1. • Pro-inflammatory T cell
activation
• Pro-inflammatory
cytokine secretion
• Myelin targeted antibody
production
OCRELIZUMAB
(anti-CD20 antibody therapy)
Improves MS progression by binding to the CD20 protein present on
the majority of B cells and significantly diminishing their numbers.
Complement-dependent
cytotoxicity
Antibody-dependent cellular
cytotoxicity
B cell
function
in MS
Phase II
Ocrelizumab vs. Placebo
with RRMS patients
Phase III
OPERA I, OPERA II
Ocrelizumab vs. Interferon
beta-1a with RMS patients
ORATORIO trial
Ocrelizumab vs. Placebo
with PPMS patients
89% and 96%
reduction of
gadolinium-
enhanced T1 lesions
showed on MRI
80%, respectively
73% reduction in
annualized
relapse rate
46%~47%
annualized
relapse rate
reduction
CDP was
reduced by 40%
at 12 and 24-
weeks
The number of
gadolinium-
enhanced T1
lesions found on
MRI were
reduced by
94~95%
The number of
new or enlarging
T2 hyperintense
lesions found on
MRI were also
reduced by
77~83%
Relative Risk of CDP
was reduced by:
• 24% at 12-weeks
• 25% at 24-weeks
25-feet walk
performance was
improved by
29.3%
Similar score in the Short
Form (SF-36) Health
Survey Physical
Component Summary: -0.7
vs. -1.1, respectively
Radiological
results
NEDA increased
from 29.2~ 25.1%
to 47.9~ 47.5%
T2-weighted
brain lesions
found in MRI
were reduced
by 3.4%
Loss of brain
volume was
reduced by
0.9%
Lower incidence of new
or enlarging
hyperintense lesions by
0.31 vs. 3.88 (placebo)
In patients who received 600 mg and
2000 mg Ocrelizumab doses
The Pharmacology of Ocrelizumab in MS
disease progression
Figure 1:
Disease progression
is observed clinically
and radiologically
(B))
A) B)
2. Figure 1: Diagram showing the pharmacology of ocrelizumab in multiple sclerosis disease progression following
outline of process, ocrelizumab mechanism of action and study results. Image A) (image adapted from (Genentech,
2017)) describes a summarized process and function of B-cells and T-cells in axon demyelination occurring in
multiple sclerosis (MS). The ocrelizumab (OCR) mechanism of action concentrates on two action pathways, the
complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity, through which it exerts its
improving effect on MS disease progression by binding to the CD-20 antigen present on the majority of B-cells,
therefore reducing their numbers and impact on disease progression. New or developing T1 and T2 gadolinium-
enhanced lesions can be traced radiologically by magnetic resonance imaging (MRI), as shown in image B) (Price,
2009). Efficacy and safety of the humanised anti-CD20 monoclonal antibody therapy (OCR) was investigated in two
clinical trial phases: Phase II concentrating on relapsing-remitting multiple sclerosis (RRMS) patients and Phase III
(Opera I and Opera II) with results obtained for relapsing multiple sclerosis (RMS) patients. The effect of OCR also
showed good disease management and progression improvement in primary progressive multiple sclerosis patients
(PPMS) in a specific trial as part of the Phase III stage. (Mulero, Migdalia & Montalban, 2018)
3. Article Title Publication
Year
Article Type Summary of key facts
Humoral and T-cell
responses to SARS-
CoV-2 vaccination in
multiple sclerosis
patients treated with
ocrelizumab
2022 Primary –
research
article
The impact of ocrelizumab over the efficiency of SARS-CoV-2 vaccination has recently
been problematic in disease modifying therapies (DMTs) approaches in MS patient care.
This comparative study showed and confirmed predicted outcomes, where 80% of OCR
treated MS patients did not produce detectable antibody levels, compared to NTZ treated
patients, who did, but did result in a T-cell mediated positive response, predicted to offer
some level of protection against COVID-19. Longer time intervals between vaccination
and DMT infusions was found to generate a higher probability of antibody production.
