Is Mavenclad (Cladribine) preferable to Ocrevus (Ocrelizumab) or Kesimpta (Ofatumumab) for multiple sclerosis (MS) treatment?

Is Mavenclad Preferable to Ocrevus or Kesimpta for Multiple Sclerosis?

Mavenclad (cladribine) and Kesimpta (ofatumumab) are both classified as high-efficacy therapies with comparable effectiveness to Ocrevus (ocrelizumab), making the choice dependent on specific clinical factors rather than superiority of one agent over the others. 1

Comparative Efficacy Evidence

All three medications demonstrate high efficacy for relapsing multiple sclerosis:

• Cladribine and ofatumumab are definitively classified as high-efficacy therapies based on network meta-analysis comparing annualized relapse rates, placing them in the same efficacy tier 1
• Ocrelizumab is classified as moderate-to-high efficacy, with classification varying by analytical approach but consistently demonstrating substantial benefit 1
• Network meta-analysis shows ofatumumab is as effective as other highly efficacious monoclonal antibodies (alemtuzumab, natalizumab, ocrelizumab) for reducing relapse rates and confirmed disability progression at both 3 and 6 months 2

Key Differentiating Factors

Administration and Convenience

• Mavenclad offers the most convenient dosing: oral administration with only 8-10 treatment days per year over 2 years, then no further treatment required 3
• Kesimpta provides subcutaneous self-injection monthly after initial weekly loading doses 4
• Ocrevus requires intravenous infusions every 6 months with associated infusion time and monitoring 5

B-Cell Repopulation and Vaccination Response

This is a critical distinguishing feature:

• Ocrelizumab maintains profound B-cell depletion with only 3-5% of patients showing ≥1% B-cell repopulation at 6 months post-infusion, severely impairing vaccine responses including SARS-CoV-2 vaccination 6
• Cladribine allows B-cell recovery with 90-100% of patients exhibiting >1% B-cells during treatment, preserving vaccine responsiveness 6
• Ofatumumab's B-cell repopulation pattern is similar to other CD20 depletors but with monthly dosing may allow more flexibility 4

Safety and Monitoring Requirements

Mavenclad:

• Requires baseline lymphocyte monitoring and contraindicated in active infections 4
• No ongoing infusion-related reactions after treatment completion 3
• Provides targeted lymphocyte reduction in T and B cells with favorable intracellular metabolism in humans (unlike rodents where it failed preclinically due to species differences in deoxycytidine kinase ratios) 3

Ocrelizumab:

• Common infusion-related reactions requiring premedication 5
• Increased risk of upper respiratory and urinary tract infections 5
• Live-attenuated vaccines contraindicated during treatment 5
• Requires JC virus monitoring if switching from natalizumab 5

Kesimpta:

• Self-injection site reactions 4
• Similar infection risk profile to other CD20 depletors 4
• More convenient monitoring compared to IV therapies 4

Clinical Decision Algorithm

For patients requiring high-efficacy therapy, select based on:

1. Choose Mavenclad if:

   • Patient prioritizes minimal treatment burden after initial 2-year course 3
   • Vaccine responsiveness is important (e.g., younger patients, pandemic considerations) 6
   • Patient prefers oral administration 3
   • No contraindications to lymphocyte-depleting therapy 4

2. Choose Kesimpta if:

   • Patient prefers self-administration at home 4
   • Monthly dosing provides psychological reassurance of ongoing treatment 4
   • Avoiding infusion center visits is priority 4
   • Flexibility in B-cell repopulation timing may benefit vaccination schedules 6

3. Choose Ocrevus if:

   • Patient has primary progressive MS (only approved option among the three) 7, 8
   • Patient prefers supervised infusion setting 5
   • Extensive long-term safety data (≥7.5 years) is valued, showing sustained 39% relapse reduction and 40% disability progression reduction 5
   • Vaccination concerns are not paramount 6

Critical Caveats

The profound B-cell depletion with ocrelizumab significantly impairs seroconversion after vaccination, which became clinically relevant during COVID-19 but applies to all vaccines 6. If vaccination response is anticipated (routine immunizations, pandemic vaccines, travel vaccines), delaying ocrelizumab dosing intervals by 3-6 months may allow B-cell repopulation sufficient for seroconversion 6.

For progressive MS specifically, ocrelizumab remains the only approved option among these three for primary progressive disease, though its efficacy is limited primarily to slowing disability progression rather than preventing it 7, 8.

None of these agents should be discontinued prematurely as treatment should continue indefinitely in stable patients, with discontinuation exposing patients to unnecessary disease reactivation risk 5.