Multiple Sclerosis And Related Disorders[JOURNAL]
Sun
200 papers
Limited availability of live CBA for MOG-IgG testing and its consequences for the diagnosis and treatment of MOGAD in Latin American countries.
Boldrini V, Carnero Contentti E
Mult Scler Relat Disord · 2026 May · PMID 41926865 · Publisher ↗
In recent years, increasing evidence has highlighted live-cell-based assay (live CBA) as the best available tool for screening for Myelin oligodendrocyte glycoprotein (MOG) autoantibodies (MOG-IgG) during MOG antibody-as...
In recent years, increasing evidence has highlighted live-cell-based assay (live CBA) as the best available tool for screening for Myelin oligodendrocyte glycoprotein (MOG) autoantibodies (MOG-IgG) during MOG antibody-associated disease (MOGAD). However, in resource-limited settings in Latin America (LATAM), where even commercial kits (fixed CBA) can be scarce, accessing local live CBA is challenging due to its higher costs and technical complexity. In this narrative review, we identified 24 published studies that provide evidence of CBA locally used in LATAM countries. We identified only 4 studies (16.7 %) that used "live CBA" as the exclusive MOG-IgG testing method. Another 7 studies (29.2 %) reported using live CBA in combination with commercial tests ("live CBA and fixed CBA") to detect MOG-IgG. Brazil is the only country that has participated in all published studies using live CBA, either exclusively or alongside a commercial fixed assay. Argentina had the second largest participation in studies combining both methods (n = 4, 16.7 %), followed by Chile (n = 2, 8.3 %), Mexico (n = 2, 8.3 %), Ecuador (n = 2, 8.3 %), Colombia (n = 2, 8.3 %), Venezuela (n = 1, 4.1 %) and Peru (n = 1, 4.1 %), respectively. Our literature review suggests that live CBA availability is 16.7 % when considered as a single testing method, or up to 45.9 % when used to varying degrees in conjunction with fixed CBA. Importantly, more than half of the studies we analyzed (n = 13, 54.1 %) relied solely on commercial fixed assays ("fixed CBA" and "CBA") for MOG-IgG screening. Based on our findings, we critically discuss the pressing need for live CBA dissemination across LATAM countries. This initiative will lead to more accurate epidemiological data, enable faster diagnosis, and improve access to highly effective therapies for MOGAD patients living in this part of the world.
Calprotectin reveals distinct innate immune signatures in NMOSD, MOGAD, and multiple sclerosis.
Johnsson M, Lycke J, Novakova L … +4 more , Rosenstein I, Hafsteinsdottir B, Malmeström C, Axelsson M
Mult Scler Relat Disord · 2026 May · PMID 41926864 · Publisher ↗
BACKGROUND: Granulocyte-mediated injury contributes to the immunopathology of aquaporin-4 neuromyelitis optica spectrum disease (AQP4-NMOSD) and myelin oligodendrocyte glycoprotein-associated disease (MOGAD), yet calprot...
BACKGROUND: Granulocyte-mediated injury contributes to the immunopathology of aquaporin-4 neuromyelitis optica spectrum disease (AQP4-NMOSD) and myelin oligodendrocyte glycoprotein-associated disease (MOGAD), yet calprotectin, a myeloid-derived inflammatory marker, has not been evaluated in these disorders. OBJECTIVE: To assess the diagnostic and activity-related potential of cerebrospinal fluid (CSF) and serum calprotectin concentrations in AQP4-NMOSD, MOGAD, seronegative or double-negative NMOSD (DNNMOSD) and RRMS. METHODS: In this observational study, CSF and serum calprotectin were measured using a turbidimetric assay in patients with AQP4-NMOSD (n = 10), DNNMOSD (n = 6), MOGAD (n = 9), RRMS (n = 10), and healthy controls (HC; n = 8). Group comparisons, correlations with clinical and laboratory variables, and relapse analyses were performed. RESULTS: Serum calprotectin was markedly elevated in AQP4-NMOSD, DNNMOSD, and MOGAD (p < 0.001), separating these disorders from RRMS and HCs (AUC = 1.0 at 1.18 mg/L). CSF calprotectin was detectable in all samples (range; 0.18-0.82 mg/L) and was significantly lower in patients with MOGAD compared with other groups (p = 0.025). In RRMS, serum and CSF calprotectin concentrations inversely correlated with time since last relapse, whereas no such relationship was observed in NMOSD or MOGAD. CONCLUSION: Serum calprotectin shows promise as a diagnostic biomarker distinguishing NMOSD and MOGAD from RRMS and supports predominant systemic myeloid activation in these disorders.
The comparative efficacy of cladribine tablets versus alternative disease-modifying treatments for relapsing-remitting multiple sclerosis: Updated meta-regression estimates by patient subgroup.
Harty GT, Jones M, J S … +1 more , Maheshwari V
Mult Scler Relat Disord · 2026 May · PMID 41926863 · Publisher ↗
BACKGROUND: A previously published meta-regression compared cladribine tablets with key disease-modifying treatments (DMTs) for patients with relapsing-remitting multiple sclerosis (RRMS). This analysis updates and exten...
