
==== Front
Drugs Real World Outcomes
Drugs Real World Outcomes
Drugs - Real World Outcomes
2199-1154
2198-9788
Springer International Publishing Cham

39039377
445
10.1007/s40801-024-00445-y
Original Research Article
Impact of Third-Generation Antiseizure Medications on People with Epilepsy in a Low-Income Population: The Brivaracetam Experience in a Real-World Study
http://orcid.org/0000-0001-5268-1141
Espinosa-Jovel Camilo camiloespinosajovel@gmail.com

12
Valencia Natalia 2
Gaitán Lisa 2
Riveros Sandra 12
1 Epilepsy Program, Hospital de Kennedy, Subred de Servicios de Salud Sur Occidente, Av. 1 de Mayo #40B-54, Hospital de Kennedy, Epilepsy Program, Bogotá, Colombia
2 https://ror.org/02sqgkj21 grid.412166.6 0000 0001 2111 4451 Neurology Postgraduate Program, Universidad de la Sabana, Chía, Colombia
23 7 2024
23 7 2024
9 2024
11 3 477485
30 6 2024
© The Author(s) 2024
2024
https://creativecommons.org/licenses/by-nc/4.0/ Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.
Background

Third-generation antiseizure medications, such as brivaracetam, are recognized for their superior safety, tolerability, and pharmacokinetic profiles. However, their potential benefits are often limited in low-income populations because of challenges related to availability and affordability.

Objective

We aimed to evaluate the effectiveness and safety of brivaracetam for treating epilepsy in a low-income population, within a real-world setting.

Methods

This retrospective cohort study included individuals with epilepsy from a low-income population in Bogotá, Colombia, who were treated with brivaracetam between January 2020 and July 2023. Effectiveness (mean seizure reduction and ≥ 50% seizure reduction) and safety (retention rate and adverse events) were evaluated.

Results

A total of 106 individuals were included, with a median age of 33 years (interquartile range: 24–44). Most had focal epilepsy with a median disease duration of 25.4 years (standard deviation: 13.6). The baseline seizure frequency was 4 seizures per month (interquartile range: 2–15) and individuals had previously received a mean of 4.4 (standard deviation: 1.8) antiseizure medications. The mean percentage seizure reduction at 3, 6, and 12 months was 55.3%, 66.9%, and 63.8%, respectively. Additionally, 60%, 63.8%, and 65.9% of individuals achieved a ≥ 50% seizure reduction at 3, 6, and 12 months, respectively. Retention rate at 3 months was 89% (n = 95) and 18.7% (n = 20) reported adverse effects.

Conclusions

In a real-world setting, brivaracetam has been shown to be safe and effective for the treatment of epilepsy in individuals from a low-income population. This study suggests that people with epilepsy living in this context can significantly benefit from the use of third-generation antiseizure medications.

issue-copyright-statement© Springer Nature Switzerland AG 2024
==== Body
pmcKey Points

Few patients in low-income populations benefit from third-generation antiseizure medications. In this sociodemographic context, brivaracetam proved to be safe and effective.	
Brivaracetam exhibited a sustained response throughout the 12 months of follow-up.	
Cost-effectiveness studies should be performed in low-income populations.	

Introduction

Nearly 70% of people with epilepsy (PWE) can lead a normal life if diagnosed and treated properly [1]. However, most people with this condition living in low-income populations either do not receive treatment or receive it inappropriately [2]. This situation, known as the treatment gap, can affect up to 75% of PWE residing in low-income populations [3]. This leads to a higher risk of mortality, a lower quality of life, an increase in social stigma, and greater workplace discrimination [4]. The treatment gap in epilepsy is multifactorial and is attributed to various factors, encompassing both healthcare system-related issues and the psychosocial conditions of the PWE [5]. Nevertheless, the availability and affordability of antiseizure medications (ASM) are among the primary barriers to accessing treatment, significantly contributing to the treatment gap [6]. It has been demonstrated that the availability and affordability of ASM are limited in low-income populations, and this disparity is even more pronounced in the case of second-generation or third-generation ASM [7]. In line with this, a study found that more than 90% of high-income countries have at least one third-generation medication, in contrast, only 30% of low-income countries have access to these medications [7]. Considering all the aforementioned information, the Intersectoral Global Action Plan on epilepsy has devised a strategy to ensure that, by 2031, at least 80% of PWE have access to appropriate, affordable, and safe ASM, including those of newer generations [8]. Second-generation and third-generation ASM typically exhibit similar efficacy to those of the first generation; however, they offer several advantages in terms of safety, tolerability, and pharmacokinetic properties [9]. This has a positive impact on therapeutic adherence and, consequently, on the prognosis of the disease [10]. Nevertheless, because of availability and affordability issues, very few PWE in low-income populations can benefit from these medications [11]. In this context, the choice of ASM is often determined by costs rather than the clinical conditions and comorbidities of each individual [11].

Brivaracetam is a third-generation ASM that has been approved as adjunctive therapy for the treatment of focal seizures in both children and adults [12]. Its scientific evidence arises from various controlled clinical trials that have confirmed its effectiveness and safety [13–15]. Brivaracetam exhibits a selective affinity for the synaptic vesicle protein 2A up to 30 times greater than levetiracetam, and, unlike the latter, it presents a significantly more favorable neuropsychiatric safety profile [16, 17]. Furthermore, it has a linear pharmacokinetics that provides several therapeutic advantages. In this regard, it has a time to peak drug concentration of 1 h, reaches its steady state in less than 24–48 h, and lacks active transport across the blood–brain barrier, resulting in a highly efficient entry into the central nervous system [18]. All of the above makes brivaracetam one of the ASM with the fastest therapeutic onset and without the need for pharmacological titration [19]. In this study, we decided to assess the effectiveness and safety of brivaracetam for the treatment of epilepsy in a low-income population, within a real-world setting. To the best of our knowledge, this is one of the few published studies assessing brivaracetam in a low-income population in Latin America.

