Prolonged SARS-CoV-2 Illness in a Patient Receiving Ocrelizumab for Multiple Sclerosis.
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ABSTRACT:
SUBMITTER: Gibson EG
PROVIDER: S-EPMC8083367 | biostudies-literature | 2021 Jul
REPOSITORIES: biostudies-literature
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Prolonged SARS-CoV-2 Illness in a Patient Receiving Ocrelizumab for Multiple Sclerosis.
Gibson Elena G EG Pender Melissa M Angerbauer Michael M Cook Craig C Jones Barbara B Spivak Adam M AM Spivak Emily S ES Swaminathan Sankar S
Open forum infectious diseases 20210408 7
We describe a case of prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a patient receiving ocrelizumab for multiple sclerosis. Viral RNA shedding, signs, and symptoms persisted for 69 days with resolution after administration of convalescent plasma and antiviral therapy. This case suggests risk for persistent SARS-CoV-2 infection in patients treated with anti-CD-20 monoclonal antibodies and supports a role for humoral immunity in disease resolution. ...[more]
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Project description:ObjectiveB-cell-depletion via CD20 antibodies is a safe and effective treatment for active relapsing multiple sclerosis (RMS). Both ocrelizumab (OCR) and ofatumumab (OFA) have demonstrated efficacy in randomized controlled trials and are approved for treatment of RMS, yet nothing is known on their comparative effectiveness, especially in the real-world setting.MethodsThis prospective cohort study includes patients that were started on either OCR or OFA between September 2021 and December 2023. Patients were followed until June 2024 and recruited at 3 large tertiary centers in Germany (Duesseldorf, Essen, and Giessen). Propensity-score-matching was used to address baseline imbalances among patients. Clinical relapses, presence of new or enlarging MRI lesions and 6-month confirmed disability worsening were evaluated. Non-inferiority of OFA compared to OCR was evaluated through comparison of Kaplan-Meier-estimates.ResultsA total of 1,138 patients were initially enrolled in the cohort. Following patient selection and propensity-score-matching, 544 OCR and 417 OFA patients were included in the final analysis. In our primary analysis, OFA was non-inferior to OCR in terms of relapses, disability progression, and accrual of MRI lesions. Subgroup analyses confirmed findings in previously naïve and platform-treated patients. Potential differences between OFA and OCR were seen in patients switching from S1P receptor modulators or natalizumab.ConclusionWe here provide comparative data on the effectiveness of OCR and OFA in patients with active RMS. OFA was non-inferior to OCR in the overall cohort. Potential differences observed in patients switching from S1P receptor modulators or natalizumab require further validation. ANN NEUROL 2025;97:583-595.
| S-EPMC11831887 | biostudies-literature
Project description:BackgroundThe COVID-19 epidemic raises important questions about the efficacy of vaccines for people treated with ocrelizumab, an anti-CD20 therapy. Ocrelizumab has been shown to reduce the humoral response to SARS-CoV-2 infection and vaccination, but the T-cell response to vaccination has not been fully characterized. We sought to provide data regarding B and T-cell mediated responses to SARS-CoV-2 vaccination in ocrelizumab-treated patients, and to determine what variables correlate with vaccine immunogenicity. We hypothesized that patients without a humoral response to SARS-CoV-2 vaccination would still have intact T-cell responses.MethodsWe conducted a prospective, observational, single center cohort study of patients with MS treated with either ocrelizumab or natalizumab as a comparator between March 2, 2021, and July 1, 2021. Eligible patients were age 18 to 55 and had no known prior infection with, or vaccination against, SARS-CoV-2. Patients with prior use of immunosuppressive or chemotherapeutic agents, or treatment with any anti-CD20 therapy other than ocrelizumab within 12 months of enrollment, were excluded. The Roche Elecsys anti-SARS-CoV-2 S immunoassay was performed prior to and 3-4 weeks post vaccination to evaluate the antibody response to SARS-CoV-2 spike IgG. The Adaptive Biotechnologies T-Detect COVID Test was performed to evaluate the adaptive T-cell immune response to SARS-CoV-2 in OCR-treated patients with no detectable antibodies. Data were analyzed using descriptive statistics, Fisher's exact test, and Wilcoxon rank sum.ResultsForty-eight patients were enrolled in the study, 69% treated with ocrelizumab and 31% treated with natalizumab. Eighteen percent of ocrelizumab and 100% of natalizumab patients had a positive antibody response. In ocrelizumab-treated patients, there was no correlation between age, sex, BMI, total number of infusions, immunoglobulin G, CD19, or absolute lymphocyte count and antibody response. There was a trend suggesting that a longer interval between the last infusion and vaccination increased the likelihood of producing antibodies (P = 0.062). All ocrelizumab patients with negative antibody responses had positive T-cell responses.ConclusionsTreatment with ocrelizumab substantially impaired the humoral response to SAR-CoV-2 vaccination but did not impair T-cell responses. Further research is needed to determine if the T-cell response to SARS-CoV-2 vaccination is sufficient to prevent infection or reduce severity of COVID in patients who did not produce antibodies.
