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Background and Objectives: Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by inflammation and neurodegeneration. Ocrelizumab, a humanized anti-CD20 monoclonal antibody, has shown promise in reducing disease activity in MS patients. This prospective study aims to assess the effectiveness of ocrelizumab in reducing confirmed disability progression in patients with relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) over a two-year period. By evaluating clinical data, and MRI findings, this study seeks to provide comprehensive insights into ocrelizumab's impact on disease dynamics and disability. Materials and Methods: Ninety-eight patients aged 18 to 65 with confirmed MS were enrolled under ocrelizumab therapy at the Neurology Department of "Pius Brinzeu" Clinical Emergency Hospital in Romania between July 2020 and July 2024. Participants were assessed at baseline and every six months over two years. The key outcomes measured were changes in the Expanded Disability Status Scale (EDSS) as a measure of confirmed disability progression (CDP), annualized relapse rate (ARR), and MRI findings. Results: Over the two-year period, the mean EDSS score significantly decreased from 5.2 ± 1.8 to 4.6 ± 1.7 (mean change = −0.6 ± 0.9; p = 0.032), indicating improved neurological function. The proportion of patients experiencing relapses dropped markedly from 61.2% to 14.3% (p < 0.001). The MRI results showed significant reductions in patients with new or enlarging T2 lesions from 68.4% to 27.6% (p < 0.001) and gadolinium-enhancing lesions from 44.9% to 15.3% (p < 0.001). Patients previously treated with natalizumab exhibited a greater reduction in EDSS scores (−1.0 ± 0.8; p = 0.001) compared to other treatments. Multivariate regression identified the baseline EDSS score (β = 0.65; p < 0.001), previous natalizumab use (β = −0.30; p = 0.013), and age at diagnosis (β = 0.02; p = 0.048) as significant predictors of two-year EDSS scores. While markers of active inflammation decreased, the proportion of patients with brain atrophy increased from 31.6% to 43.9% (not statistically significant; p = 0.105). SPMS patients had higher rates of brain atrophy at baseline (61.1% vs. 25.0%; p = 0.007) and at two years (100.0% vs. 31.3%; p < 0.001) compared to RRMS patients. Conclusions: Ocrelizumab effectively reduced disease activity and improved neurological disability over two years in both RRMS and SPMS patients. Significant reductions in relapse rates and MRI markers of inflammation were observed. Previous natalizumab treatment was associated with greater improvements. Despite these benefits, the progression of neurodegeneration, particularly brain atrophy in SPMS patients, underscores the need for additional strategies targeting neurodegenerative aspects of MS. [ABSTRACT FROM AUTHOR]

Objective: To ascertain the changes of serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) values in relapsing–remitting multiple sclerosis (RRMS) patients treated with ocrelizumab and their association with treatment response. Methods: Multicenter prospective study including 115 RRMS patients initiating ocrelizumab treatment between February 2020 and March 2022 followed during a year. Serum samples were collected at baseline and every 3 months to measure sNfL and sGFAP levels using single-molecule array (SIMOA) technology. Based on age and body mass index, sNfL values were standardized using z-score. NEDA (non-evidence of disease activity)-3 status was defined for patients free of disease activity after a year of follow-up. Inflammation (INFL) was considered when new relapses occurred during follow-up or new MRI lesions were found at 1-year exploration. PIRA (progression independent of relapse activity) was defined as disability progression occurring in the absence of relapses or new MRI activity. Results: After a year on ocrelizumab, 85 patients (73.9%) achieved NEDA-3. Thirty patients did not achieve NEDA: 20 (17.4%) because of INFL and 10 (8.7%) because of PIRA. Of INFL patients, 6 (30.0%) had relapses, and 17 (85.0%) had at least one new MRI lesion at the 12-month examination. At baseline, INFL patients had higher sNfL (p = 0.0003) and sGFAP (p = 0.03) than the NEDA-3 group. PIRA patients mostly exhibited low sNfL and heterogeneous sGFAP levels. After a year, NEDA-3 and INFL patients showed similar decreases in sNfL (p < 0.0001) and sGFAP (p < 0.0001 for NEDA-3 and p = 0.001 for INFL ones). However, the decrease occurred earlier in NEDA-3 patients. Accordingly, sNfL > 1.5 z-score 3 months after ocrelizumab initiation indicated a higher risk of inflammation (OR = 13.6; p < 0.0001). Decrease in sGFAP values occurred later in both groups, with significant reductions observed at 12 months for INFL and 6 and 12 months for NEDA-3. No significant changes in sNfL or sGFAP were observed in PIRA patients. Conclusion: Ocrelizumab induced normalization of sNfL and sGFAP in the majority of NEDA-3 and inflammatory patients but did not cause changes in the PIRA group. Our data suggest that normalization of sNfL and sGFAP is associated with the lack of inflammatory-associated disease progression but it may not affect non-inflammatory PIRA. [ABSTRACT FROM AUTHOR]

