Does Ocrevus (ocrelizumab) infusion for multiple sclerosis (MS) make a patient immunocompromised?

Does Ocrevus Infusion for MS Make a Patient Immunocompromised?

Yes, Ocrevus (ocrelizumab) infusion for multiple sclerosis does make patients immunocompromised through its mechanism of CD20+ B-cell depletion, which significantly impacts the immune system. 1

Mechanism of Immunosuppression

Ocrelizumab is a humanized monoclonal antibody that selectively targets and depletes CD20+ B cells, which are important components of the adaptive immune system. This B-cell depletion creates an immunocompromised state in several ways:

• B-cell depletion: Ocrelizumab rapidly depletes peripheral B cells, which are critical for antibody production and immune response 1, 2
• Immunoglobulin reduction: Treatment decreases total immunoglobulins, with the greatest decline seen in IgM levels, though IgG levels can also be affected 1
• Increased infection risk: The FDA label explicitly states that "an increased risk of infections has been observed in patients during and following completion of treatment with anti-CD20 B-cell depleting therapies" 1

Evidence of Immunocompromised Status

The immunocompromised status of patients on Ocrevus is well-documented:

• Decreased immunoglobulins: In clinical trials, 16.5% of relapsing MS patients and 15.5% of primary progressive MS patients developed IgM levels below the lower limit of normal after treatment 1
• Serious infections: The FDA label notes that "serious, including life-threatening or fatal, bacterial, viral, parasitic, and fungal infections have been reported in patients receiving ocrelizumab" 1
• Immune system alterations: Recent research shows that ocrelizumab not only reduces CD20+ B cells but also affects CD20+ T cells, monocytes, dendritic cells, CD8+ T cells, and natural killer cells 2

Vaccination Considerations for Immunocompromised Patients on Ocrevus

Guidelines specifically address vaccination timing for MS patients on ocrelizumab, confirming its immunosuppressive effects:

• For patients scheduled to start ocrelizumab, vaccines should be administered at least 4–6 weeks before treatment initiation 3
• For patients already on ocrelizumab, vaccination should be delayed until at least 4–6 months after the last infusion 3
• Live vaccines are generally contraindicated in immunocompromised patients, including those on B-cell depleting therapies like ocrelizumab 3

Duration of Immunosuppression

The immunosuppressive effects of ocrelizumab are long-lasting:

• B-cell depletion occurs rapidly after infusion 4
• Immunosuppression persists for months after treatment, with guidelines recommending waiting 4-6 months after the last infusion before vaccination 3
• Some patients may experience delayed B-cell repopulation, extending the period of immunocompromise 2

Clinical Implications

Healthcare providers should be aware of several important clinical considerations:

• Infection monitoring: Patients on ocrelizumab require vigilant monitoring for infections, particularly upper and lower respiratory tract infections and herpes-related infections 1
• Vaccination timing: Ideally, all necessary vaccinations should be completed at least 4-6 weeks before starting ocrelizumab 3
• Immunoglobulin monitoring: Regular monitoring of immunoglobulin levels is important, as decreased IgG levels are associated with increased rates of serious infections 1
• Neutrophil counts: Decreased neutrophil counts occurred in 13% of patients in clinical trials, potentially further compromising immune function 1

Common Pitfalls and Caveats

• Underestimating infection risk: The immunosuppressive effects may be underappreciated in clinical practice, leading to inadequate infection prevention measures
• Inappropriate vaccination: Administering live vaccines to patients on ocrelizumab could pose serious risks due to their immunocompromised state 3
• Delayed recognition of immunosuppression: The immunosuppressive effects extend beyond simple B-cell depletion and affect multiple components of the immune system 2
• Inadequate monitoring: Failure to monitor immunoglobulin levels may miss patients at highest risk for serious infections 1

In conclusion, Ocrevus (ocrelizumab) definitively causes an immunocompromised state through its mechanism of B-cell depletion, with effects that extend to multiple components of the immune system and persist for months after treatment.