Disability Progression In Patients Research Articles

Use of a Machine Learning Model to Predict Disability Progression in Patients with Relapsing Multiple Sclerosis Treated with Ozanimod (P6-6.006)

Use of a Machine Learning Model to Predict Disability Progression in Patients with Relapsing Multiple Sclerosis Treated with Ozanimod (P6-6.006)

Evoked potentials after autologous hematopoietic stem cell transplantation for multiple sclerosis

ObjectiveTo investigate the effect of autologous hematopoietic stem cell transplantation (AHSCT) on functional aspects of the nervous system assessed by visual (VEP), somatosensory (SEP), and motor (MEP) evoked potentials in patients with relapsing-remitting multiple sclerosis. BackgroundSeveral studies have demonstrated the efficacy of AHSCT on inflammatory activity and disability progression in patients with multiple sclerosis. However, the impact of AHSCT on evoked potentials has not been evaluated before. MethodsTwelve AHSCT-treated patients from Uppsala University Hospital were consecutively recruited. Evoked potentials (EP) were collected at baseline and two follow-up visits, 3 and 12 months post-AHSCT. We calculated a composite EP score for each participant and compared it between different time points. ResultsThe median total EP score decreased from 5 at baseline, to 2.5 at 12 months post-ASHCT (p = 0.008). A significant improvement in tibial SEP (tSEP) latencies was observed (42.7 vs 41.5 ms, p < 0.001), with a similar trend for MEP latencies 12 months post-ASHCT. No significant changes in median SEP or VEP latencies were observed. ConclusionsTreatment with AHSCT was associated with improved transmission in some central nervous system pathways in multiple sclerosis patients.

Early Clinical Predictors of Long-term Disability Progression in Patients with Multiple Sclerosis

Background: One of the unmet therapeutic needs in the treatment of multiple sclerosis (MS) is to prevent the accumulation of irreversible disability. Formulating standardized predictors of conversion in the secondary progressive phase of the relapsing-remitting MS (RRMS) should be a step toward solving this problem. Objective: To develop a reliable score, a predictor of physical disability worsening and secondary progression in patients with RRMS. Materials and Methods: Seventy-four patients with RRMS were observed retrospectively for 15 years. Clinical and demographic parameters were analyzed with respect to the time of reaching Expanded Disability Status Scale (EDSS) 4 and/or EDSS 6, as well as EDSS at the end of 15 years. Results: Almost half of the patients observed (47%) reached irreversible disability (EDSS ≥4.0) and ¼ developed secondary progression (EDSS 6.0). The statistically significant variables selected were age at onset of MS, sex, type (afferent, efferent, and combined), and number of symptoms during the first and second attacks. Based on this selection, a predictive score for the course of the disease was formed. It has a sensitivity of 86%, specificity of 89%, positive predictive value of 85%, and negative predictive value of 81%. Conclusion: The proposed predictive score can be applied as a complementary tool in the choice of appropriate therapeutic approach at the early stages of MS, which can help avoid disability overtime.

Disease Activity and Progression of Disability in Multiple Sclerosis Patients Aged Over 50 With or Without Disease-Modifying Drug Treatment: A Retrospective Cohort Study.

