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PURPOSE OF REVIEW: B-cell depletion therapy, including anti-CD20 and anti-CD19 therapies, is increasingly used for a variety of autoimmune and conditions, including those affecting the central nervous system. However, B-cell depletion therapy use can be complicated by adverse effects associated with administration and immunosuppression. This review aims to summarize the application of anti-CD20 and anti-CD19 therapies for the pediatric neurologist and neuroimmunologist. RECENT FINDINGS: Most existing literature come from clinical trials with adult patients, although more recent studies are now capturing the effects of these therapies in children. The most common side effects include infusion related reactions and increased infection risk from immunosuppression. Several strategies can mitigate infusion related reactions. Increased infections due to persistent hypogammaglobulinemia can benefit from replacement immunoglobulin. B-cell depletion therapies can be safe and effective in pediatric patients. Anticipation and mitigation of common adverse effects through primary prevention strategies, close monitoring, and appropriate symptomatic management can improve safety and tolerability.

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BACKGROUND: Pediatric-onset multiple sclerosis (POMS) cases, defined as multiple sclerosis (MS) with onset before the age of 18, represent between 3 and 5 % of all MS patients. Anti-CD20 drugs mainly rituximab, ocrelizumab, and ofatumumab are being widely used in adult-onset MS. Their use in POMS is also being increasingly considered by experts. OBJECTIVE: to review the latest evidence on safety and efficacy of the use of anti-CD20 therapies in POMS. METHODS: An extensive search was performed in PubMed, Scopus, and Web of Science databases until the end of July 1st, 2024. Two independent reviewers screened the articles, and collected data. 832 studies were screened using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. RESULTS: 12 studies on rituximab (328 patients) and 6 studies on ocrelizumab (106 patients) were synthesized. Using monoclonal antibodies in POMS patients has a noteworthy effect on reducing relapses and lesions and achieving no evidence of disease activity especially in highly active POMS patients. However, anti-CD20 therapies in MS are associated with potential adverse events (AEs). Additional data is required on the effect of anti-CD20 therapy on disability accrual. CONCLUSION: Although anti-CD20 therapy is associated with some AEs, it can be provided in several circumstances, especially to patients with highly active disease, or ones resistant to platform therapies.

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Mycoplasma pneumoniae, a frequent respiratory pathogen, can cause neurological disease manifestations. We here present a case of M. pneumoniae as cause of meningitis and occurrence of an intracranial abscess as a complication of mastoiditis with septic cerebral venous sinus thrombosis in a patient with multiple sclerosis on anti-CD20 therapy.

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Background: Clinical trials comparing the efficacy of ocrelizumab (OCR) with other disease-modifying therapies (DMTs) other than interferon (IFN) ß-1a in relapsing multiple sclerosis (RMS) are lacking. Objectives: To compare the treatment effect of OCR vs six DMTs' (IFN ß-1a, glatiramer acetate, fingolimod, dimethyl fumarate, teriflunomide, natalizumab) treatment pathways used in clinical practice by combining clinical trial and real-world data. Methods: Patient-level data from OPERA trials and open-label extension phase, and from the German NeuroTransData (NTD) MS registry, were used to build 1:1 propensity score-matched (PSM) cohorts controlling for seven baseline covariates, including brain imaging activity. Efficacy outcomes were time to first relapse and time to 24-week confirmed disability progression over 5.5 years of follow-up. Intention-to-treat analysis using all outcome data irrespective of treatment switch was applied. Results: The analyses included 611 OPERA patients and 7141 NTD patients. We built 12 paired-matched cohorts (six for each outcome, two for each DMT) to compare efficacy of OCR in OPERA with each DMT treatment pathway in NTD. Post-matching, baseline covariates and PS were well balanced (standardized mean difference <.2 for all cohorts). Over 5.5 years, patients treated with OCR showed a statistically significant reduction in the risk of relapse (hazard ratios [HRs] .30 to .54) and disability progression (HRs .51 to .67) compared with all index therapies and their treatment switching pathways in NTD. Treatment switch and/or discontinuation occurred frequently in NTD cohorts. Conclusion: OCR demonstrates superiority in controlling relapses and disability progression in RMS compared with real-world treatment pathways over a 5.5-year period. These analyses suggest that high-efficacy DMTs and high treatment persistence are critical to achieve greatest clinical benefit in RMS. Registration: OPERA I (NCT01247324), OPERA II (NCT01412333).