Methods

Study Participants

A retrospective cohort study that included PWE treated at a referral center for the management of epilepsy in Bogotá, Colombia (Hospital de Kennedy) was conducted. Hospital de Kennedy is a public hospital in Bogotá that serves as a third-level center for the Kennedy district and its surrounding areas, representing an estimated population of 2 million people. According to government statistics, 15.3% of the population in this area of the city is experiencing monetary poverty, 5.3% face multidimensional poverty and 3.7% of the population is in a state of extreme poverty. In addition to that, PWE living in this area of the city have a high degree of social vulnerability characterized by a low socioeconomic level, as well as high rates of illiteracy and unemployment [20]. Individuals over 18 years of age, with a diagnosis of epilepsy who were prescribed brivaracetam between January 2020 and July 2023, were included. The decision to prescribe the medication was at the discretion of the treating physician.

Data Collection and Study Variables

Data were collected retrospectively based on the review of medical records. Sociodemographic and clinical variables were obtained from the registry of the initial consultation before the initiation of brivaracetam. These included: age, sex, duration of epilepsy, type of epilepsy, etiology of epilepsy, number of ASM and type of ASM previously received, number of ASM and type of ASM being received at the time brivaracetam was prescribed, non-pharmacological alternative therapies received, indication of initiation of brivaracetam and role of brivaracetam in the antiseizure scheme (replacement for another ASM in polytherapy, conversion to monotherapy or addition to the antiseizure scheme). Baseline ictal frequency was defined as the number of monthly seizures in the month immediately preceding the initiation of brivaracetam. Post-treatment information was obtained from the review of the medical records of the consults closer to months 3, 6, and 12 after the prescription, and the mean time to those consults was calculated. For the effectiveness analysis, data were included only for individuals who demonstrated good adherence to ASM and underwent no modifications to the therapeutic scheme during the follow-up. The primary effectiveness outcome was defined as the mean percentage of seizure reduction, determined by the mean difference between baseline ictal frequency and seizure frequency at 3, 6, and 12 months. Responder rates of more than 50% and seizure freedom were calculated for the same time periods. Measures for seizure reduction were determined based on the frequency of seizures occurring within a month. For the safety analysis, we calculated the retention rate, defined as the percentage of individuals who were still receiving brivaracetam at 3 months regardless of therapeutic response and adverse effects. Adverse effects were assessed in all individuals, regardless of the duration of use, and were defined as symptoms considered by the treating physician or researcher to be directly associated with the use of brivaracetam. A sub-analysis was conducted on individuals for whom brivaracetam was used as a replacement for levetiracetam and on individuals who were converted to brivaracetam monotherapy, evaluating their effectiveness and safety. This study was approved by the institutional ethics committee, with approval number 11 of 2023.

Statistical Analysis

Descriptive statistics of the variables were performed, the Shapiro–Wilk test was used to test the distribution, and measures of central tendency were chosen according to normality. For the primary outcome, the paired Wilcoxon test was used as the initial ictal frequency distribution was non-normal. A bivariate analysis was performed to determine which baseline clinical variables were associated with a better response to brivaracetam. A bivariate analysis was performed to calculate odds ratios and to assess statistical significance. Variables that reached statistical significance were planned to be included in a logistic regression model; however, as none reached statistical significance, the model was not conducted. A statistically significant result was defined with a p-value ≤ 0.05. All analyses were performed using STATA 17. The study was written according to the STROBE guidelines.

Results

Baseline Characteristics

During the follow-up time, brivaracetam was prescribed to 111 individuals; however, five were excluded because they did not have follow-up consultations with the required information. The analyzed sample consisted of 106 individuals. The median age of the participants was 33 years (interquartile range: 24–44) and 55.7% (n = 59) were women. Most individuals had focal epilepsies of structural and unknown etiology. The mean duration of the disease prior to brivaracetam was 25.4 years (standard deviation [SD]: 13.6). In the initial evaluation before brivaracetam, individuals had a median baseline ictal frequency of four seizures per month (interquartile range: 2–15) and had previously received a mean of 4.4 (SD: 1.8) ASM. The baseline clinical characteristics are summarized in Table 1. The indication for the use of brivaracetam and its role in the therapeutic scheme are described in Table 2.Table 1 Sociodemographic and clinical characteristics at baseline

Parameter	Result	
Age, years median (IQR)	33 (24–44)	
Sex: female, n (%)	59 (55.7)	
Type of epilepsy, n (%)		
Focal	91 (85.9)	
Generalized	7 (6.6)	
Unknown	8 (7.6)	
Etiology of epilepsy, n (%)		
Unknown	49 (46.2)	
Structural	49 (46.2)	
Genetic	6 (5.7)	
Immunological	2 (1.9)	
Mean epilepsy duration in years, x¯ (SD)	25.4 (13.6)	
Baseline monthly seizure frequency, median (IQR)	4 (2–15)	
Mean number of antiseizure medications received during the course of the disease, x¯ (SD)	4.4 (1.8)	
Alternative therapies prior to starting brivaracetam, n (%)		
Epilepsy surgery	11 (10.4)	
Vagal nerve stimulation	3 (2.8)	
None	93 (87.7)	
Mean number of antiseizure medications at the time brivaracetam was prescribed, x¯ (SD)	2.3 (0.9)	
Antiseizure medications being received at the time brivaracetam was prescribed, n (%)		
Lacosamide	58 (55.7)	
Clobazam	39 (36.8)	
Levetiracetam	36 (34)	
Valproic acid	26 (24.5)	
Lamotrigine	23 (21.7)	
Carbamazepine	17 (16)	
Oxcarbazepine	10 (9)	
Clonazepam	9 (8.5)	
Cannabidiol	8 (7.6)	
Topiramate	5 (4.7)	
Divalproex sodium	4 (3.8)	
Phenobarbital	4 (3.8)	
Vigabatrin	3 (2.8)	
Mean time to the nearest follow-up consultation (days), x¯ (SD)		
At 3 months	91.8 (28.3)	
At 6 months	184.5 (28.9)	
At 12 months	356 (44.9)	
IQR interquartile range, SD standard deviation

