Kesimpta (Ofatumumab) for Relapsing Multiple Sclerosis
Kesimpta is indicated for adults with relapsing forms of multiple sclerosis (including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease), administered as 20 mg subcutaneous injections with initial dosing at Weeks 0,1, and 2, followed by monthly 20 mg injections starting at Week 4. 1
Indication
Kesimpta is a fully human anti-CD20 monoclonal antibody approved for treatment of relapsing forms of MS in adults 1. This includes:
- Clinically isolated syndrome
- Relapsing-remitting disease
- Active secondary progressive disease
The drug works by depleting B cells through binding to a unique membrane-proximal CD20 epitope, achieving rapid and sustained B-cell depletion 2, 3.
Dosing Schedule
Initial Loading Phase:
- 20 mg subcutaneous injection at Week 0
- 20 mg subcutaneous injection at Week 1
- 20 mg subcutaneous injection at Week 2
Maintenance Phase:
- 20 mg subcutaneous injection once monthly starting at Week 4 1
Administration details:
- Inject into abdomen, thigh, or outer upper arm
- Avoid areas with moles, scars, stretch marks, or damaged skin
- The first injection must be performed under healthcare professional guidance 1
- Subsequent injections can be self-administered using the Sensoready® pen or prefilled syringe
- Allow medication to reach room temperature for 15-30 minutes before injection 1
If a dose is missed: Administer as soon as possible without waiting for the next scheduled dose, then resume the monthly schedule 1.
Pre-Treatment Requirements
Before initiating Kesimpta, you must complete three critical assessments 1:
1. Hepatitis B Virus Screening
- Test for HBsAg and anti-HBV antibodies
- Kesimpta is contraindicated in active HBV infection 1
- For HBsAg-negative but HBcAb-positive patients, or HBV carriers, consult liver disease experts before starting treatment
2. Serum Immunoglobulin Testing
- Measure quantitative serum immunoglobulins
- For patients with low immunoglobulins, consult immunology experts before initiating therapy 1
3. Vaccination Status
- Administer all live or live-attenuated vaccines at least 4 weeks before starting Kesimpta
- Administer inactivated vaccines at least 2 weeks before starting Kesimpta whenever possible 1
- Live vaccines are not recommended during treatment or after discontinuation until B-cell repletion occurs
Monitoring Requirements
MRI Monitoring
While the FDA label does not specify mandatory MRI intervals for ofatumumab specifically, general MS monitoring guidelines recommend 4:
- Annual brain MRI at minimum for routine disease monitoring
- MRI protocol should include T2-FLAIR, T2-weighted, and gadolinium-enhanced T1-weighted sequences
- More frequent monitoring (every 3-4 months) may be warranted when switching from other high-efficacy therapies like natalizumab due to risk of carry-over opportunistic infections 4
Clinical Monitoring
- Assess for infections, particularly in patients switching from high-efficacy therapies (infections occurred in 9.5% of HET switchers vs 0.9% of treatment-naïve patients in real-world data) 5
- Monitor for injection-related reactions, which are typically mild and transient 6, 5, 7
- Evaluate disability progression using EDSS at regular intervals
- Monitor for upper respiratory tract infections, urinary tract infections, and nasopharyngitis (most common adverse events) 6
Laboratory Monitoring
- Periodic assessment of immunoglobulin levels during treatment (no apparent association between IgG/IgM changes and serious infections after 3.5 years, but monitoring remains prudent) 6
- B-cell counts deplete rapidly (median from 214 cells/µL at baseline to 2 cells/µL by Day 14) 3
Clinical Efficacy Context
Real-world and trial data demonstrate that ofatumumab achieves:
- 94.5% reduction in annualized relapse rate 5
- 79.3-91% NEDA-3 rates at 12 months 5, 7
- Comparable outcomes between treatment-naïve patients and those switching from other therapies 5, 7
- Higher baseline EDSS is the primary predictor of suboptimal response, emphasizing the importance of early treatment initiation 7, 8
Key Safety Considerations
- Generally well-tolerated with low discontinuation rates (2.2% in real-world studies) 7
- Injection-related reactions are the most common adverse event but typically mild 6, 5
- Enhanced infection monitoring is warranted for patients switching from high-efficacy therapies 5
- Contraindicated in active HBV infection 1
- Pregnancy planning requires treatment discontinuation with favorable outcomes reported 5