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The Prevalence of Comorbidities and Their Association With Disability Progression in Individuals With Multiple Sclerosis: A Study From Brazil

 To access the article and evaluation online, go to 

 The target audience for this activity is physicians, advanced practice clinicians, nursing professionals, and other health care providers involved in the management of patients with multiple sclerosis (MS).

Recognize the importance of comorbidities in the progression of disability in patients with MS.

Apply evidence-based clinical strategies for managing comorbidities in patients with MS to improve clinical outcomes.

In support of improving patient care, this activity has been planned and implemented by the Consortium of Multiple Sclerosis Centers (CMSC) and Intellisphere, LLC. The CMSC is jointly accredited by the Accreditation Council for Continuing Medical Education, the Accreditation Council for Pharmacy Education, and the American Nurses Credentialing Center, to provide continuing education for the health care team.

This activity was planned by and for the health care team, and learners will receive 0.5 Interprofessional Continuing Education (IPCE) credit for learning and change.

 The CMSC designates this journal-based activity for a maximum of 0.5 

™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

: The CMSC designates this enduring material for 0.5 contact hour of nursing continuing professional development (none in the area of pharmacology).

 It is the policy of the CMSC to mitigate all relevant financial disclosures from planners, faculty, and other persons that can affect the content of this CE activity. For this activity, all relevant disclosures have been mitigated.

, has served as physician planner for this activity. He has disclosed no relevant financial relationships. 

, has disclosed no relevant financial relationships. Authors 

Marco Aurélio Gralha de Caneda, MD, MSc, Camila Batista de Oliveira Silva, PhD

, have disclosed no relevant financial relationships.

, CMSC, and Intellisphere, LLC, who are in a position to influence content, have disclosed no relevant financial relationships. 

, CMSC continuing education director, has served as a planner and reviewer for this activity. She has disclosed no relevant financial relationships.

Release Date: September 1, 2024; Valid for Credit through: September 1, 2025

(1) Review the continuing education information, including learning objectives and author disclosures.

(3) Complete the evaluation, which is available at https://www. highmarksce.com/mscare.

Statements of Credit are awarded upon successful completion of the evaluation. There is no fee to participate in this activity.

 This educational activity may contain discussion of published and/or investigational uses of agents that are not approved by the US Food and Drug Administration. The CMSC and Intellisphere, LLC, do not recommend the use of any agent outside of the labeled indications. The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of the CMSC or Intellisphere, LLC.

 Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any medications, diagnostic procedures, or treatments discussed in this publication should not be used by clinicians or other health care professionals without first evaluating their patients’ conditions, considering possible contraindications or risks, reviewing any applicable manufacturer’s product information, and comparing any therapeutic approach with the recommendations of other authorities.

Comorbidities negatively impact the course of multiple sclerosis (MS). Identifying them is essential, as they represent potentially modifiable prognostic factors that can adversely influence the disease course. However, comorbidity prevalence remains underexplored in certain populations, including in individuals in Brazil.

In this cross-sectional study, we describe the frequency of comorbidities and their correlation with MS disability progression in a Brazilian population by reviewing the medical records of patients from a single MS center in Brazil. Preexisting comorbidities and those present at the time of MS diagnosis were screened. We assessed the prevalence of comorbidities, their prevalence ratios (PR) and the association between them, their number, and the confirmed disability worsening (CDW) that emerged during the follow-up visits.

Comorbidities were present in 68.9% of individuals. The most prevalent comorbidities included cardiovascular diseases (19.3%), migraine (13.3%), psychiatric disorders (12.4%), smoking (12.4%), autoimmune diseases (12.0%), respiratory diseases (10.3%), and neoplasms (5.6%). Patients with 1 comorbidity and those with multiple comorbidities (≥ 3) had a significant PR for CDW (2.67, 

 = .03, respectively). Cardiovascular and autoimmune diseases presented significant PR for CDW (2.28, 

Comorbidities are more prevalent among Brazilian individuals with MS than in the general population and are associated with disease progression. Identifying and managing them may mitigate their adverse effects on disease course.