Table 2 Indications and role of brivaracetam. Indications for initiating brivaracetam and its role within the ASM scheme. Description of the last recorded dose of brivaracetam in milligrams

Parameter	Result, n (%)	
Indication for initiating brivaracetam		
 Adverse effects with other ASM	27 (25.5)	
 Lack of seizure control	79 (74.5)	
Role of brivaracetam in the ASM scheme		
 Replacement for another ASM in polytherapy	63 (59.4)	
 Addition to the ASM scheme	35 (33)	
 Conversion to monotherapy	8 (7.6)	
Dose of brivaracetam, mg/day		
 100	50 (47.2)	
 150	8 (7.6)	
 200	48 (45.2)	
ASM antiseizure medication

Effectiveness

The effectiveness analysis was performed using information from the follow-up consults at 3, 6 and 12 months, including only those individuals who received the medication continuously and in whom no changes were made in the ASM scheme. A statistically significant difference was observed in the mean number of monthly pre-brivaracetam and post-brivaracetam seizures at 3, 6, and 12 months (Fig. 1). The mean percentage reduction in seizures was 55.3%, 66.9%, and 63.8% at 3, 6, and 12 months, respectively. The percentage of individuals who achieved a ≥ 50% reduction in seizures at 3, 6, and 12 months was 60%, 63.8%, and 65.9%, respectively. The percentage of individuals who achieved seizure freedom at 3, 6, and 12 months was 28%, 31%, and 41.5%, respectively. A sub-analysis was conducted in individuals for whom brivaracetam was used as a replacement for levetiracetam (n = 36). Of these individuals, 38.9% (n = 14) discontinued levetiracetam because of adverse effects, while 61.1% (n = 22) discontinued it because of a lack of seizure control. At 3 months of follow-up, the mean percentage of seizure reduction, the percentage of individuals with a ≥ 50% reduction, and the percentage of seizure freedom were 40.4%, 62.5%, and 29.2%, respectively (p = 0.015). Another sub-analysis was conducted on individuals who were converted to brivaracetam monotherapy (n = 8). In this group, the mean monthly seizure frequency decreased from 3.5 (SD: 24.1) at baseline to 2.25 (SD: 8.74) at the 3-month follow-up (p = 0.058), indicating a mean percentage reduction in seizures of 35.7%. A bivariate analysis was conducted to examine the statistical significance of the therapeutic response to brivaracetam in relation to all clinical variables included in this study. However, no significant association was observed, and consequently, a multivariate regression model could not be conducted.Fig. 1 Change in mean monthly seizure frequency at 3, 6, and 12 months after initiation of brivaracetam. The analysis was conducted only in patients who received the medication continuously and in whom no changes were made to the antiseizure medication scheme. The mean percentage reduction in monthly seizures was 55.3%, 66.9%, and 63.8% at 3, 6, and 12 months, respectively. * The p-value was calculated using the paired Wilcoxon test owing to the non-normal distribution of the baseline ictal frequency

Safety

Safety analysis was performed in all individuals who received brivaracetam. The retention rate at 3 months was 89% (n = 95). The discontinuation of brivaracetam was because of adverse effects in seven individuals, a lack of seizure control in two individuals, and logistic difficulties with medication delivery in two individuals. During the follow-up period, 18.7% (n = 20) of the individuals experienced adverse effects, with the most common being neuropsychiatric symptoms, dizziness, and somnolence (Table 3). No serious adverse effects were reported. A sub-analysis was conducted on individuals who were switched from levetiracetam to brivaracetam (n = 36), revealing that only 2.7% (n = 1) experienced a new adverse effect.Table 3 Adverse effects attributed to brivaracetam. Some patients experienced more than one adverse effect

Parameter	Result, n (%)	
Presence of any adverse effect	20 (18.7)	
Any neuropsychiatric adverse effects	9 (8.5)	
Irritability	5 (4.7)	
Affective	2 (1.9)	
Behavioral	2 (1.9)	
Dizziness	7 (6.6)	
Somnolence	7 (6.6)	
Fatigue	2 (1.9)	
Ecchymosis	1 (0.9)	
Insomnia	1 (0.9)	
Nausea	1 (0.9)	

Discussion

In a real-world setting, within a low-income population, brivaracetam has shown to be effective and safe for the treatment of drug-resistant epilepsies. To the best of our knowledge, this is one of the few published studies assessing brivaracetam in a low-income population in Latin America, demonstrating that PWE living in this context can significantly benefit from the use of third-generation ASM. The included individuals had long-standing epilepsy with a mean disease duration of 25.4 years. They were highly refractory to medical treatment as they had previously used a mean of 4.4 ASM and had a median baseline ictal frequency of four seizures per month. In this drug-resistant context, brivaracetam showed a positive therapeutic response that was maintained throughout the 12 months of follow-up. In fact, the percentage of individuals who achieved a ≥ 50% reduction in seizures at 3, 6, and 12 months was 60%, 63.8%, and 65.9% respectively. These results are consistent with those observed in other studies conducted in populations with similar sociodemographic conditions [21, 22]. Our effectiveness results are superior to those observed in real-world studies conducted in populations with high economic resources. For instance, a recent real-world study conducted by Villanueva et al., which assessed the effectiveness and tolerability of brivaracetam in individuals from Australia, Europe, and the USA, found that at 3, 6, and 12 months, a therapeutic response (≥ 50% seizure reduction) was achieved by 32.1%, 36.7%, and 36.9% of individuals, respectively [23]. Another real-world study from the UK reported a ≥ 50% responder rate of 30.8% [24]. In this regard, several clinical scenarios have been described in which brivaracetam appears to be particularly useful and could potentially explain our higher effectiveness results. For instance, the concomitant use of sodium channel blockers has been identified as a predictor of a favorable outcome [25]. In fact, this combination has been associated with better effectiveness, improved tolerance, higher rates of therapeutic response, lower rates of adverse effects, and a reduced likelihood of treatment withdrawal because of adverse events [25, 26]. In highly active focal epilepsies, a study demonstrated that brivaracetam was more effective in individuals experiencing fewer than five seizures per month compared with those experiencing more than 20 seizures per month (45.8% vs 22.6%, p < 0.001) [27]. In the same study, brivaracetam achieved a sustained seizure response in 51.2% of participants who had previously tried fewer than five ASM, compared with 26.5% when six or more ASM had been attempted (p < 0.001) [27]. In line with this, another study demonstrated that brivaracetam was more effective when used as early adjunctive therapy (after one to two ASM), achieving a sustained therapeutic response in 60.3% compared with 34.3% when used as late adjunctive therapy (p < 0.001) [28]. In older adults (aged over 65 years) with focal epilepsies and in individuals with post-stroke epilepsy, brivaracetam has also been shown to be particularly useful [29, 30]. We could not establish a clinical profile associated with a better response to brivaracetam; however, in our cohort, 87.7% of individuals were receiving a concomitant sodium channel blocker, had a median baseline ictal frequency of four seizures per month and had previously used a mean of 4.4 ASM. Taking into account all the information mentioned above, these findings from our population could potentially explain our higher effectiveness results.