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BACKGROUND: This study evaluates the cost-effectiveness of adding ocrelizumab to supportive care for primary progressive multiple sclerosis (PPMS) in Iran. RESEARCH DESIGN AND METHODS: Using a lifetime horizon from the payer's perspective, we developed a decision analytic model with Expanded Disability Status Scales (EDSS) as Markov health states while taking transition probabilities and treatment effects into account. Data were sourced from clinical trials and other literature. The target population was PPMS patients receiving either supportive care or ocrelizumab. We assessed cost- effectiveness through total costs, quality-adjusted life-years (QALYs), and the incremental cost- effectiveness ratio (ICER). Sensitivity analyses addressed uncertainties. RESULTS: The addition of ocrelizumab to supportive care provided an incremental gain of 0.89 QALYs and an additional cost of US$76,771.34, resulting in an ICER of US$86,220.35 compared to supportive care, which is 5.2 times Iran's GDP per capita (US$16,557). Thus, ocrelizumab is not cost-effective at the threshold of one time GDP per capita. However, the probability of cost-effectiveness increases at higher thresholds. Sensitivity analyses confirmed the robustness of the results. CONCLUSION: While ocrelizumab is not cost-effective at the threshold of one-time GDP per capita, its clinical benefits are significant. Formulating healthcare policies for high-cost medications with low alternatives like ocrelizumab is essential.

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Ocrelizumab (OCR) is a humanized anti-CD20 monoclonal antibody approved for both Relapsing and Primary Progressive forms of Multiple Sclerosis (MS) treatment. OCR is postulated to act via rapid B cell depletion; however, by analogy with other anti-CD20 agents, additional effects can be envisaged, such as on Protein Kinase C (PKC). Hence, this work aims to explore novel potential mechanisms of action of OCR in peripheral blood mononuclear cells from MS patients before and after 12 months of OCR treatment. We first assessed, up-stream, PKCßII and subsequently explored two down-stream pathways: hypoxia-inducible factor 1 alpha (HIF-1α)/vascular endothelial growth factor (VEGF), and human antigen R (HuR)/manganese-dependent superoxide dismutase (MnSOD) and heat shock proteins 70 (HSP70). At baseline, higher levels of PKCßII, HIF-1α, and VEGF were found in MS patients compared to healthy controls (HC); interestingly, the overexpression of this inflammatory cascade was counteracted by OCR treatment. Conversely, at baseline, the content of HuR, MnSOD, and HSP70 was significantly lower in MS patients compared to HC, while OCR administration induced the up-regulation of these neuroprotective pathways. These results enable us to disclose the dual positive action of OCR: anti-inflammatory and neuroprotective. Therefore, in addition to B cell depletion, the effect of OCR on these molecular cascades can contribute to counteracting disease progression.

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BACKGROUND: The reason why some multiple sclerosis (MS) patients show disease activity after alemtuzumab (ALM) is still unclear, but ocrelizumab (OCR) could represent an interesting sequential therapeutic approach. OBJECTIVES: To investigate safety and efficacy of OCR in MS patients with disease activity after two ALM courses. METHODS: Observational retrospective multi-centers Italian cohort study. RESULTS: Seventy-two subjects were included. Mean follow-up (FU) was 2.4 (±1) years. Forty-five patients (62.5%) experienced at least one adverse event (AE), with infections accounting for 96.7% of cases. A reduction in total lymphocytes was observed between OCR start and 6 months FU, driven by BCD19+ lymphocytes depletion (p < 0.001). Immunoglobulin M (IgM) levels decreased between OCR start and 6 months FU (p < 0.001). At 2-year FU, relapse, magnetic resonance imaging (MRI) activity and disability worsening-free survival were 92.1%, 90.8%, and 89.2%. The evidence of inflammatory activity between the two ALM courses was associated with higher risk of relapse, MRI activity, and NEDA-3 status loss in relapsing-remitting multiple sclerosis (RRMS; p = 0.02, p = 0.05, p = 0.01, respectively). CONCLUSIONS: OCR after two ALM courses seemed to be safe and effective. Early IgM hypogammaglobulinemia occurred in a high proportion of patients. The evidence of inflammatory activity between ALM courses seemed to increase the risk of MS re-activation on OCR treatment.