From the Multiple Sclerosis and Demyelinating Disorders Unit, Department of Neurology, Hospital Moinhos de Vento, Porto Alegre, Rio Grande do Sul, Brazil (MAGC); Vecino Medical Center, Porto Alegre, Rio Grande do Sul, Brazil (CBOS); Multiple Sclerosis and Demyelinating Disorders Unit, Department of Neurology, Hospital Moinhos de Vento, Porto Alegre, Rio Grande do Sul, Brazil (MCAV). 

Marco Aurélio Gralha de Caneda, MD, Desing Office Center, 630; Ramiro Barcelos St, 5th floor, CEP 90660-020; 

mcaneda@terra.com.br; magdecaneda@gmail.com.

 The authors declare no conflicts of interest.

Multiple sclerosis (MS) is a chronic inflammatory and degenerative disease of the central nervous system that mainly affects young adults in the prime of their productive lives.

 Although substantial progress has been made in understanding MS, its etiology and heterogeneous course remain incompletely understood.

 Clinical, demographic, and psychosocial characteristics, along with individual genetic and epigenetic factors, are believed to influence disease onset and progression.

Emerging evidence also suggests that comorbidities may play a significant role in the MS clinical course.

 Comorbidities, chronic conditions distinct from the underlying disease, contribute to the overall burden of MS.

 Complications directly derived from the underlying disease, such as bladder disturbances, or transient conditions, such as acute infections, are not considered comorbidities.

 Regardless of disease phenotype, the most frequent MS comorbidities are depression, anxiety, hypertension, dyslipidemia, and chronic obstructive pulmonary disease (COPD), which are also highly prevalent even before MS diagnosis. The frequency does vary with age, highlighting the importance of monitoring these conditions across the entire population of individuals with MS.

Studies have demonstrated an association between comorbidities and various negative outcomes in MS, including delays in diagnosis, increased hospitalizations and mortality rates, higher social and individual costs, and worsening disability progression and quality of life.

 Additionally, comorbidities may influence the choice of disease-modifying drugs (DMDs) used for MS treatment, including switches between DMDs, since comorbidities may be associated with intolerance, worsening or onset of some pathologies, and adherence.

Therefore, identifying comorbidities is crucial for reducing their negative impact on the MS course, as they are potentially modifiable prognostic factors.

 Despite this, in many regions there is a paucity of research focusing on this aspect, particularly in Latin American countries, including Brazil.

 In this study, we aim to address this gap by describing the frequency of comorbidities and their correlation with disease progression in a population of individuals with MS from Brazil.

This cross-sectional study was conducted at the Multiple Sclerosis and Other Demyelinating Disorders Unit of Hospital Moinhos de Vento in Porto Alegre, Rio Grande do Sul. The local health department authority provides MS treatment, and according to information from this agency, 1944 individuals were undergoing treatment in the state of Rio Grande do Sul at the end of 2020.

The medical records of patients who received a diagnosis of MS from January 2, 1991, to December 30, 2020, designated as the prevalence day (PD; ie, the proportion of a population that has a specific characteristic in a given time period), were retrospectively reviewed. These were captured through coding, and MS diagnoses were confirmed by medical progress notes or laboratory test results. The comorbidities screened in the study were selected according to literature data and included both preexisting conditions and those present at the time of MS diagnosis.

 No particular scale was used for screening comorbidities. Instead, comorbidities were identified based on documentation in the medical records by health care providers. They encompassed cardiovascular diseases (hypertension, dyslipidemia, ischemic and other heart diseases, stroke, obesity, and type 2 diabetes mellitus); respiratory pathologies (COPD, asthma, and chronic bronchitis); neoplasms; autoimmune diseases (thyropathies, inflammatory bowel diseases, rheumatologic and dermatologic pathologies); liver diseases; epilepsy; migraine; smoking; and psychiatric disorders.

Demographic (sex and age) and clinical (phenotype and DMD treatment at the PD) data were extracted from the medical records. The initial Expanded Disability Status Scale (EDSS) score at the time of MS diagnosis (EDSSi), the final EDSS score on the PD (EDSSf), and the time elapsed between them (Δt-EDSSif) were recorded. All EDSS scores considered were at least 2 months apart from MS relapses. Confirmed disability worsening (CDW) was defined by an increase in the scale score of 1 point if the EDSSi was less than 5.5, or 0.5 points if it was greater than or equal to 5.5,

 and documented in at least 2 consecutive records before the PD.

