ofatumumab SC

Action and Spectrum

Actions and spectrum:

• B-Cell Depletion: ofatumumab targets CD20, a surface antigen found on B cells. By binding to CD20, ofatumumab triggers the immune system to recognize and eliminate B cells. This leads to a reduction in the number of circulating B cells in the body.
• Complement-Dependent Cytotoxicity (CDC): ofatumumab can activate the complement system, a part of the immune system that enhances the destruction of targeted cells. The activation of complement proteins contributes to the elimination of B cells expressing CD20.
• Antibody-Dependent Cellular Cytotoxicity (ADCC): ofatumumab can also engage immune cells, such as natural killer (NK) cells, through their Fc receptors. This interaction promotes the destruction of B cells via ADCC.
• Apoptosis Induction: ofatumumab induces programmed cell death (apoptosis) in B cells expressing CD20, contributing to the depletion of these cells.

The spectrum of action for ofatumumab SC is primarily within the context of B-cell malignancies, especially CLL and relapsing forms of MS. In CLL, ofatumumab is used as a monotherapy or in combination with other agents to target malignant B cells. In MS, it is indicated for the treatment of relapsing forms to reduce frequency of relapses and slow down progression of disability.

Drug Interaction

Adverse Reaction

Frequency defined

1-10%

Back pain (8%)

Urinary tract infection (10%)

Blood IgM decreased (6%)

>10%

Systemic injection reactions (21%)

injection-site reactions (11%)

URTI (39%)

Headache (13%)

Black Box Warning

Black Box Warning:

There was no specific black box warning associated with ofatumumab subcutaneous (SC) administration.

Contraindication / Caution

Contraindication/Caution:

Contraindication:

• Hypersensitivity: ofatumumab subcutaneous (SC) is contraindicated in individuals with a known hypersensitivity or anaphylactic reaction to ofatumumab or any of its components.
• Active Infections: Patients with active, severe infections should not receive ofatumumab SC due to the risk of exacerbating the infection.
• Live Vaccines: Concomitant use of live vaccines is contraindicated during treatment with ofatumumab SC. Administration of live vaccines may pose a risk of uncontrolled replication of the vaccine virus.
• Patients with Hepatitis B Virus (HBV) Infection: ofatumumab SC is contraindicated in patients with active hepatitis B virus (HBV) infection. Reactivation of HBV can occur, leading to severe liver complications.
• Concurrent Use with Other Monoclonal Antibodies: The concurrent use of ofatumumab SC with other monoclonal antibodies is contraindicated. Safety and efficacy in combination with other monoclonal antibodies have not been established. 

Caution:

• Infusion-Related Reactions: Patients may experience infusion-related reactions during or after administration. Close monitoring is necessary, and premedication with antihistamines and antipyretics may be considered.
• Tumor Lysis Syndrome (TLS): Patients with high tumor burden may be at risk of TLS. Monitoring and appropriate management strategies should be implemented, especially during initial doses.
• Immunizations: Live vaccines should be avoided during and after treatment. Non-live vaccines may have reduced efficacy during treatment; vaccination schedules should be coordinated with the healthcare provider.
• Cardiovascular and Respiratory Disorders: Caution is advised in patients with pre-existing cardiovascular or respiratory conditions, as ofatumumab may exacerbate these conditions.
• Neutropenia: ofatumumab may cause neutropenia. Monitoring of blood counts is recommended, and dose adjustments may be necessary in cases of severe neutropenia.
• Pregnancy and Lactation: The use of ofatumumab during pregnancy should be carefully considered, and the potential risks and benefits should be discussed with pregnant or breastfeeding individuals.

Comorbidities:

• Chronic Lymphocytic Leukemia (CLL): CLL is a primary indication for ofatumumab SC. Patients with CLL often have comorbidities such as immunosuppression, infections, and autoimmune disorders.
• Multiple Sclerosis (MS): ofatumumab SC is also indicated for relapsing forms of MS. Patients with MS may have comorbidities including depression, anxiety, and other neurological conditions.
• Immunosuppression-Related Conditions: Given that ofatumumab is an immunosuppressive medication, individuals receiving treatment may be at an increased risk of infections. Patients with comorbidities that compromise the immune system need careful monitoring.
• Cardiovascular Conditions: Patients with cardiovascular comorbidities, such as hypertension or a history of heart disease, may need cautious use of ofatumumab. Monitoring for exacerbation of cardiovascular conditions is essential.
• Autoimmune Disorders: ofatumumab is used in the treatment of autoimmune conditions like MS. Patients with comorbid autoimmune disorders may need careful monitoring for potential exacerbation of their autoimmune conditions.

Respiratory Conditions: Patients with pre-existing respiratory conditions may have comorbidities that impact the respiratory system. Caution is advised as respiratory conditions may be exacerbated.

