Annals of African medicine · 2025
Оценка воздействия терифлюномида и диметилфумарата на качество жизни в релапсирующих множестве склерозов: понимание из Восточной Саудовской Аравии.
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Alshayban Dhafer, Al-Shamrani Foziah J, Alamer Khalid A, Muazen Mohammad Y, Alqahtani Khalid A, Alsulaiman Layan, Islam Md Ashraful, Balkhi Bander, Alqahtani Saad, AlHarkan Khalid S
Аннотация
ВВЕДЕНИЕ: В Саудовской Аравии существует хроническое неврологическое состояние, вызывающее множественный склероз (RRMS). Она вызывает целый спектр неврологических нарушений, которые приводят к функциональным ограничениям и инвалидности. Физическое и психологическое бремя множественного склероза (MS) оказывает значительное воздействие на качество жизни пациентов, связанное со здоровьем (HRQOL). Однако исследования, посвященные оценке его воздействия на HRQOL в саудовском контексте, по-прежнему недостаточны. Цель этого исследования состояла в том, чтобы сравнить HRQoL пациентов, проходящих лечение с помощью терифлуномида или диметила фумарата, и выявить факторы, влияющие на результаты лечения.МЕТОДОЛОГИЯ: С ноября 2022 года по апрель 2023 года в больнице Университета им. короля Фахда было проведено перекрестное исследование, охватывающее всех пациентов, страдающих НР. Участники были разделены на две группы на основе их обработки: лица, получающие терифлуномид, и лица, имеющие диметилфумарат. Данные собирались с помощью вопросника EQ-5D-5L. Результаты: Из 280 приглашенных пациентов 82 пациента, в том числе 28 мужчин и 54 женщины, удовлетворяют критериям охвата, при этом большинство из них составляют лица старше 40 лет. Примерно 43,9 процента были обработаны терифлуномидом, а 56,1 процента получили диметилфумарат. Никаких статистически значимых различий в трех оценочных показателях состояния здоровья между этими двумя группами населения выявлено не было. Тем не менее описательный анализ показал, что пациенты, страдающие диметилфумаратом, сообщили о более высоких показателях здоровья, чем пациенты, страдающие терифлуномидом. ЗАКЛЮЧЕНИЕ: Исследование показало, что пациенты с RRMS в диметилфумарате и терифлуномиде сообщили о низкой физической и психической HRQOL. Хотя каких-либо статистически значимых различий между этими двумя группами выявлено не было, те, кто получает диметилфумарат, указали на лучший QoL по сравнению с их коллегами по терифлуномиде. Дальнейшие исследования необходимы для выявления конкретных пробелов, которые могли бы способствовать улучшению HRQoL среди пациентов RMS. Кроме того, выводы этого исследования могут послужить основой для разработки и осуществления целевых программ вмешательства, направленных на расширение HRQOL для пациентов из числа саудовского населения.
Оригинал публикации
Evaluating the Impact of Teriflunomide and Dimethyl Fumarate on Quality of Life in Relapsing-remitting Multiple Sclerosis: Insights from Eastern Saudi Arabia.
INTRODUCTION: Relapsing-remitting multiple sclerosis (RRMS) is a chronic neurological condition prevalent in Saudi Arabia. It causes a spectrum of neurological impairments that result in functional limitations and disability. The physical and psychological burdens of multiple sclerosis (MS) significantly impact patients' health-related quality of life (HRQoL). However, research evaluating its effects on HRQoL within the Saudi context remains scarce. This study aimed to compare HRQoL among RRMS patients undergoing treatment with teriflunomide or dimethyl fumarate and identify factors influencing treatment outcomes.
METHODOLOGY: A cross-sectional study involving all MS patients was conducted at King Fahd Hospital of the University from November 2022 to April 2023. Participants were categorized into two groups based on their treatment: those receiving teriflunomide and those on dimethyl fumarate. Data were collected using the EQ-5D-5L questionnaire.
RESULTS: Of the 280 patients invited, 82 RRMS patients met the inclusion criteria, comprising 28 males and 54 females, with most participants over 40. Approximately 43.9% were treated with teriflunomide, whereas 56.1% received dimethyl fumarate. No statistically significant differences were found in the three health indicators assessed between the two treatment groups. Nonetheless, the descriptive analysis indicated that RRMS patients on dimethyl fumarate reported superior health outcomes to those on teriflunomide.
CONCLUSION: The study revealed that patients with RRMS in the dimethyl fumarate and teriflunomide treatment groups reported low physical and mental HRQoL. While no statistically significant differences were observed between the two groups, those receiving dimethyl fumarate indicated a better QoL than their counterparts on teriflunomide. Future research is necessary to identify specific gaps that could facilitate improvements in HRQoL among RRMS patients. Furthermore, the findings from this study may inform the development and implementation of targeted intervention programs aimed at enhancing HRQoL for RRMS patients within the Saudi population.
