What is considered a low IgM (Immunoglobulin M) level in patients treated with Kesimpta (ofatumumab)?

IgM Levels with Kesimpta (Ofatumumab): Monitoring and Management

For patients on Kesimpta (ofatumumab), an IgM level below the lower limit of normal (LLN) should be considered low, with particular concern when levels drop below 0.34 g/L, which requires close monitoring for infection risk.

Understanding IgM Reduction with Kesimpta

• Decreased immunoglobulin M (IgM) levels are an expected effect of B-cell depleting therapies like Kesimpta, reported in 7.7% of patients treated with ofatumumab compared to 3.1% with teriflunomide in clinical trials 1
• In phase III trials, treatment with Kesimpta resulted in a decrease in serum IgM that reached values below 0.34 g/L in 14.3% of patients 1
• Mean IgM levels decrease with continued treatment but typically remain above the lower limit of normal in most patients with up to 3.5 years of exposure 2

Monitoring Recommendations

• Regular monitoring of immunoglobulin levels is recommended during Kesimpta treatment, with particular attention to IgM and IgG levels 3, 1
• Monthly monitoring of Ig levels is recommended if immunoglobulin replacement therapy is initiated 3
• Serum levels alone are not adequate to determine infection risk; monitoring the frequency of infections is more important for clinical decision-making 3

Clinical Significance of Low IgM

• Low IgM levels increase the risk of infections, particularly with encapsulated bacteria 3
• Treatment was discontinued because of decreased immunoglobulins in 3.4% of patients treated with Kesimpta and in 0.8% of patients treated with teriflunomide in clinical trials 1
• The most common cause of discontinuation in patients treated with Kesimpta in clinical trials was low IgM (3.3%), defined as IgM at 10% below the lower limit of normal 1

Management of Low IgM Levels

When to Consider Immunoglobulin Replacement Therapy

• Consider immunoglobulin replacement therapy for patients who have:
  • Experienced ≥2 severe recurrent infections by encapsulated bacteria, regardless of IgG level 3
  • A life-threatening infection 3
  • Documented bacterial infection with no or insufficient response to antibiotic therapy 3

Treatment Approach

• Monthly IVIG treatment is recommended for the duration of immunoparesis until Ig levels recover 3
• Kesimpta dosing should be maintained during immunoglobulin replacement therapy 3
• Consider discontinuing Kesimpta if a patient with low immunoglobulins develops a serious opportunistic infection, recurrent infections, or if prolonged hypogammaglobulinemia requires treatment with intravenous immunoglobulins 1

Important Considerations

• Decreased Ig levels were not associated with serious infections after 3.5 years of ofatumumab treatment in clinical studies 4, 2
• IgG and IgM serology tests for diagnosis of viral infections may be used routinely but should be interpreted with caution in patients on Kesimpta 3
• Patients may have false negative results in response to IgG and IgM serology tests due to failure to mount antibody responses to pathogens 3

Pitfalls to Avoid

• Do not rely solely on IgM levels to determine infection risk; consider the patient's clinical presentation and infection history 3
• Avoid misinterpreting serological test results in patients receiving immunoglobulin replacement therapy, as this may impact the results 3
• Do not discontinue Kesimpta based on decreased IgM levels alone without evidence of increased infection risk 1, 2