Extended interval dosing with ocrelizumab in multiple sclerosis

Multiple Sclerosis Journal, Journal Year: 2024, Volume and Issue: 30(7), P. 847 - 856

Published: April 22, 2024

Background: This study investigates clinical and biomarker differences between standard interval dosing (SID) extended (EID) of ocrelizumab therapy in multiple sclerosis (MS). Methods: is a prospective, double-arm, open-label, multi-center Denmark. Participants diagnosed with MS on >12 months were included ( n = 184). Clinical, radiological, blood-based outcomes evaluated. MRI disease activity, relapses, worsening neurostatus, No Evidence Disease Activity-3 (NEDA-3) used as combined endpoint. Results: Out 184 participants, 107 participants received EID (58.2%), whereas 77 SID (41.8%). The average extension was 9 weeks maximum 78 weeks. When comparing to SID, we found higher levels B-cells, lower serum concentrations ocrelizumab, similar age-adjusted NFL GFAP the two groups. difference NEDA-3 demonstrated (hazard ratio: 1.174, p 0.69). Higher identified activity. Body mass index correlated B-cells. Conclusion: Extending one treatment up did not result clinical, or evidence compared SID.

Language: Английский

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T cell activation markers CD38 and HLA-DR indicative of non-seroconversion in anti-CD20-treated patients with multiple sclerosis following SARS-CoV-2 mRNA vaccination

Journal of Neurology Neurosurgery & Psychiatry, Journal Year: 2024, Volume and Issue: 95(9), P. 855 - 864

Published: March 28, 2024

Background Messenger RNA (mRNA) vaccines provide robust protection against SARS-CoV-2 in healthy individuals. However, immunity after vaccination of patients with multiple sclerosis (MS) treated ocrelizumab (OCR), a B cell-depleting anti-CD20 monoclonal antibody, is not yet fully understood. Methods In this study, deep immune profiling techniques were employed to investigate the response induced by mRNA untreated MS (n=21), OCR-treated (n=57) and individuals (n=30). Results Among MS, 63% did produce detectable levels antibodies (non-seroconverted), those who have lower spike receptor-binding domain-specific IgG responses compared MS. Before vaccination, no discernible immunological differences observed between non-seroconverted seroconverted received overall more OCR infusions, had shorter intervals since their last infusion displayed higher serum concentrations at time initial vaccination. Following two vaccinations, smaller cell compartments but instead exhibited activation general CD4 + CD8 T compartments, as indicated upregulation CD38 HLA-DR surface expression, when patients. Conclusion These findings highlight importance optimising treatment regimens scheduling for maximise humoral cellular responses. This study provides valuable insights strategies including identification potential markers explore vaccine efficacy non-seroconverting

Language: Английский

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Evolution of SARS-CoV-2 antibody repertoire after successive mRNA vaccinations under immunosuppressive treatment

EBioMedicine, Journal Year: 2025, Volume and Issue: 113, P. 105620 - 105620

Published: Feb. 25, 2025

Language: Английский

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Ocrelizumab concentration and antidrug antibodies are associated with B-cell count in multiple sclerosis

Journal of Neurology Neurosurgery & Psychiatry, Journal Year: 2023, Volume and Issue: 94(6), P. 487 - 493

Published: Jan. 24, 2023

Background The majority of patients with multiple sclerosis on ocrelizumab have B-cell depletion after standard interval dosing 26 weeks. With B-cell-guided receive their next dose when repopulation occurs. Prediction using concentrations could aid in personalising treatment regimes. objectives this study were to evaluate the association between drug concentration, antidrug antibodies (ADAs) and CD19 count, define a cut-off concentration for start (defined by ≥10 CD19+ B cells/µL). Methods In investigator-initiated prospective study, blood samples at various time points during collected from biobank. Serum ADAs measured two different assays developed study. Data analysed linear mixed effect models. An receiver operating characteristic (ROC) curve was used determine Results A total 452 72 analysed. Ocrelizumab detectable up until 53.3 weeks last infusion ranged <0.0025 204 µg/mL 1–67 negatively associated body mass index identified as modifier. We found value 0.06 cells/µL. four (5.7%) corresponding low repopulation. Conclusions strongly count. Measurement play an important role further personalise predict

Language: Английский

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SARS-CoV-2-Specific Immune Cytokine Profiles to mRNA, Viral Vector and Protein-Based Vaccines in Patients with Multiple Sclerosis: Beyond Interferon Gamma