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I NTRODUCTION
Relapsing-remitting multiple sclerosis (RRMS), a prevalent form of multiple sclerosis (MS), is an inflammatory neurological disorder and a leading cause of disability among young adults globally.[ 1 2 ] With a worldwide prevalence of approximately 35.9 per 100,000 individuals,[ 3 ] MS rates are increasing in various regions, intensifying economic and healthcare burdens.[ 3 4 ] This trend is similar to that observed in the Middle East and North Africa (MENA) region, including Saudi Arabia. MS prevalence has reached 40.4 per 100,000, placing it above the low-risk category per the Kurtzke classification.[ 5 6 ] MS in the MENA region resembles Western presentations but often involves a younger age at onset and a more aggressive course, resulting in earlier disability and diverse neurological impairments.[ 7 8 ] Recent findings by Aljumah et al . further highlight the increasing RRMS prevalence and the number of hospitals providing specialized care.[ 8 ]
Despite the rising prevalence of RRMS, the field has seen rapid advancements in disease-modifying treatments (DMTs), though developing highly effective DMTs remains a complex task. These newer DMTs have shown superior outcomes and improved health-related quality of life (HRQoL) for RRMS patients compared to earlier therapies.[ 9 ] Among approved oral disease-modifying agents (DMAs), teriflunomide and dimethyl fumarate are notable for their efficacy and safety in relapsing MS. Evidence suggests that clinical and radiological disease activities are associated with poorer short- and intermediate-term prognoses.[ 10 ] Traditional clinical measures provide information about disease progression and treatment efficacy, whereas HRQoL assessments provide insights into how these treatments affect the patient’s general well-being in daily life. This attention to patient-centered outcomes has gained increased interest as researchers realize that treatments with similar clinical efficacy can still differ substantially in how they impact patients’ quality of life (QoL). While MS progression can impact overall quality of life (QoL), studies evaluating HRQoL remain limited.[ 11 ]
In Saudi Arabia, where the prevalence of RRMS is rising, assessing how new treatments impact quality of life is essential. While international studies suggest that specific treatments can stabilize or improve HRQoL in RRMS patients, region-specific data remain limited, especially for Saudi Arabia. This highlights the need for local research to evaluate the outcomes of teriflunomide and dimethyl fumarate using tools like the MSQOL-54 and EuroQOL five-dimension questionnaires.[ 11 12 13 ] These tools offer comprehensive insights into the physical and psychosocial dimensions of the disease, making them particularly relevant in Saudi Arabia, where cultural and social factors strongly shape health perceptions and treatment outcomes. By leveraging reliable, culturally adapted assessments, this research aims to provide localized evidence on the impact of these therapies and uncover factors influencing their real-world effectiveness in improving patients’ quality of life. Although both treatments have proven effective in managing RRMS, their specific impact on the quality of life of the Saudi population still needs to be explored. This study seeks to fill that gap and guide future care strategies in Eastern Saudi Arabia.
M ETHODOLOGY
Study design, settings, and selection process
A cross-sectional study was conducted from November 2022 to April 2023 at King Fahd Hospital of the University (KFHU), Dammam, Saudi Arabia. Eligible participants included patients diagnosed with RRMS, receiving treatment for at least 6 months, and giving their consent to participate in the study. Patients with MS diagnosis, who were taking medications other than teriflunomide or dimethyl fumarate, as well as those who had taken both medications or switched between them, were excluded from the study.
Figure 1 displays a total of 280 potential participants who were evaluated for eligibility. Of the 280, 198 potential participants were excluded from the study, with 185 refusing to participate and 13 individuals excluded due to missing data. Eighty-two RRMS patients were deemed eligible for the study and were allocated into two treatment arms: the teriflunomide arm and the dimethyl fumarate arm, based on their current RRMS medication. These participants were interviewed either in person or remotely by phone, depending on their preference.
The screening and recruitment process for the study
Measurement of outcome variable
The outcome variable was the health-related quality of life (HRQoL) for patients on either teriflunomide or dimethyl fumarate. The HRQoL of RRMS patients was assessed utilizing widely used validated scale EQ-5D-5L.[ 12 13 ] The RRMS patient’s health status was reported in terms of five dimensions of the EQ-5D-5L scale for example: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension consists of five levels of severity scale coded: no problem = 1, slight problem = 2, moderate problem = 3, severe problem = 4, and extreme problem = 5. The results of the patients’ perfect health stand for EQD profile “11111,” whereas score “55555” stands for worst health among all possible 3125 sets of values. Scores were transformed to a single EQ Index, by applying the EQ-5D-5L value that sets for England[ 14 ] as there is no Saudia Arabia set value. The EQ index value ranged from −0.285 to −1, where the value 0 or less represents patient health equivalent to die; however, an index score 1 represents patient’s perfect health.