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Serum neurofilament light chain (sNfL) levels have been proposed as a biomarker of the clinical activity, disability progression, and response to treatment of people with multiple sclerosis (PwMS); however, questions remain about its implementation in clinical practice. Ocrelizumab (OCR) has proven effective in improving clinical and radiological outcomes and reducing sNfL levels. This real-life study followed the sNfL levels of 30 PwMS treated for 12 months with OCR and evaluated the usefulness of this biomarker for their short-term prognosis, considering expanded disability status scale (EDSS), annualized relapse rate (ARR), radiological activity, and NEDA-3 values. OCR reduced ARR in 83% of PwMS and radiological activity in 80%. EDSS was maintained, while NEDA-3 was achieved in 70% at 12 months. OCR produced an early reduction in sNfL levels (at 3 months). At baseline, greater MRI-evaluated radiological activity was associated with higher sNfL levels. sNfL levels over the first 12 months of treatment did not predict a suboptimal response or sustained control of the disease. Longer-term studies are needed to explore the predictive usefulness of sNfL levels in PwMS treated with high-efficacy drugs.

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BACKGROUND: Ocrelizumab is the only disease-modifying therapy (DMT) approved for the treatment of people with primary progressive multiple sclerosis (pwPPMS). OBJECTIVES: To provide real-world evidence of ocrelizumab effectiveness and safety in pwPPMS in Croatian MS centers. METHODS: A retrospective observational multi-center study of pwPPMS who were started on ocrelizumab in 7 MS centers in Croatia. RESULTS: We identified 230 pwPPMS of whom 176 fulfilled the inclusion criteria. The median follow-up of the cohort was 2.73 (0.51-5.77) years. During the follow-up, 50 (28.4%) pwPPMS experienced confirmed disability worsening (CDW) and 19 (10.8%) stopped treatment with ocrelizumab. Baseline EDSS >5 was a statistically significant positive predictor for the development of CDW and/or stop of the treatment due to any cause (OR 2.482, 95% C.I. 1.192-5.166, p = 0.015). However, there was no significant difference in the development of CDW and/or stop of the treatment due to any cause if stratifying the patients based on active PPMS, age at treatment start (≤55 years vs >55 years), disease duration at treatment start (≤10 years vs >10 years), or EDSS at treatment start (≤5.0 vs >5.0). During the follow-up, 26 (14.8%) pwPPMS experienced infusion reactions, 64 (36.4%) had an infection and 4 (2.3%) developed a tumor. The percentage of pwPPMS with low levels of IgG was persistently above 10% and with low levels of IgM was persistently above 20% after cycle 4. CONCLUSION: Our real-world data support the use of ocrelizumab in a much broader pwPPMS population than in the original randomized controlled trial.

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Patients with relapsing-remitting multiple sclerosis should be offered disease-modifying therapies as part of their management. Recommended options include integrin antagonist therapy including natalizumab as well as anti-CD20 monoclonal antibodies like, ocrelizumab, rituximab, ofatumumab, and ublituximab. These therapies reduce relapse rates and slow brain lesion accumulation. Disease-modifying therapies selection may depend on patient preferences, potential fetal harm, and specific drug risks, requiring continuous monitoring via tracking clinical relapses and new MRI brain lesions. Natalizumab carries a risk of progressive multifocal leukoencephalopathy, particularly in anti-JCV antibody-positive patients, necessitating regular monitoring. Ocrelizumab, rituximab, and ublituximab are associated with an increased risk of infections (especially respiratory and skin infections), infusion reactions, and hypogammaglobulinemia. Ocrelizumab additionally poses a heightened risk of immune-mediated colitis and breast cancer, and it is contraindicated for patients with active hepatitis B due to the risk of viral reactivation. Ublituximab has been noted to be linked to potential fetal harm. We report the case of a 42-year-old male with relapsing-remitting multiple sclerosis on ocrelizumab who developed persistent fever and shortness of breath, two weeks after his last ocrelizumab dose. Despite antibiotic treatment for suspected pneumonia, his symptoms persisted. A chest CT scan revealed multifocal ground-glass opacities suggestive of organizing pneumonia, likely secondary to ocrelizumab. The patient's condition improved with high-dose corticosteroids, underscoring the importance of vigilance for extremely rare ocrelizumab-associated pulmonary side effects and the need for prompt, appropriate intervention.

