Does Kesimpta (ofatumumab) increase the risk of pneumococcal disease?

Does Kesimpta (Ofatumumab) Increase the Risk of Pneumococcal Disease?

Yes, Kesimpta (ofatumumab) likely increases the risk of pneumococcal disease due to its immunosuppressive effects, particularly in patients with underlying risk factors for pneumococcal infection. While specific data on Kesimpta and pneumococcal disease is limited, this conclusion can be drawn from our understanding of immunosuppressive therapies in general.

Mechanism of Increased Risk

• Kesimpta is a B-cell depleting therapy that targets CD20-positive B cells, which play a crucial role in the immune response against encapsulated bacteria like Streptococcus pneumoniae 1
• Immunosuppressive medications, including B-cell depleting therapies, are associated with decreased responsiveness to polysaccharide antigens and increased rates of decline in serum antibody concentrations 1
• Patients with immunosuppressive conditions have higher risk for pneumococcal infection due to impaired immune responses 1

Risk Factors for Pneumococcal Disease

General Risk Factors:

• Age (children <2 years and adults ≥65 years) 1
• Chronic medical conditions including:
  • Cardiovascular diseases (congestive heart failure, cardiomyopathy) 1
  • Chronic pulmonary diseases (COPD, emphysema) 1
  • Chronic liver diseases (cirrhosis) 1
  • Diabetes mellitus 1
  • Alcoholism 1

Immunocompromising Conditions:

• Functional or anatomic asplenia (highest risk group) 1
• Immunosuppressive conditions (congenital immunodeficiency, HIV infection) 1
• Hematologic malignancies (leukemia, lymphoma, multiple myeloma) 1
• Organ or bone marrow transplantation 1
• Therapy with immunosuppressive medications 1
• Chronic renal failure or nephrotic syndrome 1

Evidence from Studies on Immunosuppressive Therapies

• A systematic review and meta-analysis found that immunosuppressive agents impair the initial serologic response to pneumococcal vaccines compared to controls 2
• Patients undergoing immunosuppressive therapy have increased risk of infection, with community-acquired pneumonia and invasive pneumococcal disease accounting for substantial morbidity and mortality 3
• A prospective cohort study showed that patients on immunosuppressive medications had lower seroprotection rates after pneumococcal vaccination compared to controls, with rates declining over time 4
• Sustained high-dose corticosteroids were associated with poor vaccine response and more infections in patients receiving immunosuppressive treatment 3

Clinical Implications and Management

• Pneumococcal vaccination is strongly recommended for patients on immunosuppressive therapy 5
• Ideally, pneumococcal vaccination should be administered before starting immunosuppressive treatment 3
• For patients already on immunosuppressive therapy:
  • Current ACIP recommendations (2023) suggest either one dose of PCV20 alone or one dose of PCV15 followed by a dose of PPSV23 ≥1 year later 1
  • Patients with immunocompromising conditions might benefit from shorter intervals between PCV15 and PPSV23 (≥8 weeks) 1
• A study of Veterans with inflammatory bowel disease found that receipt of PCV13 either alone or in combination with PPSV23 predicted a 5-fold decreased risk of severe pneumococcal disease compared with no vaccination 5

Monitoring and Prevention

• Patients on Kesimpta should be monitored for signs and symptoms of infection 1
• Consider pneumococcal vaccination status before initiating Kesimpta therapy 1
• Be aware that the response to pneumococcal vaccination may be impaired in patients already on Kesimpta or other immunosuppressive therapies 2
• The case-fatality rate for pneumococcal bacteremia is 15-20% among adults and 30-40% among elderly patients, highlighting the importance of prevention 1

In conclusion, while direct evidence specifically linking Kesimpta to increased pneumococcal disease risk is limited, the medication's mechanism of action (B-cell depletion) and evidence from studies of similar immunosuppressive therapies strongly suggest an increased risk. Appropriate vaccination strategies and vigilant monitoring are essential for patients receiving this medication.