What monoclonal antibodies (mAbs) are commonly used in the treatment of Multiple Sclerosis (MS)?

Monoclonal Antibodies Used in Multiple Sclerosis Treatment

Natalizumab is the most commonly used monoclonal antibody in multiple sclerosis treatment, with ocrelizumab also being a significant option for both relapsing and primary progressive forms of MS. 1, 2

Primary Monoclonal Antibody Options

Natalizumab

• Mechanism of Action: Humanized monoclonal antibody that targets α4-integrin (very late antigen 4), blocking lymphocyte migration across the blood-brain barrier 1, 3
• Efficacy:
  • Reduces annual relapse rate by 68%
  • Reduces disability progression by 42%
  • Reduces contrast-enhancing lesions by 92% 3
  • 37% of patients achieve no evidence of disease activity (versus 7% on placebo) 3

Ocrelizumab

• Mechanism of Action: CD20-directed cytolytic antibody targeting B cells
• FDA Indications:
  • Relapsing forms of MS (including clinically isolated syndrome, relapsing-remitting, and active secondary progressive disease)
  • Primary progressive MS - the only FDA-approved DMT for this form 2, 4

Risk Stratification for Natalizumab

The primary concern with natalizumab is the risk of progressive multifocal leukoencephalopathy (PML), which has a 23% mortality rate 3. Risk stratification includes:

1. Anti-JCV Antibody Status:

   • Negative: Lower risk
   • Positive: Higher risk, further stratified by antibody index 1

2. Anti-JCV Antibody Index:

   • ≤1.5: Lower risk (1.37/1000 after 49-72 months of treatment)

   • 1.5: Higher risk (10.12/1000 after 49-72 months of treatment) 1

3. Prior Immunosuppressant Use: Increases risk 1

4. Duration of Treatment: Risk increases with longer exposure, particularly beyond 2 years 1, 4

Monitoring Protocol for Natalizumab Patients

• JCV Antibody Testing: Every 6 months 1, 4
• MRI Surveillance:
  • JCV negative: Annual MRI
  • JCV positive with index ≤1.5: Every 6 months
  • JCV positive with index >1.5: Every 3-4 months 1, 4

Other Monoclonal Antibodies Used in MS

Daratumumab

• Human IgG kappa monoclonal antibody targeting CD38 surface protein
• More commonly used in multiple myeloma rather than MS 1

Elotuzumab

• Monoclonal antibody targeting SLAM-F7
• Primarily used in multiple myeloma, not MS 1

Clinical Decision-Making Algorithm

1. For newly diagnosed relapsing MS:

   • Start with first-line agents (interferons, glatiramer acetate)
   • If high disease activity or poor response, consider natalizumab or ocrelizumab

2. For highly active relapsing MS:

   • Consider natalizumab if JCV antibody negative
   • Consider ocrelizumab if JCV antibody positive or other risk factors for PML

3. For primary progressive MS:

   • Ocrelizumab is the only FDA-approved option 2

4. For patients on natalizumab:

   • Monitor JCV antibody status every 6 months
   • Adjust MRI frequency based on risk factors
   • Consider switching to alternative therapy if JCV antibody becomes positive with high index

Common Pitfalls and Caveats

1. PML Risk Management:

   • Never initiate natalizumab without baseline JCV antibody testing
   • Remember that JCV status can change over time, requiring regular monitoring 1, 5

2. Treatment Duration:

   • Risk of PML increases significantly after 2 years of natalizumab treatment
   • Consider drug holiday or switching therapy in high-risk patients 5

3. Combination Therapy:

   • Avoid combining natalizumab with other immunosuppressants, as this increases PML risk 5

4. Infusion Reactions:

   • Monitor for hypersensitivity reactions, particularly during the first infusion of natalizumab 6

5. Rebound Effect:

   • Be aware of potential disease reactivation when discontinuing natalizumab
   • Plan transition to alternative therapy carefully 7

In conclusion, while natalizumab remains the most commonly used monoclonal antibody in MS treatment due to its high efficacy, ocrelizumab has emerged as another important option, particularly for primary progressive MS. The choice between these agents should be guided by disease type, JCV antibody status, and other individual risk factors.