Individuals from our cohort achieved a sustained response throughout the 12 months of follow-up. The sustained response rate has emerged as a more stringent measure of effectiveness that provides reliable information about the response to treatment [26, 31]. For brivaracetam, some prospective and retrospective studies have assessed this measure, suggesting that it has an early and sustained action [26, 31]. Our results support the idea that brivaracetam provides an advantage in this aspect. This is desirable as there is evidence that a loss of antiseizure effectiveness develops during prolonged treatment with most ASM [32]. Another important result from our cohort is that previous exposure to levetiracetam does not affect the effectiveness or safety of brivaracetam. In the 36 individuals for whom brivaracetam was used as a replacement for levetiracetam, the mean percentage of seizure reduction, the percentage of ≥ 50% seizure reduction and the percentage of seizure freedom were 40.4%, 62.5%, and 29.2%, respectively. Additionally, only one individual in this sub-population experienced adverse events after the prescription of brivaracetam. These observations suggest that the previous use of levetiracetam does not preclude the use of brivaracetam. In this regard, Hirsch et al. found that PWE previously treated with levetiracetam achieved a 21.7% of seizure freedom when switched to brivaracetam [33]. Another study conducted by Snoeren et al. found that among the non-responders to levetiracetam treatment, 46.2% had a positive response to brivaracetam treatment, and the incidence of neuropsychiatric adverse events was significantly lower (55.1% vs 22.4%, p < 0.05) [34]. This is consistent with evidence suggesting that, despite belonging to the same pharmacological class (brivaracetam and levetiracetam), there exist significant differences in the pharmacokinetics as well as in the mechanism of action, which could positively impact the therapeutic response and safety profile [35]. As mentioned before, brivaracetam exhibits a selective affinity for the synaptic vesicle protein 2A up to 30 times greater than levetiracetam, and, unlike the latter, it presents a significantly more favorable neuropsychiatric safety profile [16, 17]. Furthermore, it has a linear pharmacokinetics that provides several therapeutic advantages. In this regard, it has a time to peak drug concentration of 1 h, reaches its steady state in less than 24–48 h, and lacks active transport across the blood–brain barrier, resulting in a highly efficient entry into the central nervous system [18]. All the above makes brivaracetam one of the ASM with the fastest therapeutic onset and without the need for pharmacological titration [19].

A small number of individuals in our cohort were converted to brivaracetam monotherapy. Although this group was small, it proved to be interesting, as some drug regulatory agencies currently allow the extrapolation of monotherapy data from adjunctive therapy studies [36]. In this group, the mean monthly seizure frequency decreased from 3.5 (SD: 24.1) at baseline to 2.25 (SD: 8.74) at the 3-month follow-up (p = 0.058), indicating a mean percentage reduction in seizures of 35.7%. These findings are consistent with those recently published by Lattanzi et al., who found that at 12 months of follow-up, 58.1% of individuals were seizure free, with a retention rate of 83.9% [36]. These results suggest that in a real-life setting, brivaracetam may be useful in the treatment of focal epilepsy, not only as adjunctive therapy but also as conversion to monotherapy.

In terms of safety, the retention rate in our study was 89%, and the primary reason for withdrawal was adverse effects, consistent with findings from some of the largest real-world cohorts [23–25]. In our cohort, neuropsychiatric adverse effects were the most frequently reported, affecting 8.5% of the individuals. Among these, irritability was the most commonly described adverse effect. Nevertheless, brivaracetam appears to be a safe ASM in this regard, with a low incidence of neuropsychiatric adverse effects reported in 5.9–9.3% across the most representative real-world studies [23–25].

Our study reinforces the idea that third-generation ASM are both safe and effective for treating epilepsy in individuals residing in low-income regions of the world. Unfortunately, owing to availability and affordability issues, many individuals from these populations are unable to access the advantages offered by these newer ASM. In line with this, a recent survey revealed a significant disparity in the availability of at least one second-generation or third-generation ASM across country income classifications. More than 90% of high-income countries reported availability, whereas only 30% of low-income countries did. Additionally, certain newer ASM, including rufinamide, perampanel, and cannabinoids, were inaccessible in almost all low-income countries [7]. The most prevalent barrier to accessing newer ASM is cost. However, in the case of brivaracetam, several studies have demonstrated its cost effectiveness, resulting in potential savings for the health system in individuals with drug-resistant epilepsy, with a fixed and predictable annual cost [37–39]. These studies should be replicated within the context of low-income populations to assist physicians in these countries in choosing an ASM based on the clinical factors of each individual, rather than solely considering cost and affordability. Customized regulation of prices for ASM, expanding the coverage of individual assistance programs, enhancing governmental support, and updating the World Health Organization essential medication list, which has remained largely unchanged for the last decades, are strategies that can enhance the affordability of newer ASM across low-income regions of the world [7, 11].