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Introduction: In 2021 ofatumumab, a recombinant human anti-CD20 monoclonal antibody (mAb) already authorized for the treatment of chronic lymphocytic leukemia, received the marketing approval for the treatment of relapsing forms of multiple sclerosis (MS). Differently from ocrelizumab, that is administered intravenously, ofatumumab if the first anti-CD20 mAb to be administered subcutaneously without a premedication. Methods and objectives: In this study we aimed to describe and compare the main characteristics of Individual Case Safety Reports (ICSRs) describing the occurrence of Injective Related Reactions (IRRs) following the treatment with ocrelizumab and ofatumumab reported in the Eudravigilance (EV) database during years 2021-2023. Results: A total of 860 ICSRs with either ofatumumab and ocrelizumab as suspected drug were retrieved from Eudravigilance, of which 51% associated with ofatumumab and 49% with ocrelizumab. The majority of patients who experienced IRRs following ocrelizumab belonged to the age group of 18-64 years (73%), while the age-group was mostly not specified (55%) in ICSRs reporting ofatumumab as suspected. The distribution of gender was almost similar in the two groups, with the majority of ICSRs related to female patients. "Pyrexia" was the Preferred Term (PT) most reported for ofatumumab, while "Infusion related reaction" were more frequently reported with ocrelizumab. Premedication drugs were reported in 148 ICSRs. Out of 89 ICSRs for which the Time to Event (TTE) was calculated, 74 reported IRRs that occurred the same day of the drug administration. Discussion: Based on the results of this study, although a risk of ofatumumab-induced IRRs cannot be excluded, it should be considered as manageable considering that the drug seems to be mostly associated with the occurrence of fever. Thus, it is important to continue to closely monitor the use of these in clinical practice to improve the knowledge on their long-term safety.

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Our understanding of multiple sclerosis (MS) has led to the development of new therapeutic strategies, including ocrelizumab, a third-generation humanized anti-CD20 antibody. Ocrelizumab is largely well tolerated with favorable effectiveness, however, it has been associated with reports of colitis presenting weeks to months following infusion. We present a case of severe localized colitis in the setting of recent surgery and chronic ocrelizumab use. High-dose IV hydrocortisone was initiated, and the patient showed gradual improvement. Repeat imaging after discharge showed near-complete resolution of the patient's condition. This case aims to increase awareness of possible postoperative severe localized colitis in MS patients on Ocrevus.

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Up to 10 years ago the most common approach to the treatment of pediatric MS (ped-MS) was to start with IFNB or GA (so-called first-line therapies or moderate-efficacy disease-modifying therapies [ME-DMTs]) and to switch to more aggressive treatments (or high-efficacy disease-modifying therapies [HE-DMTs]) in non-responder patients. The use of HE-DMTs as first choice was recommended in selected cases with an active, aggressive form of MS. Indications for the treatment of ped-MS were essentially derived from data of observational studies. Recently, results of three randomized clinical trials have been published as well as data from many observational studies evaluating the effect of new and more active DMTs, with clear evidence that HE-DMTs are more effective than ME-DMTs. Therefore, the paradigm of treatment for patients with MS onset before 18 years of age should be changed, offering treatment with HE-DMTs as first option, because of their superior effectiveness to prevent relapses and disease progression. HE-DMTs present an overall reassuring safety profile and obtain better adherence to treatment.