The variables were described using means, with their respective standard deviations, or as percentages. Differences between groups of patients with vs without comorbidities, and with vs without CDW, were assessed using Student 

 tests. The Shapiro-Wilk test was employed to check for normal distribution. The prevalence of each comorbidity was calculated as the proportion of individuals with a specific condition among the total number of patients with MS on the PD. The prevalence ratios (PR) of the comorbidities, along with 95% CIs, were calculated by a generalized linear model (GLM) stepwise regression analysis. The GLM was based on a log-binomial distribution for the outcome, with a test for collinearity and adjustment by the Hosmer-Lemeshow test. Additionally, the association of the presence and number of comorbidities with CDW was assessed. The significance level was set at 

 < .05, and the results were calculated using SPSS Version 25.0 software. This study was conducted with authorization from the research ethics committee of the Hospital Moinhos de Vento.

A total of 232 individuals with MS were included, with a mean age of 45.2 ± 12.9 years, 178 (76.7%) women, and 212 (91.4%) with the relapsing-remitting phenotype. Comorbidities were present in 160 (68.9%) individuals, with an average of 1.5 comorbidities per patient. The mean EDSSi was 1.6 ± 1.5; the mean EDSSf was 2.5 ± 1.8; the Δt-EDSSif was 6.4 ± 6 years. On the PD, 180 (77.6%) patients were receiving some DMD; however, no statistically significant difference was identified between patients with and without MS CDW (

). The most prevalent comorbidities were cardiovascular diseases (19.3%; 95% CI, 14.4%-25%), migraine (13.3%; 95% CI, 9.2%-18.3%), psychiatric disorders (12.4%; 95% CI, 8.5%-17.3%), smoking (12.4%; 95% CI, 8.5%-17.3%), autoimmune diseases (12%; 95% CI, 8.1%-17%), respiratory diseases (10.3%; 95% CI, 6.7%-15%), and neoplasms (5.6%; 95% CI, 3%-9.3%), as shown in 

There were no differences between patients with vs without comorbidities in the proportion of sex, MS phenotypes, EDSSi and EDSSf scores, and of Δt-EDSSif (

). A significant difference was found between these groups in age (

 = .008), with a higher average age in patients with comorbidities (46.7 ± 12.5 vs 41.9 ± 13.3 years), and in the number of patients with CDW (

 = .04). There were 54 individuals with 1 comorbidity (33.7%), with 34 (63.0%) with CDW; 54 patients had 2 comorbidities, with 22 (40.7%) with CDW; 52 (32.5%) patients had multiple comorbidities (≥ 3 conditions), with 27 (51.9%) with CDW. Patients with 1 comorbidity were younger, with a higher number of individuals 45 years or younger (66.6%, 

 = .005), whereas patients with 2 or more comorbidities were more likely to be older than 45 years (71.7%, 

In a comparison of patients with vs without CDW, a significant difference in sex was observed, with a lower number of male patients among individuals with CDW (

 = .01) and in the number of patients with comorbidities (

 = .04). There was no significant difference in age, MS phenotype, or in the Δt-EDSSif. There was a highly significant difference in EDSSi (

 < .0001), with patients without CDW presenting a higher average score. EDSSf was also significantly higher in patients with CDW (

 < .0001). Among the 108 (46.5%) individuals with CDW, 83 (76.8%) had comorbidities. In turn, among patients without comorbidities, 77 (62.1%) did not have CDW (

After controlling for age, sex, MS phenotype, and Δt-EDSSif, the regression analysis showed a higher probability of CDW among patients with comorbidities vs patients without comorbidities, with a PR of 1.94 (95% CI, 1.06-3.57; 

 = .03). Patients with 1 comorbidity had a significant PR of 2.67 (95% CI, 1.25-5.71; 