Pregnancy / Lactation

Pregnancy consideration: US FDA pregnancy category: Not assigned

Lactation: Excreted into human milk: Unknown

Pregnancy category:

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women.
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.

Category N: There is no data available for the drug under this category.

Pharmacology

Pharmacology:

ofatumumab subcutaneous (SC) is a monoclonal antibody with immunomodulatory properties primarily used in the treatment of certain B-cell malignancies and autoimmune disorders. As a fully humanized anti-CD20 antibody, ofatumumab selectively targets B cells by binding to the CD20 antigen on their surface.

These binding triggers immune-mediated mechanisms, including complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and induction of apoptosis. By engaging these pathways, ofatumumab leads to the depletion of CD20-positive B cells, thereby modulating the immune response.

The subcutaneous formulation allows for convenient administration, making ofatumumab a valuable option for patients with chronic lymphocytic leukemia and multiple sclerosis. The pharmacological actions of ofatumumab contribute to its efficacy in reducing disease activity and improving clinical outcomes in these conditions.

Pharmacodynamics:

• CD20 Binding: ofatumumab selectively binds to the CD20 antigen, which is expressed on the surface of B cells, including malignant B cells in conditions such as chronic lymphocytic leukemia (CLL) and B-cell-mediated autoimmune disorders like multiple sclerosis (MS).
• Immune Cell Engagement: By binding to CD20, ofatumumab activates immune effector functions. This includes complement-dependent cytotoxicity (CDC), where the complement system is recruited to lyse the targeted B cells.
• Antibody-Dependent Cellular Cytotoxicity (ADCC): ofatumumab engages natural killer (NK) cells and other immune cells through their Fc receptors, triggering antibody-dependent cellular cytotoxicity. This leads to the destruction of B cells expressing CD20.
• Apoptosis Induction: The binding of ofatumumab to CD20 on B cells induces programmed cell death (apoptosis). This mechanism contributes to the depletion of B cells involved in autoimmune processes or malignant transformations.
• B-Cell Depletion: The overall pharmacodynamic effect of ofatumumab is the depletion of CD20-positive B cells. This reduction in B-cell population is beneficial in autoimmune disorders to modulate the immune response and in B-cell malignancies to target and eliminate malignant cells.
• Immunomodulation: The modulation of B-cell activity and reduction in the number of circulating B cells contribute to the immunomodulatory effects of ofatumumab. This is particularly relevant in autoimmune disorders where B cells play a role in pathogenesis.

Pharmacokinetics:

Absorption:

ofatumumab is administered subcutaneously, leading to its absorption into the systemic circulation through the subcutaneous tissue. The subcutaneous route allows for a controlled and sustained release of the medication.

Distribution:

Following absorption, ofatumumab is distributed throughout the body via the bloodstream. The distribution may be influenced by factors such as blood flow and tissue permeability.

Metabolism:

Monoclonal antibodies like ofatumumab are primarily eliminated unchanged. Metabolism of these large molecules is not a major pathway. The primary catabolic process involves proteolytic degradation into smaller peptides and amino acids.

Excretion and Elimination Half-Life:

ofatumumab is eliminated from the body, through catabolism and subsequent excretion. The primary route of excretion is through non-specific proteolytic cleavage and elimination via the reticuloendothelial system. The elimination half-life of ofatumumab represents the time it takes for half of the drug to be cleared from the body.

Adminstartion

Administration:

Preparation:

• Ensure proper storage conditions for ofatumumab SC as per the manufacturer’s recommendations.
• Inspect the medication for any signs of contamination or particles. Do not use if the solution is discoloured or contains visible particles.

Injection Site:

• ofatumumab SC is typically administered in the thigh or abdomen.
• Rotate the injection sites to minimize the risk of injection site reactions.

Subcutaneous Injection Technique:

• Clean the injection site with alcohol swab and allow it to dry.
• Use aseptic technique throughout the injection process.
• Pinch the skin and inject the ofatumumab solution subcutaneously at a 45 to 90-degree angle.

Administer the injection slowly to minimize discomfort.

Patient Information Leaflet

Patient information leaflet

Generic Name: ofatumumab SC

Pronounced: (oh-fa-TOO-mu-mab)

Why do we use ofatumumab SC?

ofatumumab is used for the treatment of CLL, a type of leukemia characterized by the overproduction of abnormal B lymphocytes. It is used in combination with other therapies for both previously untreated and refractory CLL. It is also approved for the treatment of relapsing forms of MS.

It is used to reduce the frequency of clinical relapses and delay the progression of disability in patients with MS. In addition to CLL, ofatumumab has shown efficacy in the treatment of other B-cell malignancies, including indolent B-cell non-Hodgkin’s lymphoma (NHL) in patients who are refractory to rituximab and chemotherapy.