Background This study aimed to clarify the need for disease-modifying drug (DMD) treatment in elderly patients with multiple sclerosis (MS) aged 50 years or older. MS is an autoimmune, demyelinating disease of the central nervous system that predominantly affects young women. Various DMDs are effective in preventing relapses and slowing the progression of disability in patients with MS. Although disease activity in MS is believed to decrease with aging, a consensus on the appropriate DMD treatment for elderly patients with MS is lacking. Methodology This study included elderly patients with MS (>50 years old). We compared the occurrence of relapses, worsening of disability, and conversion to secondary progressive MS (SPMS) between patients with DMD treatment and those without. Logistic regression analysis was performed to determine the predictors of these outcomes. Confounding factors were adjusted using propensity scores. Results From January 1991 to October 2022, 76 elderly patients with MS were included. The mean age at the last visit was 57.4 ± 6.3 years, with 51 patients being female. The mean age of onset of MS was 37.1 ± 10.1 years. Fifty-four patients were included in the DMD treatment group. The overall relapse rate was 38% (33% and 48% in the DMD treatment and untreated groups, respectively). No significant differences in relapse rates (p = 0.72) or in the Expanded Disability Status Scale (EDSS) scores were identified between the two groups. Kaplan-Meier curves showed no differences in the time to first relapse within five years between the two groups. Additionally, no significant predictors of relapse were identified. Among 61 patients with relapsing-remitting MS, 25% converted to SPMS during the observation period. Logistic regression analysis showed that older age at the final visit and the presence of brainstem lesions at the age of 50 years were associated with a higher rate of transition to SPMS. Conclusions In the present study, no significant difference was found in the rate of relapse, disability progression, and conversion to SPMS between the DMD treatment and untreated groups in elderly patients with MS. Therefore, in patients without long-term relapse, no poor prognostic functional factorsor predictors of conversion to SPMS, discontinuation of DMDs may beconsidered. In addition, the presence of brainstem lesions at 50 years of age may predict the conversion to SPMS. Thus, the continuation of DMD or conversion to an appropriate DMD should be considered in patients with brainstem lesions at 50 years of age.

Serum biomarker levels predict disability progression in patients with primary progressive multiple sclerosis

BackgroundWe aimed to investigate the potential of serum biomarker levels to predict disability progression in a multicentric real-world cohort of patients with primary progressive multiple sclerosis (PPMS).MethodsA total of 141...

The Use of Disease-Modifying Therapy (DMT) to Prevent Disability Progression in Patients with Multiple Sclerosis (MS) in Thailand

Background: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that leads to significant disability and economic burden for patients, families, the health system, and society. Objective: To describe the demographics, natural history, and effectiveness of disease-modifying therapies (DMTs) in MS patients. Materials and Methods: The present study was a retrospective cohort study of patients diagnosed with MS at the Prasat Neurological Institute, a tertiary referral neurological center in Bangkok, Thailand, between June 1, 2010 and June 30, 2020. Demographic data, clinical characteristics, and disease course of MS patients were explored. The primary outcome of the present study was a comparison of time to events of clinical relapse, new magnetic resonance image (MRI) T2W activity, new MRI T1W with gadolinium (Gd) enhancement, and time to disability progression between patients who received DMT and patients without DMT. Results: There were 102 patients diagnosed with MS. The female-to-male ratio was 2.4-to-1. The mean age at onset was 29.61±11.62 years. The phenotypic features of these patients were classified as RRMS 80.4%, SPMS 8.8%, PPMS 3.9%, and tumefactive demyelination 6.9%. Forty-eight patients (47.1%) received DMT, 28 (58.3%) received IFN-beta, 11 (22.9%) received fingolimod, seven (14.6%) received teriflunomide, and two (4.2%) received rituximab. Results demonstrated that patients who did not received DMT had significantly more clinical disability compared to patients who received DMT (HR 2.97; 95% CI 1.01 to 8.73; p=0.048). However, the times to clinical relapse and MRI activity, including new T2W and new T1W Gd enhancing lesion, were not significantly different between the two groups. Conclusion: Patients with a relapsing-remitting phenotype tended to progress to severe disability within ten years. Treatment with DMT may delay disability progression in patients with MS. Keywords: Multiple sclerosis (MS); Disease-modifying therapy (DMT)

Anti-CD20 therapies in multiple sclerosis: From pathology to the clinic.

