costs of managing PD patients, other general cost studies can be interpreted to hypothesize the potential economic costs. Research indicates that PD patients who are better controlled, as measured by the UPDRS and ‘Off time’, incur lower care costs [48,49]. These observation supports the hypothesis that more effective disease management could also reduce the indirect costs associated with PD. Because safinamide resulted in a treatment that induce a lower UPDRS and lower Off time over rasagiline it is possible to speculate that safinamide also provides a lower indirect cost in the management of PD patients. In this context, the direct economic advantages observed with safinamide over rasagiline in this study might represent only a fraction of the total economic benefits that safinamide treatment could offer. Future research is needed to explore this hypothesis.

The results of the present study should be interpreted taking into account several limitations. The comparative analysis of safinamide versus rasagiline was performed using a modeling methodology rather than a direct comparison, which could impact the applicability of the findings. Regarding the cost estimation, as mentioned, it is important to note that the present study only considered medication costs, which can significantly influence the total cost-effectiveness assessment. Moreover, the costs used reflect the current prices established in Spain, a condition that may differ from other countries or that may vary substantially in the future. Finally, the dataset is exclusively derived from clinical trials; therefore, for a comprehensive evaluation of these medications in routine practice settings, the incorporation of real-world data is essential. It is also important to note that while all trials included in this review evaluated safinamide or rasagiline as adjunctive treatments to levodopa, there may have been variations in the background therapies, baseline UPDRS scores, age and disease duration among the enrolled patients. These differences may introduce heterogeneity that could influence efficacy and safety outcomes. As individual patient-level data were not available for our analysis, we could not perform adjustments for baseline comparability. This limitation should be considered when interpreting the results, as it represents a potential source of indirect comparison bias. Future studies aiming to perform a similar comparison in this condition would benefit from addressing these limitations to better inform clinical and economic decision making. Despite these limitations, we consider this study to be both unique and significant. To the best of our knowledge, this is the first report on the comparative cost-effectiveness of safinamide and rasagiline in the treatment of PD.

In conclusion, notwithstanding its intrinsic limitations, the indirect comparative analysis performed in this study suggests that safinamide exhibits enhanced efficacy and safety profiles, both individually and when considering the combination of the selected variables, compared with rasagiline. From a cost-effectiveness perspective, safinamide outperformed rasagiline in terms of the NNT and the NNT-NEAR. In this sense, it is to note that although rasagiline allows for a higher number of patients to be treated within a fixed pharmacy budget, the responder/nonresponder ratio for safinamide was superior across all comparisons. In a landscape where healthcare systems are experiencing financial strain, the significance of these findings in informing clinical practice, pharmaceutical management and healthcare policy cannot be overstated. Substantiating these observations will require future research complemented by real-world data, which promises to provide valuable and robust insights for clinicians, hospital pharmacists and health administrators.

This manuscript has been funded by Zambon Spain.

MJG Heredia has received honorariums for presentations, advice and/or attendance at scientific meetings from ABBVIE, Bial, Italfarmaco, UCB, Zambon. FPE has received honorariums for presentations, advice and/or attendance at scientific meetings from ABBVIE, Alter, Bial, Esteve, Italfarmaco, TEVA, UCB, Zambon. The authors have no other competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing and editorial assistance was provided by Content Ed Net (Madrid, Spain) with funding from Zambon Spain.

This work is licensed under the Attribution-NonCommercial-NoDerivatives 4.0 Unported License. To view a copy of this license, visit https://creativecommons.org/licenses/by-nc-nd/4.0/