Health-related quality of life measurement for Brazilian patients with Myasthenia gravis

Health-related quality of life measurement for Brazilian patients with Myasthenia gravis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Health-related quality of life measurement for Brazilian patients with Myasthenia gravis Marisa Santos, Andrea Liborio, Luiza Vasconcelos, Daiane Beneduzzi This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6604495/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background : Myasthenia gravis significantly impacts patients' quality of life, yet utility data from Latin America remain scarce. This study assessed health-related quality of life and generated utility values for Brazilian patients with MG. Methods : In this cross-sectional study, 317 Brazilian patients with MG completed online questionnaires, including the EQ-5D-3 L and MG-ADL instruments. Multiple regression models were used to examine the relationships between symptom severity and utility values. Mapping algorithms were developed to convert MG-ADL scores to utility values. Results : The mean EQ-5D-3 L score was 0.55 (SD 0.16), representing a 35% reduction from Brazilian population norms. The most significant decreases in utility were associated with mobility limitations (-0.0768, p<0.001) and self-care difficulties (-0.0451, p<0.001). Each one-point increase in the MG-ADL score corresponded to a decrease in utility of 0.024 (p<0.001). The final prediction model explained 44.9% of the utility variance. Conclusions : This is the first Brazilian MG utility study to demonstrate substantial quality of life impairment and provide validated mapping tools for economic evaluation. The results enable more accurate health technology assessments and support evidence-based resource allocation in Latin American healthcare systems. Myasthenia gravis Quality of life Utility values Brazil EQ-5D-3 L MG-ADL INTRODUCTION Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by muscular weakness affecting limb, ocular, and respiratory functions( 1 , 2 ). With a prevalence worldwide of 70–320 per million inhabitants, MG is considered an ultrarare disease, although its prevalence is increasing because of improved diagnostic capacity, aging populations and increased survival rates( 3 ). The disease typically manifests in a bimodal age distribution at its onset, mainly affecting individuals aged 10–20 years and 50–60 years. Clinical presentations vary widely, ranging from mild weakness to severe tetraparesis requiring mechanical ventilation. Symptom presentation can fluctuate throughout the day, predominantly affecting ocular and bulbar muscle groups. Ocular symptoms, including diplopia (double vision) and ptosis (drooping of the upper eyelid), are common due to weakness of the ocular muscles. In the case of generalized MG, the most severe form, bulbar symptoms become prominent. These include dysarthria (difficulty articulating words), dysphagia (difficulty swallowing), loss of facial expression, and “dropped head syndrome,” which is attributed to weakened neck muscles( 4 , 5 ). In addition, respiratory muscle weakness can lead to respiratory failure, termed a “myasthenic crisis.” Such a crisis often results in the need for hospitalization and emergency care. The triggers for this critical situation can be diverse, with infections or certain medications being significant contributors. The clinical course of MG typically evolves through three phases: active, stable and remission ( 6 ). Prognosis largely depends on the severity of symptoms and the effectiveness of therapeutic interventions. Notably, individuals seropositive for acetylcholine receptor antibodies (AChR-Ab+) have been found to have increased mortality rates compared with seronegative patients.( 7 ) Additional factors that may adversely influence prognosis include the frequency of exacerbations and flares, the presence of bulbar symptoms, and age at onset. Disease severity can be assessed by several scales, such as the Myasthenia Gravis Activities of Daily Living (MG-ADL)( 6 ), the Quantitative Myasthenia Gravis score (QMG)( 7 ), and the Myasthenia Gravis Composite Score (MGC). ( 8 ) The primary goal in managing MG is to keep the patient’s disease manifestations to a minimum or better. Treatment strategies focus on preventing infections and avoiding medications that may exacerbate the disease.( 9 ). Symptomatic treatments include acetylcholinesterase inhibition, chronic immunotherapies (e.g., glucocorticoids, azathioprine, mycophenolate), and short-acting immunomodulatory treatments such as therapeutic plasmapheresis and intravenous immunoglobulin. Thymectomy is recommended for some patients, and biologics may be used for chronic immunosuppression in AChR-Ab + patients.( 10 ) The MG-ADL score (Table 1 ) is a patient-reported outcome measure that quantifies symptom severity on a scale of zero to three across several domains, including speech, chewing, swallowing, breathing, hygiene (brushing teeth and combing hair), ability to rise from a chair, double vision, and drooping eyelid. Similarly, muscle weakness, a hallmark of MG, is assessed on a scale of zero (no weakness) to four (paralysis) in muscles commonly involved in this condition.( 6 ) The MG-ADL is the instrument most adopted by randomized clinical trials to analyze the impact of new drugs. As a specific instrument, it does not generate utilities necessary for cost-effectiveness studies. The preferred instrument for utility extraction is the EQ-5D-3L or, in the newer 5L version. There are few publications that have applied EQ-5D instruments to estimate health-related quality of life (HRQoL) losses due to myasthenia gravis ( 11 – 15 ) and none in Latin America or the Caribbean region. To our knowledge, this is the first study of Brazilian patients with myasthenia using both the EQ-5D and MG-ADL instruments. The assessment of health-related quality of life (HRQoL) in individuals with chronic conditions such as myasthenia gravis requires a conceptual framework that captures the multidimensional nature of health. This study is grounded in the HRQoL model proposed by Wilson et al. ( 16 ), which links biological and physiological variables to symptom status, functional status, general health perceptions, and overall quality of life. Within this framework, the EQ-5D-3L instrument captures key domains of general health status - mobility, self-care, usual activities, pain/discomfort, and anxiety/depression - while the MG-ADL provides disease-specific symptom assessment focused on daily functioning. By integrating these two instruments, our study aligns with a conceptual model that values both generic and condition-specific measures, thereby enabling a more comprehensive and sensitive assessment of HRQoL in the Brazilian MG population. Primary Objective To assess the impact of myasthenia gravis on HRQoL in the Brazilian population, with a particular focus on the experiences of patients at different stages of disease severity. Secondary Objective To generate utility values derived from HRQoL outcomes for MG health states. These utility values serve as crucial inputs for cost‒utility models and additionally estimate the HRQoL losses with EQ values for each MG‒ADL health state. METHODS Study Design This project employed a cross-sectional study design to collect online data from a diverse, representative sample of Brazilian individuals diagnosed with myasthenia gravis. The participants included individuals from various age groups and with various levels of disease severity. An online questionnaire was created via the REDCap platform. Participant recruitment was conducted via social media in partnership with nongovernmental organizations (NGOs) supporting myasthenia patients. Ethics The study was approved by the Instituto Nacional de Cardiologia IRB with the number CAAE 65471222.5.0000.5272. The study was conducted in accordance with the Declaration of Helsinki. All the respondents signed consent to participate and receive no direct benefits for participation. Sampling and data collection We aimed to recruit at least 70 patients per health state. This strategy was designed to ensure a comprehensive understanding of the impact of Myasthenia Gravis on different levels of disease severity. The online survey was distributed through multiple channels, including the following: MG patient associations Social networks WhatsApp groups A satisfactory response rate was achieved, with 317 completed questionnaires included in the analysis. Survey Questions and Instruments The participants were asked to complete a comprehensive questionnaire that included demographic and general health data such as sex, age, and comorbidities. Health-related questions include a self-reported list of chronic physical or mental health conditions. In addition, the participants responded to questions about their socioeconomic status, health status, treatment history, and healthcare utilization. Participants were also asked to indicate whether they had been diagnosed with chronic diseases by a healthcare professional, including cardiovascular, metabolic, or autoimmune conditions. These self-reported comorbidities were included to better characterize the clinical background of the sample and explore influences on health-related quality of life outcomes. Myasthenia Gravis Activities of Daily Living (MG-ADL): This is a disease-specific instrument designed to assess the impact of MG on daily life. It is a patient-reported outcome measure developed specifically for individuals with myasthenia gravis. The MG-ADL score is a reliable, valid, and responsive measure of clinical severity in MG patients. It was created to evaluate the effects of the disease on activities of daily living. The MG-ADL is an 8-item questionnaire that focuses on symptoms that most indicate changes in MG severity, including ocular (e.g., ptosis and diplopia), bulbar (e.g., problems with speech, swallowing, and chewing), respiratory (e.g., shortness of breath), and limb-related symptoms (e.g., difficulties with motor functions). Each question is scored on a 4-point scale ranging from 0 (normal) to 3 (severe impairment), allowing patients to indicate the extent to which their daily activities are affected by MG. The total score ranges from 0 (no disability) to 24 (maximum disability). EQ-5D-3L, 5L, and VAS: These are standardized instruments used to measure health outcomes and quantify five dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The 3-level version (EQ-5D-3L) offers three possible responses: ‘no problems,’ ‘some problems,’ or ‘extreme problems.’ In contrast, the 5-level version (EQ-5D-5L) expands the response scale to ‘no problems,’ ‘mild problems,’ ‘moderate problems,’ ‘severe problems,’ and ‘extreme problems.’ In addition to these descriptive systems, the EQ-VAS, or EuroQol visual analog scale, is an integral part of the EQ-5D. The EQ-VAS serves as a global measure of patients’ self-rated health, structured as a vertically graduated visual analog scale ranging from 0 to 100 points, with the ‘Best imaginable health state’ at the top (scored as 100) and the ‘Worst imaginable health state’ at the bottom (scored as 0). Collectively, these components contribute to a comprehensive measure of health status, which is widely used in clinical trials, population health surveys, and health economic evaluations. The use of these tools was approved by the EuroQol Foundation. The EQ-5D was originally designed for self-completion in population-based surveys and clinical studies, and has demonstrated cross-cultural validity, including in Brazilian Portuguese versions ( 16 ). The selection of the EQ-5D-3L and MG-ADL instruments was guided by both conceptual and methodological considerations. The EQ-5D-3L is a generic instrument for measuring health-related quality of life and generating utility values for economic evaluations. It has been validated in the Brazilian population and provides reliable estimates across a broad range of health conditions. Its simplicity and ease of use make it suitable for self-completed online surveys. The MG-ADL, in turn, is a disease-specific instrument developed to capture functional limitations in patients with myasthenia gravis. It has demonstrated strong internal consistency (Cronbach’s alpha > 0.80), good test–retest reliability, and responsiveness to clinical change in both observational and interventional studies. Together, these instruments offer complementary perspectives - EQ-5D-3L capturing general health status and MG-ADL focusing on MG-specific symptom burden - allowing for a robust and sensitive assessment of HRQoL. These psychometric properties have been validated in prior studies, including Wolfe et al. ( 6 ) for the MG-ADL and Santos et al. for the EQ-5D-3L in Brazil ( 16 ). Disease timeline: Participants provided information about the progression of their disease. Symptom Presence: Information was collected about the presence of symptoms over the past seven days. Data Analysis Plan Descriptive statistics were calculated to summarize the demographic characteristics and health conditions of the participants. Absolute and relative frequencies are reported for categorical variables, whereas means and standard deviations are reported for numerical variables. A correlation matrix was generated to examine the relationships between key variables, including the MG-ADL total score, EQ-5D-3 L index, and individual dimensions of both scales. The Spearman correlation coefficient was used because of the mix of continuous and ordinal variables, making it suitable for capturing associations without assuming a normal distribution. This matrix helps reveal how symptom severity and quality of life measures are interrelated. Regression analysis was used to examine the relationships among myasthenia gravis (MG) symptoms, severity, and health-related quality of life (HRQoL). MG severity, quantified through MG-ADL scores and self-reported data, along with comorbidities and treatment strategies, was included as a variable. Linear regression was used for continuous outcomes (e.g., HRQoL scores), and logistic regression was used for categorical outcomes (e.g., severity levels). Initial univariate models identified individual HRQoL predictors, followed by multivariate models adjusted for confounders and interactions, such as those between severity and treatment. The data review included checks for normality, outliers, and multicollinearity, with adjustments applied as needed. Utility values were calculated via the EQ-5D-3 L. These values range from 0 (death) to 1 (full health). Weights for responses across the five EQ-5D dimensions, based on Brazilian assessments, provided contextual utility scores. The treatment types were categorized as acute (corticosteroids or plasmapheresis), immunosuppressive (azathioprine, methotrexate, cyclosporine, rituximab, mycophenolate), or no treatment. Pyridostigmine was considered standard care and was excluded from analysis. Treatment effectiveness may serve as a proxy for disease severity, with effective treatment potentially reducing symptom severity. RESULTS The characteristics of the patients are detailed in Table 1. The study sample was predominantly female (88.9%) with a mean age of 41.5 years, consistent with the known epidemiological profile of MG, which tends to affect women of reproductive age. Most participants belonged to socioeconomic classes B (49.7%) and C (30.6%) according to the Brazilian Criteria of Economic Classification. These characteristics suggest a moderately diverse sample in terms of social background, though future studies should aim to enhance male and lower-income representation to better capture the full disease burden across population subgroups. Regarding baseline comorbidities, the most frequently reported chronic conditions were hypertension (22.8%), diabetes (8.5%), and heart disease (5.7%) (Table 1). The presence of cardiovascular and metabolic conditions is clinically relevant, as they may exacerbate fatigue, dyspnea, and general functional decline in patients with MG, potentially amplifying the perceived burden of disease. These overlapping symptoms may also influence self-reported HRQoL scores, especially in the domains of mobility and usual activities. Table 2 presents the responses to the EQ-5D-3 L, showing the distribution of patients across the dimensions of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Most patients reported moderate issues in mobility (56.15%) and pain/discomfort (64.56%), with fewer patients experiencing extreme difficulties in these dimensions. With respect to self-care, 63.17% of patients reported no difficulties, whereas 35.87% reported moderate problems. Anxiety/depression was a significant concern, with 54.60% of patients reporting moderate problems and 30.48% reporting extreme problems. The mean EQ-5D-3 L score was 0.55 (standard deviation 0.16), indicating a moderately compromised quality of life among the patients evaluated. Compared with the Brazilian population average of 0.85, the average EQ-5D-3 L index (0.55) shows an absolute reduction of 0.35 points, representing a relative loss of approximately 35% in quality of life. This reflects substantial impairment, particularly in the dimensions of pain/discomfort and anxiety/depression, which had the most significant impact on patients' well-being. Table 3 shows the distribution of patients across MG-ADL items, highlighting the severity of myasthenia gravis symptoms. Most patients exhibited mild to moderate symptoms in several functions, with 57.1% reporting normal speech, 50.16% reporting normal chewing, and 32.49% not experiencing fatigue when rising from a chair. However, a significant proportion of the participants reported functional impairments, such as fatigue when chewing solid food (41.64%) and shortness of breath with exertion (48.26%). More severe impairments, such as ventilator dependence (2.84%) and gastric tube feeding (0.32%), are less common. The distribution of symptoms, particularly in areas such as double vision and drooping eyelids, underscores the variability in disease severity among patients. Regarding psychometric properties, the convergent validity between the dimensions of the EQ-5D-3 L and the MG-ADL was tested. Table 4 shows the convergence between the MG-ADL and EQ-5D-3 L instruments, demonstrating that greater functional impairment, as measured by the MG-ADL, is associated with a lower quality of life according to the EQ-5D-3 L (Table 4). The significant negative correlation between the total MG-ADL score and the EQ-5D-3 L index (-0.648) indicates that both instruments consistently capture disease severity and its impact on patients' lives. The physical dimensions of the EQ-5D-3 L, such as mobility, self-care, and usual activities, strongly correlate with the MG-ADL, reinforcing the consistency of these instruments in assessing functional status and quality of life. Table 5 presents different prediction models tested to estimate the relationship between the variables and the outcome, using evaluation criteria such as AIC (Akaike information criterion), BIC (Bayesian information criterion), R-squared, adjusted R-squared, and tests for homoscedasticity, normality, and multicollinearity. Compared with the other models, the Basic Model has the lowest AIC (-444.944) and BIC (-429.959), indicating a good fit. The R-squared value is 0.4374, indicating that approximately 43.7% of the data variability is explained by the model, with an adjusted R-squared value of 0.432. Homoscedasticity is not violated (p = 0.186), and the residuals follow normality (p = 0.68836). The mean VIF (1.09) indicates low multicollinearity, suggesting that the independent variables are not highly correlated. The Model with Interaction Terms has an AIC of -443.43 and a BIC of -420.953, which are slightly worse than those of the Basic Model. The R-squared (0.4419) and adjusted R-squared (0.4328) values show a small improvement in explaining the data variability. Homoscedasticity is preserved (p = 0.2939), and the residuals follow normality (p = 0.6037). However, the mean VIF increases to 6.68, indicating potential multicollinearity. The quadratic model has an AIC of -442.951 and a BIC of -424.22, with an R-squared of 0.4374 and an adjusted R-squared of 0.4301. Homoscedasticity (p = 0.1869) and normality (p = 0.67102) are similar to those of the basic model, but the mean variance inflation factor (VIF) is 5.71, suggesting some multicollinearity. The Log-Transformed Model has a positive AIC (23.2203) and the highest BIC (38.1923), along with a lower R-squared (0.4059) and adjusted R-squared (0.4001), suggesting a poor fit. Additionally, homoscedasticity and normality are violated (p = 0 in both cases). The average VIF (1.09) shows no multicollinearity, but the model's overall fit is poor. Finally, the Model with Control Variables has an AIC of -441.706 and a BIC of -419.306, with the highest R-squared (0.449) and adjusted R-squared (0.4399), indicating that it explains more data variation than the other models do. Homoscedasticity (p = 0.253) and normality (p = 0.50367) are not violated, and the mean VIF of 1.17 suggests low multicollinearity. In summary, the Model with Control Variables shows the best overall performance in explaining variability (highest R-squared) and in meeting the assumptions, making it the most suitable model among those tested. The Basic Model also stands out for its simplicity and good fit, whereas the models with interaction and quadratic terms present possible multicollinearity issues. The log-transformed model has a significantly poorer fit and violates key assumptions. Based on this model, the impact of impairment in each MG-ADL dimension on quality of life, as estimated by the