BACKGROUND:The main goal of treatment in relapsing-remitting multiple sclerosis (RRMS) is to reduce the occurrence of relapses. However, little is known about the natural history of relapse recovery. METHODS:We accessed data from DECIDE (n=1841), a phase 3 trial. We investigated factors associated with time to relapse recovery (defined as a return of the Expanded Disability Status Scale (EDSS) score to the pre-relapse level or lower), relapse severity (0.5, 1.0, or >1.0 EDSS score change) and the new concept of 'acute clinical events with stable MRI' (ACES). Variables used were age, sex, disease duration, treatment arm, pre-relapse EDSS, corticosteroid use, number of relapses prior to study enrolment, MRI activity, relapse severity and affected functional system (FS). RESULTS:We included 430 first relapses, of which 405 (94.2%) recovered during follow-up, 400 (93%) by 1 year (median time to recovery of 71 days, 95% CI 66 to 75 days). More severe relapses and relapses involving the bowel and bladder FS took a longer time to recover. Corticosteroids hastened the recovery of relapses but did not influence eventual relapse recovery. ACES occurred in 38% of relapses and was more frequent in older people and participants treated with daclizumab. CONCLUSIONS:Most relapses (94.2%) recover, but the process of recovery can take up to 1 year and depends mostly on relapse severity. Our findings challenge the concept of 3-month and 6-month confirmed disability progression as reliable markers of permanent disability in RRMS trials. ACES occurs frequently and is associated with age.

BACKGROUND:Phase 2 clinical trials in primary progressive multiple sclerosis (PPMS) often use MRI brain volume measures as their primary endpoint. Here, we investigate the longitudinal association between change in MRI outcomes and change in disability over 2 years of follow-up in a large and well-characterised PPMS trial dataset. METHODS:Using the dataset from PROMISE (n=943, mean age of 58.0 years, mean Expanded Disability Status Scale (EDSS) 5.0, and mean disease duration of 10.5 years at baseline), a phase 3 trial of glatiramer acetate in PPMS, we described the change in MRI and disability measures during follow-up and used multivariable logistic regression models to investigate whether change in four MRI outcomes (grey matter volume, white matter volume, brain fraction and total burden of disease) was associated with seven measures of clinical disability worsening (including the EDSS, Timed 25 Foot Walk, Nine-Hole Peg Test and Paced Auditory Serial Addition Test). RESULTS:We found only weak and inconsistent associations between change in MRI and physical and cognitive outcome measures over 2 years of follow-up. Change in MRI measures in year 1 of the trial did not predict change in physical nor cognitive disability in year 2. DISCUSSION:The association of the investigated volumetric MRI measures and clinical disability outcomes was noticeably weak and inconsistent. Our findings question the suitability of brain volume loss and lesion burden accumulation as functionally relevant trial endpoints in PPMS and inform the design and interpretation of clinical trials in PPMS.

Background and ObjectivesA pilot trial of the antioxidant lipoic acid (LA) in secondary progressive multiple sclerosis (MS) demonstrated a reduction in the whole-brain atrophy, suggesting neuroprotection. This study determined whether LA preserved walking speed, reduced brain atrophy, and was safe in progressive MS (PMS).MethodsThis phase 2, 24-month, randomized, double-blind, placebo-controlled clinical trial (2018-2023) recruited a convenience sample from 10 US sites, including 5 Veterans Affairs medical centers and 1 Canadian site. Inclusion criteria were as follows: age >= 18 years, primary or secondary PMS, Expanded Disability Status Scale (EDSS) score 3.0-6.5, and relapse-independent disability worsening in the previous 2 years. Exclusion criteria were as follows: confounders of mobility outcomes, LA use in the previous 2 years, and MRI contraindications. Concurrent disease-modifying therapy (DMT) was permitted. Participants were block-randomized by site (1:1) to receive 1,200 mg daily oral LA or placebo. The sample size (n = 118) was powered to detect Timed 25-Foot Walk (primary outcome) speed differences, allowing 25% attrition. Secondary outcomes were brain atrophy, other clinical and patient-reported disabilities, and adverse events. Study visits occurred every 6 months. Laboratory monitoring was increased to every 3 months because of treatment-related proteinuria. Intention-to-treat analysis used linear mixed-effects models.ResultsParticipants in the LA (54) and placebo (61) groups were 54.8% female (age 59.1 (SD 8.5) years), with a disease duration of 16.3 (SD 9.7) years and a median EDSS score of 6.0 (interquartile range 4.0-6.0), and 55.7% were on DMT. Groups were matched at baseline. LA participants discontinued from the study more often (37%) than placebo (17%). LA did not slow declines in walking speed (-0.39 ft/sec vs -0.30 ft/sec; -0.08 [-0.33 to 0.17]), nor showed differences in mobility, other clinical, or patient-reported outcomes from placebo. Whole-brain volume seemed stable in LA participants, whereas it trended toward a decrease in placebo, even after accounting for an increased total T2-weighted lesion volume that was greater in the LA group. Deep gray matter volume remained stable in LA participants and decreased in placebo participants. The LA group experienced more proteinuria and fewer suicidal ideation events than the placebo group.DiscussionLA did not slow decline in walking speed or have other clinical effects different from placebo and was associated with newly described adverse events. Investigating LA mechanisms may help interpretation of volumetric imaging biomarkers in PMS.Trial Registration InformationNCT03161028. clinicaltrials.gov/study//NCT03161028, first submission May 18, 2017; first patient enrolled August 17, 2018.Classification of EvidenceThis study provides Class II evidence that in people with primary or secondary PMS, oral LA did not improve timed walking speed at 24 months compared with placebo.