BACKGROUND: A previously published meta-regression compared cladribine tablets with key disease-modifying treatments (DMTs) for patients with relapsing-remitting multiple sclerosis (RRMS). This analysis updates and extends that work by evaluating the relative efficacy of cladribine tablets versus approved DMTs in specific RRMS subgroups, including high disease activity (HDA) and sub-optimal therapy (SOT). METHODS: Updated systematic literature reviews identified clinical trials evaluating cladribine tablets and other DMTs in RRMS. Baseline-risk-adjusted meta-regressions were conducted. Outcomes included 6-month confirmed disability progression (6 M-CDP) and annualised relapse rate (ARR). RESULTS: Fifty-four clinical trials assessing cladribine tablets plus 19 additional DMTs contributed to the meta-regressions. Results showed significant overlap in the hazard ratio credible intervals, with no therapy statistically dominating in terms of efficacy. At the point-estimate level in the HDA population, for 6 M-CDP, cladribine tablets were predicted to be more efficacious than placebo, fingolimod, alemtuzumab, glatiramer acetate, teriflunomide, ozanimod, interferon beta-1a, ocrelizumab, dimethyl fumarate, and ponesimod; comparable estimates were observed versus ofatumumab. For ARR, cladribine tablets were predicted to be more efficacious than placebo, dimethyl fumarate, glatiramer acetate, interferon beta-1a, interferon beta-1b, pegylated interferon beta-1a, and teriflunomide, as well as fingolimod, ozanimod, and ponesimod; comparable estimates were observed versus ocrelizumab. CONCLUSIONS: Updated meta-regressions demonstrate that cladribine tablets have comparable relative efficacy to other high-efficacy therapies in HDA and SOT patient subgroups. For disability progression outcomes, cladribine tablets showed similar efficacy to ofatumumab; for relapse reduction, cladribine tablets were comparable to ocrelizumab. Cladribine tablets also consistently outperformed most platform therapies across all analyzed subgroups.
EDSS and disease duration associate with progression independent of relapse and MRI activity in natalizumab-treated multiple sclerosis patients.
Puthenparampil M, Passamonti M, Rozzi M … +8 more , Basili E, Mauceri VA, Nosadini M, Sartori S, Di Paola A, Gallo P, Rinaldi F, Perini P
Mult Scler Relat Disord · 2026 May · PMID 41916082 · Publisher ↗
BACKGROUND: Clinical, biological and radiological data that may help in predicting and managing the Progression Independent of Relapse and MRI Activity (PIRMA) in multiple sclerosis (MS). We designed a retrospective, lon...
BACKGROUND: Clinical, biological and radiological data that may help in predicting and managing the Progression Independent of Relapse and MRI Activity (PIRMA) in multiple sclerosis (MS). We designed a retrospective, longitudinal study to identify prognostic factors of PIRMA in natalizumab (NTZ) treated patients with MS (pwMS). METHODS: Clinical and radiological data from pwMS starting NTZ in the period July 2007 to February 2017 were retrospectively collected. RESULTS: 238 patients (age of 29.1 ± 8.5 years) were followed up for 5.5 ± 4.3 years. PIRMA was observed in 70 patients (29.4%). PIRMA was predicted by both EDSS (Cox regression analysis: H.R.= 1.7, p < 0.0001) and disease duration at NTZ first administration (H.R.= 1.0, p = 0.025). Combining disease duration (138 months) and EDSS (4.0) cut-offs, pwMS with lower and disease duration had lower probability of PIRMA compared to patients with 1 risk factor (disease duration ≥138 months or EDSS ≥ 4, H.R. 5.321, IC 2.943 - 9.622, p < 0.0001) or 2 risk factors (H.R. 6.100, IC 2.100 - 17.730, p < 0.0001). To evaluate the effect of age on PIRMA, we focused the analysis on patients that reached at least the age of 45 during the follow-up (age at follow-up end: 51.8 ± 5.7; range: 45-75). Higher baseline EDSS was independently associated with an increased risk of PIRMA (HR 1.65, 95% CI 1.24-2.24, p = 0.0005). Conversely, older age at natalizumab initiation was associated with a lower risk of PIRMA (HR 0.87 per year, 95% CI 0.81-0.95, p = 0.0007). CONCLUSIONS: PIRMA was identified as the main driver of disability progression in RRMS treated with NTZ and is predicted by disease duration and EDSS at therapy initiation.
Higher ultra-processed food consumption is associated with higher likelihood of paediatric-onset multiple sclerosis.
Machado P, Mazahery H, Black LJ … +15 more , Tremlett H, Daly A, Pham NM, Tessema GA, Zhu F, Banwell B, Bar-Or A, Marrie RA, Bernstein CN, Mirza AI, Yeh EA, Waubant E, O'Mahony J, Dunlop E, Canadian Demyelinating Disease Network
Mult Scler Relat Disord · 2026 May · PMID 41916081 · Publisher ↗
BACKGROUND: Diets are increasingly dominated by ultra-processed foods, which have been linked to several chronic diseases. Emerging evidence suggests an association between ultra-processed food consumption and inflammato...
BACKGROUND: Diets are increasingly dominated by ultra-processed foods, which have been linked to several chronic diseases. Emerging evidence suggests an association between ultra-processed food consumption and inflammatory diseases, including multiple sclerosis (MS). OBJECTIVE: To assess associations between consumption of ultra-processed foods and paediatric-onset MS (PoMS). METHODS: We used data from the microbiome sub-study of the Canadian Pediatric Demyelinating Disease Network Study for PoMS cases (symptom onset aged <18 years) and unaffected controls. Data on consumption of ultra-processed foods (defined within the Nova system) were derived from dietary intake data collected using the Block Kids Food Screener. Dietary contribution of ultra-processed foods (% of total grams consumed per day) was estimated. Logistic regression models were used to examine associations between ultra-processed food consumption (continuous and tertiles) and likelihood of PoMS. Models were adjusted for age at dietary data collection, sex, race, region of residence, and total energy intake. RESULTS: Dietary data were collected from PoMS participants (females=57, males=23) aged 5-28 years and controls (females=30, males=16) aged 8-26 years. Each additional 10% in ultra-processed food consumption was associated with a 35% higher odds of being a PoMS participant (adjusted odds ratio [aOR]=1.35, 95% CI 1.05, 1.73). Participants in the highest (versus lowest) tertile for ultra-processed food consumption had over five times higher odds of being a PoMS participant (aOR=5.30, 95% CI 1.36, 20.70). CONCLUSION: Participants with PoMS reported greater consumption of ultra-processed foods compared to unaffected peers. More comprehensive longitudinal dietary histories are required to better understand this observation.