Data management
Data were checked for outlier, abnormal responses, and missing cases before final analysis to avoid undefined error and/or misleading results.[ 15 ] Data normality was assessed using formal (Kolmogorov–Smirnov test) and informal (graphical presentation) methods, as well as detecting outlier and abnormal responses that were removed before final analysis. A few missing cases were treated by “last observation carried forward method” for categorical data and “imputation” method for continuous data and the rest were removed from the final analysis.[ 16 ]
Statistical analysis
The SPSS (version 23, IBM Corp., Armonk, NY, USA) and Microsoft Excel software were used for data analysis. Grouped data were presented as a sample count ( N ) and their corresponding percentage (%), whereas count data were described and reported by mean with standard deviation (SD) and/or median with interquartile range (whereas applicable), also maximum and minimum value with range. An independent sample t -test was applied to compare between teriflunomide and dimethyl fumarate to check their influence on the HRQoL for MS patients. Demographic differentials were checked using Chi-square/Fisher’s exact test where it was applicable. The value of P < 0.05 was considered as levels of significance at a 95% confidence interval.
R ESULTS
Complete 82 samples were analyzed, among those, 36 patients (43.9%) received teriflunomide, whereas 46 patients (56.1%) were from dimethyl fumarate group. Most responses were from male patients (65.9%), married (57.3%), obtained bachelor’s degree (59.8%), and came from the lowest income (monthly income SAR: 3000–6000) group (45.1%). Around 70% (69.5%) of MS patients aged 31 years and above [ Table 1 ].
Table 1 Background characteristics of multiple sclerosis patient’s Characteristics Frequency, n (%) Gender Female 28 (34.1) Male 54 (65.9) Age group (years) 20–25 4 (4.9) 26–30 21 (25.6) 31–40 27 (32.9) 40 and above 30 (36.6) What kind of treatment do you take? Teriflunomide 36 (43.9) Dimethyl fumarate 46 (56.1) Marital status Married/partnered 47 (57.3) Single 33 (40.2) Divorced/widowed 2 (2.4) Academic level High school 25 (30.5) Bachelor 49 (59.8) Other 8 (9.8) Monthly income* SR 3000–SR 6000 37 (45.1) SR 7000–SR 10,000 27 (32.9) SR 11,000–SR 14,000 6 (7.3) Above SR 14,000 12 (14.6) *SR=Saudi Rials
Background characteristics of multiple sclerosis patient’s
*SR=Saudi Rials
Table 2 represents the results of descriptive statistics and reliability index of the main outcome, namely: EQ-5D-5L scale. The mean score for the EQ index was 0.825 (SD = 0.136) ranging from 0.30–1.00, while average EQ Vas score was found 74.79 (SD = 18.51). A moderate-to-good level of reliability (α =0.515) was observed among the items of the scale with a significant ICC value 0.515 ( P < 0.01) with the range of 0.326–0.663.
Table 2 Reliability analysis of EuroQol-5D-5L scale Measurements criteria Value Mean±SD and range of EQ index 0.825±0.136 (0.30–1.00) Mean±SD and range of EQ VAS score 74.79±18.51 (25–100) Cronbach’s alpha of EQ-5D-5L scale 0.515 Cronbach’s alpha based on standardized items 0.552 ICC (95% CI) 0.515 (0.326–0.663)
P
<0.001 IQR=Inter quartile range, ICC=Intraclass correlation coefficient, CI=Confidence interval, SD=Standard deviation, EQ=EuroQol, QoL=Quality of life
Reliability analysis of EuroQol-5D-5L scale
IQR=Inter quartile range, ICC=Intraclass correlation coefficient, CI=Confidence interval, SD=Standard deviation, EQ=EuroQol, QoL=Quality of life
RRMS patients’ health status was compared using an independent sample t -test and the results are shown in Table 3 . There was no statistically significant difference observed in all the three health indicators (EQ Index, EQ Vas score, and years of suffering for RRMS disease) between the patients receiving dimethyl fumarate or teriflunomide. Although no statistical difference was found, descriptive results suggested that more patients receiving dimethyl fumarate medicine reported good health compared to teriflunomide, for all the three indicators. Item analysis results showed that except for the factor pain/discomfort, RRMS patients taking teriflunomide reported worse health than their counterparts for the rest of the four factors [ Figure 2 ].
Table 3 Comparison of health (EuroQol-5D-5L) among relapsing-remitting multiple sclerosis patients between use of different medicine (dimethyl fumarate and teriflunomide) Indicators Medication Mean±SD MD (95% CI) P * EQ index Dimethyl fumarate 77.30±18.48 5.72 (−2.43–13.87) 0.166 Teriflunomide 71.58±18.30 EQ VAS score Dimethyl fumarate 0.830±0.122 0.013 (−0.047–0.074) 0.665 Teriflunomide 0.817±0.154 Years of suffering for MS disease Dimethyl fumarate 9.06±4.83 −0.336 (−2.402–1.731) 0.747 Teriflunomide 9.39±4.45 *Independent sample t -test applied. MS=Multiple sclerosis, CI=Confidence interval, VAS=Visual Analogue Scale, MD=Mean difference, EQ=EuroQol, QoL=Quality of life
Comparison of health (EuroQol-5D-5L) among relapsing-remitting multiple sclerosis patients between use of different medicine (dimethyl fumarate and teriflunomide)
*Independent sample t -test applied. MS=Multiple sclerosis, CI=Confidence interval, VAS=Visual Analogue Scale, MD=Mean difference, EQ=EuroQol, QoL=Quality of life
Comparison between teriflunomide and dimethyl in terms of health-related quality of life
Sociodemographic differential was also observed between those receiving either dimethyl fumarate or teriflunomide, as reported in Table 4 . Similar to the health indicators, there were no statistically significant differences observed [ Table 4 ].