 = .01), those with 2 comorbidities had a PR of 1.15 (95% CI, 0.78-1.68, 

 = .48), and individuals with multiple comorbidities had a PR of 1.25 (95% CI, 1.01-1.55; 

 = .03) for CDW. In addition, the GLM estimated that for every comorbidity, there was a mean increase of 1.15 points in the EDSS score (95% CI, 0.87-1.43). Regarding specific comorbidi-ties, patients with cardiovascular diseases had a significantly higher probability of CDW vs patients without comorbidi-ties, with a PR of 2.28 (95% CI, 1.25-4.9; 

 = .03). Patients with autoimmune diseases also had a high probability, with a PR of 4.2 (95% CI, 1.58-11.1; 

 = .004). Those who smoked were more likely to have CDW, with a PR of 2.42 (95% CI, 0.98-5.99; 

 = .055); however, that was not statistically significant (

Many of the findings of this study may seem intuitive, but they reaffirm that screening for comorbidities should be routine in MS care.

 This practice can establish expectations about the presence of specific pathologies, helping to identify at-risk patients and choose the best treatment. The identification of preexisting comorbidities at the time of MS diagnosis is crucial not only for managing the comorbidity itself, but also for reducing its impact on the course of MS. Assessing the impact of comorbidities on the progression of MS improves the quality of care and directly results in a better quality of life for patients.

In countries with significant economic limitations, such as Brazil, optimizing the treatment of high-cost conditions like MS, which is fully funded by the state, becomes crucial for more efficient resource allocation. It is important to note that demographic characteristics are likely associated with specific comorbidities and can be very heterogeneous, partly explaining the heterogeneity of the MS course.

 Therefore, it is essential to identify pathologies commonly present in specific populations. Local environmental factors such as dietary and hygiene habits, sun exposure, vaccination policies, access to the health care system, and population concentration in urban areas also can increase or reduce the risk of additional pathologies that may influence the prognosis of MS. This study, which, to the best of our knowledge is the first on the subject from Brazil, may contribute to the proper management of MS and promote research on the topic in different regions of the country.

Individuals with MS exhibit a higher prevalence of preexisting comorbidities compared with age-, sex-, and geographic-matched population controls.

 Therefore, it is not surprising to observe a comorbidity rate of 69.0% in our sample because 52% of the Brazilian population as a whole has a disorder.

 This rate is consistent with that in some previous studies, where it ranged from 65.3% to 73.2%.

 Another study, however, indicated that at least 1 comorbidity of those listed in the Charlson Comorbidity Index (CCI) was present in just 22.7% of the individuals up to 10 years prior to receiving their MS diagnosis.

 Based on self-reported information, other studies have found that the prevalence of preexisting comorbidities is quite a bit lower than prevalence at the time of MS diagnosis.

 These data suggest that instruments designed for the general population, such as the CCI or self-report methods, may not perform as well as previously reported for individuals with MS.

As expected, there was a significant correlation between age and comorbidity prevalence, given the greater risk of emergence with aging.

 The accumulation of comorbidities as individuals with MS age appears to surpass what would be expected from natural aging, exceeding the prevalence observed in the matched general population.

 This overaccumulation may be attributed to DMDs, which are associated with an increased risk of developing pathologies, and to the potential sharing of risk factors of MS and specific pathologies.

 Conversely, our findings do not support an association between aging and CDW, since the group of individuals with 1 comorbidity, which had a significantly higher number of younger individuals, showed higher probability of CDW. This result is in line with recent studies, which found higher rates of disease activity and subsequent risk of disability worsening among younger individuals with MS.

 However, prominent disease activity may justify the predominance of women with CDW. This is aligned with a recent publication that described higher inflammatory activity in women compared with men, especially before 50 years of age, suggesting sex hormones play a role in this outcome.

 Considering the averages of 6.4 years for Δt-EDSSif and a 1.15-point increase in EDSS scores for the entire cohort, our results indicate an average annual rise of 0.18 points in EDSS scores for each comorbidity. This is in line with results from previous studies that have consistently reported an association between the presence of comorbidities and CDW, with rates ranging between 0.18 and 0.28.

