Introduction
Kesimpta (ofatumumab) is a human monoclonal antibody targeting CD20-positive B lymphocytes, approved for the treatment of relapsing forms of multiple sclerosis (MS). It represents a significant advancement in MS therapy as the first fully human anti-CD20 monoclonal antibody that can be self-administered via subcutaneous injection.
Mechanism of Action
Kesimpta binds specifically to the CD20 antigen present on the surface of pre-B and mature B lymphocytes. This binding results in antibody-dependent cellular cytolysis and complement-mediated lysis of B cells. By depleting CD20+ B cells, Kesimpta modulates the immune system and reduces inflammatory activity in the central nervous system, which is believed to drive the pathophysiology of multiple sclerosis.
Indications
Kesimpta is indicated for the treatment of:
- Relapsing forms of multiple sclerosis (RMS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease in adults
Dosage and Administration
Initial dosing:- Week 0: 20 mg subcutaneous injection
- Week 1: 20 mg subcutaneous injection
- Week 2: 20 mg subcutaneous injection
- 20 mg subcutaneous injection every 4 weeks starting at week 4
- For subcutaneous use only
- Administer in thigh, abdomen, or back of upper arm
- Rotate injection sites
- Allow prefilled syringe to reach room temperature (15-30 minutes) before administration
- Renal impairment: No dosage adjustment necessary
- Hepatic impairment: No dosage adjustment necessary
- Elderly: No dosage adjustment recommended
- Pediatrics: Safety and effectiveness not established
Pharmacokinetics
Absorption: Bioavailability approximately 70-80% following subcutaneous administration Distribution: Volume of distribution approximately 5.7 L; minimal extravascular distribution Metabolism: Cleared via proteolytic pathways; no hepatic metabolism via CYP450 enzymes Elimination: Half-life approximately 16 days; clearance approximately 0.29 L/day Steady-state: Achieved at approximately 12 weeks with monthly dosingContraindications
- Active hepatitis B virus infection
- History of life-threatening infusion reactions to ofatumumab
- Severe active infection (until resolution)
Warnings and Precautions
Infections: Increased risk of serious infections including bacterial, viral, fungal, and opportunistic infections. Screen for tuberculosis before initiation. Hepatitis B reactivation: May cause reactivation of HBV. Screen all patients before treatment initiation. Immunizations: Avoid live vaccines during and after treatment until B-cell repletion Progressive multifocal leukoencephalopathy (PML): Although not reported with Kesimpta, PML has occurred with other anti-CD20 therapies Injection-related reactions: May occur including erythema, pain, pruritus, and swelling at injection site Reduction in immunoglobulins: Monitor IgG levels during treatmentDrug Interactions
- Live vaccines: Contraindicated due to risk of vaccine-induced infection
- Immunosuppressants: May increase risk of immunosuppression
- CYP450 substrates: Kesimpta does not affect CYP450 enzymes, but may affect responses to drugs metabolized by these enzymes due to cytokine changes
Adverse Effects
Most common adverse reactions (≥10%):- Upper respiratory tract infections
- Headache
- Injection-related reactions
- Urinary tract infections
- Infections
- Immunoglobulin decreased
- Neutropenia
- Erythema (20%)
- Pain (15%)
- Swelling (10%)
- Pruritus (8%)
Monitoring Parameters
Before initiation:- Complete blood count with differential
- Hepatitis B serology
- Tuberculosis screening
- Quantitative immunoglobulins (IgG)
- CBC with differential (monthly for first 6 months, then every 3 months)
- Quantitative immunoglobulins (every 6 months)
- Signs and symptoms of infection
- Liver function tests (as clinically indicated)
- Injection site reactions
- Monitor for B-cell repletion (CD19+ count >80 cells/μL or baseline)
- Continue infection monitoring for several months after discontinuation
Patient Education
Self-administration:- Proper injection technique and site rotation
- Storage requirements (refrigerate at 2-8°C, protect from light)
- Allow syringe to reach room temperature before use
- Report any signs of infection (fever, chills, cough, sores)
- Avoid contact with people who have infections
- Discuss vaccination status with healthcare provider before starting treatment
- Keep all scheduled laboratory appointments
- Report any new or worsening neurological symptoms
- Inform all healthcare providers about Kesimpta treatment
- Discuss family planning with healthcare provider
- Registry available for pregnant patients exposed to Kesimpta
References
1. Hauser SL, Bar-Or A, Cohen JA, et al. Ofatumumab versus Teriflunomide in Multiple Sclerosis. N Engl J Med. 2020;383(6):546-557. 2. Kesimpta [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2020. 3. Bar-Or A, Grove RA, Austin DJ, et al. Subcutaneous ofatumumab in patients with relapsing-remitting multiple sclerosis: The MIRROR study. Neurology. 2018;90(20):e1805-e1814. 4. Multiple Sclerosis Therapy Consensus Group (MSTCG). White Paper: Ofatumumab in the treatment of multiple sclerosis. Ther Adv Neurol Disord. 2021;14:17562864211039648. 5. US Food and Drug Administration. Kesimpta approval letter. August 2020.
This information is provided for educational purposes only and does not constitute medical advice. Patients should consult their healthcare providers for personalized medical guidance.