The immune system plays a significant role in multiple sclerosis. While MS was historically thought to be T cell-mediated, multiple pieces of evidence now support the view that B cells are essential players in multiple sclerosis pathogenic processes. High-efficacy disease-modifying therapies that target the immune system have emerged over the past two decades. Anti-CD20 monoclonal antibodies selectively deplete CD20+ B and CD20+ T cells and efficiently suppress inflammatory disease activity. These monotherapies prevent relapses, reduce new or active magnetic resonance imaging brain lesions, and lessen disability progression in patients with relapsing multiple sclerosis. Rituximab, ocrelizumab, and ofatumumab are currently used in clinical practice, while phase III clinical trials for ublituximab have been recently completed. In this review, we compare the four anti-CD20 antibodies in terms of their mechanisms of action, routes of administration, immunological targets, and pharmacokinetic properties. A deeper understanding of the individual properties of these molecules in relation to their efficacy and safety profiles is critical for their use in clinical practice.

Association of Higher Ocrelizumab Exposure With Reduced Disability Progression in Multiple Sclerosis.

Ocrelizumab improved clinical and MRI measures of disease activity and progression in three phase 3 multiple sclerosis (MS) studies. Post hoc analyses demonstrated a correlation between the ocrelizumab serum concentration and the degree of blood B-cell depletion, and body weight was identified as the most influential covariate on ocrelizumab pharmacokinetics. The magnitude of ocrelizumab treatment benefit on disability progression was greater in lighter vs heavier patients. These observations suggest that higher ocrelizumab serum levels provide more complete B-cell depletion and a greater delay in disability progression. The current post hoc analyses assessed population exposure-efficacy/safety relationships of ocrelizumab in patients with relapsing and primary progressive MS. Patients in OPERA I/II and ORATORIO were grouped in exposure quartiles based on their observed individual serum ocrelizumab level over the treatment period. Exposure-response relationships were analyzed for clinical efficacy (24-week confirmed disability progression (CDP), annualized relapse rate [ARR], and MRI outcomes) and adverse events. Ocrelizumab reduced new MRI lesion counts to nearly undetectable levels in patients with relapsing or primary progressive MS across all exposure subgroups, and reduced ARR in patients with relapsing MS to very low levels (0.13-0.18). A consistent trend of higher ocrelizumab exposure leading to lower rates of CDP was seen (0%-25% [lowest] to 75%-100% [highest] quartile hazard ratios and 95% confidence intervals; relapsing MS: 0.70 [0.41-1.19], 0.85 [0.52-1.39], 0.47 [0.25-0.87], and 0.34 [0.17-0.70] vs interferon β-1a; primary progressive MS: 0.88 [0.59-1.30], 0.86 [0.60-1.25], 0.77 [0.52-1.14], and 0.55 [0.36-0.83] vs placebo). Infusion-related reactions, serious adverse events, and serious infections were similar across exposure subgroups. The almost complete reduction of ARR and MRI activity already evident in the lowest quartile, and across all ocrelizumab-exposure groups, suggests a ceiling effect. A consistent trend of higher ocrelizumab exposure leading to greater reduction in risk of CDP was observed, particularly in the relapsing MS trials, and was not associated with a higher rate of adverse events. Higher ocrelizumab exposure may provide improved control of disability progression by reducing disease activity below that detectable by ARR and MRI, and/or by attenuating other B-cell-related pathologies responsible for tissue damage. This analysis provides Class III evidence that higher ocrelizumab serum levels are related to greater reduction in risk of disability progression in patients with multiple sclerosis. The study is rated Class III because of the initial treatment randomization disclosure that occurred after inclusion in the open-label extension. ClinicalTrials.gov Identifier: NCT01247324 (OPERA I), NCT01412333 (OPERA II), and NCT01194570 (ORATORIO).

Factors associated with time to disability progression in patients with multiple sclerosis.