EQ-5D-3 L, was calculated (Table 6). For each one-unit increase in the total MG-ADL score, reflecting greater functional impairment in daily activities among myasthenia gravis patients, there was a 0.02421 decrease in self-reported quality of life, as measured by the EQ-5D-3 L. This negative coefficient indicates that as functional impairment increases, quality of life decreases. The confidence interval for this estimate ranges from -0.02748--0.02094, underscoring the precision of the result. Additionally, the p value < 0.001 confirms the high significance of this inverse relationship between the MG-ADL score and quality of life. In this context, the MG-ADL score stands out as the central variable explaining the variation in patients' quality of life, with the model accounting for approximately 44.9% of the variability in the EQ-5D-3 L scores (R-squared = 0.449). Other variables in the model, such as age, sex, comorbidities, and socioeconomic status, serve as adjustment covariates but do not show significant associations. Thus, the model primarily emphasizes the strong negative correlation between MG-ADL and quality of life, highlighting the significant impact of functional impairment on patients' perceptions of their health and well-being. All dimensions (Swallowing, Breathing, Brushing/Combing, and Getting up from a chair) were statistically significant, with Getting up from a chair having the greatest impact (approximately 0.08 absolute points). Table 7 presents the utility losses in the EQ-5D-3 L according to different MG-ADL dimensions. The intercept is 0.7396 (p < 0.001), representing the baseline utility when there is no impairment in the MG-ADL dimensions. Several specific MG-ADL dimensions are significantly associated with reduced quality of life. Swallowing difficulties had a coefficient of -0.0263 (p = 0.029), indicating a significant utility reduction and highlighting the impact of swallowing issues on quality of life. Breathing impairments are also significant, with a coefficient of -0.0227 (p = 0.014), reflecting their direct effect on well-being. Brushing teeth or combing hair had a coefficient of -0.0451 (p < 0.001), suggesting a substantial reduction in quality of life as these routine activities became challenging. The largest impact is seen in getting up from a chair, with a coefficient of -0.0768 (p < 0.001), indicating a strong association with utility loss in the EQ-5D-3 L. Conversely, other MG-ADL dimensions, such as talking, chewing, double vision, and drooping eyelids, are not significantly associated with utility (p > 0.05). However, these findings may indicate patients’ acceptance of their situation of having lived with these symptoms for years rather than being bothersome or decreasing their utility. These findings suggest that while these factors may negatively influence quality of life, their impact is not statistically significant. Adjustment for covariates, including age, male sex, comorbidities, and the Brazil socioeconomic criterion, also did not have a significant effect on utility loss (p > 0.05), serving primarily to adjust the model without affecting the main outcome. In summary, MG-ADL dimensions related to physical functions—swallowing, breathing, brushing teeth/combing hair, and especially getting up from a chair—have a significant negative impact on quality of life. The other dimensions, despite negative coefficients, were not statistically significant. Discussion This study was grounded in a conceptual model of health-related quality of life (HRQoL) that integrates symptom severity, functional status, and global health perception as interrelated constructs. By operationalizing this framework through the use of MG-ADL and EQ-5D-3L instruments, we were able to capture both the clinical manifestations of myasthenia gravis and their subjective impact on patients' everyday lives. This dual approach aligns with the theoretical model proposed by Wilson et al., which emphasizes the continuum between biological variables and perceived well-being. Our findings confirm this linkage, showing a strong inverse association between MG-specific functional impairment and utility scores, a proxy for general HRQoL. The use of both a disease-specific (MG-ADL) and a generic (EQ-5D-3L) instrument enhances the validity and interpretability of our results. While the MG-ADL allows for nuanced measurement of myasthenia-related impairments, the EQ-5D-3L enables comparisons across diseases and supports cost-utility analyses. The significant correlations observed between the two scales reinforce their convergent validity and suggest that functional limitations in MG directly translate into measurable decrements in overall quality of life. This methodological strategy strengthens the applicability of our findings for both clinical decision-making and health policy modeling. This study reports the first comprehensive assessment of quality of life and utility values for Brazilian patients with generalized myasthenia gravis. Our findings align with previous research, demonstrating a robust statistically significant relationship between MG-ADL scale items and health utility values, with symptom worsening negatively impacting utility scores. Notably, the magnitude of this effect closely mirrors previous studies( 11 ), with our observed increase in utility of 0.024 per point improvement in the MG-ADL total score corresponding remarkably well to the 0.023 increase reported in prior research. Analysis of individual MG-ADL dimensions revealed differential impacts on utility values, with mobility impairment showing the strongest association with quality of life deterioration. Specifically, difficulty in rising from a chair demonstrated the largest utility decrement (-0.0768, p < 0.001), followed by challenges with self-care activities such as brushing one’s teeth/combing one’s hair (-0.0451, p < 0.001). Bulbar and respiratory symptoms also significantly impacted utility, with swallowing difficulties (-0.0263, p = 0.029) and breathing impairments (-0.0227, p = 0.014) showing notable effects. These findings align with previous research by Barnett et al. (2019) and Dewilde et al. (2023), who similarly identified limb weakness and respiratory symptoms as primary drivers of utility loss. Interestingly, while ocular symptoms (double vision and eyelid droop) had negative coefficients, their impact was not statistically significant, suggesting that patients may develop better adaptation strategies for these manifestations than for mobility and respiratory impairments. Other studies demonstrating the high impact of ocular symptoms on patient quality of life (22), such as the Japan registry, which uses the QOL-15 scale in their analysis, and a study of 185 patients in China (23) revealed that the item “have trouble using my eyes” was the highest scoring item in both ocular and generalized patients with MG. This pattern of impact highlights the importance of prioritizing therapeutic interventions targeting mobility and respiratory function to maximize improvements in patient quality of life. A key contribution of this study is the development of validated mapping algorithms between clinical outcomes (MG-ADL) and utility measures (EQ-5D-3 L) for the Brazilian population. Our regression models demonstrate strong predictive power (R² = 0.449) and provide practical tools for economic evaluations. However, our findings reveal important nuances: individual MG‒ADL dimensions have varying impacts on utilities, and similar total MG‒ADL scores may yield different utility values across treatment groups. This suggests the need for more sophisticated mapping approaches that account for both dimension-specific effects and treatment contexts. These refined models would be particularly valuable for accurately assessing the economic value of novel therapies, as demonstrated by Dewilde et al. (2023), who reported treatment-specific utility gains even with identical improvements in MG-ADL. Future research should focus on developing multidimensional mapping frameworks that capture these complex relationships between symptom improvements and quality of life gains. Several methodological limitations warrant consideration. First, our reliance on self-reported data introduces potential recall bias, particularly regarding symptom severity and health status reporting. While validated instruments such as the EQ-5D-3 L and MG-ADL minimize this risk, the subjective nature of symptom reporting remains a consideration. The online survey methodology presents both sampling and accessibility challenges. Digital literacy requirements and internet access may have excluded vulnerable populations, particularly elderly patients and those from lower socioeconomic backgrounds. Given that these populations often experience greater quality of life impairments, our utility estimates may be conservative. The gender imbalance in our sample (88.9% female) suggests potential selection bias, despite targeted recruitment efforts in clinical settings to increase male participation. Social desirability bias may have influenced the responses, particularly regarding sensitive topics such as mental health impacts and activity limitations. While our anonymous data collection process aimed to minimize this effect, its influence cannot be completely eliminated. Additionally, nonresponse bias may exist if study participants differ systematically from nonparticipants in disease severity or other characteristics. To address these limitations, we implemented targeted recruitment through clinical settings to reach severe cases and underrepresented demographics. The use of validated instruments with demonstrated reliability in MG populations helped ensure data quality. Clear instructions, support for questionnaire completion, anonymous response collection, and rigorous data validation procedures were employed to maximize response validity and minimize reporting bias. Future studies should consider mixed-method approaches, including in-person assessments and longitudinal designs, to complement our findings and address these methodological constraints. The integration of clinical data and objective measures could provide valuable validation of self-reported outcomes. Additionally, targeted outreach strategies to engage underrepresented populations would increase the generalizability of future research. This study underscores the heterogeneous impact of gMG symptoms on patient quality of life, with differential effects observed across ocular, bulbar, limb strength, and respiratory manifestations. Our findings demonstrate a robust correlation between functional status (measured by the MG-ADL) and quality of life outcomes, with utility decrements varying significantly by symptom domain. The developed predictive models offer a validated approach for converting MG-ADL scores to utility values, addressing a critical gap