From the FDA Drug Label
The precise mechanism by which ofatumumab exerts its therapeutic effects in multiple sclerosis is unknown, but is presumed to involve binding to CD20, a cell surface antigen present on pre-B and mature B lymphocytes.
Following cell surface binding to B lymphocytes, ofatumumab results in antibody-dependent cellular cytolysis and complement-mediated lysis.
Ofatumumab is used to treat Multiple Sclerosis (MS) by depleting B-cells. The drug works by binding to CD20, a protein on the surface of B-cells, leading to their destruction.
- The mechanism of action is not fully understood but is thought to involve antibody-dependent cellular cytolysis and complement-mediated lysis.
- B-cell depletion is achieved in most patients, with 95% of patients having CD19+ B-cell counts below the lower limit of normal (LLN) two weeks after treatment initiation 1.
- B-cell repletion occurs after treatment discontinuation, with a median time to recovery of 24.6 weeks 1.
From the Research
Ofatumumab is a highly effective treatment for relapsing multiple sclerosis (MS), with a favorable safety profile and convenient at-home administration, as demonstrated by the most recent and highest quality study 2.
Key Points
- Ofatumumab is a fully human anti-CD20 monoclonal antibody that targets CD20-positive B cells, which play a key role in the immune attack on the nervous system in MS.
- The typical regimen begins with weekly 20 mg subcutaneous injections for three weeks, followed by monthly maintenance doses of 20 mg.
- Ofatumumab works by depleting B cells in the bloodstream and lymph nodes, reducing inflammation and new lesion formation in the brain and spinal cord.
- Clinical trials have shown that ofatumumab reduces relapse rates by approximately 50-60% compared to other MS treatments, with a low annualized relapse rate of 0.05, as reported in the ALITHIOS open-label extension study 3.
- Common side effects include injection site reactions, upper respiratory infections, headache, and potential increased risk of infections due to its effects on the immune system.
- Before starting, patients should undergo screening for hepatitis B, as the medication can reactivate this virus.
- Ofatumumab offers the convenience of at-home administration and doesn't require the infusion center visits needed for similar medications like ocrelizumab.
- Regular blood monitoring is recommended during treatment to check lymphocyte counts and monitor for potential complications.
Efficacy and Safety
- The ASCLEPIOS I/II trials demonstrated the superior efficacy of ofatumumab versus teriflunomide in reducing relapse rates, disability worsening, and MRI-detected lesion activity 2.
- The ALITHIOS open-label extension study showed that ofatumumab has a favorable longer-term benefit-risk profile in RMS, with no new safety signals identified and a low cumulative 3- and 6-month confirmed disability worsening rate 3.
- The safety profile of ofatumumab is generally manageable, with the most frequently reported adverse events being infections and infestations, as reported in the safety set of the ALITHIOS study 3.