Are Kesimpta (ofatumumab) and Tysabri (natalizumab) comparable in efficacy and safety for multiple sclerosis?

Comparison of Kesimpta and Tysabri for Multiple Sclerosis

Kesimpta (ofatumumab) and Tysabri (natalizumab) are both highly effective disease-modifying therapies for multiple sclerosis, but they have different safety profiles, with Tysabri carrying a higher risk of progressive multifocal leukoencephalopathy (PML), making Kesimpta a safer option with comparable efficacy for most patients with relapsing forms of MS.

Mechanism of Action and Classification

• Kesimpta (ofatumumab): Fully human anti-CD20 monoclonal antibody that depletes B cells, self-administered subcutaneously 1
• Tysabri (natalizumab): Monoclonal antibody that blocks alpha-4 integrin interactions, preventing inflammatory cells from crossing the blood-brain barrier, administered intravenously 2

Both are classified as high-efficacy disease-modifying therapies for multiple sclerosis 3.

Efficacy Comparison

Clinical Efficacy

• Both medications significantly reduce annual relapse rates and MRI lesion activity in relapsing forms of MS
• Ofatumumab demonstrated low annualized relapse rates (ARR 0.05) through 4 years of treatment 4
• Natalizumab has shown efficacy in reducing relapses with a cumulative probability of relapse of only 1.9% in comparative studies 5
• In the Tysabri Observational Program (TOP), natalizumab reduced mean annualized relapse rate from 1.99 to 0.31 6

Comparative Efficacy

• No direct head-to-head studies comparing ofatumumab and natalizumab are available
• Both are considered high-efficacy therapies by the National Multiple Sclerosis Society and American Academy of Neurology 3
• Both medications have demonstrated superior efficacy compared to lower-efficacy treatments in their respective trials

Safety Profile Comparison

Kesimpta (ofatumumab) Safety

• Most common adverse events: nasopharyngitis, headache, upper respiratory tract infections, and urinary tract infections 1
• No apparent association between changes in immunoglobulin levels and serious infections after 3.5 years 1
• No reported cases of PML in clinical trials or post-marketing data to date
• Self-administration route (subcutaneous) increases convenience 1

Tysabri (natalizumab) Safety

• Associated with risk of progressive multifocal leukoencephalopathy (PML), especially in JCV antibody-positive patients 3
• Risk of PML is stratified by anti-JCV antibody status and index 3
• Requires regular JCV antibody testing every 6 months and MRI surveillance 3
• Requires intravenous administration in a healthcare setting

Key Differences and Considerations

1. Administration route:

   • Kesimpta: Self-administered subcutaneous injection
   • Tysabri: Intravenous infusion requiring healthcare facility visits

2. Monitoring requirements:

   • Kesimpta: Standard monitoring
   • Tysabri: Requires JCV antibody testing every 6 months and more frequent MRI surveillance in JCV-positive patients 3

3. PML risk:

   • Kesimpta: No established PML risk to date
   • Tysabri: Well-documented risk of PML, especially in JCV-positive patients with longer duration of use 3

4. Washout period:

   • Switching between these medications requires careful consideration of washout periods to avoid overlapping immunosuppressive effects

Clinical Decision Algorithm

1. For JCV antibody-negative patients: Both medications are reasonable options, with decision based on:

   • Patient preference for administration route
   • Insurance coverage and cost considerations
   • Comorbidities

2. For JCV antibody-positive patients: Kesimpta generally preferred due to lower PML risk

3. For highly active disease requiring rapid control:

   • Tysabri may have slightly faster onset of action
   • Consider short-term use of Tysabri in JCV-negative patients with aggressive disease

4. For patients with adherence concerns:

   • Tysabri offers supervised administration
   • Kesimpta requires patient self-administration but at more convenient intervals

Therapeutic Alternatives

These medications can be considered therapeutic alternatives in:

• JCV antibody-negative patients
• Patients with highly active relapsing MS requiring high-efficacy treatment
• Patients who have failed other disease-modifying therapies

They are not therapeutic alternatives in:

• JCV antibody-positive patients with high antibody index (Kesimpta preferred)
• Patients with primary progressive MS (neither is first-line)

Conclusion

While both Kesimpta and Tysabri are highly effective disease-modifying therapies for relapsing forms of MS, their different safety profiles—particularly regarding PML risk—and administration routes make them distinct options that must be carefully selected based on individual patient factors, with JCV antibody status being a critical differentiator.