in economic evaluations. Notably, mobility and respiratory impairments showed the strongest associations with utility loss, suggesting prioritized areas for therapeutic interventions. These results have important implications beyond Brazil's borders. As the first comprehensive utility study in Latin America, our findings provide reference values for neighboring countries with similar healthcare systems and socioeconomic contexts. The mapping algorithms developed here enable more accurate cost-effectiveness analyses of MG treatments, supporting evidence-based resource allocation decisions. Furthermore, our granular analysis of dimension-specific impacts contributes to the growing body of evidence linking symptom improvements to quality of life gains, which is essential for the value assessment of emerging therapies. The transferability of these findings to other Latin American healthcare systems warrants further investigation, particularly considering variations in treatment access and healthcare delivery models across the region. As this is the first study to report utility values for myasthenia gravis patients in Brazil and Latin America, it offers a regional perspective that has been absent from the global literature. These results fill a critical gap in HRQoL evidence and support economic modeling in middle-income countries, while contributing to a more inclusive global database for cross-cultural comparisons. Conclusion This study is the first comprehensive assessment of health-related quality of life and utility values for Brazilian patients with myasthenia gravis. Our findings revealed significant quality-of-life impairments across multiple domains, with mobility limitations and respiratory symptoms showing the strongest associations with utility decreases. The developed mapping algorithms between the MG-ADL scale and the EQ-5D-3 L provide valuable tools for economic evaluations in Latin American healthcare systems. Key contributions include The quantification of dimension-specific utility losses in the Brazilian MG population, The validation of mapping tools for converting clinical outcomes to utility values, and The establishment of reference data for regional health technology assessments. The strong correlation between functional improvements and utility gains supports the value of targeted therapeutic interventions. These results have important implications for clinical practice, resource allocation, and health policy. The utility values generated will inform cost-effectiveness analyses of emerging therapies, while a granular understanding of symptom impact can guide treatment prioritization. Future research should focus on longitudinal assessments of utility changes and investigations of treatment-specific effects on quality of life. This work advances our understanding of the impact of MG on patient well-being and provides essential tools for evidence-based healthcare decision-making in Brazil and neighboring countries. Declarations Funding: The study was funded by AztraZeneca Brazil with the number 01062022. Ethics The study was approved by the Instituto Nacional de Cardiologia IRB with the number CAAE 65471222.5.0000.5272. The study was conducted in accordance with the Declaration of Helsinki. All the respondents signed a Human Ethics and Consent to participate and receive no direct benefits for the participation. Consent for publication : Not applicable Availability of data: datasets are available on request with the corresponding author Conflict of interest declaration. Daiane Beneduzzi and Luiza Vasconscelos are employees of AstraZeneca, São Paulo, Brazil. Marisa Santos and Andrea Liborio have received honoraria for scientific medical consultants and support. Competing Interests : The authors declare that they have no non-financial competing interests. Author`s Contributions: M.S. and A.L, design, recruiting , data collection, analysis and article writing. D.B. and L.V. design and article review. Consent to Publish declaration : not applicable Acknowledgements : Abrami – Associação Brassileira de Miastenia (https://www.abrami.org.br/), AMMI- Associação Mineira de Miastenia, and Betania Andrade Costa (@betaniaoandradecosta.adv) for helping with patients’ recruitment. References Gilhus NE, Romi F, Hong Y, Skeie GO. Myasthenia gravis and infectious disease. J Neurol. 2018 Jun;265(6):1251–8. Gilhus NE, Tzartos S, Evoli A, Palace J, Burns TM, Verschuuren JJGM. Myasthenia gravis. Nat Rev Dis Primer. 2019 May 2;5(1):30. Salari N, Fatahi B, Bartina Y, Kazeminia M, Fatahian R, Mohammadi P, et al. Global prevalence of myasthenia gravis and the effectiveness of common drugs in its treatment: a systematic review and meta-analysis. J Transl Med. 2021 Dec;19(1):516. Task Force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America, Jaretzki A, Barohn RJ, Ernstoff RM, Kaminski HJ, Keesey JC, et al. Myasthenia gravis: Recommendations for clinical research standards. Neurology. 2000 Jul 12;55(1):16–23. Gilhus NE. Autoimmune myasthenia gravis. Expert Rev Neurother. 2009 Mar;9(3):351–8. Wolfe GI, Herbelin L, Nations SP, Foster B, Bryan WW, Barohn RJ. Myasthenia gravis activities of daily living profile. Neurology. 1999 Apr;52(7):1487–1487. Bedlack RS, Simel DL, Bosworth H, Samsa G, Tucker-Lipscomb B, Sanders DB. Quantitative myasthenia gravis score: Assessment of responsiveness and longitudinal validity. Neurology. 2005 Jun 14;64(11):1968–70. Burns TM, Conaway M, Sanders DB. The MG Composite: A valid and reliable outcome measure for myasthenia gravis. Neurology. 2010 May 4;74(18):1434–40. Barnett C, Herbelin L, Dimachkie MM, Barohn RJ. Measuring Clinical Treatment Response in Myasthenia Gravis. Neurol Clin. 2018 May;36(2):339–53. Bachmann K, Burkhardt D, Schreiter I, Kaifi J, Schurr P, Busch C, et al. Thymectomy is more effective than conservative treatment for myasthenia gravis regarding outcome and clinical improvement. Surgery. 2009 Apr;145(4):392–8. Dewilde S, Phillips G, Paci S, De Ruyck F, Tollenaar NH, Janssen MF. People Diagnosed with Myasthenia Gravis have Lower health-related quality of life and Need More Medical and Caregiver Help in Comparison to the General Population: Analysis of Two Observational Studies. Adv Ther. 2023 Oct;40(10):4377–94. Dewilde S, Phillips G, Paci S, De Ruyck F, Tollenaar NH, Janssen MF. The Burden Patients with Myasthenia Gravis Experience in Terms of Breathing, Fatigue, Sleep, Mental Health, Discomfort and Usual Activities in Comparison to the General Population. Adv Ther. 2024 Jan;41(1):271–91. Dewilde S, Philips G, Paci S, Beauchamp J, Chiroli S, Quinn C, et al. Patient-reported burden of myasthenia gravis: baseline results of the international prospective, observational, longitudinal real-world digital study MyRealWorld-MG. BMJ Open. 2023 Jan 31;13(1):e066445. Dewilde S, Qi CZ, Phillips G, Iannazzo S, Janssen MF. Association Between Myasthenia Gravis-Activities of Daily Living (MG-ADL) and EQ-5D-5L Utility Values: The Additional Effect of Efgartigimod on Utilities. Adv Ther. 2023 Apr;40(4):1818–29. Barnett C, Wilson G, Barth D, Katzberg HD, Bril V. Changes in quality of life scores with intravenous immunoglobulin or plasmapheresis in patients with myasthenia gravis. J Neurol Neurosurg Psychiatry. 2013 Jan;84(1):94–7. Santos M, Cintra MACT, Monteiro AL, et al. Brazilian Valuation of EQ-5D-3L Health States. Value in Health Regional Issues . 2016. Tables Tables 1 to 7 are available in the Supplementary Files section Additional Declarations Competing interest reported. Conflict of interest declaration. Daiane Beneduzzi and Luiza Vasconscelos are employees of AstraZeneca, São Paulo, Brazil. Marisa Santos and Andrea Liborio have received honoraria for scientific medical consultants and support. Competing Interests: The authors declare that they have no non-financial competing interests. Supplementary Files Table1.docx table2.docx Table3.docx Table4.docx table5.docx Table6.docx table7.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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Conflict of interest declaration. Daiane Beneduzzi and Luiza Vasconscelos are employees of AstraZeneca, São Paulo, Brazil. \n\nMarisa Santos and Andrea Liborio have received honoraria for scientific medical consultants and support.\n\nCompeting Interests: The authors declare that they have no non-financial competing interests.","formattedTitle":"Health-related quality of life measurement for Brazilian patients with Myasthenia gravis","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eMyasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by muscular weakness affecting limb, ocular, and respiratory functions(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). With a prevalence worldwide of 70\u0026ndash;320 per million inhabitants, MG is considered an ultrarare disease, although its prevalence is increasing because of improved diagnostic capacity, aging populations and increased survival rates(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe disease typically manifests in a bimodal age distribution at its onset, mainly affecting individuals aged 10\u0026ndash;20 years and 50\u0026ndash;60 years. Clinical presentations vary widely, ranging from mild weakness to severe tetraparesis requiring mechanical ventilation. Symptom presentation can fluctuate throughout the day, predominantly affecting ocular and bulbar muscle groups. Ocular symptoms, including diplopia (double vision) and ptosis (drooping of the upper eyelid), are common due to weakness of the ocular muscles. In the case of generalized MG, the most severe form, bulbar symptoms become prominent. These include dysarthria (difficulty articulating words), dysphagia (difficulty swallowing), loss of facial expression, and \u0026ldquo;dropped head syndrome,\u0026rdquo; which is attributed to weakened neck muscles(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). In addition, respiratory muscle weakness can lead to respiratory failure, termed a \u0026ldquo;myasthenic crisis.\u0026rdquo; Such a crisis often results in the need for hospitalization and emergency care. The triggers for this critical situation can be diverse, with infections or certain medications being significant contributors.\u003c/p\u003e \u003cp\u003eThe clinical course of MG typically evolves through three phases: active, stable and remission (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Prognosis largely depends on the severity of symptoms and the effectiveness of therapeutic interventions. Notably, individuals seropositive for acetylcholine receptor antibodies (AChR-Ab+) have been found to have increased mortality rates compared with seronegative patients.(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) Additional factors that may adversely influence prognosis include the frequency of exacerbations and flares, the presence of bulbar symptoms, and age at onset.