The limitations to this study are proper to its retrospective nature. We acknowledge the potential for missing information and the absence of a control group; however, it is important to note that the effectiveness analysis was exclusively conducted in individuals who maintained a consistent ASM scheme during the follow-up period. Therefore, it is assumable that the described effectiveness data are directly related to brivaracetam. A selection bias might be present as PWE were collected from the database of a single hospital. Additionally, there was variability in the time to each consult; however this limitation was assessed by calculating the mean time to the follow-up consults. We were able to demonstrate that the timing of the consultations closely aligned with the desired schedule. Our results belong to a very selective population of active and severe epilepsy in a specific socioeconomic context. For these reasons, the data cannot be extrapolated to the entire population. Nevertheless, this is a real-world study from a low-income population that better reflects the effectiveness and safety of brivaracetam.

Conclusions

In a real-world setting, brivaracetam has been shown to be safe and effective for the treatment of epilepsy in individuals from a low-income population. Brivaracetam exhibited a high response rate, a substantial retention rate, and a favorable neuropsychiatric safety profile, making it a suitable alternative in this socioeconomic scenario. Our results highlight that PWE living in this context can significantly benefit from the use of third-generation ASM; however, cost-effectiveness studies should be performed in these populations. The sustained response over time is also a desirable feature that requires confirmation in studies with a different methodology.

Declarations

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflict of interest

Camilo Espinosa-Jovel has served as a paid consultant for the following pharmaceutical companies: Abbott, UCB, Biopas Laboratories, Tecnofarma. Natalia Valencia, Lisa Gaitán, and Sandra Riveros have no conflicts of interest that are directly relevant to the content of this article.

Ethics approval

This study was approved by the institutional ethics committee, with approval number 11 of 2023. We certify that the study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Consent to participate

This was a retrospective cohort study based on medical records from our institution. Therefore, the individuals included did not sign an informed consent.

Consent for publication

Not applicable.

Availability of data and material

The data that support the findings of this study are available upon reasonable request from the corresponding author.

Code availability

Not applicable.

Authors’ contributions

CE-J: conceived of the presented idea, conceived and designed the analysis, wrote the paper. NV: conceived and designed the analysis, collected the data, contributed data and analysis tools. LG: collected the data. SR: collected the data, contributed data and analysis tools. All authors have read and approved the final version of the manuscript, and agree to be accountable for the work.
==== Refs
References