Motivation for the study: multiple sclerosis (MS) is a complex disease that requires management by different disciplines. Data on Latin American patients is scarce, therefore, the usually used theoretical references are from other population groups. Main findings: sociodemographic (male), clinical (concomitant neurological diseases) and radiological (active lesions in magnetic resonance imaging) factors were found to be associated with disease progression. Implications: taking the above into account when approaching patients in daily clinical practice, it is possible to identify when their condition has greater possibilities of progression and thus eventually prevent complications. To determine the sociodemographic, clinical and radiological factors associated with time to disability progression in patients with multiple sclerosis (MS). Cross-sectional descriptive study with an analytical component, based on clinical records of patients at the Neurological Institute of Colombia, between 2013 and 2021. Progression to disability in MS patients was defined as the time to an increase of at least 0.5 points in the EDSS (Expanded Disability Status Scale) score, sustained for at least six months. A Cox regression model was used to estimate the survival function and Hazard Ratios (HR) with their 95% confidence intervals (95% CI). We included 216 patients, of whom 25% progressed to disability, median survival was 78 months (95% CI: 70-83), active lesions (HR = 1.94; 95% CI: 1.10-3.44), cerebellar complications (HR = 2.03; 95% CI: 0. 99-4.16), being male (HR = 2.5; 95% CI: 1.32-4.73), and having neurological diseases (HR = 2.18; 95% CI: 1.03-4.61) were associated as risk factors. While relapsing remitting MS (HR = 0.63; 95% CI: 0.31-1.26) and age at diagnosis less than 40 years (HR = 0.96; 95% CI: 0.53-1.76) were associated as protective factors. Progression is affected by many factors, and there is no single independent factor.

Evaluation of Disability Progression in Multiple Sclerosis via Magnetic-Resonance-Based Deep Learning Techniques.

Short-term disability progression was predicted from a baseline evaluation in patients with multiple sclerosis (MS) using their three-dimensional T1-weighted (3DT1) magnetic resonance images (MRI). One-hundred-and-eighty-one subjects diagnosed with MS underwent 3T-MRI and were followed up for two to six years at two sites, with disability progression defined according to the expanded-disability-status-scale (EDSS) increment at the follow-up. The patients’ 3DT1 images were bias-corrected, brain-extracted, registered onto MNI space, and divided into slices along coronal, sagittal, and axial projections. Deep learning image classification models were applied on slices and devised as ResNet50 fine-tuned adaptations at first on a large independent dataset and secondly on the study sample. The final classifiers’ performance was evaluated via the area under the curve (AUC) of the false versus true positive diagram. Each model was also tested against its null model, obtained by reshuffling patients’ labels in the training set. Informative areas were found by intersecting slices corresponding to models fulfilling the disability progression prediction criteria. At follow-up, 34% of patients had disability progression. Five coronal and five sagittal slices had one classifier surviving the AUC evaluation and null test and predicted disability progression (AUC > 0.72 and AUC > 0.81, respectively). Likewise, fifteen combinations of classifiers and axial slices predicted disability progression in patients (AUC > 0.69). Informative areas were the frontal areas, mainly within the grey matter. Briefly, 3DT1 images may give hints on disability progression in MS patients, exploiting the information hidden in the MRI of specific areas of the brain.

Genetically modified macrophages accelerate myelin repair.

Preventing neurodegeneration‐associated disability progression in patients with multiple sclerosis (MS) remains an unmet therapeutic need. As remyelination prevents axonal degeneration, promoting this process in patients might enhance neuroprotection. In demyelinating mouse lesions, local overexpression of semaphorin 3F (Sema3F), an oligodendrocyte progenitor cell (OPC) attractant, increases remyelination. However, molecular targeting to MS lesions is a challenge. A clinically relevant paradigm for delivering Sema3F to demyelinating lesions could be to use blood‐derived macrophages as vehicles. Thus, we chose transplantation of genetically modified hematopoietic stem cells (HSCs) as means of obtaining chimeric mice with circulating Sema3F‐overexpressing monocytes. We demonstrated that Sema3F‐transduced HSCs stimulate OPC migration in a neuropilin 2 (Nrp2, Sema3F receptor)‐dependent fashion, which was conserved in middle‐aged OPCs. While demyelinating lesions induced in mice with Sema3F‐expressing blood cells showed no changes in inflammation and OPC survival, OPC recruitment was enhanced which accelerated the onset of remyelination. Our results provide a proof of concept that blood cells, particularly monocytes/macrophages, can be used to deliver pro‐remyelinating agents “at the right time and place,” suggesting novel means for remyelination‐promoting strategies in MS.