\u003c/p\u003e \u003cp\u003eDisease severity can be assessed by several scales, such as the Myasthenia Gravis Activities of Daily Living (MG-ADL)(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e), the Quantitative Myasthenia Gravis score (QMG)(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e), and the Myasthenia Gravis Composite Score (MGC). (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThe primary goal in managing MG is to keep the patient\u0026rsquo;s disease manifestations to a minimum or better. Treatment strategies focus on preventing infections and avoiding medications that may exacerbate the disease.(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Symptomatic treatments include acetylcholinesterase inhibition, chronic immunotherapies (e.g., glucocorticoids, azathioprine, mycophenolate), and short-acting immunomodulatory treatments such as therapeutic plasmapheresis and intravenous immunoglobulin. Thymectomy is recommended for some patients, and biologics may be used for chronic immunosuppression in AChR-Ab\u0026thinsp;+\u0026thinsp;patients.(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThe MG-ADL score (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) is a patient-reported outcome measure that quantifies symptom severity on a scale of zero to three across several domains, including speech, chewing, swallowing, breathing, hygiene (brushing teeth and combing hair), ability to rise from a chair, double vision, and drooping eyelid. Similarly, muscle weakness, a hallmark of MG, is assessed on a scale of zero (no weakness) to four (paralysis) in muscles commonly involved in this condition.(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) The MG-ADL is the instrument most adopted by randomized clinical trials to analyze the impact of new drugs. As a specific instrument, it does not generate utilities necessary for cost-effectiveness studies. The preferred instrument for utility extraction is the EQ-5D-3L or, in the newer 5L version.\u003c/p\u003e \u003cp\u003eThere are few publications that have applied EQ-5D instruments to estimate health-related quality of life (HRQoL) losses due to myasthenia gravis (\u003cspan additionalcitationids=\"CR12 CR13 CR14\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e) and none in Latin America or the Caribbean region. To our knowledge, this is the first study of Brazilian patients with myasthenia using both the EQ-5D and MG-ADL instruments.\u003c/p\u003e \u003cp\u003eThe assessment of health-related quality of life (HRQoL) in individuals with chronic conditions such as myasthenia gravis requires a conceptual framework that captures the multidimensional nature of health. This study is grounded in the HRQoL model proposed by Wilson et al. (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e), which links biological and physiological variables to symptom status, functional status, general health perceptions, and overall quality of life. Within this framework, the EQ-5D-3L instrument captures key domains of general health status - mobility, self-care, usual activities, pain/discomfort, and anxiety/depression - while the MG-ADL provides disease-specific symptom assessment focused on daily functioning. By integrating these two instruments, our study aligns with a conceptual model that values both generic and condition-specific measures, thereby enabling a more comprehensive and sensitive assessment of HRQoL in the Brazilian MG population.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003ePrimary Objective\u003c/strong\u003e \u003cp\u003eTo assess the impact of myasthenia gravis on HRQoL in the Brazilian population, with a particular focus on the experiences of patients at different stages of disease severity.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eSecondary Objective\u003c/strong\u003e \u003cp\u003eTo generate utility values derived from HRQoL outcomes for MG health states. These utility values serve as crucial inputs for cost‒utility models and additionally estimate the HRQoL losses with EQ values for each MG‒ADL health state.\u003c/p\u003e \u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design\u003c/h2\u003e \u003cp\u003eThis project employed a cross-sectional study design to collect online data from a diverse, representative sample of Brazilian individuals diagnosed with myasthenia gravis. The participants included individuals from various age groups and with various levels of disease severity.\u003c/p\u003e \u003cp\u003eAn online questionnaire was created via the REDCap platform. Participant recruitment was conducted via social media in partnership with nongovernmental organizations (NGOs) supporting myasthenia patients.\u003c/p\u003e \u003cp\u003e\u003cb\u003eEthics\u003c/b\u003e The study was approved by the Instituto Nacional de Cardiologia IRB with the number CAAE 65471222.5.0000.5272. The study was conducted in accordance with the Declaration of Helsinki. All the respondents signed consent to participate and receive no direct benefits for participation.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSampling and data collection\u003c/h3\u003e\n\u003cp\u003eWe aimed to recruit at least 70 patients per health state. This strategy was designed to ensure a comprehensive understanding of the impact of Myasthenia Gravis on different levels of disease severity.\u003c/p\u003e \u003cp\u003eThe online survey was distributed through multiple channels, including the following:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eMG patient associations\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eSocial networks\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eWhatsApp groups\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eA satisfactory response rate was achieved, with 317 completed questionnaires included in the analysis.\u003c/p\u003e\n\u003ch3\u003eSurvey Questions and Instruments\u003c/h3\u003e\n\u003cp\u003eThe participants were asked to complete a comprehensive questionnaire that included demographic and general health data such as sex, age, and comorbidities. Health-related questions include a self-reported list of chronic physical or mental health conditions. In addition, the participants responded to questions about their socioeconomic status, health status, treatment history, and healthcare utilization. Participants were also asked to indicate whether they had been diagnosed with chronic diseases by a healthcare professional, including cardiovascular, metabolic, or autoimmune conditions. These self-reported comorbidities were included to better characterize the clinical background of the sample and explore influences on health-related quality of life outcomes.\u003c/p\u003e \u003cp\u003eMyasthenia Gravis Activities of Daily Living (MG-ADL): This is a disease-specific instrument designed to assess the impact of MG on daily life. It is a patient-reported outcome measure developed specifically for individuals with myasthenia gravis. The MG-ADL score is a reliable, valid, and responsive measure of clinical severity in MG patients. It was created to evaluate the effects of the disease on activities of daily living. The MG-ADL is an 8-item questionnaire that focuses on symptoms that most indicate changes in MG severity, including ocular (e.g., ptosis and diplopia), bulbar (e.g., problems with speech, swallowing, and chewing), respiratory (e.g., shortness of breath), and limb-related symptoms (e.g., difficulties with motor functions). Each question is scored on a 4-point scale ranging from 0 (normal) to 3 (severe impairment), allowing patients to indicate the extent to which their daily activities are affected by MG. The total score ranges from 0 (no disability) to 24 (maximum disability).\u003c/p\u003e \u003cp\u003eEQ-5D-3L, 5L, and VAS: These are standardized instruments used to measure health outcomes and quantify five dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The 3-level version (EQ-5D-3L) offers three possible responses: \u0026lsquo;no problems,\u0026rsquo; \u0026lsquo;some problems,\u0026rsquo; or \u0026lsquo;extreme problems.\u0026rsquo; In contrast, the 5-level version (EQ-5D-5L) expands the response scale to \u0026lsquo;no problems,\u0026rsquo; \u0026lsquo;mild problems,\u0026rsquo; \u0026lsquo;moderate problems,\u0026rsquo; \u0026lsquo;severe problems,\u0026rsquo; and \u0026lsquo;extreme problems.\u0026rsquo; In addition to these descriptive systems, the EQ-VAS, or EuroQol visual analog scale, is an integral part of the EQ-5D. The EQ-VAS serves as a global measure of patients\u0026rsquo; self-rated health, structured as a vertically graduated visual analog scale ranging from 0 to 100 points, with the \u0026lsquo;Best imaginable health state\u0026rsquo; at the top (scored as 100) and the \u0026lsquo;Worst imaginable health state\u0026rsquo; at the bottom (scored as 0). Collectively, these components contribute to a comprehensive measure of health status, which is widely used in clinical trials, population health surveys, and health economic evaluations. The use of these tools was approved by the EuroQol Foundation. The EQ-5D was originally designed for self-completion in population-based surveys and clinical studies, and has demonstrated cross-cultural validity, including in Brazilian Portuguese versions (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe selection of the EQ-5D-3L and MG-ADL instruments was guided by both conceptual and methodological considerations. The EQ-5D-3L is a generic instrument for measuring health-related quality of life and generating utility values for economic evaluations. It has been validated in the Brazilian population and provides reliable estimates across a broad range of health conditions. Its simplicity and ease of use make it suitable for self-completed online surveys. The MG-ADL, in turn, is a disease-specific instrument developed to capture functional limitations in patients with myasthenia gravis. It has demonstrated strong internal consistency (Cronbach\u0026rsquo;s alpha\u0026thinsp;\u0026gt;\u0026thinsp;0.80), good test\u0026ndash;retest reliability, and responsiveness to clinical change in both observational and interventional studies. Together, these instruments offer complementary perspectives - EQ-5D-3L capturing general health status and MG-ADL focusing on MG-specific symptom burden - allowing for a robust and sensitive assessment of HRQoL. These psychometric properties have been validated in prior studies, including Wolfe et al. (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) for the MG-ADL and Santos et al. for the EQ-5D-3L in Brazil (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDisease timeline: Participants provided information about the progression of their disease.\u003c/p\u003e \u003cp\u003eSymptom Presence: Information was collected about the presence of symptoms over the past seven days.