Ocrelizumab and similars (Ocrevus®, Kesimpta®, Briumvi®, rituximab)

Class: Monoclonal antibodies, anti-CD20

Name: Ocrelizumab (Ocrevus®), ofatumumab (Kesimpta®), ublituximab (Briumvi®), rituximab (Rituxan®) (used off-label)

Frequency: Once every 6 month infusion (ocrelizumab, rituximab). Once monthly self-administered injection (ofatumumab). Once every 24 weeks infusion (ublituximab).

Mechanism of Action: Selectively depletes circulating B lymphocytes, one type of white blood cell.

Effectiveness: Compared to older therapies, decreases relapse rate by 50%; decreases MRI disease activity by 95%; decreases brain atrophy by 45%.

Possible Side Effects: Infusion reactions, risk of infection, Hep B reactivation in Hep B positive patients, TB reactivation in those with prior exposure, Shingles, and others including possible heightened risk for PML***.

Ocrelizumab, ofatumumab, ublituximab, and rituximab are in a class of medications called monoclonal antibodies. They work by stopping certain cells of the immune system from reaching the brain and spinal cord and causing damage. Specifically, they bind to CD20 molecules on B cells and deplete them from circulation, thus they are sometimes referred to as “anti-CD20” medications.

Ocrelizumab is an infusion used to treat adults with various forms of multiple sclerosis,  including:

• Relapsing forms of MS, including:
  • clinically isolated syndrome (CIS; nerve symptom episodes that last at least 24 hours),
  • active relapsing-remitting MS (course of disease where symptoms flare up from time to time),
  • active secondary progressive (with recent relapses and/or MRIs with active lesions).
• Primary-progressive forms of MS (those who are diagnosed with slow progression from the outset).

Ofatumumab is an injection is used to prevent episodes of symptoms and slow the worsening of disability in adults who have relapsing forms of multiple sclerosis , including:

• clinically isolated syndrome (CIS; nerve symptom episodes that last at least 24 hours),
• active relapsing-remitting MS (course of disease where symptoms flare up from time to time),
• active secondary progressive (with recent relapses and/or MRIs with active lesions).

Ublituximab is an infused therapy and is approved for individuals with clinically isolated syndrome, relapsing-remitting MS, and active secondary progressive MS.  The infusion is about one hour. Sold under the brand name Briumvi, it is administered via an hour-long intravenous infusion every 24 weeks after an initial two infusions two weeks apart.

Rituximab is an infusion that is used to treat certain forms of cancer and is often prescribed off-label for use in multiple sclerosis. Rituximab is made by the same company that makes Ocrelizumab (Genentech). Despite their very similar mechanisms of action, effectiveness and potential side effects and risks, many insurance providers will decline to cover it because of its off-label use. Medicaid, Kaiser, the VA and others will often use rituximab due to the great similarities between the drugs and much lower cost. In addition, because of cost, it is extremely challenging to adjust the dose or frequency of ocrelizumab, but much easier with rituximab. Use of rituximab biosimilars (akin to generics) are in widespread use and further lower the costs.

*** PML (Progressive Multifocal Leukoencephalopathy): PML is a rare but serious brain infection that is caused by the JC Virus (JCV). PML is seen in MS patients who are JC virus (JCV) positive and on disease modifying therapies known to increase the risk of PML. At least 50% of the general population has been exposed to JCV, but the infection is generally asymptomatic. But, in immunocompromised patients, including those taking certain MS DMTs, the JC Virus can infect the brain and result in PML. PML The first case of PML in MS was discovered in 2005 with the use of Tysabri.