Importance:Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) lacks proven relapse-preventive therapies. While clinical trials are ongoing, safety data may be limited and approved drugs are costly. Studies of interleukin 6 receptor blocker (IL-6RB) in MOGAD are limited by small numbers and no comparative studies, contributing to low use. Objective:To evaluate the impact of IL-6RB therapy on relapse rates in MOGAD and compare relapse frequency with intravenous immunoglobulin (IVIG). Design, Setting, and Participants:This international, multicenter, retrospective cohort study (January 1, 2015, through December 31, 2025) included a historical IVIG-treated cohort of varying doses. The study took place across sites in North and South America (US, Canada, Mexico, Argentina, Brazil, Chile, Colombia, and Peru). Patients with MOGAD (n = 116, no excluded patients) who received at least 1 dose of an IL-6RB were included. These data were analyzed in January 2026. Exposures:Tocilizumab or satralizumab. Main Outcomes and Measures:Annualized relapse rate (ARR) during IL-6RB therapy, time to next relapse after treatment initiation, and adverse events. Outcomes were compared with the IVIG cohort using inverse probability of treatment weighting (IPTW) adjusted for age, sex, prior ARR, and concomitant therapies. Results:A total of 116 patients with MOGAD (89% relapsing) receiving IL-6RB (tocilizumab, 104 [90%] and satralizumab, 12 [10%]) were included; overall, 60.3% were female, 39.7% were male, and 18% were younger than 18 years. The median (IQR) IL-6RB treatment follow-up was 1.4 (0.7-2.5) years and 23 relapses occurred during 241.8 person-years of IL-6RB therapy. The ARR decreased from 0.64 (95% CI, 0.58-0.70) for relapsing MOGAD before IL-6RB to 0.09 (95% CI, 0.06-0.14) during IL-6RB treatment (incidence rate ratio, 0.08; 95% CI, 0.04-0.16). Adverse events occurred in 58 patients (50%), most commonly mild infections, although 10 (9%) had severe infections. In the IVIG cohort (n = 59), 30 relapses occurred over 133.8 person-years (ARR, 0.22; 95% CI, 0.15-0.32). After IPTW, IL-6RB was associated with a lower hazard ratio (HR) than the group who underwent IVIG therapy less than 1 g/kg every 4 weeks (HR, 4.5; 95% CI, 2.0-9.8), with no significant difference vs the group who underwent IVIG 1 g/kg or more every 4 weeks (HR, 2.0; 95% CI, 0.8-4.5). Conclusions and Relevance:In this multicenter observational cohort, IL-6RB use in MOGAD was associated with low relapse rates and a favorable safety profile, though severe infections occurred occasionally. Relapse rates were lower than the group who underwent IVIG less than 1 g/kg every 4 weeks but not significantly different from the group who underwent IVIG 1 g/kg or more every 4 weeks. This supports IL-6RB as a potential relapse-prevention therapy in MOGAD; the wide availability and relative affordability of tocilizumab may enable broad global use.