Table 4 Comparison between different demographics and multiple sclerosis patients use of medication dimethyl fumarate and teriflunomide Variables Types of treatment received by MS patients
P
Teriflunomide, n (%) Dimethyl fumarate, n (%) Gender Female 10 (35.7) 18 (64.3) 0.282 Male 26 (48.1) 28 (51.9) Age group (years) 20–25 1 (25.0) 3 (75.0) 0.216* 26–30 6 (28.6) 15 (71.4) 31–40 12 (44.4) 15 (55.6) 40 and above 17 (56.7) 13 (43.3) Marital status Married/partner 21 (44.7) 26 (55.3) 0.586 Single 15 (45.5) 18 (54.5) Divorced/widowed 0 2 (100.0) Level of education High school 13 (52.0) 12 (48.0) 0.670 Bachelor 20 (40.8) 29 (59.2) Other 3 (37.5) 5 (62.5) Income SR 3000–SR 6000 16 (43.2) 21 (56.8) 0.904 SR 7000–SR 10,000 13 (48.1) 14 (51.9) SR 11,000–SR 14,000 2 (33.3) 4 (66.7) Above SR 14,000 5 (41.7) 7 (58.3) *Fisher’s exact test. MS=Multiple sclerosis, SR=Saudi Rials
Comparison between different demographics and multiple sclerosis patients use of medication dimethyl fumarate and teriflunomide
*Fisher’s exact test. MS=Multiple sclerosis, SR=Saudi Rials
D ISCUSSION
To our knowledge, this study, involving 82 participants, is the first in Saudi Arabia to investigate the relationship between RRMS, its treatments, and HRQoL using the EQ-5D-5L scale. The sample comprised mostly female participants, reflecting the established gender predisposition toward RRMS. The majority of participants were aged 31 and older, indicating that RRMS affects a wide age range without significant differentiation. It is essential to recognize that demographic characteristics can differ across studies due to geographic and cultural factors.
Comparative research has highlighted the decline in HRQoL associated with increasing RRMS disability. The EQ-5D-5L, recommended over the EQ-5D-3L for broader research applicability, offers a nuanced assessment of health states but still faces limitations in evaluating severe health conditions.[ 17 ] In this study, the EQ-5D-5L effectively distinguished HRQoL levels among RRMS patients, though its sensitivity varied across health dimensions. As the tool is adopted more widely, its effectiveness in diverse populations will become clearer. Our findings confirm a decline in HRQoL with advancing MS disability, underscoring the urgent need for innovative therapeutic options.[ 17 18 ]
Recognizing the essential role of the EQ-5D-5L scale in our study, we assessed its reliability, finding moderate consistency at α = 0.515, in alignment with standard health index norms. Our findings show an EQ Index mean score of 0.825 and an EQ VAS average of 74.79, indicating a relatively favorable HRQoL among RRMS participants. These results are comparable to, and in some cases slightly exceed, those of Bencsik et al ., underscoring the significance of regional context in HRQoL assessments.[ 19 ]
In addition, our analysis found no significant effect of sociodemographic factors on medication selection, suggesting that factors such as gender, age, marital status, educational attainment, and income did not substantially influence the type of medication chosen or its perceived efficacy. This aligns with prior research indicating that variables such as age, gender, RRMS type, education, and time since diagnosis have an impact, while living arrangements do not affect health states.[ 20 ] This insight supports healthcare providers in making treatment decisions independent of broad demographic criteria, highlighting the importance of personalised medicine that considers individual patient characteristics over-generalized sociodemographic categories.[ 21 ]
Our study provides valuable insights when comparing the dimethyl fumarate and teriflunomide treatment groups. While statistical differences between the groups were not significant ( P = 0.655 for teriflunomide and P = 0.663 for Dimethyl fumarate), an observational trend indicated that patients on dimethyl fumarate generally reported better health across various indicators. This finding suggests the need for future studies on the potential long-term effects and factors influencing HRQoL in RRMS patients, aligning with prior research on the impact of dimethyl fumarate on HRQoL. Although patients on dimethyl fumarate reported a lower quality of life than the general population, they showed improvements in HRQoL and work productivity and experienced less fatigue and depression, supported by DEFINE and CONFIRM studies on dimethyl fumarate’s benefits in MS treatment.[ 22 23 ]
In contrast, findings related to teriflunomide highlight a different outcome. While our study observed varied health results, another study involving 147 RRMS patients found that those on teriflunomide experienced challenges in most health areas, aside from pain and discomfort, where they showed resilience.[ 24 ] Our evaluation of dimethyl fumarate and teriflunomide in a Saudi cohort using the EQ-5D-5L scale similarly revealed poorer health outcomes for teriflunomide, particularly outside of the pain/discomfort domain. These results emphasize the nuances in MS treatment responses and can aid in making informed therapeutic choices for RRMS patients in Saudi Arabia.