Previous literature has systematically identified cardiovascular comorbidities as among the most frequent in individuals with MS, even before diagnosis.

 The prevalence of 19.3% found in our study was higher than the 12.9% described in a study performed at diagnosis; however, the study excluded patients with hyperlipidemia.

 Hypertension was found to be the most frequent cardiovascular comorbidity in our study, with a prevalence of 10.3%, which was slightly higher than previous publications, which reported rates from 7.4% to 8.8%.

 Notably, Marrie et al reported a prevalence of 15.2% at the time of MS diagnosis, attributing this to disproportionately higher rates of hypertension in men compared with matched controls.

 We found a hyperlipidemia prevalence of 6.4%, which is in line with the literature, which ranges from 6.9% to 7.2%.

 Our data showed that patients with vascular comorbidities are 1.28 times more likely to have CDW, which is in agreement with findings reported in several previous publications.

Migraine is twice as common in individuals with MS compared with the general population,

 possibly resulting from chronic inflammatory mechanisms. A previous study identified migraine as the second most common comorbidity prior to MS diagnosis, although the reported prevalence of 20.2% was higher than the 13.3% we found.

 In a Brazilian publication, a significantly higher prevalence of migraine (approximately 54.0%) was reported. However, 55.4% of patients attributed the headache onset to MS treatment, which may be a common adverse effect of DMDs.

Smoking seems to have a dose-dependent duration and intensity correlation with MS, is a contributing factor to the negative effects of other comorbidities on the MS course, and is associated with a higher risk of other autoimmune diseases.

 The 12.4% prevalence of smokers in our study was practically the same as the 12.6% reported for the general Brazilian population.

 It was lower than the 20.7% and 22% at the time of MS diagnosis, as reported in 2 previous studies.

 This lower rate may be attributed to the intense Brazilian government control policies implemented in recent decades.

The 12.4% prevalence of psychiatric disorders observed in our study aligns with the rate of 11.8% reported in a Swedish study on comorbidities present before MS diagnosis.

 In contrast, a study from Australia reported a rate of 32.5%, and a Danish study found a prevalence of 5.1%.

 This wide range could be attributed to the insidious nature of psychiatric conditions, which may be secondary to pathological mechanisms present before the MS onset and that may emerge independently of the disease stage.

 Depression was the most common psychiatric pathology in our sample, with a prevalence of 9.4%, an intermediate rate between the 6.5% and 15.8% reported by previous publications.

 In previous Brazilian studies, the prevalence of depression ranged from 18.3% to 34%, however these described the depression as emerging after diagnosis.

 Likewise, another Latin study found a higher rate of 40.0% throughout the disease course.

 Early detection of psychiatric comorbidities may be a viable strategy to reduce the severity of so-called invisible MS symptoms, thereby enhancing quality of life for individuals with MS. Moreover, it may mitigate the higher risk of suicide during the diagnostic process and early stages of the disease.

Autoimmune diseases had a prevalence of 12.0%, which was higher than previous studies (range, 6.1%-8.4%).

 In fact, a systematic review found rates that varied from 3.0% to 26.0%, with these discrepancies attributable to the methodological heterogeneity.

 Thyropathies were the most common autoimmune comorbidities in our study, with a prevalence of 7.7%, higher than the rates reported at the time of MS diagnosis (range, 3.3%-4.5%).

 Another Latin American study reported a 15.7% prevalence of thyropathies, but this was throughout the MS course.

 Few studies have evaluated the impact of autoimmune diseases on MS course. Our results indicate that individuals with these comorbidities are 3.2 times more likely to have CDW, which is in line with a previous publication that found risk increased by 3.02 times in individuals with rheumatoid arthritis.

Respiratory pathologies had a prevalence of 10.3%, which is close to a previously reported 12.0% rate at the time of MS diagnosis.

 Asthma was the most frequent respiratory pathology, with a prevalence of 6.9%, which is similar to the 7.6% reported in a study that assessed patients up to 1 year before the MS diagnosis.

 In contrast, some studies reported asthma prevalence ranging from 16.5% to 18.7%.