BACKGROUND AND OBJECTIVES:It remains uncertain whether the relative benefit of disease-modifying treatments (DMTs) diminish as patients age because of a natural decline of inflammatory disease activity. To better capture the balance of benefit and harm, the statistical concept of the Number Needed to Treat (NNT) provides a useful and easily interpretable metric. METHODS:We examined the relationship between treatment efficacy and age by applying the NNT concept to three pivotal randomized clinical trials of high-efficacy DMTs: AFFIRM, SENTINEL, and DECIDE (3,954 participants together). NNTs were calculated to determine how many individuals within each age group would need to be treated to prevent one additional inflammatory event (by different definitions of significant inflammation). RESULTS:Inflammatory disease activity decreased with advancing age, resulting in progressively higher NNTs in older participants. For instance, in the SENTINEL trial, the NNT to prevent one additional new/enlarging T2 lesion annually was one for the youngest patients (⩽30 years) compared with 10 for the oldest (>50 years). Similarly, in AFFIRM, the NNT to prevent one relapse was two in the youngest group (⩽30 years) versus four in the oldest (41-50 years). DISCUSSION:NNTs provide a framework for contextualizing treatment efficacy against potential harms, supporting more individualized therapeutic decision-making.

Cognitive impairment is common in multiple sclerosis (MS). Accurate measurement of cognitive change is essential for clinical trials. The change in cognitive scores, clinical metrics of physical disability, and neuroradiological metrics was quantified in data from a phase-3 randomized controlled trial of natalizumab in secondary progressive MS (SPMS). The adults diagnosed with SPMS for ≥ 2 years and Expanded Disability Status Scale (EDSS) scores from 3 to 6.5 were randomized to receive natalizumab or placebo for 96 weeks. We evaluated change in Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), Selective Reminding Test (SRT), Brief Visuospatial Memory Test (BVMT-R), two subjective cognitive measures, Beck Depression Inventory (BDI-FS), Timed 25-foot Walk Test, Nine Hole Peg Test, measures of brain volume, and T2 lesion volume. The outcomes were evaluated at baseline, 48-, and 96-week follow-up. There were no significant differences in cognitive change between treatment arms. SDMT and PASAT scores improved over 96-weeks: mean SDMT scores by 4.5 points (SD 9.3), mean PASAT scores by 2.4 points (SD 9.4). Verbal and visuospatial memory test performance showed no consistent change. All MRI measures showed decreased brain volumes. NHPT scores worsened little and T25FW showed steadily worsening scores. Improvements in SDMT and PASAT performance were observed regardless of treatment arm. These findings are consistent with prior studies in MS. As it is unlikely that cognition improves over time in people with a chronic neurologic disease, these results support the need for cognitive outcomes that overcome practice and learning effects to accurately quantify change.

BACKGROUND AND OBJECTIVES:A pilot trial of the antioxidant lipoic acid (LA) in secondary progressive multiple sclerosis (MS) demonstrated a reduction in the whole-brain atrophy, suggesting neuroprotection. This study determined whether LA preserved walking speed, reduced brain atrophy, and was safe in progressive MS (PMS). METHODS:This phase 2, 24-month, randomized, double-blind, placebo-controlled clinical trial (2018-2023) recruited a convenience sample from 10 US sites, including 5 Veterans Affairs medical centers and 1 Canadian site. Inclusion criteria were as follows: age ≥18 years, primary or secondary PMS, Expanded Disability Status Scale (EDSS) score 3.0-6.5, and relapse-independent disability worsening in the previous 2 years. Exclusion criteria were as follows: confounders of mobility outcomes, LA use in the previous 2 years, and MRI contraindications. Concurrent disease-modifying therapy (DMT) was permitted. Participants were block-randomized by site (1:1) to receive 1,200 mg daily oral LA or placebo. The sample size (n = 118) was powered to detect Timed 25-Foot Walk (primary outcome) speed differences, allowing 25% attrition. Secondary outcomes were brain atrophy, other clinical and patient-reported disabilities, and adverse events. Study visits occurred every 6 months. Laboratory monitoring was increased to every 3 months because of treatment-related proteinuria. Intention-to-treat analysis used linear mixed-effects models. RESULTS:Participants in the LA (54) and placebo (61) groups were 54.8% female (age 59.1 (SD 8.5) years), with a disease duration of 16.3 (SD 9.7) years and a median EDSS score of 6.0 (interquartile range 4.0-6.0), and 55.7% were on DMT. Groups were matched at baseline. LA participants discontinued from the study more often (37%) than placebo (17%). LA did not slow declines in walking speed (-0.39 ft/sec vs -0.30 ft/sec; -0.08 [-0.33 to 0.17]), nor showed differences in mobility, other clinical, or patient-reported outcomes from placebo. Whole-brain volume seemed stable in LA participants, whereas it trended toward a decrease in placebo, even after accounting for an increased total T2-weighted lesion volume that was greater in the LA group. Deep gray matter volume remained stable in LA participants and decreased in placebo participants. The LA group experienced more proteinuria and fewer suicidal ideation events than the placebo group. DISCUSSION:LA did not slow decline in walking speed or have other clinical effects different from placebo and was associated with newly described adverse events. Investigating LA mechanisms may help interpretation of volumetric imaging biomarkers in PMS. TRIAL REGISTRATION INFORMATION:NCT03161028. clinicaltrials.gov/study//NCT03161028, first submission May 18, 2017; first patient enrolled August 17, 2018. CLASSIFICATION OF EVIDENCE:This study provides Class II evidence that in people with primary or secondary PMS, oral LA did not improve timed walking speed at 24 months compared with placebo.