In addition, an Italian study found that around 29% of RRMS patients discontinued teriflunomide due to efficacy or side effect concerns, with 28% reporting disease worsening, particularly in patients with a higher disability score (EDSS > 4.0). This indicates that teriflunomide may be most effective for treatment-naive patients or those who struggled with prior treatments.[ 25 ] Comparing our study to this Italian research provides insight into teriflunomide’s impact in the Saudi context, underscoring the importance of regional research to tailor treatments to patients’ unique backgrounds and needs.
The influence of patient experiences on treatment choices is paramount. A comprehensive study of 2708 participants emphasized the role of patient feedback in refining treatment approaches and care protocols.[ 26 ] Similarly, Anna He’s research with 780 patients advocated for an RRMS management strategy that extends beyond medication, favoring a holistic, patient-centered approach.[ 27 ]
Limitations of the study
Despite being the first study to evaluate the differences in HRQoL impacts between teriflunomide and dimethyl fumarate in RRMS patients, this research has limitations. The modest sample size of 82 participants raises concerns regarding the generalizability of our findings to the broader Saudi population. Additionally, the reliance on self-reported EQ-5D-5L data, while valuable, may introduce subjective biases and fail to capture the complexities of participants’ experiences. The study did not account for other potentially influential factors affecting HRQoL outcomes. Furthermore, the cross-sectional design provides only a snapshot of participants’ experiences, limiting causal inferences regarding the relationship between teriflunomide, dimethyl fumarate, and HRQoL in RRMS patients.
C ONCLUSION
This study is the first in Saudi Arabia to evaluate differences between teriflunomide and dimethyl fumarate on HRQoL in patients with RRMS. Our findings indicate that the majority of RRMS patients experience a lower quality of life. Although no statistically significant differences were observed between the two groups, preliminary results suggest that patients on dimethyl fumarate reported higher HRQoL across all domains of the EQ-5D-5L, except in the pain/discomfort domain, compared to those on teriflunomide. These findings could assist policymakers in selecting interventions to enhance HRQoL for RRMS patients. Future research should explore the cost-effectiveness of RRMS treatments.
Conflicts of interest
There are no conflicts of interest.
Relapsing-remitting multiple sclerosis (RRMS), a prevalent form of multiple sclerosis (MS), is an inflammatory neurological disorder and a leading cause of disability among young adults globally.[ 1 2 ] With a worldwide prevalence of approximately 35.9 per 100,000 individuals,[ 3 ] MS rates are increasing in various regions, intensifying economic and healthcare burdens.[ 3 4 ] This trend is similar to that observed in the Middle East and North Africa (MENA) region, including Saudi Arabia. MS prevalence has reached 40.4 per 100,000, placing it above the low-risk category per the Kurtzke classification.[ 5 6 ] MS in the MENA region resembles Western presentations but often involves a younger age at onset and a more aggressive course, resulting in earlier disability and diverse neurological impairments.[ 7 8 ] Recent findings by Aljumah et al . further highlight the increasing RRMS prevalence and the number of hospitals providing specialized care.[ 8 ]
Despite the rising prevalence of RRMS, the field has seen rapid advancements in disease-modifying treatments (DMTs), though developing highly effective DMTs remains a complex task. These newer DMTs have shown superior outcomes and improved health-related quality of life (HRQoL) for RRMS patients compared to earlier therapies.[ 9 ] Among approved oral disease-modifying agents (DMAs), teriflunomide and dimethyl fumarate are notable for their efficacy and safety in relapsing MS. Evidence suggests that clinical and radiological disease activities are associated with poorer short- and intermediate-term prognoses.[ 10 ] Traditional clinical measures provide information about disease progression and treatment efficacy, whereas HRQoL assessments provide insights into how these treatments affect the patient’s general well-being in daily life. This attention to patient-centered outcomes has gained increased interest as researchers realize that treatments with similar clinical efficacy can still differ substantially in how they impact patients’ quality of life (QoL). While MS progression can impact overall quality of life (QoL), studies evaluating HRQoL remain limited.[ 11 ]
In Saudi Arabia, where the prevalence of RRMS is rising, assessing how new treatments impact quality of life is essential. While international studies suggest that specific treatments can stabilize or improve HRQoL in RRMS patients, region-specific data remain limited, especially for Saudi Arabia. This highlights the need for local research to evaluate the outcomes of teriflunomide and dimethyl fumarate using tools like the MSQOL-54 and EuroQOL five-dimension questionnaires.[ 11 12 13 ] These tools offer comprehensive insights into the physical and psychosocial dimensions of the disease, making them particularly relevant in Saudi Arabia, where cultural and social factors strongly shape health perceptions and treatment outcomes. By leveraging reliable, culturally adapted assessments, this research aims to provide localized evidence on the impact of these therapies and uncover factors influencing their real-world effectiveness in improving patients’ quality of life. Although both treatments have proven effective in managing RRMS, their specific impact on the quality of life of the Saudi population still needs to be explored. This study seeks to fill that gap and guide future care strategies in Eastern Saudi Arabia.