 The prevalence of asthma in the Brazilian population ranges from 7.7% to 9.3%, whereas in the locations where these studies were conducted, it ranges from 14.0% to 21.0%. Conversely, some studies have indicated lower occurrence of asthma in individuals with MS, with a prevalence as low as 3.2%, which may be explained by genetic and environmental factors.

The prevalence of neoplasms in our study was 5.6%, which was higher than in previous studies, where it ranged from 2.0% to 3.6%.

 Our higher rate may be attributed to breast neoplasms, which accounted for 30% of cases and is highly prevalent in the Brazilian population, especially among young women. A study from Belgrade, Serbia, reported a breast cancer prevalence of 0.95%, whereas in our patients it was about 80% higher, and another, from Sweden, showed a prevalence of 0.7%, which was 140% lower than ours.

 Women with MS have a 28% increased risk of mortality from breast cancer compared with the general population.

 Therefore, along with assessing personal and family histories, considering the possible effects of some DMDs on the occurrence of specific malignancies and their differential effects according to sex is advisable.

This study has several limitations. First, its retrospective design may restrict the generalizability of the findings. Second, the sample was selected from a tertiary center dedicated to demyelinating diseases, which may have led to earlier and more frequent comorbidity diagnoses compared with the general population due to the higher frequency of health care use. Despite the relatively small sample size, the study cohort accounts for approximately 12% of the population of patients with MS registered in the state at the end of 2020, according to data from the local health department authority. We believe this sample size is sufficient to obtain reliable data on the prevalence of MS comorbidities within the local community. Third, variables that could be related to both the presence of comorbidities and CDW, such as socioeconomic status, physical activity, alcohol and drug consumption, diet, and the continuous use of medications other than DMDs, were not assessed.

The presence of comorbidities further complicates the complex management of MS. Our data emphasize the importance of early treatment of these conditions to avoid a worse prognosis. Health care professionals should establish expectations and routine practices regarding the presence of specific comorbidities at the time of MS diagnosis and implement care models for their prevention and treatment. Our results show a significant association between comorbidities and disability progression, highlighting the need for further research to determine whether early treatment of comorbidities can effectively reduce disability progression and improve clinical outcomes for individuals with MS.

To access the article, post-test, and evaluation online, go to 

The target audience for this activity is physicians, physician assistants, nursing professionals, and other health-care providers involved in the management of patients with multiple sclerosis (MS).

1) Describe new approaches to optimize adherence through shared decision-making and patient engagement principles.

2) Integrate shared decision-making principles and models into clinical practice.

In support of improving patient care, this activity has been planned and implemented by the Consortium of Multiple Sclerosis Centers (CMSC) and Delaware Media Group. CMSC is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

The CMSC designates this journal-based activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

The CMSC designates this enduring material for 1.0 contact hours (none in the area of pharmacology).

Francois Bethoux, MD, Editor in Chief of the International Journal of MS Care (IJMSC), has served as Physician Planner for this activity. He has received royalties from Springer Publishing, served on a speakers' bureau for Biogen, and done contracted research for Adamas Pharmaceuticals.Francois Bethoux, MD

Laurie Scudder, DNP, NP, has served as reviewer for this activity. She has disclosed no relevant financial relationships.

Aliza Ben-Zacharia, DNP, ANP, MSCN, has received consulting fees from Biogen, Bayer, EMD Serono, Celgene, Novartis, Genentech, and Genzyme and research grants from Biogen and Novartis.

Meagan Adamson, DNP, FNP-BC, MSCN, has served on speakers' bureaus for Biogen, EMD Serono, Genentech, Novartis, Genzyme, Acorda, Teva, and Mallinckrodt.

Allison Boyd, MPAS, PA-C, MSCS, has received consulting fees from Genzyme, served on a speakers' bureau/advisory board for EMD Serono, and has been a speaker for Teva Neurosciences and Biogen.

Paula Hardeman, MPAS, PA-C, has disclosed no relevant financial relationships.

Jennifer Smrtka, MSN, ARNP-C, MSCN, has served on advisory boards for Biogen, EMD Serono, Genentech, Novartis, Sanofi Genzyme, and Teva Neuroscience and as a speaker for EMD Serono, Genentech, Mallinckrodt, Sanofi Genzyme, and Teva Neuroscience; she receives salary from Biogen.

