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Comparative Study
. 2025 Mar;97(3):583-595.
doi: 10.1002/ana.27143. Epub 2024 Nov 25.

Different Treatment Outcomes of Multiple Sclerosis Patients Receiving Ocrelizumab or Ofatumumab

Sven G Meuth  1 , Stephanie Wolff  2 , Anna Mück  2 , Alice Willison  1 , Konstanze Kleinschnitz  3 , Saskia Räuber  1 , Marc Pawlitzki  1 , Franz Felix Konen  4 , Thomas Skripuletz  4 , Matthias Grothe  5 , Tobias Ruck  1 , Hagen B Huttner  2 , Christoph Kleinschnitz  3 , Tobias Bopp  6   7 , Refik Pul  3 , Bruce A C Cree  8 , Hans-Peter Hartung  1 , Kathrin Möllenhoff  9   10 , Steffen Pfeuffer  2
Affiliations
Comparative Study

Different Treatment Outcomes of Multiple Sclerosis Patients Receiving Ocrelizumab or Ofatumumab

Sven G Meuth et al. Ann Neurol. 2025 Mar.

Abstract

Objective: B-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.

Methods: This 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.

Results: A 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.

Conclusion: We 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.

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Conflict of interest statement

Relevant entities are Roche (market authorization holder for ocrelizumab) and Novartis (ofatumumab). S.G.M.: honoraria for lecturing, travel expenses for attending meetings and financial research support from Novartis and Roche. S.W.: honoraria for lecturing and research grants from Novartis. S.R.: research grants from Novartis. M.P.: honoraria for lecturing and travel expenses for attending meetings from Novartis and Roche. F.K.: travel grants from Novartis. T.S.: honoraria for lecturing, travel expenses for attending meetings and financial research support from Novartis and Roche. M.G.: honoraria for lecturing, travel expenses for attending meetings and financial research support from Novartis and Roche. T.R.: honoraria for lecturing and travel expenses for attending meetings and financial research from Roche. H.B.H.: financial research support from Novartis. C.K.: honoraria for lecturing, travel expenses for attending meetings and financial research support from Novartis and Roche. R.P.: honoraria for lecturing, travel expenses for attending meetings and financial research support from Novartis and Roche. H.P.H.: honoraria for lecturing and travel expenses for attending meetings from Novartis and Roche. B.A.C.: honoraria for lecturing and travel expenses for attending meetings from Novartis. S.P.: honoraria for lecturing, travel expenses for attending meetings and financial research support from Novartis and Roche. The remaining authors have nothing to report.

Figures

Figure 1
Figure 1
Flowchart depicting the composition of the study cohort. BCT, B‐cell–depleting therapy; IRT, immune reconstitution therapy (alemtuzumab, cladribine); OCR, ocrelizumab; OFA, ofatumumab; SPMS, secondary progressive multiple sclerosis. Among patients with previous BCT, 5 patients switched from rituximab to OCR, whereas 40 patients switched from OCR to OFA. Among patients with previous exposure to IRT, 1 patient was previously treated with alemtuzumab, and 4 patients were previously treated with cladribine.
Figure 2
Figure 2
Treatment outcomes of ofatumumab (OFA) vs. ocrelizumab (OCR) patients. (A−C) Kaplan–Meier plots indicating proportion of patients without a clinical MS relapse (REL; A), new or enlarging T2‐hyperintense MRI lesions (new/enl T2L; B), and 3‐months confirmed worsening of disability (CDW; C). Patients at risk are indicated below the respective plots. (D−F) Non‐inferiority analysis regarding the respective endpoints. Solid red lines indicate the non‐inferiority margin of Δ = 0.15; dashed lines indicate Δ = 0.10. [Color figure can be viewed at www.annalsofneurology.org]
Figure 3
Figure 3
Treatment outcomes among ofatumumab (OFA) vs. ocrelizumab (OCR) patients who were either previously treatment‐naïve or received platform treatment. (A) Kaplan–Meier‐plots indicating proportion of previously naïve patients without a clinical MS relapse (REL), new or enlarging T2‐hyperintense MRI lesions (new/enl T2L), and 3‐months confirmed worsening of disability (CDW). Patients at risk are indicated below the respective plots. (B) Non‐inferiority analysis regarding the respective endpoints. (C) Kaplan–Meier plots indicating the above‐mentioned treatment outcomes among patients switching from platform treatment to OFA or OCR. (D) Non‐inferiority analysis regarding the respective endpoints. Solid red lines indicate the non‐inferiority margin of Δ = 0.15; dashed lines indicate Δ = 0.10 (B and D). [Color figure can be viewed at www.annalsofneurology.org]
Figure 4
Figure 4
Treatment outcomes among ofatumumab (OFA) vs. ocrelizumab (OCR) among patients switching from S1P receptor modulators (S1PRM) or natalizumab (NTZ). (A) Kaplan–Meier plots indicating proportion of previously fingolimod‐treated patients without a clinical MS relapse (REL), new or enlarging T2‐hyperintense MRI lesions (T2L), and 3‐months confirmed worsening of disability (CDW). Patients at risk are indicated below the respective plots. (B) Non‐inferiority analysis regarding the respective endpoints. (C) Kaplan–Meier plots indicating the above‐mentioned treatment outcomes among patients switching from NTZ treatment to OFA or OCR. (D) Non‐inferiority analysis regarding the respective endpoints. Solid red lines indicate the non‐inferiority margin of Δ = 0.15; dashed lines indicate Δ = 0.10 (B and D). NTZ, natalizumab; S1PRM, S1P receptor modulator. [Color figure can be viewed at www.annalsofneurology.org]
Figure 5
Figure 5
Evaluation of CD19+ B cells in the peripheral blood. CD19+ B cells prior to treatment initiation were assessed on the day of first treatment before first infusion/injection. Follow‐up assessments were made prior to next scheduled drug administration. Numbers below the graph represent sample sizes. OCR, ocrelizumab; OFA, ofatumumab. [Color figure can be viewed at www.annalsofneurology.org]
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