M ETHODOLOGY
Study design, settings, and selection process
A cross-sectional study was conducted from November 2022 to April 2023 at King Fahd Hospital of the University (KFHU), Dammam, Saudi Arabia. Eligible participants included patients diagnosed with RRMS, receiving treatment for at least 6 months, and giving their consent to participate in the study. Patients with MS diagnosis, who were taking medications other than teriflunomide or dimethyl fumarate, as well as those who had taken both medications or switched between them, were excluded from the study.
Figure 1 displays a total of 280 potential participants who were evaluated for eligibility. Of the 280, 198 potential participants were excluded from the study, with 185 refusing to participate and 13 individuals excluded due to missing data. Eighty-two RRMS patients were deemed eligible for the study and were allocated into two treatment arms: the teriflunomide arm and the dimethyl fumarate arm, based on their current RRMS medication. These participants were interviewed either in person or remotely by phone, depending on their preference.
The screening and recruitment process for the study
Measurement of outcome variable
The outcome variable was the health-related quality of life (HRQoL) for patients on either teriflunomide or dimethyl fumarate. The HRQoL of RRMS patients was assessed utilizing widely used validated scale EQ-5D-5L.[ 12 13 ] The RRMS patient’s health status was reported in terms of five dimensions of the EQ-5D-5L scale for example: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension consists of five levels of severity scale coded: no problem = 1, slight problem = 2, moderate problem = 3, severe problem = 4, and extreme problem = 5. The results of the patients’ perfect health stand for EQD profile “11111,” whereas score “55555” stands for worst health among all possible 3125 sets of values. Scores were transformed to a single EQ Index, by applying the EQ-5D-5L value that sets for England[ 14 ] as there is no Saudia Arabia set value. The EQ index value ranged from −0.285 to −1, where the value 0 or less represents patient health equivalent to die; however, an index score 1 represents patient’s perfect health.
Data management
Data were checked for outlier, abnormal responses, and missing cases before final analysis to avoid undefined error and/or misleading results.[ 15 ] Data normality was assessed using formal (Kolmogorov–Smirnov test) and informal (graphical presentation) methods, as well as detecting outlier and abnormal responses that were removed before final analysis. A few missing cases were treated by “last observation carried forward method” for categorical data and “imputation” method for continuous data and the rest were removed from the final analysis.[ 16 ]
Statistical analysis
The SPSS (version 23, IBM Corp., Armonk, NY, USA) and Microsoft Excel software were used for data analysis. Grouped data were presented as a sample count ( N ) and their corresponding percentage (%), whereas count data were described and reported by mean with standard deviation (SD) and/or median with interquartile range (whereas applicable), also maximum and minimum value with range. An independent sample t -test was applied to compare between teriflunomide and dimethyl fumarate to check their influence on the HRQoL for MS patients. Demographic differentials were checked using Chi-square/Fisher’s exact test where it was applicable. The value of P < 0.05 was considered as levels of significance at a 95% confidence interval.
R ESULTS
Complete 82 samples were analyzed, among those, 36 patients (43.9%) received teriflunomide, whereas 46 patients (56.1%) were from dimethyl fumarate group. Most responses were from male patients (65.9%), married (57.3%), obtained bachelor’s degree (59.8%), and came from the lowest income (monthly income SAR: 3000–6000) group (45.1%). Around 70% (69.5%) of MS patients aged 31 years and above [ Table 1 ].
Table 1 Background characteristics of multiple sclerosis patient’s Characteristics Frequency, n (%) Gender Female 28 (34.1) Male 54 (65.9) Age group (years) 20–25 4 (4.9) 26–30 21 (25.6) 31–40 27 (32.9) 40 and above 30 (36.6) What kind of treatment do you take? Teriflunomide 36 (43.9) Dimethyl fumarate 46 (56.1) Marital status Married/partnered 47 (57.3) Single 33 (40.2) Divorced/widowed 2 (2.4) Academic level High school 25 (30.5) Bachelor 49 (59.8) Other 8 (9.8) Monthly income* SR 3000–SR 6000 37 (45.1) SR 7000–SR 10,000 27 (32.9) SR 11,000–SR 14,000 6 (7.3) Above SR 14,000 12 (14.6) *SR=Saudi Rials
Background characteristics of multiple sclerosis patient’s
*SR=Saudi Rials
Table 2 represents the results of descriptive statistics and reliability index of the main outcome, namely: EQ-5D-5L scale. The mean score for the EQ index was 0.825 (SD = 0.136) ranging from 0.30–1.00, while average EQ Vas score was found 74.79 (SD = 18.51). A moderate-to-good level of reliability (α =0.515) was observed among the items of the scale with a significant ICC value 0.515 ( P < 0.01) with the range of 0.326–0.663.