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INTRODUCTION: Switching disease-modifying therapy (DMT) may be considered for relapsing-remitting multiple sclerosis (RRMS) if a patient's current therapy is no longer optimal. This was particularly important during the recent COVID-19 pandemic because of considerations around immune deficiency and impaired vaccine response associated with B cell-depleting DMTs. This real-world, single-center study aimed to evaluate change or decline in functional ability and overall disease stability in people with RRMS who were switched from B cell-depleting ocrelizumab (OCRE) to diroximel fumarate (DRF) because of safety concern related to the COVID-19 pandemic. METHODS: Adults with RRMS were included if they had been clinically stable for ≥ 1 year on OCRE. Data collected at baseline and 1 year post switch included relapse rate, magnetic resonance imaging (MRI), blood work for assessment of peripheral immune parameters, the Cognitive Assessment Battery (CAB), optical coherence tomography (OCT), and patient-reported outcomes (PROs). RESULTS: Participants (N = 25) had a mean (SD) age of 52 (9) years, and a mean (SD) duration of 26 (8) months' treatment with OCRE before the switch to DRF. Median washout duration since the last OCRE infusion was 7 months (range 4-18 months). No participants relapsed on DRF during follow-up, and all remained persistent on DRF after 1 year. There were no significant changes in peripheral immune parameters, other than an increase in the percentage of CD19+ cells 1 year after switching (p < 0.05). Similarly, there were no significant changes in CAB, OCT, and PROs. CONCLUSION: These preliminary findings suggest that transition to DRF from OCRE may be an effective treatment option for people with RRMS who are clinically stable but may need to switch for reasons unrelated to effectiveness. Longer follow-up times on larger samples are needed to confirm these observations.

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BACKGROUND: In December 2021, the U.S. Food and Drug Administration issued emergency use authorization for the combination monoclonal antibodies tixagevimab and cilgavimab (Evusheld - AstraZeneca) for COVID-19 pre-exposure prophylaxis. While COVID-19 vaccination is recommended for multiple sclerosis (MS) patients, there is concern for insufficient antibody response in patients receiving B-cell depleting therapies. The literature is sparse regarding the safety and efficacy of Evusheld use in MS patients. OBJECTIVE: We sought to investigate the administration, safety, and efficacy of Evusheld in MS patients. METHODS: Participants were consecutively recruited from the UCSD MS Center from July 2022 to October 2022. We conducted both a review of medical records and a prospective cohort study. Inclusion criteria included prior diagnosis of MS and eligibility for Evusheld injection due to use of B-cell depleting disease modifying therapy (DMT). All eligible patients were evaluated to determine uptake of Evusheld use. Participant surveys were distributed to Evusheld recipients that evaluated for potential Evusheld side effects and COVID-19 vaccination and infection history. The proportion of COVID-19 infections among participants with or without Evusheld use were compared using Fisher's exact test, and a negative binomial regression analysis was used to evaluate risk for COVID-19 infection after Evusheld administration. RESULTS: A review of medical records showed that 79 MS patients were offered Evusheld by their clinicians during the recruitment period; 48 patients ultimately received the injection. Forty-two participants consented to the prospective cross-sectional study (mean age 46.4 years, 71.8 % female), of which 33 individuals received Evusheld. All participants received at least one COVID-19 vaccination dose, with 92.3 % receiving the initial series and at least one booster dose. One-third (30.8 %) of participants had a previous COVID-19 infection. DMTs included ocrelizumab, rituximab, and ofatumumab. Of the 33 participants who received Evusheld, 10 (30.3 %) reported experiencing at least one side effect. Injection site reactions included pain (most common), itchiness, and redness. General side effects included fatigue (most common), headache, muscle pain, and weakness. Of the 33 participants who received Evusheld, seven participants (21.2 %) tested positive for COVID-19 within 6 months of Evusheld injection. In an unadjusted binomial regression analysis, Evusheld administration was associated with a reduction in COVID-19 infection risk (OR 0.22, 95 % CI 0.05 - 1.02, p = 0.05). After adjusting for age and sex, Evusheld administration was still associated with a lower COVID-19 infection risk though it did not achieve nominal significance (OR 0.21, 95 % CI 0.04 - 1.09, p = 0.06). Of the 9 participants who were offered but did not receive Evusheld, five (55.6 %) tested positive for COVID-19 (p = 0.04 with Pearson's chi square test and p = 0.09 on Fisher's exact test). CONCLUSIONS: Our medical records data demonstrated that only 61 % of MS patients offered Evusheld received the injection. Evusheld seems to be largely well-tolerated. No serious adverse effects were reported. The use of Evusheld was associated with fewer COVID-19 infections, but this did not reach nominal statistical significance in the modest sample size. The lessons learned from the initial Evusheld experience may be applied to future interventions directed at infection prevention in MS patients on immunomodulatory therapies.

