Health-related quality of life in multiple sclerosis in Azerbaijan: an SF-36 case-control study

Abstract

AimTo assess health-related quality of life (HRQL) in patients with multiple sclerosis (MS) in Azerbaijan using the SF-36, compare scores with control participants, and analyze the Physical Component Summary (PCS) and Mental Component Summary (MCS) by sex and place of residence.MethodsThis cross-sectional case-control analysis included 238 patients with MS selected from a 2013–2022 registry and 291 control participants. In 2022, at the end of the study period, participants completed the Azerbaijani-language SF-36 once. We compared domain and summary scores using the Mann–Whitney U test, and calculated effect sizes as r from the standardized Z statistic.ResultsThe groups did not differ significantly in age, sex, or place of residence (all P > .05). Patients with MS had lower scores across all eight domains and both summary scores (all P < .001), with large effect sizes for all comparisons (r = 0.505–0.574). The largest effect sizes were observed for role-physical (r = 0.574), mental health (r = 0.557), general health (r = 0.547), and PCS (r = 0.547). PCS and MCS did not differ significantly by sex in either group. Within the MS group, PCS was higher among rural than urban participants (P = .042; r = 0.132), whereas MCS did not differ by residence.ConclusionPatients with MS had substantially lower HRQL than control participants across all SF-36 domains and both summary components. SF-36 assessment may provide additional information about functional and psychosocial needs and may inform rehabilitation and medical and social care planning.

Keywords

Introduction

Quality of life is a multidimensional and subjective concept reflecting how individuals perceive their position in life within their cultural and value systems and in relation to their goals, expectations, standards, and concerns.¹ A comprehensive assessment should also consider objective clinical and functional indicators alongside subjective perception.² Health-related quality of life (HRQL) describes the relationship between health status and quality of life. It includes domains such as physical activity, work capacity, emotional status, social relationships, and somatic sensations.²
Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system that substantially affects patients’ quality of life, functional status, and social activity.³ Its impact extends beyond neurological impairment and includes disability, loss of work capacity, reduced social participation, psychological problems, and limitations in daily activities.^3-5 Disability, fatigue, depression, cognitive impairment, and unemployment have been reported as key factors associated with poorer quality of life in patients with MS.⁴
Deterioration in quality of life among patients with MS is closely related to disease course, disability level, psychological status, and socioeconomic factors. In some patients, progression from relapsing-remitting MS to secondary progressive MS is accompanied by persistent neurodegeneration and functional decline.⁶ Therefore, HRQL assessment has become an important component of MS evaluation. HRQL questionnaires reflect the patient-perceived impact of disease, daily activity limitations, emotional and social consequences, and the potential effects or side effects of treatment.^2,7 Both generic and disease-specific instruments, including the EQ-5D-5L, SF-36, and MSQOL-54, are used to evaluate HRQL in MS.⁷ The SF-36, which covers physical functioning, role limitations, bodily pain, general health, vitality, social functioning, emotional status, and mental health, is widely used to assess the physical and psychological components of HRQL in patients with MS.^8,9
Because clinical, demographic, and social characteristics vary between countries, local assessment of HRQL in MS is necessary. In Azerbaijan, comparing the HRQL profile of patients with MS with that of control participants may help identify patient needs and support rehabilitation and medical and social care planning.ObjectiveTo assess HRQL indicators in patients with MS in Azerbaijan using the SF-36 questionnaire, compare the results with a control group, and analyze the physical and mental component summary scores according to sex and place of residence.