1. Chen Z Brodie MJ Liew D Kwan P Treatment outcomes in patients with newly diagnosed epilepsy treated with established and new antiepileptic drugs: a 30-year longitudinal cohort study JAMA Neurol 2018 75 279 286 10.1001/jamaneurol.2017.3949 29279892
Chen Z, Brodie MJ, Liew D, Kwan P. Treatment outcomes in patients with newly diagnosed epilepsy treated with established and new antiepileptic drugs: a 30-year longitudinal cohort study. JAMA Neurol. 2018;75:279–86.29279892 10.1001/jamaneurol.2017.3949
2. Kwon CS Wagner RG Carpio A Jetté N Newton CR Thurman DJ The worldwide epilepsy treatment gap: a systematic review and recommendations for revised definitions. A report from the ILAE Epidemiology Commission Epilepsia 2022 63 551 564 10.1111/epi.17112 35001365
Kwon CS, Wagner RG, Carpio A, Jetté N, Newton CR, Thurman DJ. The worldwide epilepsy treatment gap: a systematic review and recommendations for revised definitions. A report from the ILAE Epidemiology Commission. Epilepsia. 2022;63:551–64.35001365 10.1111/epi.17112
3. Meyer AC Dua T Ma J Saxena S Birbeck G Global disparities in the epilepsy treatment gap: a systematic review Bull World Health Organ 2010 88 260 266 10.2471/BLT.09.064147 20431789
Meyer AC, Dua T, Ma J, Saxena S, Birbeck G. Global disparities in the epilepsy treatment gap: a systematic review. Bull World Health Organ. 2010;88:260–6.20431789 10.2471/BLT.09.064147
4. Espinosa-Jovel C Toledano R Aledo-Serrano Á García-Morales I Gil-Nagel A Epidemiological profile of epilepsy in low income populations Seizure. 2018 56 67 72 10.1016/j.seizure.2018.02.002 29453113
Espinosa-Jovel C, Toledano R, Aledo-Serrano Á, García-Morales I, Gil-Nagel A. Epidemiological profile of epilepsy in low income populations. Seizure. 2018;56:67–72.29453113 10.1016/j.seizure.2018.02.002
5. Mbuba CK Ngugi AK Newton CR Carter JA The epilepsy treatment gap in developing countries: a systematic review of the magnitude, causes, and intervention strategies Epilepsia 2008 49 1491 1503 10.1111/j.1528-1167.2008.01693.x 18557778
Mbuba CK, Ngugi AK, Newton CR, Carter JA. The epilepsy treatment gap in developing countries: a systematic review of the magnitude, causes, and intervention strategies. Epilepsia. 2008;49:1491–503.18557778 10.1111/j.1528-1167.2008.01693.x
6. Cameron A Bansal A Dua T Hill SR Moshe SL Mantel-Teeuwisse AK Saxena S Mapping the availability, price, and affordability of antiepileptic drugs in 46 countries Epilepsia 2012 53 962 969 10.1111/j.1528-1167.2012.03446.x 22432967
Cameron A, Bansal A, Dua T, Hill SR, Moshe SL, Mantel-Teeuwisse AK, Saxena S. Mapping the availability, price, and affordability of antiepileptic drugs in 46 countries. Epilepsia. 2012;53:962–9.22432967 10.1111/j.1528-1167.2012.03446.x
7. Pironi V Ciccone O Beghi E Paragua-Zuellig H Patel AA Giussani G Survey on the worldwide availability and affordability of antiseizure medications: report of the ILAE Task Force on Access to Treatment Epilepsia 2022 63 335 351 10.1111/epi.17155 34981508
Pironi V, Ciccone O, Beghi E, Paragua-Zuellig H, Patel AA, Giussani G, et al. Survey on the worldwide availability and affordability of antiseizure medications: report of the ILAE Task Force on Access to Treatment. Epilepsia. 2022;63:335–51.34981508 10.1111/epi.17155
8. International League Against Epilepsy International League Against Epilepsy. Intersectoral global action plan on epilepsy and other neurogical disorders (IGAP). https://www.ilae.org/about-ilae/how-the-ilae-works/policy-and-advocacy/international-epilepsy-policy/draft-intersectoral-global-action-plan-on-epilepsy-and-other-neurological-disorders/igap-strategic-objectives-and-global-targets. Accessed 6 July 2024.
9. Perucca E Brodie MJ Kwan P Tomson T 30 years of second-generation antiseizure medications: impact and future perspectives Lancet Neurol 2020 19 544 556 10.1016/S1474-4422(20)30035-1 32109411
Perucca E, Brodie MJ, Kwan P, Tomson T. 30 years of second-generation antiseizure medications: impact and future perspectives. Lancet Neurol. 2020;19:544–56.32109411 10.1016/S1474-4422(20)30035-1
10. Chen Z Brodie MJ Kwan P What has been the impact of new drug treatments on epilepsy? Curr Opin Neurol 2020 33 185 190 10.1097/WCO.0000000000000803 32049739
Chen Z, Brodie MJ, Kwan P. What has been the impact of new drug treatments on epilepsy? Curr Opin Neurol. 2020;33:185–90.32049739 10.1097/WCO.0000000000000803
11. Fong SL Le Thuy MA Lim KS Khosama H Ohnmar O Savath S Affordability of newer antiseizure medications in Asian resource-limited countries Epilepsia 2023 64 2116 2125 10.1111/epi.17668 37243851
Fong SL, Le Thuy MA, Lim KS, Khosama H, Ohnmar O, Savath S, et al. Affordability of newer antiseizure medications in Asian resource-limited countries. Epilepsia. 2023;64:2116–25.37243851 10.1111/epi.17668
12. Makke Y Abou-Khalil B Brivaracetam efficacy and safety in focal epilepsy Expert Rev Neurother 2019 19 955 964 10.1080/14737175.2019.1631160 31195850
Makke Y, Abou-Khalil B. Brivaracetam efficacy and safety in focal epilepsy. Expert Rev Neurother. 2019;19:955–64.31195850 10.1080/14737175.2019.1631160
13. Ryvlin P Werhahn KJ Blaszczyk B Johnson ME Lu S Adjunctive brivaracetam in adults with uncontrolled focal epilepsy: results from a double-blind, randomized, placebo-controlled trial Epilepsia 2014 55 47 56 10.1111/epi.12432 24256083
Ryvlin P, Werhahn KJ, Blaszczyk B, Johnson ME, Lu S. Adjunctive brivaracetam in adults with uncontrolled focal epilepsy: results from a double-blind, randomized, placebo-controlled trial. Epilepsia. 2014;55:47–56.24256083 10.1111/epi.12432
14. Klein P Schiemann J Sperling MR Whitesides J Liang W Stalvey T A randomized, double-blind, placebo-controlled, multicenter, parallel-group study to evaluate the efficacy and safety of adjunctive brivaracetam in adult patients with uncontrolled partial-onset seizures Epilepsia 2015 56 1890 1898 10.1111/epi.13212 26471380
Klein P, Schiemann J, Sperling MR, Whitesides J, Liang W, Stalvey T, et al. A randomized, double-blind, placebo-controlled, multicenter, parallel-group study to evaluate the efficacy and safety of adjunctive brivaracetam in adult patients with uncontrolled partial-onset seizures. Epilepsia. 2015;56:1890–8.26471380 10.1111/epi.13212
