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Peer-reviewedCC BY 4.0Journal of Clinical Medicine

Rituximab and Ocrelizumab in Multiple Sclerosis: Does Comparative Evidence Redefine Anti-CD20 Therapy?

  • Valentino Rački1
  • Andrej Belančić2
  • Almir Fajkić3
  • Slobodan Janković4
4 affiliations
  1. 1Department of Neurology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia
  2. 2Department of Basic and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia
  3. 3Department of Pathophysiology, Faculty of Medicine, University of Sarajevo, 71000 Sarajevo, Bosnia and Herzegovina
  4. 4Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia
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Abstract

B-cell depletion has transformed multiple sclerosis treatment, with rituximab and ocrelizumab providing highly effective CD20-directed therapy. This narrative review aims to critically compare these agents from the mechanistic, clinical, safety, regulatory, and economic perspectives. Despite their shared target, differences in pharmacology, dosing, regulatory status, and cost may influence treatment selection. Observational studies generally suggest similar effectiveness, although interpretation is limited by confounding and heterogeneous treatment strategies. The randomized, double-blind OVERLORD-MS trial provides the strongest direct evidence, demonstrating non-inferiority of rituximab to ocrelizumab for suppression of new or enlarging inflammatory lesions on magnetic resonance imaging (MRI) in newly diagnosed relapsing MS. However, evidence remains insufficient to establish equivalence for disability progression, long-term outcomes, or rare and cumulative adverse events. Uncertainty persists regarding infections, hypogammaglobulinemia (reduced immunoglobulin levels), pregnancy, optimal dosing, and long-term immune effects. Rituximab’s substantially lower cost could improve access to high-efficacy treatment; however, current evidence does not directly support assuming universal interchangeability with ocrelizumab.

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Cite

BibTeXRIS
BibTeX
@article{racki2026rituximab,
  title = {{Rituximab and Ocrelizumab in Multiple Sclerosis: Does Comparative Evidence Redefine Anti-CD20 Therapy?}},
  author = {Valentino Rački and Andrej Belančić and Almir Fajkić and Slobodan Janković},
  journal = {Journal of Clinical Medicine},
  year = {2026},
  month = oct,
  doi = {10.3390/jcm15218223},
  url = {https://www.mdpi.com/2077-0383/15/21/8223},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Rituximab and Ocrelizumab in Multiple Sclerosis: Does Comparative Evidence Redefine Anti-CD20 Therapy?
AU  - Valentino Rački
AU  - Andrej Belančić
AU  - Almir Fajkić
AU  - Slobodan Janković
PY  - 2026
DA  - 2026/10/22
JO  - Journal of Clinical Medicine
DO  - 10.3390/jcm15218223
UR  - https://www.mdpi.com/2077-0383/15/21/8223
AB  - B-cell depletion has transformed multiple sclerosis treatment, with rituximab and ocrelizumab providing highly effective CD20-directed therapy. This narrative review aims to critically compare these agents from the mechanistic, clinical, safety, regulatory, and economic perspectives. Despite their shared target, differences in pharmacology, dosing, regulatory status, and cost may influence treatment selection. Observational studies generally suggest similar effectiveness, although interpretation is limited by confounding and heterogeneous treatment strategies. The randomized, double-blind OVERLORD-MS trial provides the strongest direct evidence, demonstrating non-inferiority of rituximab to ocrelizumab for suppression of new or enlarging inflammatory lesions on magnetic resonance imaging (MRI) in newly diagnosed relapsing MS. However, evidence remains insufficient to establish equivalence for disability progression, long-term outcomes, or rare and cumulative adverse events. Uncertainty persists regarding infections, hypogammaglobulinemia (reduced immunoglobulin levels), pregnancy, optimal dosing, and long-term immune effects. Rituximab’s substantially lower cost could improve access to high-efficacy treatment; however, current evidence does not directly support assuming universal interchangeability with ocrelizumab.
SN  - 2077-0383
ER  -