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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.

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. [ABSTRACT FROM AUTHOR]

Severe SARS-CoV-2 infections may still be observed in people bearing risk factors, such as the use of anti-CD20 monoclonal antibodies (mAbs), which are adopted in several autoimmune disorders including multiple sclerosis (MS). COVID-19 diagnosis is routinely based on nasopharyngeal swab testing, but suboptimal sensitivity for SARS-CoV-2 detection compared to bronchoalveolar lavage (BAL) may lead to misdiagnosis in some cases. Such diagnostic issues were described in a few MS patients receiving anti-CD20 mAbs, including middle-aged people and lacking information on subsequent MS therapeutic management, a debated topic as no evidence-based guidance on de-risking strategies is currently available. Here, we report the case of a young MS patient who developed severe COVID-19 pneumonia under treatment with the anti-CD20 mAb ocrelizumab, and who was finally diagnosed with SARS-CoV-2 by BAL despite repeatedly negative nasopharyngeal swabs. Ocrelizumab was then discontinued, and treatment with a sphingosine-1 phosphate receptor modulator was started, followed by maintenance of clinical and radiological MS stability. Challenges in diagnosing COVID-19 pneumonia in people without risk factors other than immunomodulatory treatment are hence discussed, as well as potential strategies for de-risking MS therapies. The latter topic is increasingly debated based on raising concerns for potential long-term safety issues of high-efficacy treatments, including anti-CD20 mAbs. [ABSTRACT FROM AUTHOR]

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. Summary: 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. [ABSTRACT FROM AUTHOR]

This article examines the stability of ocrelizumab, a medication used to treat multiple sclerosis, when blood samples are delayed in centrifugation. The study finds that delaying centrifugation for up to 24 hours at room temperature does not significantly impact the concentration of ocrelizumab in the serum. This research is important for evaluating the feasibility of in-home blood collection for patients with mobility disabilities, as it can improve convenience and adherence to treatment. While the findings suggest that in-home collection may be applicable to other similar medications, further studies are needed for confirmation. [Extracted from the article]

Background: Clinical trials comparing the efficacy of ocrelizumab (OCR) with other disease-modifying therapies (DMTs) other than interferon (IFN) β-1a in relapsing multiple sclerosis (RMS) are lacking. Objectives: To compare the treatment effect of OCR vs six DMTs' (IFN β-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) [ABSTRACT FROM AUTHOR]

Abstract 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.