Vaccines, Journal Year: 2024, Volume and Issue: 12(6), P. 684 - 684

Published: June 19, 2024

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 elucidate characteristics of involved antigen-specific T cells via measurement broad cytokine profiles pwMS on various DMTs. We examined SARS-CoV-2-specific cell responses whole blood cultures characterized by release 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 antibodies (AB) targeting SARS-CoV-2 spike protein following either two or three doses mRNA viral vector (VVV). For vaccination non-responders, NVX-CoV2373 protein-based vaccine was administered, were evaluated. Our findings indicate that are skewed towards a Th1 phenotype, IL-2 IFN-γ. Additionally, Th2 lesser extent is observed. Therefore, IL-5 levels could complement traditional IFN-γ assays more comprehensively characterize vaccines. results provide comprehensive profile for receiving different DMTs offer valuable insights designing strategies patient population.

Language: Английский

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Humoral and cellular immune response from first to fourth SARS-CoV-2 mRNA vaccination in anti-CD20-treated multiple sclerosis patients—a longitudinal cohort study

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 5, 2024

This study examines the humoral and cellular response in multiple sclerosis (MS) patients on anti-CD20 therapy before after 1st to 4th BNT162b2 mRNA SARS-CoV-2 vaccination relationship with breakthrough infection.

Language: Английский

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Humoral and cellular responses to repeated COVID-19 exposure in multiple sclerosis patients receiving B-cell depleting therapies: a single-center, one-year, prospective study

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: June 28, 2023

Multiple sclerosis patients treated with anti-CD20 therapy (aCD20-MS) are considered especially vulnerable to complications from SARS-CoV-2 infection due severe B-cell depletion limited viral antigen-specific immunoglobulin production. Therefore, multiple vaccine doses as part of the primary vaccination series and booster updates have been recommended for this group immunocompromised individuals. Even though much less studied than antibody-mediated humoral responses, T-cell responses play an important role against CoV-2 induced efficiently in vaccinated aCD20-MS patients. For individuals such decoupled adaptive immunity, understanding contribution mediated immunity is essential better assess protection infection. Here, we present results a prospective, single-center study assessment cellular immune (203 donors/350 samples) compared healthy control (43/146) after initial exposure spike antigen subsequent re-challenges. Low rates seroconversion RBD-hACE2 blocking activity were observed patients, even exposures (responders 1st = 17.5%; 2nd 29.3%). Regarding increase number spike-specific monofunctional IFNγ

Language: Английский

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A Liquid Chromatography - Tandem Mass Spectrometry Method for Determination of Ocrelizumab in Serum of Patients with Multiple Sclerosis

Published: Jan. 1, 2024

Language: Английский

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A liquid chromatography - tandem mass spectrometry method for determination of ocrelizumab in serum of patients with multiple sclerosis

Talanta, Journal Year: 2024, Volume and Issue: 283, P. 127111 - 127111

Published: Oct. 30, 2024

Language: Английский

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Clinical and humoral response after SARS-CoV-2 breakthrough infection in patients receiving immunosuppressant therapy

Journal of Allergy and Clinical Immunology, Journal Year: 2024, Volume and Issue: 154(3), P. 754 - 766.e7

Published: May 17, 2024

Background Despite impaired humoral responses in patients treated with immunosuppressants (ISPs), recent studies found similar severity of SARS-CoV-2 breakthrough infections compared to controls. One potential explanation is the rapid generation upon infection, but evidence lacking. Objectives To investigate longitudinal dynamics antibody repertoire after delta and omicron immune-mediated inflammatory diseases (IMID) on ISPs Methods As prospective sub-study national Target-to-B! (T2B!) consortium, we included IMID controls who reported between July 1, 2021, April 2022. get an impression repertoire, three titers wild-type RBD, S, RBD were measured at four time points infections. Results We 302 178 Antibody increased up 28 days both groups. However, anti-CD20 therapy sphingosine-1 phosphate receptor (S1P) modulators, considerably lower In anti-TNF group, observed slightly early stages a faster decline antibodies infection Breakthrough mostly mild hospitalization was required less than 1% cases. Conclusions Most do not influence exhibit recall response cross-reactive clones towards new viral variants. or S1P greatly impaired, lesser extent those anti-TNF. Nevertheless, only few severe cases reported.

Language: Английский

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