Table 2 Reliability analysis of EuroQol-5D-5L scale Measurements criteria Value Mean±SD and range of EQ index 0.825±0.136 (0.30–1.00) Mean±SD and range of EQ VAS score 74.79±18.51 (25–100) Cronbach’s alpha of EQ-5D-5L scale 0.515 Cronbach’s alpha based on standardized items 0.552 ICC (95% CI) 0.515 (0.326–0.663)
P
<0.001 IQR=Inter quartile range, ICC=Intraclass correlation coefficient, CI=Confidence interval, SD=Standard deviation, EQ=EuroQol, QoL=Quality of life
Reliability analysis of EuroQol-5D-5L scale
IQR=Inter quartile range, ICC=Intraclass correlation coefficient, CI=Confidence interval, SD=Standard deviation, EQ=EuroQol, QoL=Quality of life
RRMS patients’ health status was compared using an independent sample t -test and the results are shown in Table 3 . There was no statistically significant difference observed in all the three health indicators (EQ Index, EQ Vas score, and years of suffering for RRMS disease) between the patients receiving dimethyl fumarate or teriflunomide. Although no statistical difference was found, descriptive results suggested that more patients receiving dimethyl fumarate medicine reported good health compared to teriflunomide, for all the three indicators. Item analysis results showed that except for the factor pain/discomfort, RRMS patients taking teriflunomide reported worse health than their counterparts for the rest of the four factors [ Figure 2 ].
Table 3 Comparison of health (EuroQol-5D-5L) among relapsing-remitting multiple sclerosis patients between use of different medicine (dimethyl fumarate and teriflunomide) Indicators Medication Mean±SD MD (95% CI) P * EQ index Dimethyl fumarate 77.30±18.48 5.72 (−2.43–13.87) 0.166 Teriflunomide 71.58±18.30 EQ VAS score Dimethyl fumarate 0.830±0.122 0.013 (−0.047–0.074) 0.665 Teriflunomide 0.817±0.154 Years of suffering for MS disease Dimethyl fumarate 9.06±4.83 −0.336 (−2.402–1.731) 0.747 Teriflunomide 9.39±4.45 *Independent sample t -test applied. MS=Multiple sclerosis, CI=Confidence interval, VAS=Visual Analogue Scale, MD=Mean difference, EQ=EuroQol, QoL=Quality of life
Comparison of health (EuroQol-5D-5L) among relapsing-remitting multiple sclerosis patients between use of different medicine (dimethyl fumarate and teriflunomide)
*Independent sample t -test applied. MS=Multiple sclerosis, CI=Confidence interval, VAS=Visual Analogue Scale, MD=Mean difference, EQ=EuroQol, QoL=Quality of life
Comparison between teriflunomide and dimethyl in terms of health-related quality of life
Sociodemographic differential was also observed between those receiving either dimethyl fumarate or teriflunomide, as reported in Table 4 . Similar to the health indicators, there were no statistically significant differences observed [ Table 4 ].
Table 4 Comparison between different demographics and multiple sclerosis patients use of medication dimethyl fumarate and teriflunomide Variables Types of treatment received by MS patients
P
Teriflunomide, n (%) Dimethyl fumarate, n (%) Gender Female 10 (35.7) 18 (64.3) 0.282 Male 26 (48.1) 28 (51.9) Age group (years) 20–25 1 (25.0) 3 (75.0) 0.216* 26–30 6 (28.6) 15 (71.4) 31–40 12 (44.4) 15 (55.6) 40 and above 17 (56.7) 13 (43.3) Marital status Married/partner 21 (44.7) 26 (55.3) 0.586 Single 15 (45.5) 18 (54.5) Divorced/widowed 0 2 (100.0) Level of education High school 13 (52.0) 12 (48.0) 0.670 Bachelor 20 (40.8) 29 (59.2) Other 3 (37.5) 5 (62.5) Income SR 3000–SR 6000 16 (43.2) 21 (56.8) 0.904 SR 7000–SR 10,000 13 (48.1) 14 (51.9) SR 11,000–SR 14,000 2 (33.3) 4 (66.7) Above SR 14,000 5 (41.7) 7 (58.3) *Fisher’s exact test. MS=Multiple sclerosis, SR=Saudi Rials
Comparison between different demographics and multiple sclerosis patients use of medication dimethyl fumarate and teriflunomide
*Fisher’s exact test. MS=Multiple sclerosis, SR=Saudi Rials
D ISCUSSION
To our knowledge, this study, involving 82 participants, is the first in Saudi Arabia to investigate the relationship between RRMS, its treatments, and HRQoL using the EQ-5D-5L scale. The sample comprised mostly female participants, reflecting the established gender predisposition toward RRMS. The majority of participants were aged 31 and older, indicating that RRMS affects a wide age range without significant differentiation. It is essential to recognize that demographic characteristics can differ across studies due to geographic and cultural factors.