\u003c/p\u003e\n\u003ch3\u003eData Analysis Plan\u003c/h3\u003e\n\u003cp\u003eDescriptive statistics were calculated to summarize the demographic characteristics and health conditions of the participants. Absolute and relative frequencies are reported for categorical variables, whereas means and standard deviations are reported for numerical variables.\u003c/p\u003e \u003cp\u003eA correlation matrix was generated to examine the relationships between key variables, including the MG-ADL total score, EQ-5D-3 L index, and individual dimensions of both scales. The Spearman correlation coefficient was used because of the mix of continuous and ordinal variables, making it suitable for capturing associations without assuming a normal distribution. This matrix helps reveal how symptom severity and quality of life measures are interrelated.\u003c/p\u003e \u003cp\u003eRegression analysis was used to examine the relationships among myasthenia gravis (MG) symptoms, severity, and health-related quality of life (HRQoL). MG severity, quantified through MG-ADL scores and self-reported data, along with comorbidities and treatment strategies, was included as a variable. Linear regression was used for continuous outcomes (e.g., HRQoL scores), and logistic regression was used for categorical outcomes (e.g., severity levels). Initial univariate models identified individual HRQoL predictors, followed by multivariate models adjusted for confounders and interactions, such as those between severity and treatment. The data review included checks for normality, outliers, and multicollinearity, with adjustments applied as needed.\u003c/p\u003e \u003cp\u003eUtility values were calculated via the EQ-5D-3 L. These values range from 0 (death) to 1 (full health). Weights for responses across the five EQ-5D dimensions, based on Brazilian assessments, provided contextual utility scores.\u003c/p\u003e \u003cp\u003eThe treatment types were categorized as acute (corticosteroids or plasmapheresis), immunosuppressive (azathioprine, methotrexate, cyclosporine, rituximab, mycophenolate), or no treatment. Pyridostigmine was considered standard care and was excluded from analysis. Treatment effectiveness may serve as a proxy for disease severity, with effective treatment potentially reducing symptom severity.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eThe characteristics of the patients are detailed in Table 1. The study sample was predominantly female (88.9%) with a mean age of 41.5 years, consistent with the known epidemiological profile of MG, which tends to affect women of reproductive age. Most participants belonged to socioeconomic classes B (49.7%) and C (30.6%) according to the Brazilian Criteria of Economic Classification. These characteristics suggest a moderately diverse sample in terms of social background, though future studies should aim to enhance male and lower-income representation to better capture the full disease burden across population subgroups.\u003c/p\u003e\n\u003cp\u003eRegarding baseline comorbidities, the most frequently reported chronic conditions were hypertension (22.8%), diabetes (8.5%), and heart disease (5.7%) (Table 1). The presence of cardiovascular and metabolic conditions is clinically relevant, as they may exacerbate fatigue, dyspnea, and general functional decline in patients with MG, potentially amplifying the perceived burden of disease. These overlapping symptoms may also influence self-reported HRQoL scores, especially in the domains of mobility and usual activities.\u003c/p\u003e\n\u003cp\u003eTable 2 presents the responses to the EQ-5D-3 L, showing the distribution of patients across the dimensions of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.\u003c/p\u003e\n\u003cp\u003eMost patients reported moderate issues in mobility (56.15%) and pain/discomfort (64.56%), with fewer patients experiencing extreme difficulties in these dimensions. With respect to self-care, 63.17% of patients reported no difficulties, whereas 35.87% reported moderate problems. Anxiety/depression was a significant concern, with 54.60% of patients reporting moderate problems and 30.48% reporting extreme problems.\u003c/p\u003e\n\u003cp\u003eThe mean EQ-5D-3 L score was 0.55 (standard deviation 0.16), indicating a moderately compromised quality of life among the patients evaluated. Compared with the Brazilian population average of 0.85, the average EQ-5D-3 L index (0.55) shows an absolute reduction of 0.35 points, representing a relative loss of approximately 35% in quality of life. This reflects substantial impairment, particularly in the dimensions of pain/discomfort and anxiety/depression, which had the most significant impact on patients\u0026apos; well-being.\u003c/p\u003e\n\u003cp\u003eTable 3 shows the distribution of patients across MG-ADL items, highlighting the severity of myasthenia gravis symptoms. Most patients exhibited mild to moderate symptoms in several functions, with 57.1% reporting normal speech, 50.16% reporting normal chewing, and 32.49% not experiencing fatigue when rising from a chair. However, a significant proportion of the participants reported functional impairments, such as fatigue when chewing solid food (41.64%) and shortness of breath with exertion (48.26%). More severe impairments, such as ventilator dependence (2.84%) and gastric tube feeding (0.32%), are less common. The distribution of symptoms, particularly in areas such as double vision and drooping eyelids, underscores the variability in disease severity among patients.\u003c/p\u003e\n\u003cp\u003eRegarding psychometric properties, the convergent validity between the dimensions of the EQ-5D-3 L and the MG-ADL was tested.\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u0026nbsp;Table 4 shows the convergence between the MG-ADL and EQ-5D-3 L instruments, demonstrating that greater functional impairment, as measured by the MG-ADL, is associated with a lower quality of life according to the EQ-5D-3 L (Table 4). The significant negative correlation between the total MG-ADL score and the EQ-5D-3 L index (-0.648) indicates that both instruments consistently capture disease severity and its impact on patients\u0026apos; lives. The physical dimensions of the EQ-5D-3 L, such as mobility, self-care, and usual activities, strongly correlate with the MG-ADL, reinforcing the consistency of these instruments in assessing functional status and quality of life.\u003c/p\u003e\n\u003cp\u003eTable 5 presents different prediction models tested to estimate the relationship between the variables and the outcome, using evaluation criteria such as AIC (Akaike information criterion), BIC (Bayesian information criterion), R-squared, adjusted R-squared, and tests for homoscedasticity, normality, and multicollinearity.\u003c/p\u003e\n\u003cp\u003eCompared with the other models, the Basic Model has the lowest AIC (-444.944) and BIC (-429.959), indicating a good fit. The R-squared value is 0.4374, indicating that approximately 43.7% of the data variability is explained by the model, with an adjusted R-squared value of 0.432. Homoscedasticity is not violated (p = 0.186), and the residuals follow normality (p = 0.68836). The mean VIF (1.09) indicates low multicollinearity, suggesting that the independent variables are not highly correlated.\u003c/p\u003e\n\u003cp\u003eThe Model with Interaction Terms has an AIC of -443.43 and a BIC of -420.953, which are slightly worse than those of the Basic Model. The R-squared (0.4419) and adjusted R-squared (0.4328) values show a small improvement in explaining the data variability. Homoscedasticity is preserved (p = 0.2939), and the residuals follow normality (p = 0.6037). However, the mean VIF increases to 6.68, indicating potential multicollinearity.\u003c/p\u003e\n\u003cp\u003eThe quadratic model has an AIC of -442.951 and a BIC of -424.22, with an R-squared of 0.4374 and an adjusted R-squared of 0.4301. Homoscedasticity (p = 0.1869) and normality (p = 0.67102) are similar to those of the basic model, but the mean variance inflation factor (VIF) is 5.71, suggesting some multicollinearity.\u003c/p\u003e\n\u003cp\u003eThe Log-Transformed Model has a positive AIC (23.2203) and the highest BIC (38.1923), along with a lower R-squared (0.4059) and adjusted R-squared (0.4001), suggesting a poor fit. Additionally, homoscedasticity and normality are violated (p = 0 in both cases). The average VIF (1.09) shows no multicollinearity, but the model\u0026apos;s overall fit is poor.\u003c/p\u003e\n\u003cp\u003eFinally, the Model with Control Variables has an AIC of -441.706 and a BIC of -419.306, with the highest R-squared (0.449) and adjusted R-squared (0.4399), indicating that it explains more data variation than the other models do. Homoscedasticity (p = 0.253) and normality (p = 0.50367) are not violated, and the mean VIF of 1.17 suggests low multicollinearity.\u003c/p\u003e\n\u003cp\u003eIn summary, the Model with Control Variables shows the best overall performance in explaining variability (highest R-squared) and in meeting the assumptions, making it the most suitable model among those tested. The Basic Model also stands out for its simplicity and good fit, whereas the models with interaction and quadratic terms present possible multicollinearity issues. The log-transformed model has a significantly poorer fit and violates key assumptions. Based on this model, the impact of impairment in each MG-ADL dimension on quality of life, as estimated by the EQ-5D-3 L, was calculated (Table 6).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFor each one-unit increase in the total MG-ADL score, reflecting greater functional impairment in daily activities among myasthenia gravis patients, there was a 0.02421 decrease in self-reported quality of life, as measured by the EQ-5D-3 L. This negative coefficient indicates that as functional impairment increases, quality of life decreases. The confidence interval for this estimate ranges from -0.02748--0.02094, underscoring the precision of the result. Additionally, the p value \u0026lt; 0.001 confirms the high significance of this inverse relationship between the MG-ADL score and quality of life.\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u0026nbsp;In this context, the MG-ADL score stands out as the central variable explaining the variation in patients\u0026apos; quality of life, with the model accounting for approximately 44.9% of the variability in the EQ-5D-3 L scores (R-squared = 0.449). Other variables in the model, such as age, sex, comorbidities, and socioeconomic status, serve as adjustment covariates but do not show significant associations. Thus, the model primarily emphasizes the strong negative correlation between MG-ADL and quality of life, highlighting the significant impact of functional impairment on patients\u0026apos; perceptions of their health and well-being.