What is the role of Inebulizumab (generic name: Inebulizumab, a monoclonal antibody) in the treatment of Neuromyelitis Optica (NMO)?

From the FDA Drug Label

The precise mechanism by which inebilizumab-cdon exerts its therapeutic effects in NMOSD is unknown but is presumed to involve binding to CD19, a cell surface antigen presents on pre-B and mature B lymphocytes. Treatment with UPLIZNA reduces CD20+ B cell counts in blood by 8 days after infusion In Study 1 [see Clinical Studies (14)], CD20+ B-cell counts were reduced below the lower limit of normal by 4 weeks in 100% of patients treated with UPLIZNA and remained below the lower limit of normal in 94% of patients for 28 weeks after initiation of treatment.

Inebulizumab in NMO: Inebulizumab-cdon is presumed to exert its therapeutic effects in Neuromyelitis Optica Spectrum Disorder (NMOSD) by binding to CD19, a cell surface antigen on pre-B and mature B lymphocytes, resulting in antibody-dependent cellular cytolysis.

• Key Points:
  • Reduces CD20+ B cell counts in blood by 8 days after infusion
  • CD20+ B-cell counts remain below the lower limit of normal in 94% of patients for 28 weeks after initiation of treatment 1
  • The precise mechanism of action is unknown, but presumed to involve binding to CD19 1

From the Research

Inebulizumab is a highly effective treatment for neuromyelitis optica spectrum disorder (NMOSD) in adults who are anti-aquaporin-4 (AQP4) antibody positive, including those with prior rituximab use, as evidenced by the most recent study 2.

Key Points

• The standard dosing regimen for inebulizumab consists of 300 mg intravenous infusions initially given on Day 1 and Day 15, followed by 300 mg every 6 months thereafter.
• Inebulizumab works as a B-cell depleting monoclonal antibody that targets CD19, reducing the production of pathogenic AQP4 antibodies that cause the inflammatory attacks characteristic of NMOSD.
• Clinical trials, including the N-MOmentum trial 3, have shown that inebulizumab significantly reduces the risk of NMOSD attacks by approximately 73% compared to placebo.
• Common side effects include urinary tract infections, headache, joint pain, and infusion reactions.
• Patients should receive appropriate premedication before infusions to minimize infusion reactions, typically including antihistamines, antipyretics, and sometimes corticosteroids.
• Before starting treatment, patients should be screened for hepatitis B virus, as B-cell depleting therapies can cause reactivation of the virus.
• Vaccination status should also be updated before initiating therapy, as immune responses to vaccines may be diminished during treatment.
• Regular monitoring of B-cell counts and immunoglobulin levels is recommended during treatment.

Efficacy in Prior Rituximab Use

• A post hoc analysis of the N-MOmentum trial 2 found that inebulizumab was effective in reducing the risk of NMOSD attacks in patients with prior rituximab use.
• The annualized attack rate was significantly lower in patients treated with inebulizumab compared to those treated with placebo, regardless of prior rituximab use.

Safety Considerations

• Infections, including urinary tract infections, were common in patients treated with inebulizumab, highlighting the need for clinical vigilance in monitoring for infections.
• Serious adverse events, including opportunistic infections, were rare, but patients should be closely monitored for signs of infection.
• The safety profile of inebulizumab was similar to that of other B-cell depleting therapies, with no new safety concerns identified in the N-MOmentum trial 3 or other studies 4, 5.