Therapeutic plasma exchange in Myelin oligodendrocyte glycoprotein associated disorders-an ambispective study.
Panigrahi B, Bhatia R, Singh MB … +7 more , Padma Srivastava MV, Rajan R, Vishnu VY, Gupta A, Tripathi M, Srivastava AK, Upadhyay AD
Mult Scler Relat Disord · 2026 May · PMID 41916080 · Publisher ↗
INTRODUCTION: Myelin oligodendrocyte glycoprotein-associated disease (MOGAD) is a heterogeneous neuroimmunological disease. Attacks are primarily treated using corticosteroids, with a subset of refractory cases treated w...
INTRODUCTION: Myelin oligodendrocyte glycoprotein-associated disease (MOGAD) is a heterogeneous neuroimmunological disease. Attacks are primarily treated using corticosteroids, with a subset of refractory cases treated with plasma exchange (PLEX). However, the response to PLEX and the optimal timing of its initiation remain uncertain as compared to other disorders. This study evaluates the impact of PLEX and it's time to initiation on clinical outcomes, as measured by the Expanded Disability Status Scale (EDSS). MATERIALS AND METHODS: All consecutive patients of MOGAD requiring PLEX from January 2019 to July 2023 at a tertiary care centre were included. Inclusion criteria were ages 10-60 with a positive anti-MOG antibody test and use of PLEX due to inadequate steroid response. Exclusion criteria were pseudo-relapse and denial of consent. The primary outcome was the percentage improvement in EDSS at 90 days. RESULTS: Among 38 patients with MOGAD, the mean percentage improvement in EDSS at 90 days was 37.7% (SD 28.2). Twenty-three patients (60.5%) achieved ≥33% improvement in EDSS at 90 days. An inverse correlation was observed between time to PLEX and percentage EDSS improvement (p = 0.049). In linear regression analysis, each day of treatment delay was associated with a 0.26 percentage point reduction in EDSS improvement. PLEX-related complications occurred in only 7.9% of patients. CONCLUSION: PLEX is effective and safe in MOGAD, but delaying its initiation is associated with reduced clinical improvement, highlighting the importance of early intervention.
Advancing consensus priorities for high-impact provider behaviors in multiple sclerosis care: A Delphi study.
Green CC, Roberts MK, Alschuler KN
Mult Scler Relat Disord · 2026 May · PMID 41905021 · Publisher ↗
PURPOSE: Access to high-quality MS care remains a critical issue, particularly for patients living in rural or underserved areas. Project ECHO (Extension for Community Health Outcomes) programming includes mentorship and...
PURPOSE: Access to high-quality MS care remains a critical issue, particularly for patients living in rural or underserved areas. Project ECHO (Extension for Community Health Outcomes) programming includes mentorship and education from MS specialists to generalist providers in the United States. This study sought to identify and define specific provider behaviors that can 1) be evaluated following participation in Project ECHO and 2) are likely to impact patient outcomes. METHODS: A two-phase mixed-methods study design was used. In Phase 1, 42 participants representing four key stakeholder groups participated in qualitative, semi-structured interviews. Interviews were coded to generate a list of high-priority provider behaviors, which informed a Delphi exercise in Phase 2 of the study to reach consensus and reduce dominance bias. Phase 2 involved two rounds of Delphi surveys, through which participants endorsed the behaviors they found most valuable. RESULTS: Following the second round of Delphi surveys, a consensus was reached on 13 provider behaviors that were endorsed by 73.9% or greater of participants. These behaviors span several impactful domains, including accurate and timely diagnosis, effective use of disease-modifying therapies (DMTs), system monitoring and management, patient education, patient-centered communication, multidisciplinary referrals, continued education, and use of resources such as the National MS Society. CONCLUSIONS: This study identified a consensus-driven set of measurable provider behaviors relevant to high-quality MS care, forming a practical framework for evaluating the effectiveness of Project ECHO MS. Future research may focus on validating these behaviors as outcome metrics and exploring their application to broader clinical and educational settings.
More questions than answers: Why is cognitive dysfunction associated with less use of evidence-based psychotherapy in multiple sclerosis?
Freedman DE, Oh J, Feinstein A
Mult Scler Relat Disord · 2026 May · PMID 41904840 · Publisher ↗
BACKGROUND: Cognitive-behavioural therapy (CBT) and mindfulness-based interventions (MBI) can reduce depressive symptoms and anxiety in people with multiple sclerosis (pwMS). Yet, psychotherapy remains underutilized by p...