In clinical trials, the percentage of patients discontinuing treatment with ocrelizumab due to adverse events was low. However, real-world populations are often more diverse than randomized controlled trials (RCTs), therefore it is important to assess discontinuation rates in real-world studies. This systematic literature review (SLR) was conducted to identify real-world discontinuation and persistence data for ocrelizumab in studies of patients with relapsing remitting multiple sclerosis (RRMS) and primary progressive multiple sclerosis (PPMS). Searches were conducted in MEDLINE and Embase to identify relevant real-world studies that met pre-determined Population, Intervention, Comparison, Outcomes, and Study (PICOS) criteria. Only articles published in English were included, but the study country was not restricted. A total of 30 studies were included, with the majority reporting real-world persistence data that appear to be similar to or better than in the pivotal clinical trials, with only 1 study reporting higher discontinuation rates due to adverse events compared with the clinical trials. Other studies identified reported that the risk of discontinuation was higher for other disease-modifying therapies (DMTs) compared with ocrelizumab, and adherence was also higher for ocrelizumab versus other DMTs. These findings have clinical relevance, as other studies have reported improved clinical outcomes and lower care costs for patients that are persistent or adherent to other DMTs. [ABSTRACT FROM AUTHOR]

Open-label extension (OLE) studies help inform long-term safety and efficacy of disease-modifying therapies in multiple sclerosis (MS). We report exploratory analyses from a phase 2 trial on the longest follow-up to date of ocrelizumab-treated patients with relapsing-remitting MS (RRMS). The primary treatment period (PTP) comprised four 24-week treatment cycles; participants were randomized to double-blind ocrelizumab (2000 mg or 600 mg), placebo, or interferon β-1a (open label) for one cycle, then dose-blinded ocrelizumab 1000 mg or 600 mg for the remaining cycles. The PTP was followed by consecutive assessed and unassessed treatment-free periods (TFPs) and then the OLE (ocrelizumab 600 mg every 24 weeks). Safety and efficacy were prospectively assessed. Of 220 participants randomized, 183 (84%) completed the PTP. After the TFP, 103 entered OLE (median OLE ocrelizumab exposure 6.5 years). Most common adverse events across all periods were infusion-related reactions. MRI activity, annualized relapse rate, and confirmed disability progression (CDP) rates remained low throughout. During the assessed TFP, there was a trend toward less and later B-cell repletion, and later CDP, for patients randomized to ocrelizumab; MRI activity was observed in 16.3% of patients, the earliest 24 weeks after the last ocrelizumab dose. This is the longest follow-up of ocrelizumab-treated patients with RRMS, with no new safety signals emerging during an observation period from 2008 to 2020. Results reinforce the sustained efficacy of long-term ocrelizumab. Reduced disease activity was maintained following interruption of 6-month dosing cycles, with no evidence of rebound.