15. Villanueva V López-González FJ Mauri JA Rodriguez-Uranga J Olivé-Gadea M Montoya J BRIVA-LIFE-A multicenter retrospective study of the long-term use of brivaracetam in clinical practice Acta Neurol Scand 2019 139 360 368 10.1111/ane.13059 30506559
Villanueva V, López-González FJ, Mauri JA, Rodriguez-Uranga J, Olivé-Gadea M, Montoya J, et al. BRIVA-LIFE-A multicenter retrospective study of the long-term use of brivaracetam in clinical practice. Acta Neurol Scand. 2019;139:360–8.30506559 10.1111/ane.13059
16. Wood MD Sands ZA Vandenplas C Gillard M Further evidence for a differential interaction of brivaracetam and levetiracetam with the synaptic vesicle 2A protein Epilepsia 2018 59 e147 e151 10.1111/epi.14532 30144048
Wood MD, Sands ZA, Vandenplas C, Gillard M. Further evidence for a differential interaction of brivaracetam and levetiracetam with the synaptic vesicle 2A protein. Epilepsia. 2018;59:e147–51.30144048 10.1111/epi.14532
17. Steinhoff BJ Klein P Klitgaard H Laloyaux C Moseley BD Ricchetti-Masterson K Behavioral adverse events with brivaracetam, levetiracetam, perampanel, and topiramate: a systematic review Epilepsy Behav 2021 118 107939 10.1016/j.yebeh.2021.107939 33839453
Steinhoff BJ, Klein P, Klitgaard H, Laloyaux C, Moseley BD, Ricchetti-Masterson K, et al. Behavioral adverse events with brivaracetam, levetiracetam, perampanel, and topiramate: a systematic review. Epilepsy Behav. 2021;118: 107939.33839453 10.1016/j.yebeh.2021.107939
18. Klein P Diaz A Gasalla T Whitesides J A review of the pharmacology and clinical efficacy of brivaracetam Clin Pharmacol 2018 10 1 22 29403319
Klein P, Diaz A, Gasalla T, Whitesides J. A review of the pharmacology and clinical efficacy of brivaracetam. Clin Pharmacol. 2018;10:1–22.29403319
19. Nicolas JM Hannestad J Holden D Kervyn S Nabulsi N Tytgat D Brivaracetam, a selective high-affinity synaptic vesicle protein 2A (SV2A) ligand with preclinical evidence of high brain permeability and fast onset of action Epilepsia 2016 57 201 209 10.1111/epi.13267 26663401
Nicolas JM, Hannestad J, Holden D, Kervyn S, Nabulsi N, Tytgat D, et al. Brivaracetam, a selective high-affinity synaptic vesicle protein 2A (SV2A) ligand with preclinical evidence of high brain permeability and fast onset of action. Epilepsia. 2016;57:201–9.26663401 10.1111/epi.13267
20. Espinosa Jovel CA Pardo CM Moreno CM Vergara J Hedmont D Sobrino Mejía FE Demographic and social profile of epilepsy in a vulnerable low-income population in Bogotá Colombia. Neurologia. 2016 31 528 534 10.1016/j.nrl.2014.10.016 25524043
Espinosa Jovel CA, Pardo CM, Moreno CM, Vergara J, Hedmont D, Sobrino Mejía FE. Demographic and social profile of epilepsy in a vulnerable low-income population in Bogotá. Colombia Neurologia. 2016;31:528–34.25524043 10.1016/j.nrl.2014.10.016
21. Caraballo RH Reyes G Chacón S Fortini PS Brivaracetam as add-on therapy in children with developmental epileptic encephalopathies: a study of 42 patients Epilepsy Behav 2024 150 109561 10.1016/j.yebeh.2023.109561 38070405
Caraballo RH, Reyes G, Chacón S, Fortini PS. Brivaracetam as add-on therapy in children with developmental epileptic encephalopathies: a study of 42 patients. Epilepsy Behav. 2024;150: 109561.38070405 10.1016/j.yebeh.2023.109561
22. Siddiqui F Soomro BA Badshah M Rehman EU Numan A Ikram A Efficacy and safety of brivaracetam in persons with epilepsy in a real-world setting: a prospective, non-interventional study Cureus. 2023 15 e50313 38205459
Siddiqui F, Soomro BA, Badshah M, Rehman EU, Numan A, Ikram A, et al. Efficacy and safety of brivaracetam in persons with epilepsy in a real-world setting: a prospective, non-interventional study. Cureus. 2023;15: e50313.38205459
23. Villanueva V Laloyaux C D’Souza W Faught E Klein P Reuber M Effectiveness and tolerability of 12-month brivaracetam in the real world: EXPERIENCE, an international pooled analysis of individual patient records CNS Drugs 2023 37 819 835 10.1007/s40263-023-01033-4 37684497
Villanueva V, Laloyaux C, D’Souza W, Faught E, Klein P, Reuber M, et al. Effectiveness and tolerability of 12-month brivaracetam in the real world: EXPERIENCE, an international pooled analysis of individual patient records. CNS Drugs. 2023;37:819–35.37684497 10.1007/s40263-023-01033-4
24. Naddell S Manuel M Cavill R White P Sieradzan K BRIVEST: a ‘real-world’ observational, single-centre study investigating the efficacy, safety, and tolerability of Brivaracetam Epilepsy Behav 2023 138 108985 10.1016/j.yebeh.2022.108985 36442261
Naddell S, Manuel M, Cavill R, White P, Sieradzan K. BRIVEST: a ‘real-world’ observational, single-centre study investigating the efficacy, safety, and tolerability of Brivaracetam. Epilepsy Behav. 2023;138: 108985.36442261 10.1016/j.yebeh.2022.108985
25. Lattanzi S Canafoglia L Canevini MP Casciato S Chiesa V Dainese F Adjunctive brivaracetam in focal epilepsy: real-world evidence from the BRIVAracetam add-on First Italian netwoRk STudy (BRIVAFIRST) CNS Drugs 2021 35 1289 1301 10.1007/s40263-021-00856-3 34476770
Lattanzi S, Canafoglia L, Canevini MP, Casciato S, Chiesa V, Dainese F, et al. Adjunctive brivaracetam in focal epilepsy: real-world evidence from the BRIVAracetam add-on First Italian netwoRk STudy (BRIVAFIRST). CNS Drugs. 2021;35:1289–301.34476770 10.1007/s40263-021-00856-3
26. Lattanzi S Ascoli M Canafoglia L Paola Canevini M Casciato S Cerulli Irelli E Sustained seizure freedom with adjunctive brivaracetam in patients with focal onset seizures Epilepsia 2022 63 e42 50 10.1111/epi.17223 35278335
Lattanzi S, Ascoli M, Canafoglia L, Paola Canevini M, Casciato S, Cerulli Irelli E, et al. Sustained seizure freedom with adjunctive brivaracetam in patients with focal onset seizures. Epilepsia. 2022;63:e42-50.35278335 10.1111/epi.17223
27. Lattanzi S Canafoglia L Canevini MP Casciato S Cerulli Irelli E Chiesa V Adjunctive brivaracetam and sustained seizure frequency reduction in very active focal epilepsy Epilepsia 2023 64 2922 2933 10.1111/epi.17740 38079181