BACKGROUND: Cognitive-behavioural therapy (CBT) and mindfulness-based interventions (MBI) can reduce depressive symptoms and anxiety in people with multiple sclerosis (pwMS). Yet, psychotherapy remains underutilized by pwMS. OBJECTIVE: To evaluate whether cognitive dysfunction is linked to psychotherapy use in pwMS. METHODS: In a consecutive sample of 253 pwMS who received psychiatric treatment at a Canadian neuropsychiatry clinic, cognitive impairment (CI) was defined as scores >1.5 SD below normative data on >2 Minimal Assessment of Cognitive Function in MS tests. Prior psychiatric treatment use was stratified into medications alone, evidence-based psychotherapies (CBT or MBI), or supportive/unspecified psychotherapies. Covariates included age, sex, education, employment, Expanded Disability Status Scale (EDSS) scores, disease duration, subtype, disease-modifying therapy use, and Hospital Anxiety and Depression Scale scores. Multinomial logistic regression models were undertaken to evaluate the relationship between CI and prior psychiatric treatment use, adjusting for covariates. RESULTS: Mean age was 43.3 years, 73.5% were female, median EDSS was 2.0, 51.0% had CI, and 36.0% had received CBT or MBI. Controlling for confounding variables, CI was associated with reduced use of evidence-based psychotherapy (OR=0.34, 95%CI[0.15-0.79], p = 0.012), but not supportive/unspecified psychotherapy (OR=0.79, 95%CI[0.37-1.71], p = 0.55). CONCLUSION: Among pwMS, cognitive dysfunction is independently connected to decreased use of evidence-based psychotherapies.
Dynamic emotion recognition and authenticity detection in multiple sclerosis: preliminary cognitive, behavioral, and neuroimaging evidence.
Ziccardi S, Pezzetta R, Schincariol A … +5 more , Guarnaccia F, Tamanti A, Marastoni D, Calabrese M, Scarpazza C
Mult Scler Relat Disord · 2026 May · PMID 41904839 · Publisher ↗
BACKGROUND: Facial emotion recognition (FER) is affected in multiple sclerosis (MS), impacting interpersonal functioning. Standard FER tests utilize static/posed stimuli, lacking in ecological validity. In this pilot stu...
BACKGROUND: Facial emotion recognition (FER) is affected in multiple sclerosis (MS), impacting interpersonal functioning. Standard FER tests utilize static/posed stimuli, lacking in ecological validity. In this pilot study, we used the Emotion Authenticity Recognition (EAR) test, featuring both genuine/posed dynamic expressions, to assess FER in an MS sample, also investigating behavioral/neuroimaging correlates. METHODS: A group of 54 MS patients (36 F; age = 41.4 ± 11.0, education = 14.7 ± 2.8) and a matched age/sex/education sample of 54 healthy controls (HCs) completed the EAR test, which provides two indices: Emotion Recognition (ER) and Emotion Authenticity (EA). Associations were explored with clinical/neuropsychological/self-report/MRI data. Structural 3T-MRI was analyzed using Voxel-Based Morphometry (VBM) for regional gray matter volumes. RESULTS: No significant differences were found with standard t-tests for ER and EA between MS and HCs. Bayesian independent t-tests revealed moderate evidence for no group difference in ER (BF10 = 0.210, % error = 0.029) and anecdotal evidence in favor of the null hypothesis for EA (BF10 = 0.658, % error = 0.017). In MS, ER correlated with age (r = -0.50, p < 0.001), disease duration (R = -0.30, p = 0.030), education (R = 0.34, p = 0.012), and with domain-specific/global cognitive functioning (all r indexes among 0.3 - 0.5). EA was lower in patients with severe cognitive impairment (r = 0.47, p < 0.001) and associated with empathy (R = 0.29, p = 0.037). ER was associated with bilateral widespread cortical regions and cerebellum, while EA with fronto-temporal cortices and amygdala. CONCLUSIONS: Despite no statistically significant differences observed compared to HCs, EAR in MS reflected age, cognition, and brain damage: this test captures subtle alterations, underscoring the value of dynamic and genuineness-based measures in MS assessment. These preliminary findings warrant further investigation into emotion-cognition interactions in MS.
Predictors of early NEDA-3 status after first disease-modifying therapy in a real-world Brazilian multiple sclerosis cohort.
Albuquerque FT, de Menezes FTL, Bessa NPA … +3 more , de Souza NA, Bichuetti DB, de Oliveira EML
Mult Scler Relat Disord · 2026 May · PMID 41904838 · Publisher ↗
BACKGROUND: No evidence of disease activity (NEDA-3) is widely recognized as a key therapeutic goal in multiple sclerosis (MS), reflecting complete suppression of both clinical and radiological activity. Despite its impo...
BACKGROUND: No evidence of disease activity (NEDA-3) is widely recognized as a key therapeutic goal in multiple sclerosis (MS), reflecting complete suppression of both clinical and radiological activity. Despite its importance, there is limited real-world evidence on NEDA-3 attainment following the initiation of first-line disease-modifying therapy (DMT), particularly in middle-income countries. This study evaluated the proportion of people with MS (PwMS) who achieved NEDA-3 after the first year of treatment and identified clinical predictors associated with this outcome. METHODS: We retrospectively analyzed 332 participants with relapsing-remitting MS who initiated their first DMT at a large tertiary neuroimmunology center in São Paulo, Brazil, between 1994 and 2019. NEDA-3 was defined as the simultaneous absence of relapses, confirmed disability progression, and MRI activity after one year. Logistic regression models identified independent predictors of NEDA-3 status. RESULTS: After one year, 29.2% of participants met NEDA-3 criteria. Lower baseline disability (EDSS ≥3: OR = 0.51, 95% CI: 0.28-0.93; p = 0.027), fewer pre-treatment relapses (OR = 0.84, 95% CI: 0.72-0.98; p = 0.031), and use of moderate/high-efficacy DMTs (OR = 2.94, 95% CI: 1.47-5.88; p = 0.002) increased the likelihood of NEDA-3. In the multivariate model, both pre-treatment relapse counts and DMT efficacy remained independent predictors. CONCLUSIONS: In this real-world cohort, about one-third met NEDA-3 criteria after the first treatment year. Early disease control was more likely with moderate/high-efficacy therapy and a lower prior inflammatory burden. This result highlights the importance of timely and effective treatment in optimizing long-term MS outcomes.