BACKGROUND:Clinical trials of disease-modifying therapies (DMTs) for multiple sclerosis (MS) increasingly incorporate cognitive outcomes, although effects of DMTs on cognition remain unknown. METHODS:In this secondary analysis of data from SPRINT-MS, a phase 2 randomized, placebo-controlled trial of ibudilast for progressive MS, we evaluated performance on Symbol Digit Modalities Test (SDMT) and Selective Reminding Test (SRT) in relation to physical disability, brain volume assessed with magnetic resonance imaging, and retinal nerve fiber layer (RNFL) thickness over 96-week follow-up. We hypothesize that trial participants would show a decline in cognitive test scores over 96 weeks of follow-up, with a possible between-group difference in favor of ibudilast. RESULTS:Data from 255 participants were analyzed. On average, physical outcome measures, brain parenchymal fraction, and RNFL thickness worsened; average SDMT and SRT scores remained largely unchanged. There were no differences between treatment groups in cognitive outcomes at 96-week follow-up. Practice effects likely contributed to results. CONCLUSIONS:Observed stability of cognitive scores in individuals with progressive MS over 96-week follow-up may reflect true cognitive stability. However, the possibility that current cognitive measurement instruments are psychometrically flawed remains, warranting further research.

While relapsing-remitting multiple sclerosis (MS) has many therapeutic options, progressive forms of MS remain largely untreatable. Phase 2 clinical trials are our main tool to advance new treatments for progressive MS. Given the complexities of progressive MS, it will likely require many phase 2 trials to improve its treatment. To conduct informative and efficient phase 2 trials, it is important that such trials are designed in a way that they can identify a successful treatment as quickly and with as few participants as possible. In this topical review, we discuss cohort selection, outcome selection, cohort enrichment, and dosing selection as strategies to optimize the efficiency of phase 2 clinical trials in progressive MS.

WHAT IS THIS SUMMARY ABOUT?:This summary describes how researchers worked with people with multiple sclerosis (MS), neurologists and measurement experts to create an easy-to-use questionnaire to measure the physical function of people with MS. This questionnaire covers topics that are relevant and important to people with MS and their doctors.The ability to do what you want to do, when you want to do it, is one of the most important concerns for people with MS. This questionnaire could help doctors to record and manage how much MS affects people's lives.MS can bring a range of challenging symptoms such as 'brain fog', tiredness, and problems with movement and balance. Many of these symptoms can make day-to-day activities, like working, very difficult for people with MS. Doctors currently use examinations like the Expanded Disability Status Scale (EDSS) and the MS Functional Composite (MSFC), but these do not fully consider what is important to people living with MS. A questionnaire that specifically measures physical functioning of people with MS could help doctors and people with MS to better understand, communicate and manage the physical effects of MS. In this study, people with MS were asked to help create a questionnaire about physical function that reflects topics that are important to them. WHAT WERE THE RESULTS?:The PROMIS®nq physical function - Multiple Sclerosis 15a (the PROMIS® PF MS questionnaire) was successfully created with the help of people with MS. People with MS thought that the PROMIS® PF MS questionnaire covered issues important to their physical function. Scores were in line with results of other physical symptom measurement scales like the EDSS. WHAT DO THE RESULTS MEAN?:The PROMIS® PF MS questionnaire could be used to meaningfully record physical function among people with MS.