Comparative research has highlighted the decline in HRQoL associated with increasing RRMS disability. The EQ-5D-5L, recommended over the EQ-5D-3L for broader research applicability, offers a nuanced assessment of health states but still faces limitations in evaluating severe health conditions.[ 17 ] In this study, the EQ-5D-5L effectively distinguished HRQoL levels among RRMS patients, though its sensitivity varied across health dimensions. As the tool is adopted more widely, its effectiveness in diverse populations will become clearer. Our findings confirm a decline in HRQoL with advancing MS disability, underscoring the urgent need for innovative therapeutic options.[ 17 18 ]
Recognizing the essential role of the EQ-5D-5L scale in our study, we assessed its reliability, finding moderate consistency at α = 0.515, in alignment with standard health index norms. Our findings show an EQ Index mean score of 0.825 and an EQ VAS average of 74.79, indicating a relatively favorable HRQoL among RRMS participants. These results are comparable to, and in some cases slightly exceed, those of Bencsik et al ., underscoring the significance of regional context in HRQoL assessments.[ 19 ]
In addition, our analysis found no significant effect of sociodemographic factors on medication selection, suggesting that factors such as gender, age, marital status, educational attainment, and income did not substantially influence the type of medication chosen or its perceived efficacy. This aligns with prior research indicating that variables such as age, gender, RRMS type, education, and time since diagnosis have an impact, while living arrangements do not affect health states.[ 20 ] This insight supports healthcare providers in making treatment decisions independent of broad demographic criteria, highlighting the importance of personalised medicine that considers individual patient characteristics over-generalized sociodemographic categories.[ 21 ]
Our study provides valuable insights when comparing the dimethyl fumarate and teriflunomide treatment groups. While statistical differences between the groups were not significant ( P = 0.655 for teriflunomide and P = 0.663 for Dimethyl fumarate), an observational trend indicated that patients on dimethyl fumarate generally reported better health across various indicators. This finding suggests the need for future studies on the potential long-term effects and factors influencing HRQoL in RRMS patients, aligning with prior research on the impact of dimethyl fumarate on HRQoL. Although patients on dimethyl fumarate reported a lower quality of life than the general population, they showed improvements in HRQoL and work productivity and experienced less fatigue and depression, supported by DEFINE and CONFIRM studies on dimethyl fumarate’s benefits in MS treatment.[ 22 23 ]
In contrast, findings related to teriflunomide highlight a different outcome. While our study observed varied health results, another study involving 147 RRMS patients found that those on teriflunomide experienced challenges in most health areas, aside from pain and discomfort, where they showed resilience.[ 24 ] Our evaluation of dimethyl fumarate and teriflunomide in a Saudi cohort using the EQ-5D-5L scale similarly revealed poorer health outcomes for teriflunomide, particularly outside of the pain/discomfort domain. These results emphasize the nuances in MS treatment responses and can aid in making informed therapeutic choices for RRMS patients in Saudi Arabia.
In addition, an Italian study found that around 29% of RRMS patients discontinued teriflunomide due to efficacy or side effect concerns, with 28% reporting disease worsening, particularly in patients with a higher disability score (EDSS > 4.0). This indicates that teriflunomide may be most effective for treatment-naive patients or those who struggled with prior treatments.[ 25 ] Comparing our study to this Italian research provides insight into teriflunomide’s impact in the Saudi context, underscoring the importance of regional research to tailor treatments to patients’ unique backgrounds and needs.
The influence of patient experiences on treatment choices is paramount. A comprehensive study of 2708 participants emphasized the role of patient feedback in refining treatment approaches and care protocols.[ 26 ] Similarly, Anna He’s research with 780 patients advocated for an RRMS management strategy that extends beyond medication, favoring a holistic, patient-centered approach.[ 27 ]
Limitations of the study
Despite being the first study to evaluate the differences in HRQoL impacts between teriflunomide and dimethyl fumarate in RRMS patients, this research has limitations. The modest sample size of 82 participants raises concerns regarding the generalizability of our findings to the broader Saudi population. Additionally, the reliance on self-reported EQ-5D-5L data, while valuable, may introduce subjective biases and fail to capture the complexities of participants’ experiences. The study did not account for other potentially influential factors affecting HRQoL outcomes. Furthermore, the cross-sectional design provides only a snapshot of participants’ experiences, limiting causal inferences regarding the relationship between teriflunomide, dimethyl fumarate, and HRQoL in RRMS patients.
C ONCLUSION
This study is the first in Saudi Arabia to evaluate differences between teriflunomide and dimethyl fumarate on HRQoL in patients with RRMS. Our findings indicate that the majority of RRMS patients experience a lower quality of life. Although no statistically significant differences were observed between the two groups, preliminary results suggest that patients on dimethyl fumarate reported higher HRQoL across all domains of the EQ-5D-5L, except in the pain/discomfort domain, compared to those on teriflunomide. These findings could assist policymakers in selecting interventions to enhance HRQoL for RRMS patients. Future research should explore the cost-effectiveness of RRMS treatments.
Conflicts of interest
There are no conflicts of interest.