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Disease-modifying therapies (DMTs) impact the cellular immune response to severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccines in patients with multiple sclerosis (pwMS). In this study, we aim to elucidate the characteristics of the involved antigen-specific T cells via the measurement of broad cytokine profiles in pwMS on various DMTs. We examined SARS-CoV-2-specific T cell responses in whole blood cultures characterized by the release of interleukin (IL)-2, IL-4, IL-5, IL-10, IL-13, IL-17A, interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α), as well as antibodies (AB) targeting the SARS-CoV-2 spike protein in pwMS following either two or three doses of mRNA or viral vector vaccines (VVV). For mRNA vaccination non-responders, the NVX-CoV2373 protein-based vaccine was administered, and immune responses were evaluated. Our findings indicate that immune responses to SARS-CoV-2 vaccines in pwMS are skewed towards a Th1 phenotype, characterized by IL-2 and IFN-γ. Additionally, a Th2 response characterized by IL-5, and to a lesser extent IL-4, IL-10, and IL-13, is observed. Therefore, the measurement of IL-2 and IL-5 levels could complement traditional IFN-γ assays to more comprehensively characterize the cellular responses to SARS-CoV-2 vaccines. Our results provide a comprehensive cytokine profile for pwMS receiving different DMTs and offer valuable insights for designing vaccination strategies in this patient population.

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BACKGROUND: Observational studies looking at clinical a++nd MRI outcomes of treatments in pediatric MS, could assess current treatment algorithms, and provide insights for designing future clinical trials. OBJECTIVE: To describe baseline characteristics and clinical and MRI outcomes in MS patients initiating ocrelizumab and fingolimod under 18 years of age. METHODS: MS patients seen at 12 centers of US Network of Pediatric MS were included in this study if they had clinical and MRI follow-up and started treatment with either ocrelizumab or fingolimod prior to the age of 18. RESULTS: Eighty-seven patients initiating fingolimod and 52 initiating ocrelizumab met the inclusion criteria. Before starting fingolimod, mean annualized relapse rate was 0.43 (95 % CI: 0.29 - 0.65) and 78 % developed new T2 lesions while during treatment it was 0.12 (95 % CI: 0.08 - 1.9) and 47 % developed new T2 lesions. In the ocrelizumab group, the mean annualized relapse rate prior to initiation of treatment was 0.64 (95 % CI: 0.38-1.09) and a total of 83 % of patients developed new T2 lesions while during treatment it was 0.09 (95 % CI: 0.04-0.21) and none developed new T2 lesions. CONCLUSION: This study highlights the importance of evaluating current treatment methods and provides insights about the agents in the ongoing phase III trial comparing fingolimod and ocrelizumab.

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BACKGROUND: Ocrelizumab (OCR) is an anti-CD20 monoclonal antibody approved for the treatment of relapsing-remitting and primary-progressive multiple sclerosis (MS). We aimed to evaluate the effectiveness of an individualized OCR extended interval dosing (EID), after switching from standard interval dosing (SID). METHODS: This was a retrospective, observational, single-centre study including MS patients regularly followed at the Neurocenter of Southern Switzerland. After a cumulative OCR dose ⩾1200 mg, stable patients were switched to EID (OCR infusions following CD19+ 27+ memory B cell repopulation). RESULTS: A total of 128 patients were included in the study, and 113 (88.3%) were switched to EID with a median interval of 9.9 (8.8-11.8) months between infusions. No clinical relapses occurred; 2 (1.8%) patients experienced disability worsening. Three (2.7%) and 2 (1.8%) patients experienced new T2 brain and spinal lesions, respectively. There was a mild decrease in IgG and IgM concentrations during both SID and EID OCR regimens (ß = -0.23, p = 0.001 and ß = -0.07, p < 0.001, respectively). CONCLUSION: Switch to personalized dosing of OCR based on CD19+ 27+ memory B cell repopulation led to a great extension of the interval between infusions, with maintained clinical and radiological efficacy. Given the potential advantages in terms of safety and health costs, EID OCR regimens should be further investigated.