The study examined changes in the plasma proteome, metabolome, and lipidome of N = 14 patients with relapsing-remitting multiple sclerosis (RRMS) initiating treatment with ocrelizumab, assayed at baseline, 6 months, and 12 months. Analyses of >4000 circulating biomarkers identified depletion of B-cell associated proteins as the early effect observed following ocrelizumab (OCR) initiation, accompanied by the reduction in plasma abundance of cytokines and cytotoxic proteins, markers of neuronaxonal damage, and biologically active lipids including ceramides and lysophospholipids, at 6 months. B-cell depletion was accompanied by decreases in B-cell receptor and cytokine signaling but a pronounced increase in circulating plasma B-cell activating factor (BAFF). This was followed by an upregulation of a number of signaling and metabolic pathways at 12 months. Patients with higher baseline brain MRI lesion load demonstrated both higher levels of cytotoxic and structural proteins in plasma at baseline and more pronounced biomarker change trajectories over time. Digital cytometry identified a putative increase in myeloid cells and a pro-inflammatory subset of T-cells. Therapeutic effects of ocrelizumab extend beyond CD20-mediated B-cell lysis and implicate metabolic reprogramming, juxtaposing the early normalization of immune activation, cytokine signaling and metabolite and lipid turnover in periphery with changes in the dynamics of immune cell activation or composition. We identify BAFF increase following CD20 depletion as a tentative compensatory mechanism that contributes to the reconstitution of targeted B-cells, necessitating further research.

Background and ObjectivesProgression independent of relapse activity (PIRA) is increasingly used as a measure of disability worsening in multiple sclerosis (MS) and is believed to reflect the more chronic neurodegenerative aspect of MS. However, while conceptually appealing, PIRA and its counterpart relapse-associated worsening (RAW) have not been validated as outcome measures for clinical trials. Here, we study the co-occurrence of MRI activity in patients experiencing PIRA and RAW in a clinical trial setting. To illustrate the problem of random variation and measurement error of these new outcomes, we contrasted PIRA and RAW with similarly defined improvement.MethodsWe reanalyzed individual patient-level data of AFFIRM (NCT00027300) and SENTINEL (NCT00030966), 2 multicenter randomized controlled trials investigating natalizumab compared with interferon beta or placebo in RRMS, with trial visits occurring every 3 months for 2 years. We calculated 3-month-confirmed disability worsening (3M-CDW), RAW, and PIRA events based on worsening on the Expanded Disability Status Scale, 9-hole peg test, or timed 25-foot walk for every trial visit. We related worsening and improvement events to MRI activity throughout follow-up and contrasted worsening of disability with similarly defined improvement.ResultsOur analysis included 2,113 participants, 42.4% of whom developed radiologic disease activity during follow-up. Only 8% of participants had a 3M-CDW event. Although the majority of those 3M-CDW events were PIRA (6.8%) and not RAW (0.9%), 42.2% of participants with PIRA had MRI activity in the first year of follow-up and 30.9% in the second. Improvement events exceeded PIRA events throughout follow-up and occurred in all trial arms. Finally, there was no difference in time-to-PIRA between participants with and without radiologic disease activity.DiscussionPIRA and RAW in their current definitions do not reliably distinguish between disability worsening due to inflammatory disease activity and neurodegeneration in RRMS. In addition, PIRA and RAW have similar and troubling issues of random variation and measurement error as currently used trial outcome measures. Our analysis requires confirmation in other clinical data sets; a meaningful next step would be to study the co-occurrence of PIRA with radiologic disease activity in a setting with more comprehensive MRI monitoring.

