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. 2025 Aug;31(9):1110-1120.
doi: 10.1177/13524585251361330. Epub 2025 Jul 30.

Disease outcomes following lateral switch among different CD20-antibodies in active multiple sclerosis

Franziska Axhausen  1 , Anne Mrochen  1 , Pia Winter  1 , Romy Baumgart  1 , Pauline Mühlenbrock  1 , Anna Mück  1 , Stephanie Wolff  1 , Sven G Meuth  2 , Kathrin Möllenhoff  3 , Steffen Pfeuffer  1
Affiliations

Disease outcomes following lateral switch among different CD20-antibodies in active multiple sclerosis

Franziska Axhausen et al. Mult Scler. 2025 Aug.

Abstract

Background: Ocrelizumab (OCR) and ofatumumab (OFA)are approved and their differences in dosing route and interval allow personalized treatment. However, there are no data on whether lateral switches between both substances affect treatment effectiveness or safety.

Methods: We screened our local cohort of MS patients, who began OCR since 09/2020 or OFA since 09/2021. Patients with a lateral switch were matched to controls who continuously received initial B-cell depleting therapy (BCT). We compared disease courses including effectiveness outcomes as well as peripheral CD19+ B-cell counts and serum IgG levels.

Results: From 09/2020 to 03/2024, 713 patients were subjected to BCT (OCR: 396; OFA: 317 [as in Fig.1]). The matched OCR cohort included 38 switchers and 149 controls. The OFA cohort consisted of 24 switchers and 83 controls. Effectiveness outcomes were comparable among switchers and controls. B cell depletion appeared slightly pronounced following a switch. Serum IgG levels declined faster among switchers compared to controls (OCR: 9.7 vs 9.0 g/L; p = 0.007; manifest hypogammaglobulinemia (HGG) in 13.2% vs 6.0%; OFA: 9.7 vs 8.4 g/L; p = 0.016; manifest HGG in 8.3% vs 2.4%).

Conclusions: Lateral switching between BCT does not abate effectiveness in this matched real-world cohort. Our observation of increased loss of IgG warrants further validation, but may indicate niche-specific immunological effects of OFA and OCR.

Keywords: Multiple sclerosis; hypogammaglobulinemia; lateral switch; ocrelizumab; ofatumumab.

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Conflict of interest statement

Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Franziska Axhausen: declares no conflicts of interest.Anne Mrochen: received honoraria for lecturing and consulting from Alexion and Roche and travel reimbursements from Alexion.Pia Winter: declares no conflicts of interest.Romy Baumgart: received travel reimbursements from Sanofi-Aventis.Pauline Mühlenbrock: declares no conflicts of interest.Anna Mück: declares no conflicts of interest.Hagen B. Huttner: declares no conflicts of interest.Stephanie Wolff: received honoraria for lecturing from Mylan and Novartis and received research support from Novartis.Sven G. Meuth: received honoraria for lecturing, travel expenses and for attending meetings from Academy 2, Argenx, Alexion, Almirall, Amicus Therapeutics Germany, AstraZeneca, Bayer Health Care, Biogen, BioNtech, BMS, Celgene, Datamed, Demecan, Desitin, Diamed, Diaplan, DPmed, Gen Medicine and Healthcare products, Genzyme, Hexal AG, IGES, Impulze GmbH, Janssen Cilag, KW Medipoint, MedDay Pharmaceuticals, Medmile, Merck Serono, MICE, Mylan, Neuraxpharm, Neuropoint, Novartis, Novo Nordisk, ONO Pharma, Oxford PharmaGenesis, QuintilesIMS, Roche, Sanofi, STADA, Chugai Pharma, Teva, UCB, Viatris, Wings for Life international and Xcenda. He received research support from Alexion, Almirall, Amicus Therapeutics Germany, Argenx, Bayer Vital GmbH, BGP Products Operations (Viatris Company), Biogen, BMS, Demecan, Diamed, Fresenius Medical Care, Genzyme, HERZ Burgdorf, Hexal, Janssen, Merck Serono, Novartis, Novo Nordisk Pharma, ONO Pharma, Roche and Teva.Kathrin Möllenhoff: declares no conflicts of interest.Steffen Pfeuffer: received honoraria for lecturing and consulting from argenx, Sanofi-Avents, Merck Healthcare, Biogen, Novartis Pharma, Roche, Alexion and Hexal, travel reimbursements from Sanofi-Aventis, Merck Healthcare, Novartis Pharma, Roche, and Biogen, and research funding from Merck Healthcare, Novartis Pharma and Biogen.

