Usage
Ofatumumab is prescribed for the treatment of relapsing forms of multiple sclerosis (MS) in adults. This includes clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease. Ofatumumab is classified as a disease-modifying therapy (DMT) specifically, a monoclonal antibody and further, a CD20-directed cytolytic antibody. It works by targeting and depleting CD20-positive B cells, which are thought to play a key role in the autoimmune response that drives MS.
Alternate Names
Ofatumumab is also known by the brand name Kesimpta. Arzerra is another brand name but relates to an intravenous formulation used in oncology and is distinct from the subcutaneous formulation used for MS.
How It Works
Pharmacodynamics: Ofatumumab binds to the CD20 antigen on the surface of B cells. This triggers a cascade of immunological mechanisms, including antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and apoptosis (programmed cell death), leading to the depletion of B cells. Ofatumumab’s targeted action on B cells modulates the immune system, reducing the inflammatory attacks on the myelin sheath that characterize MS.
Pharmacokinetics: Ofatumumab, when administered subcutaneously for MS, is thought to be primarily absorbed through the lymphatic system. It demonstrates non-linear pharmacokinetics due to its decreasing clearance over time as B cells are depleted. The half-life at steady state is approximately 16 days following repeated subcutaneous administration of 20 mg. Elimination pathways are predominantly through B-cell lysis and not specifically through hepatic or renal routes.
Dosage
Standard Dosage
Adults:
The standard dose is 20 mg administered subcutaneously. The initial dosing regimen consists of 20 mg injections at weeks 0, 1, and 2. After the initial doses, maintenance dosing continues with 20 mg once a month, starting at week 4.
Children:
The safety and efficacy of ofatumumab have not been established in children under 18 years of age.
Special Cases:
- Elderly Patients (≥55 years): No dedicated studies have been conducted in this age group due to limited clinical experience. Dose adjustments are not specifically recommended, but close monitoring is advisable.
- Patients with Renal Impairment: No dedicated studies have been conducted in patients with renal impairment. As elimination is not primarily renal, dose adjustments may not be necessary.
- Patients with Hepatic Dysfunction: No dedicated studies have been conducted in patients with hepatic impairment. As elimination is not primarily hepatic, dose adjustments may not be necessary.
- Patients with Comorbid Conditions: Patients with active HBV infection should not receive ofatumumab. Pre-screening for HBV and other infections and quantitative serum immunoglobulins is essential. Use with caution in patients with a history of HBV or other infections. Dose adjustments based on other comorbidities are not specified, but individualized assessment and monitoring are crucial.
Clinical Use Cases
Ofatumumab is specifically indicated for the long-term management of relapsing MS, not for acute situations like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
If a dose is missed, it should be administered as soon as possible without waiting until the next scheduled dose. Subsequent doses should then be administered at the recommended monthly intervals.
Side Effects
Common Side Effects:
Upper respiratory tract infections (e.g., common cold), injection-related reactions (e.g., flushing, itching, hives), injection site reactions (e.g., redness, pain, swelling), urinary tract infections, headache, fever, and muscle pain.
Rare but Serious Side Effects:
Serious infections (including life-threatening and fatal infections), reactivation of hepatitis B virus (HBV) in patients with prior infection, progressive multifocal leukoencephalopathy (PML), and decreased immunoglobulin levels.
Long-Term Effects:
The long-term effects of ofatumumab treatment are still being evaluated, but continued monitoring for infections and immunoglobulin levels is essential.
Adverse Drug Reactions (ADR):
Anaphylaxis, severe injection-related reactions, and signs of PML (e.g., new or worsening neurological symptoms) require immediate medical attention.
Contraindications
Absolute contraindications include active HBV infection, severe active infections, known active malignancy, a history of PML, and a severely immunocompromised state.
Drug Interactions
Ofatumumab can interact with other medications, including live attenuated or live vaccines (not recommended during and after treatment until B-cell repletion), and may reduce the efficacy of some vaccines. Consult a comprehensive drug interaction resource before co-administering with other medications. It is important to disclose all concurrent medications, including over-the-counter drugs and supplements, to the prescribing physician.
Pregnancy and Breastfeeding
- Pregnancy: The safety of ofatumumab in pregnancy has not been fully established. It is recommended to avoid pregnancy during treatment and for 6 months after discontinuation.
- Breastfeeding: Current guidelines suggest breastfeeding is acceptable while using ofatumumab.
Drug Profile Summary
- Mechanism of Action: CD20-directed cytolytic antibody that depletes B cells.
- Side Effects: Common: Upper respiratory infections, injection-related reactions, injection site reactions, urinary tract infections. Serious: Severe infections, HBV reactivation, PML.
- Contraindications: Active HBV infection, severe active infections, active malignancy, history of PML, severely immunocompromised state.
- Drug Interactions: Live vaccines, consult a drug interaction resource for a complete list.
- Pregnancy & Breastfeeding: Avoid pregnancy during and for 6 months following treatment. Breastfeeding generally acceptable.
- Dosage: 20 mg subcutaneously at weeks 0, 1, and 2, followed by 20 mg monthly starting at week 4.
- Monitoring Parameters: B-cell counts, immunoglobulin levels, liver function tests (for patients with HBV history), signs of infection.
Popular Combinations
Ofatumumab is typically used as monotherapy in MS. Combining it with other DMTs is not standard practice and requires careful consideration and monitoring due to the increased risk of immunosuppression and adverse events.
Precautions
- General Precautions: Screen for HBV and other infections, assess immunoglobulin levels before and during treatment.
- Specific Populations: Pregnant women: Assess the risks and benefits carefully. Breastfeeding mothers: Monitor infant for potential side effects. Children and Elderly: No specific recommendations, but close monitoring is advisable.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Ofatumumab in relapsing MS?
A: 20 mg subcutaneously at weeks 0, 1, and 2, followed by 20 mg monthly starting at week 4.
Q2: What is the mechanism of action of Ofatumumab?
A: It’s a CD20-directed cytolytic antibody that targets and depletes B cells.
Q3: What are the most common side effects of Ofatumumab?
A: Upper respiratory tract infections, injection site reactions, injection-related reactions, and urinary tract infections.
Q4: Is Ofatumumab safe to use during pregnancy?
A: The safety in pregnancy hasn’t been fully established. Avoid pregnancy during treatment and for 6 months after the last dose.
Q5: Can patients breastfeed while taking Ofatumumab?
A: Current guidelines indicate it is generally acceptable to breastfeed.
Q6: What are the contraindications for Ofatumumab?
A: Active HBV infection, severe active infections, active malignancy, history of PML, and severely immunocompromised state.
Q7: Does Ofatumumab interact with other medications?
A: Yes, it can interact with live vaccines and potentially other medications. Consult a drug interaction resource or pharmacist before starting any new medications.
Q8: What monitoring is required for patients on Ofatumumab?
A: B-cell counts, immunoglobulin levels, liver function (for patients with HBV history) and vigilance for signs of infections.
Q9: How is Ofatumumab administered?
A: Via subcutaneous injection.
Q10: What should be done if a dose of Ofatumumab is missed?
A: Administer the missed dose as soon as possible and continue with the regular monthly schedule thereafter.