Comparative assessment of treatment switching in patients with multiple sclerosis receiving cladribine tablets versus fingolimod, dimethyl fumarate, and teriflunomide.
Lobo C, Rey GG, Zhao X … +7 more , Anderson J, Kim S, Kozma C, Cai C, Evans E, Phillips AL, Chen X
Mult Scler Relat Disord · 2026 May · PMID 41894909 · Publisher ↗
BACKGROUND: Comparative data on cladribine tablets (CladT) versus other disease modifying therapies (DMTs) for multiple sclerosis (MS) in the United States (US) are limited. We compared treatment switching and time-to-sw...
BACKGROUND: Comparative data on cladribine tablets (CladT) versus other disease modifying therapies (DMTs) for multiple sclerosis (MS) in the United States (US) are limited. We compared treatment switching and time-to-switch within 1- and 2-year follow-ups between CladT-treated and fingolimod-, dimethyl fumarate-, or teriflunomide-treated patients with MS. METHODS: Data for this retrospective observational study were sourced from the Komodo Healthcare Map™ database and included patients aged ≥18 years in the US with ≥2 MS diagnoses ≥30 days apart; ≥1 claim for CladT, fingolimod, dimethyl fumarate, or teriflunomide between 1 April 2019, and 31 December 2020 (initiation date = index); no index DMT in the year prior to the index date (baseline); and continuous enrollment in healthcare insurance from baseline to 2 years after the index date (follow-up). Propensity score weighting with covariate adjusted logistic regression, Kaplan-Meier and Cox regression were employed to assess switching outcomes between groups. RESULTS: Eligible patients (n = 4709) treated with CladT (n = 269), dimethyl fumarate (n = 2314), fingolimod (n = 677), and teriflunomide (n = 1449) were identified from the database. CladT-treated patients were less likely to switch treatment during the 2-year follow-up (10%) compared to fingolimod- (27%), dimethyl fumarate- (44%), or teriflunomide-treated (34%) patients in the weighted cohorts. The adjusted odds ratios (95% confidence interval [CI]) for treatment switching at 2 years were 3.25 (2.03-5.32), 6.75 (4.29-10.92), and 4.65 (2.92-7.59) for fingolimod, dimethyl fumarate, and teriflunomide, respectively, relative to CladT. Cox regression results suggested significant differences in time-to-switch compared to CladT, with hazard ratios of 2.99 (95% CI: 1.89-4.71) for fingolimod, 5.45 (95% CI: 3.73-7.97) for dimethyl fumarate, and 4.06 (95% CI: 2.73-6.06) for teriflunomide. CONCLUSION: This real-world study revealed significantly lower treatment switching rates in CladT-treated patients than in fingolimod-, dimethyl fumarate- and teriflunomide-treated patients with MS.
A real-world study on the long-term efficacy of rituximab in relapsing myelin oligodendrocyte glycoprotein antibody-associated disease.
Yu C, Chen X, Jiang W … +5 more , Sun H, Gao S, Huang D, Wu L, Yu S
Mult Scler Relat Disord · 2026 May · PMID 41894908 · Publisher ↗
OBJECTIVE: Data on the long-term efficacy and safety of rituximab (RTX) in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are scarce. The potential for a relapsing-remitting disease course in pat...
OBJECTIVE: Data on the long-term efficacy and safety of rituximab (RTX) in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are scarce. The potential for a relapsing-remitting disease course in patients with MOGAD also requires further investigation. The study aimed to evaluate the long-term clinical outcomes in relapsing MOGAD patients receiving RTX maintenance therapy. METHODS: A retrospective analysis was performed on MOGAD patients. Clinical features, relapse frequency, and Expanded Disability Status Scale (EDSS) scores were evaluated pre- and post-administration of 0.5g RTX. RESULTS: Thirty-five MOGAD patients who met inclusion criteria were identified with a median RTX duration of 1.25 (0.5-4) years. RTX reduced both annualized relapse rate (ARR) (from 1.64 to 0.1; P <0.0001) and person-year relapse rate (PRR) (from 0.61 to 0.12). 74 % (26/35) of patients remained relapse-free; 26 % (9/35) experienced relapses, of whom 78 % (7/9) had B-cell repopulation or discontinuation of RTX maintenance treatment. Most relapsing patients had mild clinical symptoms, with mean EDSS scores increasing to 1.65 (range, 1-4). All patients who reinfused ≥2 RTX after relapse remained relapse-free. Seroconversion to MOG-IgG negativity occurred in 43 % (15/35), with 6 patients exhibiting recurrent seropositivity, and 3 of whom experienced relapses. Three patients who discontinued RTX after seroreversion maintained relapse-free status. Importantly, no serious adverse events were observed, except that three patients suffered from infection or a rash during infusion. CONCLUSION: RTX treatment is associated with lower recurrence rates and high seroconversion rates in MOGAD patients. Post-treatment relapses did not exacerbate disability severity, supporting RTX as a favorable therapeutic option to prevent relapse.