Serum neurofilament light chain levels predict long-term disability progression in patients with progressive multiple sclerosis

ObjectiveThere is a lack of sensitive and specific biomarkers for use in progressive multiple sclerosis (MS). The study aimed to assess the potential of serum neurofilament light chain (sNfL) levels...

Editors' Note: Serum Neurofilament Light Association With Progression in Natalizumab-Treated Patients With Relapsing-Remitting Multiple Sclerosis

In “Serum Neurofilament Light Association With Progression in Natalizumab-Treated Patients With Relapsing-Remitting Multiple Sclerosis,” Bridel et al. evaluated serum neurofilament light chain (sNfL) levels serially after initiation of natalizumab in patients with relapsing-remitting multiple sclerosis (RRMS) and found that they do not capture or predict clinical/radiologic trajectory. Kropshofer et al. commented that their conclusion that sNfL is not a valid biomarker for disease progression is in opposition to the results from other large studies, noting that the editorial about this article, written by Goldschmidt and Fox, suggested that this may be because prior studies demonstrate natural history, without natalizumab treatment. Nonetheless, Kropshofer et al. noted that they found an association between baseline sNfL and 3-month disability progression in patients treated with siponimod, irrespective of prior disease activity, indicating that baseline sNfL can be used for neuroprognostication, regardless of treatment with anti-inflammatory therapy. Bridel et al. clarified that their conclusion was that sNfL may not be well suited to monitor or predict progression in patients with RRMS on natalizumab. They noted that their results may differ from those from other studies because their patients (1) all had RRMS and (2) were all treated with natalizumab. They also commented that almost half of patients on siponimod in the EXPAND study developed new or enlarging brain lesions on 2-year follow-up imaging, so that is not the ideal population to study the relationship between sNfL and progression. They recommend performance of additional larger studies on the relationship between sNfL and progression in patients on natalizumab and/or ocrelizumab. In “Serum Neurofilament Light Association With Progression in Natalizumab-Treated Patients With Relapsing-Remitting Multiple Sclerosis,” Bridel et al. evaluated serum neurofilament light chain (sNfL) levels serially after initiation of natalizumab in patients with relapsing-remitting multiple sclerosis (RRMS) and found that they do not capture or predict clinical/radiologic trajectory. Kropshofer et al. commented that their conclusion that sNfL is not a valid biomarker for disease progression is in opposition to the results from other large studies, noting that the editorial about this article, written by Goldschmidt and Fox, suggested that this may be because prior studies demonstrate natural history, without natalizumab treatment. Nonetheless, Kropshofer et al. noted that they found an association between baseline sNfL and 3-month disability progression in patients treated with siponimod, irrespective of prior disease activity, indicating that baseline sNfL can be used for neuroprognostication, regardless of treatment with anti-inflammatory therapy. Bridel et al. clarified that their conclusion was that sNfL may not be well suited to monitor or predict progression in patients with RRMS on natalizumab. They noted that their results may differ from those from other studies because their patients (1) all had RRMS and (2) were all treated with natalizumab. They also commented that almost half of patients on siponimod in the EXPAND study developed new or enlarging brain lesions on 2-year follow-up imaging, so that is not the ideal population to study the relationship between sNfL and progression. They recommend performance of additional larger studies on the relationship between sNfL and progression in patients on natalizumab and/or ocrelizumab.

