Ocrevus Cancels RRMS Patient’s Immunity to Chickenpox Virus, Case Study Finds

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by Steve Bryson, PhD |

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Ocrevus and PML report

Ocrevus (ocrelizumab) eliminated the immunity, acquired through vaccination, to the varicella-zoster virus — the virus that causes chickenpox and shingles — in a man with relapsing-remitting multiple sclerosis (RRMS), a case study reported. 

Its authors recommended that MS patients being treated with Ocrevus be retested for immunity against the varicella-zoster virus.

The study, “Varicella Zoster immunity loss in multiple sclerosis patient treated with ocrelizumab,” was published in the journal Clinical Immunology.

Ocrevus (developed by Genentech) is an antibody-based therapy approved for patients with relapsing MS and primary progressive MS (PPMS). It is designed to suppress immune system attacks on the myelin sheath, the coating that protects nerve fibers.

The treatment targets mature B-cells, a type of immune cell that produces a protein called CD20 on its surface. While depleting mature B-cells, Ocrevus has been shown to preserve the ability to generate new B-cells as well as maintain pre-existing immunity acquired from previous infections or vaccinations. 

But evidence shows that some patients given vaccines to protect against the influenza virus or pneumococcal bacteria lose such immunity after Ocrevus treatment. 

Current guidelines recommend assessing the vaccination status of MS patients before prescribing therapies that suppress or modulate the immune system. However, there are no specific recommendations about reassessing vaccine-based immunity after treatment with Ocrevus.

Researchers at the Magna Graecia University of Catanzaro in Italy described the case of a 48-year-old man with RRMS who lost vaccine-based immunity against varicella-zoster virus after the first Ocrevus treatment. 

The man had a past medical history of diabetes mellitus type 2, high blood pressure, abnormal levels of blood fats, and coronary artery disease

After being diagnosed with RRMS, he was first treated with the anti-inflammatory medicine Rebif (interferon beta-1a, marketed by Merck KGaA) for 10 years, but stopped due to relapses and injection site reactions. 

The patient was then started on the immunomodulating therapy Aubagio (teriflunomide, marketed by Sanofi) for seven months, but this treatment was ineffective for him. 

He next moved to the antibody-based therapy Tysabri (natalizumab, manufactured by Biogen), which was discontinued after about two years due to an increased risk of the rare brain infection progressive multifocal leukoencephalopathy (PML).

The patient was then recommended for Ocrevus treatment. 

Before beginning Ocrevus, the man was vaccinated against the varicella-zoster virus. He was screened for active or latent infections and antibodies generated by vaccination against vaccine-preventable diseases such as chickenpox, which confirmed his immunity against the virus. 

Four months after the vaccination, he received his first 300 mg Ocrevus treatment and a second dose two weeks later.

After five months, the patient was re-screened. Results showed he no longer had protective levels of anti-varicella-zoster virus antibodies in his blood, and he was given a second vaccine. 

Eight weeks later he was retested, and a continued absence of vaccine immunity against the virus was found. 

“Thus, we decided not to re-vaccinate the patient, and recommended prevention strategy thought vaccination of close contacts and avoidance of subjects with active VZV [varicella-zoster virus] infection,” the researchers wrote. “Cocooning (immunization of the family) should be highly recommended in case of contraindication for updating vaccinations in negative patients.”

Three months later, after the last vaccination, the patient had a new infusion of Ocrevus.

“This case evidenced that [protective levels] of anti-VZV [antibodies] before the initiation of [Ocrevus] treatment may not ensure permanent immunity against VZV after treatment,” the researcher wrote. “Consequently, we suggest to retest patients for anti-VZV antibodies, mainly subjects with comorbidities such as diabetes.”

“Further studies among wide cohort of patients are needed to assess the incidence of vaccinal immunity loss in patients treated with [Ocrevus],” the team added. 

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