Ocular toxicity associated with anti-CD20 monoclonal antibodies: A pharmacovigilance analysis using the FAERS database.
Kuang Y, Guo Y, Liu Y … +7 more , Li T, Xie J, Huang L, Ma J, Xiang Y, Yang G, Guo C
Mult Scler Relat Disord · 2026 May · PMID 41894907 · Publisher ↗
OBJECTIVES: Anti-CD20 monoclonal antibodies are widely used to treat B-cell malignancies and autoimmune diseases, but their ocular toxicity remains insufficiently characterized. To comprehensively evaluate ocular adverse...
OBJECTIVES: Anti-CD20 monoclonal antibodies are widely used to treat B-cell malignancies and autoimmune diseases, but their ocular toxicity remains insufficiently characterized. To comprehensively evaluate ocular adverse events (OAEs) associated with anti-CD20 antibodies and identify potential safety signals. METHODS: A pharmacovigilance study was conducted using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) data from Q4 2014 to Q3 2024. Disproportionality analyses with Bayesian shrinkage estimators and subgroup analyses by clinical indication were performed. RESULTS: A total of 29363 OAE reports were identified, mainly linked to rituximab (67.44 %), followed by ofatumumab (8.88 %), ocrelizumab (21.68 %), obinutuzumab (1.87 %), and ublituximab (0.14 %). Females represented 74.25 % of cases, median age 61 years. Over half of OAEs occurred within 15 days of treatment start. All five agents showed positive signals for ocular infections, suggesting a class effect. Ofatumumab was associated with increased blepharospasm risk in multiple sclerosis patients (ROR=1.62), possibly due to effects on ocular motor control in central nervous system (CNS) disease. Rituximab was linked to an increased risk of dyschromatopsia in multiple sclerosis patients (ROR=18.90), suggesting possible optic nerve or retinal pathway dysfunction related to immune-mediated demyelination. CONCLUSIONS: Anti-CD20 antibodies require careful ocular monitoring, particularly in multiple sclerosis patients. The elevated blepharospasm risks with ofatumumab and dyschromatopsia with rituximab highlights potential CNS-and optic pathway-related effects that warrant further study to improve MS treatment safety.
Physical activity and social cognitive theory variables in Hispanic and non-Hispanic adults with multiple sclerosis.
Najafi P, Flores VA, Zheng P … +1 more , Motl RW
Mult Scler Relat Disord · 2026 May · PMID 41886881 · Publisher ↗
BACKGROUND: Physical activity (PA) is lower in persons with multiple sclerosis (MS) than the general population, partly explained by social-cognitive theory (SCT) variables. To date, little is known about PA and SCT cons...
BACKGROUND: Physical activity (PA) is lower in persons with multiple sclerosis (MS) than the general population, partly explained by social-cognitive theory (SCT) variables. To date, little is known about PA and SCT constructs among Hispanics adults with MS, a group that experiences notable health disparities. We compared PA and SCT variables between Hispanic and non-Hispanic adults with MS and examined associations among these variables within each group. METHODS: Hispanic (n = 35; mean age=41.5 ± 12.5 years) and non-Hispanic (n = 35; mean age=41.7 ± 12.1 years) adults with MS completed online REDCap surveys. PA was measured using the Godin Leisure-Time Exercise Questionnaire (GLTEQ). SCT constructs included exercise self-efficacy, barriers self-efficacy, outcome expectations, social support, goal setting, and planning. Group differences were evaluated using independent-samples t-tests, and associations between PA and SCT variables were examined with Spearman correlation coefficients. RESULTS: No significant group differences were observed in PA or SCT constructs. Exercise self-efficacy was associated with PA in both groups (Hispanic: r=0.43, p = 0.010; Non-Hispanic: r=0.58-0.56, p < 0.001). Exercise planning was also associated with PA in both groups (Hispanic: r=0.42, p = 0.013; Non-Hispanic: r=0.45, p = 0.006). Barriers self-efficacy was associated with PA in the non-Hispanic group (r=0.44-0.47, p = 0.004-0.007) and with GLTEQ health contribution scores among Hispanic participants (r=0.37, p = 0.030). Goal setting was associated with PA only among Hispanic participants (r=0.33, p = 0.049). CONCLUSIONS: Hispanic and non-Hispanic adults with MS demonstrated similar PA levels and SCT profiles. Exercise self-efficacy and planning were consistent moderate correlates of PA regardless of ethnicity. These results suggest that SCT may serve as a basis for interventions targeting PA in Hispanic and non-Hispanic adults with MS.
Autonomic reactivity to stress in multiple sclerosis: A meta-analytic review.
Ranfaing S, Degraeve B, Lenne B … +1 more , Sequeira H
Mult Scler Relat Disord · 2026 May · PMID 41886880 · Publisher ↗
BACKGROUND: Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease of the central nervous system, often accompanied by anxiety and depression exacerbating physical symptoms and reducing qual...
BACKGROUND: Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease of the central nervous system, often accompanied by anxiety and depression exacerbating physical symptoms and reducing quality of life. OBJECTIVES: Given the central role of the autonomic nervous system in emotional reactivity and regulation, this meta-analytic review examined whether people with MS (PwMS) show altered autonomic responses to emotional or stress-related stimuli compared to controls. METHODS: Fourteen studies were included exploring autonomic signals, such as heart rate (HR) variability (HRV), blood pressure, electrodermal activity, and pupil response, during emotional or psychological stress. Quantitative analyses focused on HR, HRV and blood pressure. RESULTS: Between-group analysis (PwMS vs. controls, k = 6) revealed a large reduction in stress-induced autonomic responses in PwMS (d = -1.21), suggesting a blunted physiological response. Qualitative analysis from other autonomic indices confirmed this alteration. Within-group analysis in PwMS showed a moderate increase in autonomic responsiveness (d = 0.71, p = .079), though non-significant, suggesting residual but reduced reactivity. CONCLUSIONS: Overall, these results reveal attenuated autonomic responses to psychological stress in MS, possibly linked to central lesions affecting stress-regulation networks, and support autonomic reactivity as a potential physiological marker of emotional and functional impairment in MS.