Materials and Methods

Study Design and SettingThe present cross-sectional case-control analysis was nested within a larger prospective registry-based investigation of the clinical and epidemiological characteristics of multiple sclerosis in Azerbaijan. The MS registry covered the period from January 1, 2013, to December 31, 2022, and included 1,796 patients with confirmed or reconfirmed MS.
Patients were examined and followed up at the [blinded for review]. Patients with newly diagnosed MS, those requiring differential diagnosis, and those requiring clinical follow-up either presented directly to the [blinded for review] or were referred by neurologists working in different regions of Azerbaijan. Diagnostic and treatment procedures were performed in accordance with the “Clinical Protocol for the Diagnosis and Treatment of Multiple Sclerosis” approved by the Ministry of Health of the Republic of Azerbaijan. Health-related quality of life was assessed once for each participant in 2022.Participant Recruitment and SelectionIn 2022, patients included in the MS registry were recruited for the health-related quality-of-life assessment either during scheduled follow-up visits at the study center or after telephone contact and invitation to attend a subsequent clinical examination. We administered the SF-36 questionnaire once during the corresponding study visit.
Of the 1,796 patients included in the registry, those who participated in the 2022 health-related quality-of-life assessment and had complete data for all eight SF-36 domains, as well as the Physical Component Summary (PCS) and Mental Component Summary (MCS) scores, were eligible for the present analysis. A total of 238 patients with MS met these criteria and were included in the complete-case analysis.
We recruited control participants during the same 2022 assessment period from individuals accompanying patients at the study center. First-degree relatives of patients enrolled in the MS group were not eligible for inclusion as controls. We included individuals in the control group if they reported no history of neurological or autoimmune disease and had complete SF-36 data. We included 291 control participants in the analysis.Inclusion and Exclusion CriteriaPatients were eligible for inclusion in the MS group if they were citizens of the Republic of Azerbaijan, were included in the MS registry, had a diagnosis of MS confirmed or reconfirmed in accordance with the “Clinical Protocol for the Diagnosis and Treatment of Multiple Sclerosis” of the Ministry of Health, participated in the SF-36 assessment, and had complete clinical and questionnaire data.
Patients were excluded from the present analysis if their medical documentation was incomplete or internally inconsistent; if they had not undergone or were unable to undergo the examinations required for diagnostic confirmation; if another diagnosis subsequently replaced their initial diagnosis of MS; or if one or more SF-36 domain or summary scores could not be calculated because of incomplete questionnaire data.
Control participants were eligible if they accompanied patients attending the study center, were not first-degree relatives of patients included in the MS group, reported no history of neurological or autoimmune disease, and completed the SF-36 questionnaire. We excluded first-degree relatives, individuals reporting a neurological or autoimmune disease, and those with incomplete SF-36 data from the control group.Study SizeNo formal a priori sample size calculation was performed because this study was a secondary cross-sectional analysis within an established registry-based investigation. We determined the study size by the number of eligible patients and control participants who took part in the end-of-study health-related quality-of-life assessment in 2022 and had complete data for all SF-36 domains and summary scores. Accordingly, we included 238 patients with MS and 291 control participants in the complete-case analysis.Clinical AssessmentA neurologist examined all patients with MS. When clinically indicated, the diagnostic work-up included magnetic resonance imaging of the brain and spinal cord, lumbar puncture with assessment of oligoclonal bands, visual evoked potentials, and optical coherence tomography. The diagnosis of MS was confirmed based on medical history, clinical presentation, and relevant laboratory and instrumental findings. Functional status was assessed using the Expanded Disability Status Scale (EDSS).Assessment of Health-Related Quality of LifeHealth-related quality of life was assessed once, in 2022, at the end of the study period, using the patient-reported SF-36 questionnaire.^8,10 The SF-36 questionnaire was administered in the Azerbaijani language. The questionnaire comprises eight domains: physical functioning (PF), role limitations due to physical health (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role limitations due to emotional problems (RE), and mental health (MH).^8,10
The eight domain scores were transformed to a scale ranging from 0 to 100, with higher scores indicating better health-related quality of life. The Physical Component Summary and Mental Component Summary scores were calculated using the standard SF-36 scoring procedures.¹⁰Outcome MeasuresThe predefined primary outcome measures were the eight SF-36 domain scores and the PCS and MCS scores. The primary analysis compared these outcomes between patients with MS and control participants.
The predefined secondary outcome measures were the PCS and MCS scores, analyzed by sex and place of residence within the MS and control groups.Ethical ApprovalThe study was approved by the Ethics Committee of the Neurology Center of the Ministry of Health of the Republic of Azerbaijan. (Date: 26.10.2021, Decision No. 09/2021).Statistical AnalysisStatistical analyses were performed using IBM SPSS Statistics for Windows, version 27.0 (IBM Corp) and Microsoft Excel 2016 (Microsoft Corp). The distribution of continuous variables was assessed using the Kolmogorov–Smirnov and Shapiro–Wilk tests together with visual inspection of the distributions.
Because the continuous variables were not normally distributed, we summarized them as medians and interquartile ranges and presented them as median (IQR). We presented categorical variables as numbers and percentages. We compared age and SF-36 scores between independent groups using the Mann–Whitney U test. Categorical characteristics, including sex and place of residence, were compared using the Pearson chi-square test. The Mann–Whitney U test was also used to compare PCS and MCS scores according to sex and place of residence within the MS and control groups.
All statistical tests were two-sided, and a P < .05 was considered statistically significant. Effect sizes were calculated for Mann–Whitney U comparisons using the following formula:
r = |Z|/√N
where Z represents the standardized Mann–Whitney U test statistic and N represents the total number of participants included in the two groups being compared. Effect sizes were interpreted as small at approximately 0.10, moderate at approximately 0.30, and large at 0.50 or greater.¹¹
Analyses were performed using complete cases, and missing SF-36 data were not imputed.Reporting GuidelinesThis study was reported in accordance with the STROBE guideline.