\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u0026nbsp;All dimensions (Swallowing, Breathing, Brushing/Combing, and Getting up from a chair) were statistically significant, with Getting up from a chair having the greatest impact (approximately 0.08 absolute points).\u003cbr\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eTable 7 presents the utility losses in the EQ-5D-3 L according to different MG-ADL dimensions. The intercept is 0.7396 (p \u0026lt; 0.001), representing the baseline utility when there is no impairment in the MG-ADL dimensions.\u003c/p\u003e\n\u003cp\u003eSeveral specific MG-ADL dimensions are significantly associated with reduced quality of life. Swallowing difficulties had a coefficient of -0.0263 (p = 0.029), indicating a significant utility reduction and highlighting the impact of swallowing issues on quality of life. Breathing impairments are also significant, with a coefficient of -0.0227 (p = 0.014), reflecting their direct effect on well-being. Brushing teeth or combing hair had a coefficient of -0.0451 (p \u0026lt; 0.001), suggesting a substantial reduction in quality of life as these routine activities became challenging. The largest impact is seen in getting up from a chair, with a coefficient of -0.0768 (p \u0026lt; 0.001), indicating a strong association with utility loss in the EQ-5D-3 L.\u003c/p\u003e\n\u003cp\u003eConversely, other MG-ADL dimensions, such as talking, chewing, double vision, and drooping eyelids, are not significantly associated with utility (p \u0026gt; 0.05). However, these findings may indicate patients\u0026rsquo; acceptance of their situation of having lived with these symptoms for years rather than being bothersome or decreasing their utility.\u003c/p\u003e\n\u003cp\u003eThese findings suggest that while these factors may negatively influence quality of life, their impact is not statistically significant.\u003c/p\u003e\n\u003cp\u003eAdjustment for covariates, including age, male sex, comorbidities, and the Brazil socioeconomic criterion, also did not have a significant effect on utility loss (p \u0026gt; 0.05), serving primarily to adjust the model without affecting the main outcome.\u003c/p\u003e\n\u003cp\u003eIn summary, MG-ADL dimensions related to physical functions\u0026mdash;swallowing, breathing, brushing teeth/combing hair, and especially getting up from a chair\u0026mdash;have a significant negative impact on quality of life. The other dimensions, despite negative coefficients, were not statistically significant.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study was grounded in a conceptual model of health-related quality of life (HRQoL) that integrates symptom severity, functional status, and global health perception as interrelated constructs. By operationalizing this framework through the use of MG-ADL and EQ-5D-3L instruments, we were able to capture both the clinical manifestations of myasthenia gravis and their subjective impact on patients' everyday lives. This dual approach aligns with the theoretical model proposed by Wilson et al., which emphasizes the continuum between biological variables and perceived well-being. Our findings confirm this linkage, showing a strong inverse association between MG-specific functional impairment and utility scores, a proxy for general HRQoL.\u003c/p\u003e \u003cp\u003eThe use of both a disease-specific (MG-ADL) and a generic (EQ-5D-3L) instrument enhances the validity and interpretability of our results. While the MG-ADL allows for nuanced measurement of myasthenia-related impairments, the EQ-5D-3L enables comparisons across diseases and supports cost-utility analyses. The significant correlations observed between the two scales reinforce their convergent validity and suggest that functional limitations in MG directly translate into measurable decrements in overall quality of life. This methodological strategy strengthens the applicability of our findings for both clinical decision-making and health policy modeling.\u003c/p\u003e \u003cp\u003eThis study reports the first comprehensive assessment of quality of life and utility values for Brazilian patients with generalized myasthenia gravis. Our findings align with previous research, demonstrating a robust statistically significant relationship between MG-ADL scale items and health utility values, with symptom worsening negatively impacting utility scores. Notably, the magnitude of this effect closely mirrors previous studies(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e), with our observed increase in utility of 0.024 per point improvement in the MG-ADL total score corresponding remarkably well to the 0.023 increase reported in prior research.\u003c/p\u003e \u003cp\u003eAnalysis of individual MG-ADL dimensions revealed differential impacts on utility values, with mobility impairment showing the strongest association with quality of life deterioration. Specifically, difficulty in rising from a chair demonstrated the largest utility decrement (-0.0768, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), followed by challenges with self-care activities such as brushing one\u0026rsquo;s teeth/combing one\u0026rsquo;s hair (-0.0451, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Bulbar and respiratory symptoms also significantly impacted utility, with swallowing difficulties (-0.0263, p\u0026thinsp;=\u0026thinsp;0.029) and breathing impairments (-0.0227, p\u0026thinsp;=\u0026thinsp;0.014) showing notable effects. These findings align with previous research by Barnett et al. (2019) and Dewilde et al. (2023), who similarly identified limb weakness and respiratory symptoms as primary drivers of utility loss. Interestingly, while ocular symptoms (double vision and eyelid droop) had negative coefficients, their impact was not statistically significant, suggesting that patients may develop better adaptation strategies for these manifestations than for mobility and respiratory impairments. Other studies demonstrating the high impact of ocular symptoms on patient quality of life (22), such as the Japan registry, which uses the QOL-15 scale in their analysis, and a study of 185 patients in China (23) revealed that the item \u0026ldquo;have trouble using my eyes\u0026rdquo; was the highest scoring item in both ocular and generalized patients with MG. This pattern of impact highlights the importance of prioritizing therapeutic interventions targeting mobility and respiratory function to maximize improvements in patient quality of life.\u003c/p\u003e \u003cp\u003eA key contribution of this study is the development of validated mapping algorithms between clinical outcomes (MG-ADL) and utility measures (EQ-5D-3 L) for the Brazilian population. Our regression models demonstrate strong predictive power (R\u0026sup2; = 0.449) and provide practical tools for economic evaluations. However, our findings reveal important nuances: individual MG‒ADL dimensions have varying impacts on utilities, and similar total MG‒ADL scores may yield different utility values across treatment groups. This suggests the need for more sophisticated mapping approaches that account for both dimension-specific effects and treatment contexts. These refined models would be particularly valuable for accurately assessing the economic value of novel therapies, as demonstrated by Dewilde et al. (2023), who reported treatment-specific utility gains even with identical improvements in MG-ADL. Future research should focus on developing multidimensional mapping frameworks that capture these complex relationships between symptom improvements and quality of life gains.\u003c/p\u003e \u003cp\u003eSeveral methodological limitations warrant consideration. First, our reliance on self-reported data introduces potential recall bias, particularly regarding symptom severity and health status reporting. While validated instruments such as the EQ-5D-3 L and MG-ADL minimize this risk, the subjective nature of symptom reporting remains a consideration.\u003c/p\u003e \u003cp\u003eThe online survey methodology presents both sampling and accessibility challenges. Digital literacy requirements and internet access may have excluded vulnerable populations, particularly elderly patients and those from lower socioeconomic backgrounds. Given that these populations often experience greater quality of life impairments, our utility estimates may be conservative. The gender imbalance in our sample (88.9% female) suggests potential selection bias, despite targeted recruitment efforts in clinical settings to increase male participation.\u003c/p\u003e \u003cp\u003eSocial desirability bias may have influenced the responses, particularly regarding sensitive topics such as mental health impacts and activity limitations. While our anonymous data collection process aimed to minimize this effect, its influence cannot be completely eliminated. Additionally, nonresponse bias may exist if study participants differ systematically from nonparticipants in disease severity or other characteristics.\u003c/p\u003e \u003cp\u003eTo address these limitations, we implemented targeted recruitment through clinical settings to reach severe cases and underrepresented demographics. The use of validated instruments with demonstrated reliability in MG populations helped ensure data quality. Clear instructions, support for questionnaire completion, anonymous response collection, and rigorous data validation procedures were employed to maximize response validity and minimize reporting bias.\u003c/p\u003e \u003cp\u003eFuture studies should consider mixed-method approaches, including in-person assessments and longitudinal designs, to complement our findings and address these methodological constraints. The integration of clinical data and objective measures could provide valuable validation of self-reported outcomes. Additionally, targeted outreach strategies to engage underrepresented populations would increase the generalizability of future research.\u003c/p\u003e \u003cp\u003eThis study underscores the heterogeneous impact of gMG symptoms on patient quality of life, with differential effects observed across ocular, bulbar, limb strength, and respiratory manifestations. Our findings demonstrate a robust correlation between functional status (measured by the MG-ADL) and quality of life outcomes, with utility decrements varying significantly by symptom domain. The developed predictive models offer a validated approach for converting MG-ADL scores to utility values, addressing a critical gap in economic evaluations. Notably, mobility and respiratory impairments showed the strongest associations with utility loss, suggesting prioritized areas for therapeutic interventions.