Long-term outcomes of cladribine tablets in multiple sclerosis: Treatment completion, persistence, and subsequent therapy transitions in Southeast Europe.
Krbot Skorić M, Brecl Jakob G, Rajda C … +10 more , Jerčinović K, Abičić A, Adamec I, Rot U, Barun B, Gabelić T, Horvat Ledinek A, Gomezelj S, Klivényi P, Habek M
Mult Scler Relat Disord · 2026 May · PMID 41886879 · Publisher ↗
OBJECTIVES: This study aimed to assess treatment completion rates, persistence, administration of a third course of cladribine tablets, and switching to other disease-modifying therapies (DMTs) in people with multiple sc...
OBJECTIVES: This study aimed to assess treatment completion rates, persistence, administration of a third course of cladribine tablets, and switching to other disease-modifying therapies (DMTs) in people with multiple sclerosis (pwMS) treated with cladribine tablets in Southeast European MS centers. METHODS: We conducted a retrospective, observational, multi-center, and multi-national study including 195 pwMS who initiated cladribine tablets at three centers across three European countries. The mean follow-up period was 4.06±1.17 years. RESULTS: Among the participants, 184 (94.4 %) completed both courses of cladribine tablets, while 7 (3.6 %) were lost to follow-up. Four (2.1 %) switched to another DMT due to disease activity before receiving the second course. Over the follow-up period, 132 (67.7 %) did not require any additional treatment after completing two courses. Eighteen (9.2 %) received a third course of cladribine tablets, while 40 (20.5 %) switched to another DMT, with two of these switches occurring after the third course. The median time to the third course was significantly longer (3.18 years [IQR 2.20-3.91]) compared to the median time to switch (2.27 years [IQR 1.79-3.13]) from the administration of the second course (p = 0.009). An exploratory and hypothesis-generating multivariate logistic regression analysis identified prior DMT use as the only significant predictor for requiring a third course of cladribine tablets and/or switching to another DMT (exp(B) 2.429, 95 % CI 1.034-5.707, p = 0.042). CONCLUSION: A substantial proportion of pwMS treated with cladribine tablets remain treatment-free for over four years. In selected cases, a third course of cladribine tablets may be beneficial.
Single-institution experience with efgartigimod in patients with GFAP astrocytopathy: Treatment response and adverse events.
Li Z, Wu H, Bian Z … +7 more , Yan C, Chen Y, Huang Y, Wang Y, Peng F, Qiu W, Zhang B
Mult Scler Relat Disord · 2026 May · PMID 41865561 · Publisher ↗
BACKGROUND: Autoimmune glial fibrillary acidic protein astrocytopathy (GFAPA) is a recently recognized autoimmune disorder of the central nervous system. While many patients respond to conventional immunotherapies, a sub...
BACKGROUND: Autoimmune glial fibrillary acidic protein astrocytopathy (GFAPA) is a recently recognized autoimmune disorder of the central nervous system. While many patients respond to conventional immunotherapies, a subset exhibits suboptimal responses, highlighting the need for alternative treatment strategies. OBJECTIVE: To report real-world clinical experience with efgartigimod in GFAPA patients, providing preliminary data on its safety and effectiveness. DESIGN: This retrospective case-control study was conducted at a single center in China and included patients with GFAPA who received efgartigimod, with a minimum follow-up of 8 weeks. METHODS: We analyzed data from 36 patients diagnosed with GFAPA between January 2021 and July 2024. Patients were categorized into two groups: those treated with efgartigimod (n = 16) and those who were not (control group, n = 20). Clinical outcomes were evaluated using the modified Rankin Scale, Clinical Assessment Scale in Autoimmune Encephalitis (CASE), Glasgow Coma Scale (GCS), and assessment of clinical symptoms. Additionally, we monitored treatment-emergent adverse events (TEAEs), changes in cerebrospinal fluid (CSF) parameters (total protein, leukocyte count, anti-GFAP antibody titers), and serum immunoglobulin G (IgG) levels. RESULTS: Compared to the control group, patients receiving efgartigimod demonstrated greater clinical improvement, as reflected by borderline significant reductions in CASE scores at discharge (p = 0.04). Improvements in GCS scores were also observed at both time points. The efgartigimod group showed significant decreases in CSF total protein, leukocyte count, anti-GFAP antibody titers, and serum IgG levels. The most common TEAEs were mild to moderate infections; no serious safety concerns were identified. CONCLUSION: Efgartigimod appears to be safe and potentially effective in patients with GFAPA, and may be associated with improvements in clinical symptoms and neurological function. However, larger prospective, randomized controlled trials are warranted to confirm these findings and establish its role in the treatment algorithm.
Patterns of emergency department utilization among persons with multiple sclerosis across seven medical institutions.
Kinnett-Hopkins D, Sotelo J, Muhammad LN … +5 more , Kayle M, Bussell L, Mao-Draayer Y, Heinemann AW, Maimone C
Mult Scler Relat Disord · 2026 May · PMID 41865560 · Publisher ↗
BACKGROUND: Persons with multiple sclerosis (MS) rely heavily on the emergency department (ED) for acute care, with marginalized populations bearing an unequal MS burden of disease. Understanding how social determinants...