Results

The analysis included 238 patients with MS and 291 control participants who had complete data for all SF-36 domains and summary scores. We compared the MS and control groups by age, sex, and place of residence, and found no statistically significant differences for these characteristics (P > .05; Table 1). In the MS group, the most common clinical phenotype was relapsing-remitting MS, observed in 190 patients (79.8%). The median disease duration, calculated from the first attack, was 9.0 [7.0–11.0] years, the median diagnostic delay was 4.0 [1.0–6.0] years, and the median EDSS score at diagnosis was 2.0 [1.0–3.0] (Table 1). Comparison of SF-36 results showed that HRQL indicators were significantly lower in patients with MS than in the control group across all domains and both summary scores (Table 2). In the MS group, the lowest median values were observed for RP, PCS, GH, and VT. In the control group, SF-36 domain scores were generally high, with particularly high median values for PF, RP, SF, and RE. The Mann–Whitney U test showed statistically significant differences between the MS and control groups across all SF-36 domains and PCS/MCS summary scores (P < .001 for all comparisons; Table 2). Effect sizes were large for all comparisons (r = 0.505–0.574). The largest differences were observed for role limitations due to physical health (RP; r = 0.574), mental health (MH; r = 0.557), general health (GH; r = 0.547), and the Physical Component Summary (PCS; r = 0.547) (Figure 1). Comparisons by sex showed no statistically significant differences in PCS and MCS scores within either the MS group or the control group (P > .05; Table 3). In the comparison by place of residence, no significant differences in PCS or MCS were found in the control group. In the MS group, place of residence differed significantly only for PCS: PCS was 33.5 [28.4–44.5] among urban residents and 37.0 [30.1–52.1] among rural residents (P = .042). However, this difference was small (r = 0.132). No statistically significant difference by place of residence was found for the MCS score in the MS group (P = .395).