Lattanzi S, Canafoglia L, Canevini MP, Casciato S, Cerulli Irelli E, Chiesa V, et al. Adjunctive brivaracetam and sustained seizure frequency reduction in very active focal epilepsy. Epilepsia. 2023;64:2922–33.38079181 10.1111/epi.17740
28. Lattanzi S Canafoglia L Canevini MP Casciato S Cerulli Irelli E Chiesa V Brivaracetam as early add-on treatment in patients with focal seizures: a retrospective, multicenter, real-world study Neurol Ther. 2022 11 1789 1804 10.1007/s40120-022-00402-3 36109431
Lattanzi S, Canafoglia L, Canevini MP, Casciato S, Cerulli Irelli E, Chiesa V, et al. Brivaracetam as early add-on treatment in patients with focal seizures: a retrospective, multicenter, real-world study. Neurol Ther. 2022;11:1789–804.36109431 10.1007/s40120-022-00402-3
29. Lattanzi S Canafoglia L Canevini MP Casciato S Cerulli Irelli E Chiesa V Adjunctive brivaracetam in older patients with focal seizures: evidence from the BRIVAracetam add-on First Italian netwoRk Study (BRIVAFIRST) Drugs Aging 2022 39 297 304 10.1007/s40266-022-00931-4 35344198
Lattanzi S, Canafoglia L, Canevini MP, Casciato S, Cerulli Irelli E, Chiesa V, et al. Adjunctive brivaracetam in older patients with focal seizures: evidence from the BRIVAracetam add-on First Italian netwoRk Study (BRIVAFIRST). Drugs Aging. 2022;39:297–304.35344198 10.1007/s40266-022-00931-4
30. Lattanzi S Canafoglia L Canevini MP Casciato S Irelli EC Chiesa V Brivaracetam as add-on treatment in patients with post-stroke epilepsy: real-world data from the BRIVAracetam add-on First Italian netwoRk Study (BRIVAFIRST) Seizure. 2022 97 37 42 10.1016/j.seizure.2022.03.007 35320736
Lattanzi S, Canafoglia L, Canevini MP, Casciato S, Irelli EC, Chiesa V, et al. Brivaracetam as add-on treatment in patients with post-stroke epilepsy: real-world data from the BRIVAracetam add-on First Italian netwoRk Study (BRIVAFIRST). Seizure. 2022;97:37–42.35320736 10.1016/j.seizure.2022.03.007
31. Klein P Johnson ME Schiemann J Whitesides J Time to onset of sustained ≥50% responder status in patients with focal (partial onset) seizures in three phase III studies of adjunctive brivaracetam treatment Epilepsia 2017 58 e21 e25 10.1111/epi.13631 27988967
Klein P, Johnson ME, Schiemann J, Whitesides J. Time to onset of sustained ≥50% responder status in patients with focal (partial onset) seizures in three phase III studies of adjunctive brivaracetam treatment. Epilepsia. 2017;58:e21–5.27988967 10.1111/epi.13631
32. Löscher W Schmidt D Experimental and clinical evidence for loss of effect (tolerance) during prolonged treatment with antiepileptic drugs Epilepsia 2006 47 1253 1284 10.1111/j.1528-1167.2006.00607.x 16922870
Löscher W, Schmidt D. Experimental and clinical evidence for loss of effect (tolerance) during prolonged treatment with antiepileptic drugs. Epilepsia. 2006;47:1253–84.16922870 10.1111/j.1528-1167.2006.00607.x
33. Hirsch M Hintz M Specht A Schulze-Bonhage A Tolerability, efficacy and retention rate of Brivaracetam in patients previously treated with levetiracetam: a monocenter retrospective outcome analysis Seizure. 2018 61 98 103 10.1016/j.seizure.2018.07.017 30118932
Hirsch M, Hintz M, Specht A, Schulze-Bonhage A. Tolerability, efficacy and retention rate of Brivaracetam in patients previously treated with levetiracetam: a monocenter retrospective outcome analysis. Seizure. 2018;61:98–103.30118932 10.1016/j.seizure.2018.07.017
34. Snoeren A Majoie MHJM Fasen KCFM Ijff DM Brivaracetam for the treatment of refractory epilepsy in patients with prior exposure to levetiracetam: a retrospective outcome analysis Seizure. 2022 96 102 107 10.1016/j.seizure.2022.02.007 35184005
Snoeren A, Majoie MHJM, Fasen KCFM, Ijff DM. Brivaracetam for the treatment of refractory epilepsy in patients with prior exposure to levetiracetam: a retrospective outcome analysis. Seizure. 2022;96:102–7.35184005 10.1016/j.seizure.2022.02.007
35. Steinhoff BJ Staack AM Levetiracetam and brivaracetam: a review of evidence from clinical trials and clinical experience Ther Adv Neurol Disord 2019 12 1756286419873518 10.1177/1756286419873518 31523280
Steinhoff BJ, Staack AM. Levetiracetam and brivaracetam: a review of evidence from clinical trials and clinical experience. Ther Adv Neurol Disord. 2019;12:1756286419873518.31523280 10.1177/1756286419873518
36. Lattanzi S Foschi N Martellino C Audenino D Boero G Bonanni P Conversion to brivaracetam monotherapy in clinical practice: a retrospective study Neurol Ther. 2024 13 389 398 10.1007/s40120-024-00580-2 38300459
Lattanzi S, Foschi N, Martellino C, Audenino D, Boero G, Bonanni P, et al. Conversion to brivaracetam monotherapy in clinical practice: a retrospective study. Neurol Ther. 2024;13:389–98.38300459 10.1007/s40120-024-00580-2
37. Barrachina-Martínez I Vivas-Consuelo D Piera-Balbastre A Budget impact analysis of brivaracetam adjunctive therapy for partial-onset epileptic seizures in Valencia community, Spain Clin Drug Investig 2018 38 353 363 10.1007/s40261-017-0615-z 29270790
Barrachina-Martínez I, Vivas-Consuelo D, Piera-Balbastre A. Budget impact analysis of brivaracetam adjunctive therapy for partial-onset epileptic seizures in Valencia community, Spain. Clin Drug Investig. 2018;38:353–63.29270790 10.1007/s40261-017-0615-z
38. Barrachina-Martinez I Vivas-Consuelo D Reyes-Santias F Cost-utility model of brivaracetam in the adjunctive treatment of patients with epilepsy in Spain Expert Rev Pharmacoecon Outcomes Res 2021 21 1081 1090 10.1080/14737167.2021.1838899 33074031
Barrachina-Martinez I, Vivas-Consuelo D, Reyes-Santias F. Cost-utility model of brivaracetam in the adjunctive treatment of patients with epilepsy in Spain. Expert Rev Pharmacoecon Outcomes Res. 2021;21:1081–90.33074031 10.1080/14737167.2021.1838899
39. Väätäinen S Soini E Peltola J Charokopou M Taiha M Kälviäinen R Economic value of adjunctive brivaracetam treatment strategy for focal onset seizures in Finland Adv Ther 2020 37 477 500 10.1007/s12325-019-01155-6 31808053
Väätäinen S, Soini E, Peltola J, Charokopou M, Taiha M, Kälviäinen R. Economic value of adjunctive brivaracetam treatment strategy for focal onset seizures in Finland. Adv Ther. 2020;37:477–500.31808053 10.1007/s12325-019-01155-6