Sociodemographic and clinical factors related to the progression of disability in patients with multiple sclerosis

Sociodemographic and clinical factors related to the progression of disability in patients with multiple sclerosis

A lymphocyte-glia connection sets the pace for smoldering inflammation

Successful therapeutic options directly targeting disability progression in patients with multiple sclerosis (MS), a chronic inflammatory disorder of the central nervous system, are lacking. Now, a study published in Nature by Absinta and colleagues profiles a lymphocyte-glia connection at the edge of chronic active lesions that continuously drives neurodegenerative pathways.

Information processing speed as a prognostic marker of physical impairment and progression in patients with multiple sclerosis

BackgroundPrediction of disability progression in patients with MS (pwMS) is challenging. So far, scarce evidence exists suggesting knowledge about how cognitive performance may potentially improve prediction of physical impairment and disability progression in MS. Therefore, we wanted to assess the prognostic value of cognitive performance regarding physical impairment and disability progression in pwMS. Methods85 patients (64% female; 60% relapse-remitting MS; mean age=36.78 ± 9.63 years) underwent clinical, neuropsychological (Brief Repeatable Battery for Neuropsychological Test (BRB-N)) and brain MRI (T1-weighted and T2-weighted FLAIR images) assessment at baseline and after an average of 7 years (SD=3.75) at follow-up. We assessed physical impairment and annualized disability progression (disability progression divided by follow-up duration) using the Expanded Disability Status Scale (EDSS). To compare patients with no or mild physical impairment (EDSS≤2.5) and patients with moderate to severe physical impairment (EDSS≥3.0), we used an EDSS score ≥3.0 as cut-off. Silent progression was defined by an EDSS worsening of at least 0.5 in the absence of relapses and inflammation in relapsing-remitting MS. ResultsIn hierarchical regression models (method “STEPWISE”, forward) performance in information processing speed was a significant and independent predictor of physical impairment (EDSS≥3.0) at follow-up (model R²=0.671, b=-1.46, OR=0.23, p=0.001) and annualized disability progression (adjusted model R²=0.257, β=-0.26, 95% CI: -0.066, -0.008, p=0.012), in addition to demographics (age, education, individual follow-up time), clinical (EDSS, disease duration, clinical phenotype, annualized-relapse-rate) and MRI measures (brain volumes and T2-lesion load). In a MANCOVA controlled for age, disease duration and individual follow-up time, worse baseline performance in information processing speed was found in patients with higher EDSS at follow-up (m=-1.91, SD=1.18, p<0.001) and silent progression (m=-2.19, SD=1.01, p=0.038). ConclusionPerformance in information processing speed might help to identify patients at risk for physical impairment. Therefore, neuropsychological assessment should be integrated in clinical standard care to support disease management in pwMS.

Measuring Treatment Response in Progressive Multiple Sclerosis-Considerations for Adapting to an Era of Multiple Treatment Options.

Disability in multiple sclerosis accrues predominantly in the progressive forms of the disease. While disease-modifying treatment of relapsing MS has drastically evolved over the last quarter-century, the development of efficient drugs for preventing or at least delaying disability in progressive MS has proven more challenging. In that way, many drugs (especially disease-modifying treatments) have been researched in the aspect of delaying disability progression in patients with a progressive course of the disease. While there are some disease-modifying treatments approved for progressive multiple sclerosis, their effect is moderate and limited mostly to patients with clinical and/or radiological signs of disease activity. Several phase III trials have used different primary outcomes with different time frames to define disease progression and to evaluate the efficacy of a disease-modifying treatment. The lack of sufficiently sensitive outcome measures could be a possible explanation for the negative clinical trials in progressive multiple sclerosis. On the other hand, even with a potential outcome measure that would be sensitive enough to determine disease progression and, thus, the efficacy or failure of a disease-modifying treatment, the question of clinical relevance remains unanswered. In this systematic review, we analyzed outcome measures and definitions of disease progression in phase III clinical trials in primary and secondary progressive multiple sclerosis. We discuss advantages and disadvantages of clinical and paraclinical outcome measures aiming for practical ways of combining them to detect disability progression more sensitively both in future clinical trials and current clinical routine.