\u003c/p\u003e \u003cp\u003eThese results have important implications beyond Brazil's borders. As the first comprehensive utility study in Latin America, our findings provide reference values for neighboring countries with similar healthcare systems and socioeconomic contexts. The mapping algorithms developed here enable more accurate cost-effectiveness analyses of MG treatments, supporting evidence-based resource allocation decisions. Furthermore, our granular analysis of dimension-specific impacts contributes to the growing body of evidence linking symptom improvements to quality of life gains, which is essential for the value assessment of emerging therapies.\u003c/p\u003e \u003cp\u003eThe transferability of these findings to other Latin American healthcare systems warrants further investigation, particularly considering variations in treatment access and healthcare delivery models across the region.\u003c/p\u003e \u003cp\u003e As this is the first study to report utility values for myasthenia gravis patients in Brazil and Latin America, it offers a regional perspective that has been absent from the global literature. These results fill a critical gap in HRQoL evidence and support economic modeling in middle-income countries, while contributing to a more inclusive global database for cross-cultural comparisons.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study is the first comprehensive assessment of health-related quality of life and utility values for Brazilian patients with myasthenia gravis. Our findings revealed significant quality-of-life impairments across multiple domains, with mobility limitations and respiratory symptoms showing the strongest associations with utility decreases. The developed mapping algorithms between the MG-ADL scale and the EQ-5D-3 L provide valuable tools for economic evaluations in Latin American healthcare systems.\u003c/p\u003e\n\u003cp\u003eKey contributions include\u003c/p\u003e\n\u003cp\u003eThe quantification of dimension-specific utility losses in the Brazilian MG population,\u003c/p\u003e\n\u003cp\u003eThe validation of mapping tools for converting clinical outcomes to utility values, and\u003c/p\u003e\n\u003cp\u003eThe establishment of reference data for regional health technology assessments. The strong correlation between functional improvements and utility gains supports the value of targeted therapeutic interventions.\u003c/p\u003e\n\u003cp\u003eThese results have important implications for clinical practice, resource allocation, and health policy. The utility values generated will inform cost-effectiveness analyses of emerging therapies, while a granular understanding of symptom impact can guide treatment prioritization. Future research should focus on longitudinal assessments of utility changes and investigations of treatment-specific effects on quality of life.\u003c/p\u003e\n\u003cp\u003eThis work advances our understanding of the impact of MG on patient well-being and provides essential tools for evidence-based healthcare decision-making in Brazil and neighboring countries.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThe study was funded by AztraZeneca Brazil with the number 01062022.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics\u0026nbsp;\u003c/strong\u003eThe study was approved by the Instituto Nacional de Cardiologia IRB with the number \u0026nbsp;CAAE 65471222.5.0000.5272. The study was conducted in accordance with the Declaration of Helsinki. All the respondents signed a Human Ethics and Consent \u0026nbsp;to participate and receive no direct benefits for the participation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e: Not applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data:\u003c/strong\u003e datasets are available on request with the corresponding author\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest declaration.\u0026nbsp;\u003c/strong\u003eDaiane Beneduzzi and Luiza Vasconscelos are employees of AstraZeneca, São Paulo, Brazil. Marisa Santos and Andrea Liborio have received honoraria for scientific medical consultants and support.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e: The authors declare that they have no non-financial competing interests.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor`s Contributions:\u003c/strong\u003e M.S. and A.L, design, recruiting , data collection, analysis and article writing. D.B. and L.V. design and article review.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Publish declaration\u003c/strong\u003e: not applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e: Abrami – Associação Brassileira de Miastenia (https://www.abrami.org.br/), AMMI- Associação Mineira de Miastenia, and Betania Andrade Costa (@betaniaoandradecosta.adv) for helping with patients’ recruitment.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eGilhus NE, Romi F, Hong Y, Skeie GO. Myasthenia gravis and infectious disease. J Neurol. 2018 Jun;265(6):1251\u0026ndash;8.\u003c/li\u003e\n \u003cli\u003eGilhus NE, Tzartos S, Evoli A, Palace J, Burns TM, Verschuuren JJGM. Myasthenia gravis. Nat Rev Dis Primer. 2019 May 2;5(1):30.\u003c/li\u003e\n \u003cli\u003eSalari N, Fatahi B, Bartina Y, Kazeminia M, Fatahian R, Mohammadi P, et al. Global prevalence of myasthenia gravis and the effectiveness of common drugs in its treatment: a systematic review and meta-analysis. J Transl Med. 2021 Dec;19(1):516.\u003c/li\u003e\n \u003cli\u003eTask Force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America, Jaretzki A, Barohn RJ, Ernstoff RM, Kaminski HJ, Keesey JC, et al. Myasthenia gravis: Recommendations for clinical research standards. Neurology. 2000 Jul 12;55(1):16\u0026ndash;23.\u003c/li\u003e\n \u003cli\u003eGilhus NE. Autoimmune myasthenia gravis. Expert Rev Neurother. 2009 Mar;9(3):351\u0026ndash;8.\u003c/li\u003e\n \u003cli\u003eWolfe GI, Herbelin L, Nations SP, Foster B, Bryan WW, Barohn RJ. Myasthenia gravis activities of daily living profile. Neurology. 1999 Apr;52(7):1487\u0026ndash;1487.\u003c/li\u003e\n \u003cli\u003eBedlack RS, Simel DL, Bosworth H, Samsa G, Tucker-Lipscomb B, Sanders DB. Quantitative myasthenia gravis score: Assessment of responsiveness and longitudinal validity. Neurology. 2005 Jun 14;64(11):1968\u0026ndash;70.\u003c/li\u003e\n \u003cli\u003eBurns TM, Conaway M, Sanders DB. The MG Composite: A valid and reliable outcome measure for myasthenia gravis. Neurology. 2010 May 4;74(18):1434\u0026ndash;40.\u003c/li\u003e\n \u003cli\u003eBarnett C, Herbelin L, Dimachkie MM, Barohn RJ. Measuring Clinical Treatment Response in Myasthenia Gravis. Neurol Clin. 2018 May;36(2):339\u0026ndash;53.\u003c/li\u003e\n \u003cli\u003eBachmann K, Burkhardt D, Schreiter I, Kaifi J, Schurr P, Busch C, et al. Thymectomy is more effective than conservative treatment for myasthenia gravis regarding outcome and clinical improvement. Surgery. 2009 Apr;145(4):392\u0026ndash;8.\u003c/li\u003e\n \u003cli\u003eDewilde S, Phillips G, Paci S, De Ruyck F, Tollenaar NH, Janssen MF. People Diagnosed with Myasthenia Gravis have Lower health-related quality of life and Need More Medical and Caregiver Help in Comparison to the General Population: Analysis of Two Observational Studies. Adv Ther. 2023 Oct;40(10):4377\u0026ndash;94.\u003c/li\u003e\n \u003cli\u003eDewilde S, Phillips G, Paci S, De Ruyck F, Tollenaar NH, Janssen MF. The Burden Patients with Myasthenia Gravis Experience in Terms of Breathing, Fatigue, Sleep, Mental Health, Discomfort and Usual Activities in Comparison to the General Population. Adv Ther. 2024 Jan;41(1):271\u0026ndash;91.\u003c/li\u003e\n \u003cli\u003eDewilde S, Philips G, Paci S, Beauchamp J, Chiroli S, Quinn C, et al. Patient-reported burden of myasthenia gravis: baseline results of the international prospective, observational, longitudinal real-world digital study MyRealWorld-MG. BMJ Open. 2023 Jan 31;13(1):e066445.\u003c/li\u003e\n \u003cli\u003eDewilde S, Qi CZ, Phillips G, Iannazzo S, Janssen MF. Association Between Myasthenia Gravis-Activities of Daily Living (MG-ADL) and EQ-5D-5L Utility Values: The Additional Effect of Efgartigimod on Utilities. Adv Ther. 2023 Apr;40(4):1818\u0026ndash;29.\u003c/li\u003e\n \u003cli\u003eBarnett C, Wilson G, Barth D, Katzberg HD, Bril V. Changes in quality of life scores with intravenous immunoglobulin or plasmapheresis in patients with myasthenia gravis. J Neurol Neurosurg Psychiatry. 2013 Jan;84(1):94\u0026ndash;7.\u003c/li\u003e\n \u003cli\u003eSantos M, Cintra MACT, Monteiro AL, et al. Brazilian Valuation of EQ-5D-3L Health States. \u003cem\u003eValue in Health Regional Issues\u003c/em\u003e. 2016.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 7 are available in the Supplementary Files section\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Myasthenia gravis, Quality of life, Utility values, Brazil, EQ-5D-3 L, MG-ADL","lastPublishedDoi":"10.21203/rs.3.rs-6604495/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6604495/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: Myasthenia gravis significantly impacts patients' quality of life, yet utility data from Latin America remain scarce. This study assessed health-related quality of life and generated utility values for Brazilian patients with MG.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: In this cross-sectional study, 317 Brazilian patients with MG completed online questionnaires, including the EQ-5D-3 L and MG-ADL instruments. Multiple regression models were used to examine the relationships between symptom severity and utility values. Mapping algorithms were developed to convert MG-ADL scores to utility values.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: The mean EQ-5D-3 L score was 0.55 (SD 0.16), representing a 35% reduction from Brazilian population norms. The most significant decreases in utility were associated with mobility limitations (-0.0768, p\u0026lt;0.001) and self-care difficulties (-0.0451, p\u0026lt;0.001). Each one-point increase in the MG-ADL score corresponded to a decrease in utility of 0.024 (p\u0026lt;0.001). The final prediction model explained 44.9% of the utility variance.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e: This is the first Brazilian MG utility study to demonstrate substantial quality of life impairment and provide validated mapping tools for economic evaluation. The results enable more accurate health technology assessments and support evidence-based resource allocation in Latin American healthcare systems.\u003c/p\u003e","manuscriptTitle":"Health-related quality of life measurement for Brazilian patients with Myasthenia gravis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-29 10:08:15","doi":"10.21203/rs.3.rs-6604495/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"70e697da-1fb5-476b-bba6-b46fc15adc5d","owner":[],"postedDate":"May 29th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-06-16T11:53:56+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-29 10:08:15","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6604495","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6604495","identity":"rs-6604495","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}