| S-EPMC8575541 | biostudies-literature
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| S-EPMC8461553 | biostudies-literature
Project description:BackgroundOcrelizumab maintains B-cell depletion via six-monthly dosing. Whilst this controls relapsing multiple sclerosis, it also inhibits seroconversion following SARS-CoV-2 vaccination unlike that seen following alemtuzumab and cladribine treatment. Emerging reports suggest that 1-3% B-cell repopulation facilitates seroconversion after CD20-depletion.ObjectiveTo determine the frequency of B-cell repopulation levels during and after ocrelizumab treatment.MethodsRelapse data, lymphocyte and CD19 B-cell numbers were obtained following requests to clinical trial data-repositories. Information was extracted from the phase II ocrelizumab extension (NCT00676715) trial and the phase III cladribine tablet (NCT00213135) and alemtuzumab (NCT00530348/NCT00548405) trials obtained clinical trial data requests RESULTS: Only 3-5% of people with MS exhibit 1% B-cells at 6 months after the last infusion following 3-4 cycles of ocrelizumab, compared to 50-55% at 9 months, and 85-90% at 12 months. During this time relapses occurred at consistent disease-breakthrough rates compared to people during standard therapy. In contrast most people (90-100%) exhibited more than 1% B-cells during treatment with either cladribine or alemtuzumab.ConclusionsMost people demonstrate B cell repletion within 3 months of the last treatment of alemtuzumab and cladribine. However, few people repopulate peripheral B-cells with standard ocrelizumab dosing. Controlled studies are warranted to examine a view that delaying the dosing interval by 3-6 months may allow more people to potentially seroconvert after vaccination.
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Project description:ObjectiveThis study aimed to evaluate safety (infusion-related reactions [IRRs]) and patient satisfaction (patient-reported outcomes [PROs]) for at-home ocrelizumab administration for patients with multiple sclerosis (MS).MethodsThis open-label study included adult patients with an MS diagnosis who had completed a ≥ 600-mg ocrelizumab dose, had a patient-determined disease steps score of 0 to 6 and had completed PROs. Eligible patients received a 600-mg ocrelizumab home-based infusion over 2 h, followed by 24-h and 2-week post-infusion follow-up calls. IRRs and adverse events (AEs) were documented during infusions and follow-up calls. PROs were completed before and 2 weeks post infusion.ResultsOverall, 99 of 100 expected patients were included (mean [SD] age, 42.3 [7.7] years; 72.7% female; 91.9% White). The mean (SD) infusion time was 2.5 (0.6) hours, and 75.8% of patients completed their ocrelizumab infusion between 2 to 2.5 h. The IRR incidence rate was 25.3% (95% CI: 16.7%, 33.8%)-similar to other shorter ocrelizumab infusion studies-and all AEs were mild/moderate. In total, 66.7% of patients experienced AEs, including itch, fatigue, and grogginess. Patients reported significantly increased satisfaction with the at-home infusion process and confidence in the care provided. Patients also reported a significant preference for at-home infusion compared with prior infusion center experiences.InterpretationIRRs and AEs occurred at acceptable rates during in-home infusions of ocrelizumab over a shorter infusion time. Patients reported increased confidence and comfort with the home infusion process. Findings from this study provide evidence of the safety and feasibility of home-based ocrelizumab infusion over a shorter infusion period.
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