BACKGROUND: Persons with multiple sclerosis (MS) rely heavily on the emergency department (ED) for acute care, with marginalized populations bearing an unequal MS burden of disease. Understanding how social determinants of health influence ED utilization is crucial for optimizing MS management. OBJECTIVES: Examine the relationship between ED utilization, race, insurance type, and the Distressed Communities Index in patients with MS. METHODS: We analyzed encounters from seven healthcare institutions in the Chicago Area Patient-Centered Outcomes Research Network. Differences in ED utilization across patient groups were assessed using Chi-square tests and risk ratios for each characteristic combination investigated. RESULTS: The sample included 217,184 encounters from 12,770 patients between 2015 and 2021. Each factor had a statistically significant relationship with ED utilization. Increased ED utilization was associated with living in At risk or Distressed neighborhoods, being Black or Hispanic, lacking private insurance, and not having prior neurology encounters. Combined, these factors resulted in over three times the relative risk of ED encounters compared to White patients with private insurance living in more affluent areas who saw a neurologist (risk ratio 3.57, 95% CI [3.12, 4.08]). CONCLUSIONS: These findings can guide efforts to address systemic inequities, and individual healthcare needs to improve MS management.
Nationwide prevalence and incidence of MOG antibody-associated disease (MOGAD) in Denmark.
Papp V, Mamoei S, Frederiksen JL … +6 more , Nilsson AC, Svendsen KB, Christensen JR, Sellebjerg F, Magyari M, Illes Z
Mult Scler Relat Disord · 2026 May · PMID 41865559 · Publisher ↗
OBJECTIVES: To estimate the nationwide population-based incidence and prevalence of MOGAD in the Danish adult population (age ≥18 years) based on the 2023 International MOGAD Panel proposed criteria. METHODS: In this pop...
OBJECTIVES: To estimate the nationwide population-based incidence and prevalence of MOGAD in the Danish adult population (age ≥18 years) based on the 2023 International MOGAD Panel proposed criteria. METHODS: In this population-based historically prospective study, data were sourced from laboratories providing MOG-IgG test, the Danish Multiple Sclerosis Registry, and departments of neurology in Denmark. We computed the crude-, sex-, age-, race- specific incidence and prevalence. RESULTS: We confirmed MOGAD in 71 cases between 2016 and 2020. The incidence of MOGAD in the Danish adult population was 0.205 per 100,000 person-years (95% CI: 0.145-0.281), and the prevalence was 1.51 per 100,000 persons (95% CI: 1.18-1.91). The incidence in the female adult population was 0.192 and in the male population 0.218 per 100,000 person-years (95% CI: 0.114-0.303 and 0.133-0.337). The prevalence among female was 1.43 while in male 1.6 per 100,000 persons, respectively (95% CI: 0.99-2.00 and 1.13-2.20). The incidence and prevalence peaked in the age group 18-39 years, however MOGAD occurred in all age groups inclusive in elderly (age 65≤). No difference in the race-specific data was found. CONCLUSIONS: We report estimates of incidence and prevalence of MOGAD in a national population-based design according to the 2023 criteria. Considering recent national population-based data in neuromyelitis optica spectrum disorder (NMOSD) obtained with similar approaches in the Danish adult population, the incidence and prevalence of MOGAD are 3 times and 1.4 times higher, respectively.
Impact of autoimmune comorbidity on inflammatory activity and disability accumulation in multiple sclerosis.
Shabo S, Yafa Lazar A, Zmira O … +1 more , MSBase Investigators
Mult Scler Relat Disord · 2026 May · PMID 41865558 · Publisher ↗
BACKGROUND: Autoimmune comorbidities occur more frequently in patients with multiple sclerosis (MS) and have been proposed to exacerbate disease through a putative increase in immune burden. Whether the coexistence of au...
BACKGROUND: Autoimmune comorbidities occur more frequently in patients with multiple sclerosis (MS) and have been proposed to exacerbate disease through a putative increase in immune burden. Whether the coexistence of autoimmune disease translates into greater inflammatory activity or accelerated disability progression in relapsing MS remains uncertain. METHODS: We performed a large retrospective matched cohort study using the international MSBase registry, including patients with relapsing - remitting MS or clinically isolated syndrome. Autoimmune comorbidity was defined by documented diagnoses present before or at baseline. Patients with and without autoimmune comorbidity were matched 1:2 using propensity scores. Clinical and radiological outcomes included annualized relapse rate, time to first relapse, MRI inflammatory activity, and 6-month confirmed disability worsening (6M-CDW), analyzed using negative binomial and Cox proportional hazards models. RESULTS: The matched cohort comprised 1773 patients, of whom 591 had at least one autoimmune comorbidity. Autoimmune comorbidity was not associated with higher relapse rates, shorter time to first relapse, or increased MRI inflammatory activity. In contrast, patients with autoimmune comorbidity had a significantly higher risk of confirmed disability worsening over time (hazard ratio 1.21, 95% CI 1.04-1.41). CONCLUSIONS: In relapsing multiple sclerosis, autoimmune comorbidity is not associated with increased relapse activity or inflammatory MRI findings. However, patients with autoimmune comorbidity experience a higher risk of disability worsening over time. This pattern suggests that autoimmune comorbidity does not intensify acute inflammatory disease activity, but may increase susceptibility to chronic, relapse-independent mechanisms of disability accumulation.
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