This week we had the suggestion that there were more infections in people treated with rituximab than oreclizumab, I suggested that there wre differences in the way that rituximab kill B cells and I also suggested that people got a third more rituximab than ocrelizumab and that it may travel round the body and you then said that the double dose study with ocrelizumab has failed to show differences between the doses. So that was a good point.
Here is a head to head study of rituximab and ocrelizumab
Abstract Number: 1617/P1630 Abstract Number: 1617/P1630 Head to head comparison of B cell depletion with rituximab and ocrelizumab: efficacy, side effects, impact on immune cells and immunoglobulins. Head to head comparison of B cell depletion with rituximab and ocrelizumab: efficacy, side effects, impact on immune cells and immunoglobulins Jakob Stögbauer * et al.
Introduction: The principle of anti-CD20-based B-cell depletion is widely used in neuroimmunology. The parent compound rituximab continues to be used in a wide range of less well characterised antibody-mediated diseases. Ocrelizumab is used to treat relapsing forms of MS (RMS) and primary progressive MS (PPMS). In addition to the desired immunosuppression, there is an increased susceptibility to infection due the changes in the humoral and cellular immune response. Nevertheless, there is a paucity of head-to-head comparisons between the various substances.
Objectives/Aims: Our aim was to compare both substances with regard to paraclinical events and changes in immune cells and antibody titres over a period of several years.
Methods: 166 patients (139 RMS, 27 PPMS) treated with ocrelizumab and 52 patients treated with rituximab (including vasculitis, autoimmune encephalitis, neuromyelitis optica spectrum disease) were followed up for a median of 39 and 42 months respectively. During this period, clinical data (occurrence of relapses, infections, malignancies) were observed. The cellular immunity parameters (lymphocytes, granulocytes, basophils, eosinophils, natural killer cells, T cells, CD19+ B cells, CD4+ T cells and CD8+ T cells) were measured using flow cytometry on a semi-annual basis. In addition, the levels of immunoglobulins were measured.
Results: The patients in the rituximab group were older (mean ± SD: 53 ± 15 versus 46 ± 12) and had more comorbidities than those in the ocrelizumab group. There were no significant treatment-related changes in the T or NK cells in the group comparison. The median B-cell count was consistently 0 in both groups, but there were significantly more patients without complete B-cell depletion in the rituximab group. (So would this explain the suggestion that ocrelizumab is more effective than rituximab, but why would it cause more infections than ocrelizumab. This is having your cake and eating it), Despite this, there was treatment-related IgM hypogammaglobulinaemia in this group (p = 0.005), which was significantly more pronounced than in the ocrelizumab group. (So there is loss of cells giving the first line of defence against infection. This could explain the increased infection risk). This effect could not be demonstrated for IgG (Loss of IgM happens quickly after treatment onset but loss of IgG takes years) Conclusion: Overall, B cell depletion was well tolerated and treatment adherence was high in both groups. There were few relevant changes in the immune cells. Over a period of more than 3 years, however, rituximab appears to lead to significantly greater IgM hypogammaglobulinaemia. It can be hypothesised that other, primarily IgM producing B cells are affected here than under treatment with ocrelizumab. This may be helpful for future therapy selection.
So does this mean that rituximab is hitting the cells that will produce antibody like the transitional/naive B cells which are depleted but typically repopulate the quickest.
Abstract Number: 2039/P361 Abstract Number:
Extended Versus Standard Interval Dosing of Ocrelizumab in MS: Meta-Analysis with Meta-regression Alessandro Cruciani et al.
Introduction: Ocrelizumab is a high efficacy therapy licensed for treatment of both RRMS and PPMS. Long-term studies confirm its sustained efficacy, though it carries risks such as infections and hypogammaglobulinemia. In the context of the COVID-19 pandemic, extended interval dosing (EID) was occasionally adopted, offering realworld insights into its safety and effectiveness. Objectives/Aims: Objectives/Aims: This meta-regression analysis aims to compare treatment outcomes between patients on a standard interval dosing (SID) and those on EID.
Methods: We searched scientific databases (PubMed/MEDLINE, Scopus and Google Scholar) to identify real-world studies published until 31 March, 2025 according to the following PICOS framewok: Population (P): adult persons (aged ≥ 18 years) with MS; Intervention (I): ocrelizumab EID; Comparison (C): ocrelizumab SID; Outcomes (O): risk of relapse, confirmed disability worsening (CDW), new or enhancing lesions on brain magnetic resonance imaging (MRI), and B-cell depletion rate (defined as proportion of patients with < 10 cells/μL); Setting (S): real-world setting. We fitted inverse-variance weighted meta-analyses with random effects models to estimate the odds ratio (OR) for the aforementioned outcomes
Results: Our search retrieved 90 articles; after an independent screening, 13 articles (all observational studies) met the eligibility criteria. We extracted data of patients treated with ocrelizumab on EID (n = 1494) or SID (n = 1517) followed for a median time of 10 (interval 5 to 36) months, yielding 2195 patient-years on EID and 1943 patient-years on SID. The mean (SD) delay on EID compared to SID was 15 (6) weeks. There was no difference in the number of patients experiencing relapse (OR = 0.82, 95 CI% 0.58 to 1.17 p = 0.28; k = 13), disability worsening (OR = 1.10, 95 CI% 0.75 to 1.63, p = 0.61; k = 10), and MRI activity (OR = 0.84, 95 CI% 0.61 to 1.15, p = 0.27; k = 13). between EID and SID. We observed no statistical heterogeneity in all the clinical outcomes across included studies. Visual inspection of Funnel plots revealed no publication bias. B-cell depletion rates were lower on EID than on SID (OR = 0.29, 95% CI 0.12 to 0.68, p = 0.005; k = 9), with substantial heterogeneity (tau-squared = 1.49, I-squared = 94.6%). A meta-regression analysis showed a reduced B-depletion rate on EID than SID in studies with longer extended intervals between infusions.
Conclusion: Our findings suggest that extending the ocrelizumab interval dosing does not impact the clinical effectiveness of ocrelizumab, despite being associated with lower frequency of B-cell depletion. Ongoing non inferiority trials are comparing 6-monthly vs 12-monthly intervals of ocrelizumab
Disclaimer my views alone
Source: multiple-sclerosis-research.org