Figures

The image compares the development of two cohorts, OCR and OFA, in a study. The OCR cohort, focused on ocrelizumab, initially had 396 individuals, with 30 excluded for various reasons, leading to 366 included and 328 with a control group. The OFA cohort, with ofatumumab, had 317 individuals, with 9 exclusions, resulting in 308 included and 284 with a control group. Both cohorts underwent propensity score matching, with the OCR cohort seeing 38 individuals matched to the control group and 149 for the treatment group, while the OFA cohort matched 24 individuals to the control group and 83 to the treatment group. EID refers to extended interval dosing, SPMS to secondary progressive multiple sclerosis, BCT to B-cell therapy, IRT to immune reconstitution therapy.
Figure 1.
Development of both cohorts that were analyzed in this study. Left column displays the “OCR cohort”; right column displays the “OFA cohort.” All comparisons were made within cohorts. OCR: ocrelizumab; OFA: ofatumumab. SPMS: secondary progressive multiple sclerosis; BCT: B-cell therapy; IRT: immune reconstitution therapy. EID: extended interval dosing. PSM: propensity score matching (here: patients included in the respective cohorts following PSM).
Effectiveness and timing outcomes of ocrelizumab switch in patient cohort. A: Switch reasons; B: time to first ofatumumab dose; C: switch vs control time to first IDA; D: switch vs control time to first 6-mo CDW. IAR, AE, IDA.
Figure 2.
Effectiveness outcomes and conditions of the treatment switch in the ocrelizumab cohort. A: Reasons for treatment switch from ocrelizumab to ofatumumab. B: time from last dose of ocrelizumab to first dose of ofatumumab among switch patients. C: Kaplan-Meier plots for time to first IDA among switch and control patients. Significance was determined using a log-rank test. Numbers at risk are indicated below the plot. D: Kaplan-Meier plots for time to first (6 months) CDW. IAR: infusion-associated reaction; AE: adverse event; pat.pref: patient preference; IDA: inflammatory disease activity; CDW: confirmed worsening of disability.
Effectiveness outcomes and conditions of the treatment switch in the ofatumumab cohort. A: Reasons for treatment switch from ofatumumab to ocrelizumab. B: time from last dose of ofatumumab to first dose of ocrelizumab among switch patients. C: Kaplan-Meier plots for time to first IDA among switch and control patients. Significance was determined using a log-rank test. Numbers at risk are indicated below the plot. D: Kaplan-Meier plots for time to first (6 months) CDW. IAR: infusion-associated reaction; AE: adverse event; pat.pref: patient preference; IDA: inflammatory disease activity; CDW: confirmed worsening of disability.
Figure 3.
Effectiveness outcomes and conditions of the treatment switch in the ofatumumab cohort. A: Reasons for treatment switch from ofatumumab to ocrelizumab. B: time from last dose of ofatumumab to first dose of ocrelizumab among switch patients. C: Kaplan-Meier plots for time to first IDA among switch and control patients. Significance was determined using a log-rank test. Numbers at risk are indicated below the plot. D: Kaplan-Meier plots for time to first (6 months) CDW. IAR: infusion-associated reaction; AE: adverse event; pat.pref: patient preference; IDA: inflammatory disease activity; CDW: confirmed worsening of disability.
“Long-term effects of crelizumab and ofatumumab on CD19+ B cells and serum IgG levels.”
Figure 4.
Peripheral CD19+ B cells and serum IgG levels among both cohorts. A: Development of peripheral CD19+ B cells among the ocrelizumab cohort. Numbers at risk are indicated below the respective time points. Data are shown as mean ± standard deviation. B: Development of peripheral CD19+ B cells among the ofatumumab cohort. C: Serum IgG levels among the ocrelizumab cohort. The dot plot below indicates time point of drug switch toward ofatumumab within the switch cohort. Numbers at risk are indicated below the respective time points. D: Serum IgG levels among the ofatumumab cohort. OCR: ocrelizumab; OFA: ofatumumab; IgG: Immunoglobulin G.
See this image and copyright information in PMC

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