Bryan Walker, MHS, PA-C, has received consulting fees from Biogen, EMD Serono, and Sanofi Genzyme and served on speakers' bureaus for Novartis and Biogen.

Tracy Walker, FNP-C, WOCN, MSCN, has received grant support from EMD Serono, Genzyme, and Teva and personal fees from Acorda, Genentech, Sanofi Genzyme, Mallinckrodt, and Teva, and served on speakers' bureaus for EMD Serono, Acorda, Teva, and Genzyme.

 has received consulting fees from and participated on speakers' bureaus for Biogen, Novartis, Genentech, Sanofi Genzyme, and EMD Serono. The other peer reviewer disclosed no relevant financial relationships. 

The staff at the IJMSC, CMSC, and Delaware Media Group who are in a position to influence content have disclosed no relevant financial relationships.

 Financial relationships for some authors may have changed in the interval between listing these disclosures and publication of the article.

Valid for Credit Through: December 1, 2019

In order to receive CME/CNE credit, participants must:

1) Review the continuing education information, including learning objectives and author disclosures.

3) Complete the post-test and evaluation, which are available at 

Statements of Credit are awarded upon successful completion of the post-test with a passing score of >70% and the evaluation.

There is no fee to participate in this activity.

This educational activity may contain discussion of published and/or investigational uses of agents that are not approved by the FDA. CMSC and Delaware Media Group do not recommend the use of any agent outside of the labeled indications. The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of CMSC or Delaware Media Group.

Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any medications, diagnostic procedures, or treatments discussed in this publication should not be used by clinicians or other health-care professionals without first evaluating their patients' conditions, considering possible contraindications or risks, reviewing any applicable manufacturer's product information, and comparing any therapeutic approach with the recommendations of other authorities.

Shared decision making (SDM) and adherence to treatment are an integral part of multiple sclerosis (MS) care. A collaborative process, SDM actively involves the patient, the health care provider, and an extended network in making treatment decisions. Adherence to disease-modifying drug therapies in patients with MS presents an ongoing challenge for patients and health care providers due to the chronic nature of this disease. This narrative review aims to explore the impact of SDM on adherence based on existing literature and to identify new approaches to optimizing adherence.

A search was conducted using medical subject heading terms, including 

decision-making, adherence, shared decision-making, compliance

Shared decision making between patients and clinicians promotes adherence to the treatment plan in MS. A proactive SDM approach is based on patient preferences, education, and engagement. Providing credible and accurate sources of information is essential for improving patient engagement. Home monitoring, computerized models, and active patient engagement are a few new approaches to improve adherence in patients with MS.

Shared decision-making interventions can have a positive effect on patient adherence to disease-modifying drug therapy in MS care. A range of new strategies is emerging that may help promote optimal disease management.

The authors thank Stacey Reeber and Lindsay Craik of Caudex, New York, NY, USA (supported by EMD Serono), for editorial assistance in drafting the manuscript, collating the comments of authors, and assembling figures.

Multiple sclerosis (MS) is a chronic, heterogeneous, inflammatory, neurodegenerative autoimmune disease that leads to physical, emotional, and cognitive disability. Although there is no cure for MS, there have been remarkable advances in the treatment of MS during the past 20 years. The goals of MS treatment are to reduce disease activity and delay disability. Several disease-modifying drugs (DMDs) are approved for the treatment of relapsing forms of MS, and recently a DMD has also been approved for primary progressive MS. The approved DMD landscape includes medications with various routes of administration (injectable, oral, and infusion), frequencies, mechanisms of action, and safety and tolerability profiles.

 These drug-related factors—combined with patient preference, lifestyle, disease course, disability, and motivation, as well as insurance status and cost of DMDs—can potentially affect treatment adherence. In general, rates of adherence in MS range from 49% to 88%, with variations reported across studies.

The efficacy of DMDs in MS depends on high levels of adherence. Data from managed care databases show that the incidence of relapses and relapse-associated hospitalizations increased in patients who were nonadherent or discontinued treatment with DMDs.