Abstract Objective Postpartum, patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) have increased risk for disease activity. Anti‐CD20 IgG1 monoclonal antibodies (mAb) are increasingly used as disease‐modifying therapies (DMTs). Patients may wish to both breastfeed and resume DMT postpartum. This study aimed to determine the transfer of anti‐CD20 IgG1 mAbs, ocrelizumab, and rituximab (OCR/RTX), into mature breastmilk and describe maternal and infant outcomes. Methods Fifty‐seven cis‐women receiving OCR/RTX after 59 pregnancies and their infants were enrolled and followed up to 12M postpartum or 90 days post‐infusion. Breastmilk was collected pre‐infusion and serially up to 90 days and assayed for mAb concentration. Medical records and patients' questionnaire responses were obtained to assess neurologic, breastfeeding, and infant development outcomes. Results The median average concentration of mAb in breastmilk was low (OCR: 0.08 μg/mL, range 0.05–0.4; RTX: 0.03 μg/mL, range 0.005–0.3). Concentration peaked 1–7 days post‐infusion in most (77%) and was nearly undetectable after 90 days. Median average relative infant dose was <1% (OCR: 0.1%, range 0.07–0.7; RTX: 0.04%, range 0.005–0.3). Forty‐three participants continued to breastfeed post‐infusion. At 8–12 months, the proportion of infants' growth between the 3rd and 97th World Health Organization percentiles did not differ for breastfed (36/40) and non‐breastfed (14/16, p > 0.05) infants; neither did the proportion with normal development (breastfed: 37/41, non‐breastfed: 11/13; p > 0.05). After postpartum infusion, two mothers experienced a clinical relapse. Interpretation These confirm minimal transfer of mAb into breastmilk. Anti‐CD20 mAb therapy stabilizes MS activity before conception to the postpartum period, and postpartum treatments appears to be safe and well‐tolerated for both mother and infant.

BackgroundFocal inflammatory disease activity in relapsing-remitting multiple sclerosis (RRMS) diminishes with increasing age. Here we use patient-level data from randomised controlled trials (RCTs) of natalizumab treatment in RRMS to investigate the association of age and inflammatory disease activity. MethodsWe used patient-level data from the AFFIRM (natalizumab vs placebo in relapsing-remitting MS, NCT00027300) and SENTINEL (natalizumab plus interferon beta vs interferon beta in relapsing remitting MS, NCT00030966) RCTs. We determined the proportion of participants developing new T2 lesions, contrast-enhancing lesions (CELs) and relapses over 2 years of follow-up as a function of age, and investigated the association of age with time to first relapse using time-to-event analyses. ResultsAt baseline, there were no differences between age groups in T2 lesion volume and number of relapses in the year before inclusion. In SENTINEL, older participants had a significantly lower number of CELs. During both trials, the number of new CELs and the proportion of participants developing new CELs were significantly lower in older age groups. The number of new T2 lesions and the proportion of participants with any radiological disease activity during follow-up were also lower in older age groups, especially in the control arms. ConclusionsOlder age is associated with a lower prevalence and degree of focal inflammatory disease activity in treated and untreated RRMS. Our findings inform the design of RCTs, and suggest that patient age should be taken into consideration when deciding on immunomodulatory treatment in RRMS.

The timed 25‐foot walk (T25FW) and nine‐hole peg test (NHPT) exhibit random variability in the short term. A threshold of ≥20% change from baseline has been used to indicate true disability change, but other threshold definitions may be better suited to exclude false and include true change events. The aim of this study was to use patient‐level original trial data to investigate the short‐term variation in T25FW and NHPT, and to compare its extent with disability change at 12‐month follow‐up in people with primary progressive multiple sclerosis (PPMS).

Introduction: Natalizumab is associated with a risk of progressive multifocal leukoencephalopathy (PML) in multiple sclerosis (MS) patients infected with John Cunningham virus (JCV). Ocrelizumab has demonstrated efficacy to treat MS; however, its safety in patients previously treated with natalizumab is unclear. Objective: To evaluate the safety and efficacy of ocrelizumab in patients with relapsing MS (RMS) previously treated with natalizumab. Methods: Clinically and radiographically stable RMS patients, ages 18–65 treated with natalizumab for ⩾ 12 months, were enrolled in the study and initiated ocrelizumab 4–6 weeks after their final dose of natalizumab. Relapse assessment, expanded disability status scale, and brain magnetic resonance imaging (MRI) were performed prior to starting ocrelizumab and at months 3, 6, 9, and 12. Results: Forty-three patients were enrolled, and 41 (95%) completed the study. Two patients had a relapse while on ocrelizumab, one at month 9 and the other at month 12, without changes on brain MRI. Two additional patients had new brain MRI lesions detected at month 3, with no new symptoms. Thirteen serious adverse events (SAEs) were recorded, four of which were considered possibly related to ocrelizumab. Conclusion: Overall, our study indicates clinical and MRI stability for most patients transitioning from natalizumab to ocrelizumab. ClinicalTrials.gov Identifier: NCT03157830