Does Ocrelizumab (Ocrelizumab) cause immunocompromise?

From the Guidelines

Ocrelizumab does cause immunocompromise by depleting CD20-positive B cells, which are crucial components of the immune system. This intentional immune suppression increases the risk of infections, particularly respiratory infections, herpes virus reactivations, and progressive multifocal leukoencephalopathy (PML) in rare cases 1. The medication is primarily used to treat multiple sclerosis, both relapsing and primary progressive forms. Patients on ocrelizumab should receive certain vaccinations before starting treatment, as live or live-attenuated vaccines are contraindicated during therapy.

Some key considerations for patients on ocrelizumab include:

• Receiving vaccinations at least 4-6 weeks before starting ocrelizumab therapy or at least 4-6 months after the last ocrelizumab infusion 1
• Avoiding live or live-attenuated vaccines during therapy
• Regular monitoring for infections while on this medication
• Promptly reporting signs of infection to their healthcare provider

The immune effects of ocrelizumab can last for months after the last dose, with B cell recovery typically taking 72 weeks or longer. The standard dosing regimen is 300 mg intravenously for the first dose, followed by another 300 mg two weeks later, then 600 mg every six months thereafter. It is essential to weigh the benefits of ocrelizumab therapy against the potential risks of immunocompromise and to closely monitor patients for signs of infection.

From the FDA Drug Label

Serious cases of infections caused by herpes simplex virus and varicella zoster virus, including central nervous system infections (encephalitis and meningitis), intraocular infections, and disseminated skin and soft tissue infections, have been reported in the postmarketing setting in multiple sclerosis patients receiving ocrelizumab. Hepatitis B virus (HBV) reactivation has been reported in MS patients treated with ocrelizumab in the postmarketing setting. Possible Increased Risk of Immunosuppressant Effects With Other Immunosuppressants When initiating OCREVUS ZUNOVO after an immunosuppressive therapy or initiating an immunosuppressive therapy after OCREVUS ZUNOVO, consider the potential for increased immunosuppressive effects Cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients with MS treated with ocrelizumab in the postmarketing setting. PML is an opportunistic viral infection of the brain caused by the JC virus (JCV) that typically only occurs in patients who are immunocompromised As expected with any B-cell depleting therapy, decreased immunoglobulin levels are observed with ocrelizumab treatment

Yes, Ocrelizumab can cause immunocompromise, as evidenced by the increased risk of serious infections, HBV reactivation, and PML, as well as decreased immunoglobulin levels. Key points include:

• Increased risk of serious infections, such as herpes simplex and varicella zoster virus
• Risk of HBV reactivation
• Potential for increased immunosuppressive effects when used with other immunosuppressants
• Risk of PML, an opportunistic viral infection
• Decreased immunoglobulin levels, which can increase the risk of serious infections 2

From the Research

Immunocompromise and Ocrelizumab

• Ocrelizumab is a humanized anti-CD20 monoclonal antibody used to treat multiple sclerosis (MS) 3.
• It works by depleting CD20+ B cells, which are thought to play a role in the pathogenesis of MS 3, 4.
• Studies have shown that ocrelizumab can also affect other immune cells, including CD8+ T cells, monocytes, and dendritic cells 4, 5.
• The treatment can lead to a reduction in immunoglobulins, including IgG 5.
• Some patients may experience a "wearing-off" phenomenon, where the treatment's effects seem to decrease over time, which can be associated with reduced immunomodulation and increased neuroaxonal damage 6.

Effects on Humoral and Cellular Immunity

• Ocrelizumab has been shown to reduce total lymphocyte count and subpopulations, including CD19 and CD20 lymphocytes 5.
• The treatment can also lead to a progressive reduction of CD8 lymphocytes over time 5.
• Changes in humoral response are immediate and sustained, while modulation of cellular immunity occurs progressively through regular re-treatment 5.
• Disability progression has been associated with lower CD8 cytotoxic T-lymphocyte reduction 5.

Novel Mechanisms of Action

• Ocrelizumab may have additional effects beyond B cell depletion, including modulation of Protein Kinase C (PKC) and its down-stream targets 7.
• The treatment has been shown to counteract an inflammatory cascade involving PKCβII, HIF-1α, and VEGF, and to up-regulate neuroprotective pathways involving HuR, MnSOD, and HSP70 7.
• These novel mechanisms of action may contribute to the treatment's ability to counteract disease progression 7.