 In addition, data from an observational, multinational, postmarketing study of 2566 patients with relapsing-remitting MS demonstrated that adherent patients had a better Multiple Sclerosis International Quality of Life Questionnaire score compared with nonadherent patients.

 Studies have also shown that higher rates of adherence are linked with a lower risk of severe relapses. Longer gaps in DMD therapy (>90 days) may be associated with a higher risk of relapse.

 Because adherence to DMD therapy is critical for the treatments to be fully effective in MS, maximizing adherence is essential. Interdisciplinary expertise and services in a treatment plan may facilitate treatment adherence.

In a survey of patients with mild-to-moderate MS, patient-centered care and shared decision making (SDM) were significantly associated with better adherence rates.

 Shared decision making is a collaborative approach that actively involves the patient, the health care provider, and possibly an extended network in the decision-making process. Throughout the disease course of MS, there are many points where decisions are required, including if and when to initiate DMD therapy and which DMD therapy to initiate. These are issues in which the patient's values and preferences should contribute to the final decision.

 The purpose of this narrative review is to explore the impact of SDM on adherence to DMDs in MS and to present new and emerging approaches to optimize adherence through enhanced patient support and engagement.

A narrative literature search was conducted using the CINAHL, Embase, MEDLINE, and PsyclNFO databases, including publications from 1946 to present. We applied the search to the earliest limits of the databases to track the evolution of patient participation in their own care. Medical subject heading terms used were 

multiple sclerosis, multiple sclerosis – psychology, patient compliance, adherence, personal autonomy, risk factors, physician-patient relations, decision-making, shared decision-making, patient participation, patient participation – psychology, motivation, patient-centered care, quality of life

. Initial searches were performed using each term, and subsequent searches used different combinations of the terms. Inclusion criteria consisted of peer-reviewed articles written in English, with no limitations on publication date or country. Exclusion criteria included focus on adherence responses related to specific DMDs. Final results yielded 156 publications, 62 of which were determined to be relevant to the review.

 defines patient adherence to long-term therapy as “the extent to which a person's behavior—taking medication, following a diet, and/or executing lifestyle changes—corresponds with agreed recommendation from a healthcare provider.”

 This definition puts the responsibility of continuously taking treatment on the patient but does not consider the collaborative network involved in the treatment paradigm. Continued vigilance of patient adherence to DMD therapy requires an interdisciplinary approach that involves the patient, health care providers, and care-givers (eg, physician, family, MS center staff).

Shared decision making is a process in which patients, health care professionals, and caregivers work together and collaborate to select appropriate diagnostic tests, treatment, and disease management strategies based on clinical evidence and the values and preferences of patients.

 It represents a distinct departure from the conventional paternalistic model, which assumed a passive role for the patient in the treatment decision-making process.

 “shared decision making is seen as a mechanism to decrease the informational and power asymmetry between doctors and patients by increasing patients' information, sense of autonomy and/or control over treatment decisions that affect their well-being.”

An SDM model has been shown to be valuable in preference-sensitive conditions, in which several treatment options of similar efficacy but with differences in risks and benefits are available.

 Moreover, a study that assessed decision-making preferences in 283 patients with MS who were considering starting DMD treatment or reconsidering their current DMD treatment revealed that 90% of patients preferred to make an autonomous or shared decision, compared with 10% of patients who preferred to have the physician alone make the decision.

 These findings have also been borne out in a survey of nearly 7000 respondents conducted by the North American Research Committee on Multiple Sclerosis investigators in which most participants taking a DMD preferred patient-centered decision making or SDM.

 This further illustrates that an overall collaborative network may be an important factor for treatment success and optimal health and wellness (

It is worth noting that challenges associated with defining these concepts have been identified in the literature. Trenaman et al.

 identified variation in how adherence has been defined and measured in clinical trials, distinguishing trials measuring adherence to medication choice from those measuring adherence to treatment. The authors concluded that further study is warranted to help standardize how adherence is conceptualized, measured, and reported.

Maria Cecília Aragon de Vecino, MD

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