CSF Chitinase 3-Like 2 Is Associated With Long-term Disability Progression in Patients With Progressive Multiple Sclerosis.

ObjectiveThis study aimed to identify long-term prognostic protein biomarkers associated with disease progression in patients with progressive multiple sclerosis (MS).MethodsCSF samples were collected from a discovery cohort of 28 patients with progressive MS who participated in a clinical trial with interferon beta. Patients were classified into high and low disability progression phenotypes according to numeric progression rates (NPR) and step-based progression rates (SPR) after a mean follow-up time of 12 years. Protein abundance was measured by shotgun proteomics. Selected proteins from the discovery cohort were quantified by parallel reaction monitoring in CSF samples from an independent validation cohort of 41 patients with progressive MS classified also into high and low disability progression phenotypes after a mean follow-up time of 7 years.ResultsOf 2,548 CSF proteins identified in the discovery cohort, 10 were selected for validation based on their association with long-term disability progression: SPATS2-like protein, chitinase 3–like 2 (CHI3L2), plasma serine protease inhibitor, metallothionein-3, phospholipase D4, beta-hexosaminidase, neurexophilin-1, adipocyte enhancer-binding protein 1, cathepsin L1, and lipopolysaccharide-binding protein. Only CHI3L2 was validated, and patients with high disability progression exhibited significantly higher CSF protein levels compared with patients with low disability progression (p = 0.03 for NPR and p = 0.02 for SPR). CHI3L2 levels showed good performance to discriminate between high and low disability progression in patients with progressive MS (area under the curve 0.73; sensitivity 90% and specificity 63%).ConclusionsAlthough further confirmatory studies are needed, we propose CSF CHI3L2 as a prognostic protein biomarker associated with long-term disability progression in patients with progressive MS.Classification of EvidenceThis study provides Class II evidence that high CSF CHI3L2 levels identified higher disability progression in patients with progressive MS.

Modelling Disability Progression in Patients with Secondary Progressive Multiple Sclerosis Shows Non-linearity of EDSS Changes over Time (4091)

Modelling Disability Progression in Patients with Secondary Progressive Multiple Sclerosis Shows Non-linearity of EDSS Changes over Time (4091)

Low vitamin D, but not tobacco use or high BMI, is associated with long-term disability progression in multiple sclerosis

BackgroundLow vitamin D levels, tobacco use and high body mass index (BMI) have been linked to adverse disease outcomes in multiple sclerosis (MS), but their influence on long-term disability progression remains unclear. Therefore, we explored whether these modifiable lifestyle factors were associated with 10-year clinical disability progression in patients with MS. MethodsIn this prospective study, a cohort of 88 patients with relapsing-remitting MS completed a randomized controlled study on ω-3 fatty acids between 2004 and 2008. During 24 months, serum 25-hydroxyvitamin D (25(OH)D), serum cotinine (nicotine metabolite), and BMI were repeatedly measured. In 2017, a follow-up study was conducted among 80 of the participants, including disability assessment by the Expanded Disability Status Scale (EDSS). Linear regression was used to explore associations between the lifestyle factors and the EDSS change over 10 years. ResultsHigher seasonally adjusted 25(OH)D levels were associated with lower 10-year EDSS progression (change in EDSS per 1 SD increase in 25(OH)D in a model adjusted for sex, age and baseline EDSS: -0.45 point, 95% CI: -0.75 to -0.16, p=0.003). Further adjustments for potential confounders related to lifestyle and disease status gave similar results. The association was mainly driven by low 25(OH)D levels during spring, as well as seasonally adjusted levels below 80 nmol/L. No clear association was found for BMI and cotinine. ConclusionLower 25(OH)D levels, but apparently not tobacco use or higher BMI, were significantly associated with worse long-term disability progression in MS.