(Katz et al., 2022)
Tolerability and
Safety of Switching
from Rituximab to
Ocrelizumab:
Evaluating Factors
Associated with
Infusion Related
Reactions
2022 Primary –
research
article
In this study the safety considerations of switching from Rituximab to OCR are observed,
on the basis of infusion related reactions (IRRs). The rate of IRRs in patients who switched
from Rituximab to OCR (12%, 14%) was close to patients who continued Rituximab
treatment (14%), with a magnitude of mild to moderate, specifically after the first OCR
infusion. 27.5% of patients receiving OCR as treatment for MS for the first-time
experienced IRRs, compared to a decreased IRR rate in patients who were previously
exposed to anti-CD20 treatment (Rituximab). (Alvarez et al., 2022)
Ocrelizumab depletes
T-lymphocytes more
than rituximab in
multiple sclerosis
2021 Primary –
research
article
10% of ocrelizumab treated patients (4 patients) developed lower CD4 lymphocytes levels,
compared to 22% on rituximab (11 patients). Similarly, 65% of the ocrelizumab group (25
patients) developed lower CD8 lymphocytes compared to 30% on rituximab (15 patients).
This study showed that ocrelizumab is more efficient especially in T lymphocytes, as well
as B-lymphocyte depletion, with decreased immunogenicity. (Capasso et al., 2021)
The wearing off
phenomenon of
ocrelizumab in
patients with multiple
sclerosis
2022 Primary-
research
article
It is common for patients undergoing ocrelizumab therapy to experience the wearing-off
phenomenon. 61% of such patients taking part in this study reported sensory, cognitive
disability and fatigue like symptoms starting between 1 and 4 weeks for the majority of
them (49%) and disappearing soon after the first administered ocrelizumab infusion.
However, this has not been reported to have any impact on the overall ocrelizumab
treatment outcome. A body mass index (BMI) of ≥ 25 was found to be a wearing-off
prevalence increasing factor. (Toorop et al., 2022)
Development of anti-
CD20 therapy for
multiple sclerosis
2011 Review
article
This review brings forward the acknowledgement of B-cell involvement in MS
pathogenesis, their functions of pro-inflammatory T-cell activation, stimulation of
inflammatory cytokines and leukocyte infiltration through produced chemokines and
myelin directed antibody production that were considered a baseline paradigm in anti-
CD20 antibody therapies developing at the time, including the ocrelizumab Phase II
clinical trials (Bartok & Silverman, 2011).
Table of Literature
4. Reference List
Alvarez, E., Nair, K. V., Sillau, S., Shelton, I., Seale, R., Selva, S., … Vollmer, T. L. (2022). Tolerability and Safety of
Switching from Rituximab to Ocrelizumab: Evaluating Factors Associated with Infusion Related Reactions. Multiple
Sclerosis Journal - Experimental, Translational and Clinical, 8(1), 205521732110693.
https://doi.org/10.1177/20552173211069359
Bartok, B., & Silverman, G. J. (2011). Development of anti-CD20 therapy for multiple sclerosis. Experimental Cell Research,
317(9), 1312–1318. https://doi.org/10.1016/j.yexcr.2011.04.002
Capasso, N., Nozzolillo, A., Scalia, G., Lanzillo, R., Carotenuto, A., De Angelis, M., … Moccia, M. (2021). Ocrelizumab
depletes T-lymphocytes more than rituximab in multiple sclerosis. Multiple Sclerosis and Related Disorders, 49,
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Genentech. (2017). The Immune System in Multiple Sclerosis. Retrieved February 13, 2022, from Genentech: Breakthrough
science. One moment, one day, one person at a time. website: https://www.gene.com/stories/the-immune-system-in-
multiple-sclerosis?topic=multiple-sclerosis
Katz, J. D., Bouley, A. J., Jungquist, R. M., Douglas, E. A., O’Shea, I. L., & Lathi, E. S. (2022). Humoral and T-cell
responses to SARS-CoV-2 vaccination in multiple sclerosis patients treated with ocrelizumab. Multiple Sclerosis and
Related Disorders, 57, 103382. https://doi.org/10.1016/j.msard.2021.103382
Mulero P., Migdalia L & Montalban X. (2018). Ocrelizumab: a new milestone in multiple sclerosis therapy. Therapeutic
Advances in Neurological Disorders, Vol. 11: 1-6, http://doi.org/10.1177/1756286418773025
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Orthopt J 2009; 6: 5-14. DOI: 10.22599/bioj.2
Toorop, A. A., van Lierop, Z. Y. G. J., Strijbis, E. M. M., Teunissen, C. E., Barkhof, F., Uitdehaag, B. M. J., … Killestein, J.
(2022). The wearing-off phenomenon of ocrelizumab in patients with multiple sclerosis. Multiple Sclerosis and
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