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OBJECTIVE: The wearing-off phenomenon is common in people with multiple sclerosis (MS) treated with ocrelizumab. We aim to evaluate the presence and severity of wearing-off to ocrelizumab in relation to demographic and MS clinical variables, immune profiling, and a marker of neuroaxonal damage (plasma neurofilament light chain (pNfl)). METHODS: This cross-sectional study included MS patients treated with ocrelizumab from at least 1 year. Wearing-off questionnaire and blood samples were collected between 21 and 23 weeks after the previous ocrelizumab infusion. Lymphocyte subpopulations were evaluated on peripheral blood using flow cytometry. PNfl was evaluated using fully automated chemiluminescent enzyme immunoassay. RESULTS: We included 106 people with MS (age 49.5 ± 11.6 years; females 42.3%; wearing-off 57.6%). On regression models, wearing-off was associated with higher pNfl, CD8, CD3, and CD3CD27 lymphocytes. Most frequent wearing-off symptoms were cognitive, sensory, and balance problems; wearing-off started < 1 week (9.4%), 1-4 weeks (10.7%) or > 4 weeks (10.7%) before infusion; 44.8% of the complaints were moderate to severe. Severity of wearing-off was associated with higher pNfl and CD8 lymphocytes. CONCLUSIONS: Wearing-off is common in people with MS treated with ocrelizumab, and is associated with reduced immunomodulation (higher T lymphocytes) and increased neuroaxonal damage, suggesting reduced treatment response.

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OBJECTIVE: The aim of this study was to evaluate postmarketing ocrelizumab safety and effectiveness in a real-world population with multiple sclerosis (MS) and matching these parameters among MS disease types. METHODS: This was a retrospective, single-center study with MS patients treated with ocrelizumab. Demographic, clinical characteristics and immunological data were analyzed, including annualized relapse rate (ARR), relapse-free rate, Expanded Disability Status Scale (EDSS), complete blood count parameters, immunoglobulin (Ig) levels, liver function tests (LFT), hepatitis markers and adverse events in the 4-year follow-up. A total of 96 patients, 22 with relapsing-remitting MS (RRMS), 54 with secondary progressive MS (SPMS), and 20 with primary progressive MS (PPMS) who were treated with at least two doses of ocrelizumab between January 2018 and September 2023 were included in the study. RESULTS: Sixty-five (68%) were women and 31 (32%) were men. The mean age was 48.4 ± 11.1 years (20-70 years). Ninety-three patients were evaluated in the first year, 65 in the second year, 39 in the third year and 24 in the fourth year of treatment. 96% of patients were relapse-free rate in the first year, 91% in the second year, 85% in the third year and 75% in the fourth year. Eighty-six percent of patients were progression free in the 1st year of treatment, 71% in the 2nd year, in 64% in the 3rd year, and in 62% in the 4th year. During the follow-up of the cases, EDSS remained stable in 77% of RRMS patients, improved in 14%, and worsened in 9%; while EDSS remained stable in 65% of SPMS patients with attacks, it improved in 9% and worsened in 26%; while EDSS remained stable in 60% of PPMS patients, worsening was observed in 40%. There is a significant decrease in IgM and IgG values during the follow-up of ocrelizumab therapy (p < 0.001, p = 0.014). There is no significant difference in IgA, lymphocyte and neutrophil values (p = 0.713, p = 0.086, p = 0.999). No significant relationship was found between low serum IgM levels and the risk of developing infection (p > 0.05). Liver function tests was found to be within normal limits in 94% of the patients over a 4-year period. No hepatitis B, C or A infection, hepatitis B reactivation, tuberculosis, HIV infection, malignancy or drug related death occurred during 4-years follow-up. The most common side effect during ocrelizumab treatment is urinary tract infection (29%); others were upper respiratory tract infections (13%), numbness/tingling of the face, trunk, or extremities (8%), insomnia (6%), headache (5%), and soft tissue infections (cellulitis and dental abscess, 2%). CONCLUSIONS: Our results show that ocrelizumab reduces the frequency of attacks and prevent the disease progression in RRMS patients, and reducing the disease progression by primarily stabilizing EDSS scores in SPMS with attacks and PPMS. It is thought that the relatively high rates of urinary tract infection detected in this study may be related with advanced stage of the disease. The absence of hepatitis B reactivation, chronic infection or malignancy in the 4-year follow-up of our cases supports the long-term safety of ocrelizumab treatment. Ocrelizumab may be preferred as an effective and reliable treatment of different types of MS due to non-serious side effects.

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