Discussion

The main finding of this study is that health-related quality of life in patients with MS was significantly lower than that in the control group across all SF-36 domains and both summary scores. Large effect sizes across all domains indicate that MS substantially affects both physical and mental aspects of HRQL. This finding confirms the multidimensional burden of MS and the importance of incorporating HRQL into clinical assessment.^3,4,7
The largest differences were observed for role-physical, mental health, general health, and PCS. The markedly low median score for the role-physical domain in the MS group indicates that the disease substantially affects performance of daily activities and social/work-related functions. The significantly lower PCS score in patients with MS compared with controls suggests that physical functioning, fatigue, pain, mobility limitations, and general health perception may play a leading role in HRQL impairment among patients with MS. These findings are consistent with international studies; previous research has also reported that HRQL in people with MS is lower than population-based norms and that the disease has broad effects across physical, social, and psychological domains.¹² The DISCOVER study conducted among ambulatory patients with secondary progressive MS also demonstrated the important impact of physical limitation, fatigue, cognitive impairment, and high indirect cost burden on HRQL.¹³
At the same time, our findings showed that HRQL impairment in patients with MS was not limited to physical domains. We also found significant differences compared with the control group in mental health and the Mental Component Summary. This indicates that MS also has a negative impact on emotional well-being, social relationships, and subjective perception of the disease. The literature has reported that depression, fatigue, disability, marital status, physical activity, and employment status are closely associated with quality of life in patients with MS.^4,14 In addition, the high prevalence of depression and anxiety in patients with MS highlights the need to consider psychological components separately in HRQL assessment.¹⁵ In this regard, broad-profile assessment tools such as the SF-36 may be useful not only for identifying physical limitations, but also for detecting psychosocial burden.^8,9
The sex-based analysis showed no statistically significant differences in PCS and MCS scores within either the MS group or the control group, indicating that the reduction in summary HRQL scores in this sample was not limited to a specific sex subgroup. Comparisons by place of residence also showed no significant differences in the control group, whereas in the MS group, rural residents had a relatively higher PCS score. However, this difference should be interpreted with caution because it had a small effect size. This finding suggests that multiple clinical and social factors influence the association between residence and HRQL. Recent studies have also shown that lower HRQL in patients with MS is heterogeneously associated with age, disease duration, symptom profile, disability, comorbidity, and patient-reported outcomes.¹⁶
The findings of this study indicate that clinical assessment of patients with MS should not be limited to neurological examination and disability measures alone. Regular assessment of HRQL indicators, particularly PCS and MCS, may provide a more comprehensive reflection of patients’ daily functioning, functional needs, psychological status, and need for social support. This approach provides additional clinical information for planning rehabilitation, psychological support, fatigue management, physical activity programs, and multidisciplinary follow-up strategies.^7,9 Recent systematic reviews and meta-analyses have reported that exercise programs may improve well-being and HRQL indicators in patients with MS. At the same time, non-pharmacological interventions may have positive effects on both physical and psychological components of quality of life.^17,18 Although the available evidence on multidisciplinary approaches is heterogeneous, such approaches have been emphasized as potentially important for organizing MS care and optimizing patient outcomes.^19,20
A strength of this study is the comparison of HRQL across all SF-36 domains between patients with MS and controls, including subgroup analyses by sex and residence.

Limitations

Several limitations should be considered. First, HRQL was assessed only once, at the end of the study period in 2022. Because baseline and repeated SF-36 measurements were not available, we could not evaluate changes in quality of life over time. Second, the study was conducted at a single center, although this center served as the main specialized institution to which patients with MS were referred nationwide. Third, this analysis did not include a separate model for factors that may influence HRQL, such as fatigue, depression, anxiety, cognitive impairment, social support, and comorbidity. Therefore, the findings should be interpreted as descriptive rather than causal.

Conclusion

Patients with MS had significantly lower HRQL than control participants across all eight SF-36 domains and both the physical and mental component summary scores. PCS and MCS scores did not differ significantly by sex, while a small residence-related difference was observed only for PCS within the MS group. Routine use of the SF-36 may help identify the functional and psychosocial needs of patients with MS and support more targeted planning of rehabilitation and medical and social care.

Declarations

Abbreviations

References

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