Ofatumumab
Overview
Ofatumumab is a fully human immunoglobulin G1 monoclonal antibody that targets the CD20 antigen expressed on the surface of B lymphocytes. Binding to CD20 results in depletion of B cells through immune mechanisms including complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity. The molecule belongs to the class of CD20-directed monoclonal antibodies and is administered either by subcutaneous injection or intravenous infusion depending on the approved indication and formulation. By reducing circulating B cells, ofatumumab modulates abnormal immune responses involved in autoimmune disease and B-cell malignancies. Clinically, it plays an important role in reducing relapse activity and disease progression in relapsing forms of multiple sclerosis and in controlling disease burden in chronic lymphocytic leukemia. Its targeted mechanism allows for focused immunomodulation under specialist supervision.
Background and Date of Approval
Ofatumumab was first approved by the United States Food and Drug Administration on October 26, 2009 for the treatment of relapsed or refractory chronic lymphocytic leukemia. This approval was based on clinical studies demonstrating B-cell depletion and disease control in patients who had failed prior therapies. A subcutaneous formulation of ofatumumab was later developed for autoimmune indications, leading to FDA approval in August 2020 for the treatment of relapsing forms of multiple sclerosis. In the European Union, ofatumumab received centralized marketing authorization on March 26, 2021 for relapsing multiple sclerosis. These approvals established ofatumumab as a therapy spanning both hematologic and neurologic disease areas.
Uses
Ofatumumab is indicated for the treatment of relapsing forms of multiple sclerosis in adults, including clinically isolated syndrome, relapsing-remitting multiple sclerosis, and active secondary progressive multiple sclerosis. It is also approved for use in chronic lymphocytic leukemia, where it may be used alone or as part of combination therapy in patients with relapsed or refractory disease. Its use is guided by disease activity, prior treatment exposure, and patient-specific clinical factors.
Administration
In multiple sclerosis, ofatumumab is administered by subcutaneous injection with an initial loading phase followed by once-monthly maintenance dosing. The standard regimen consists of three initial doses given at weekly intervals, followed by ongoing monthly administration. In chronic lymphocytic leukemia, ofatumumab is administered as an intravenous infusion according to defined treatment cycles and dosing schedules. Dosing decisions are individualized based on indication, treatment response, tolerability, and clinical monitoring requirements.
Side Effects
Common side effects associated with ofatumumab include injection site reactions, upper respiratory tract infections, headache, fatigue, fever, and nasopharyngitis. In patients receiving intravenous therapy for chronic lymphocytic leukemia, additional commonly reported effects include neutropenia, anemia, diarrhea, cough, rash, and pneumonia. The severity and frequency of side effects vary among individuals and are generally manageable with appropriate medical oversight.
Warnings
Serious adverse events linked to ofatumumab include an increased risk of serious infections, reactivation of hepatitis B virus, and rare cases of progressive multifocal leukoencephalopathy. Severe infusion-related or injection-related reactions and significant hematologic abnormalities may occur. Ofatumumab is contraindicated in patients with active hepatitis B infection and should be used cautiously in individuals with underlying immunosuppression. Treatment interruption or discontinuation may be required in the presence of serious toxicity or uncontrolled infection. Pregnancy-related risks should be assessed before initiating therapy.
Precautions
Baseline evaluation before starting ofatumumab includes screening for hepatitis B infection, assessment of infection risk, complete blood counts, and review of vaccination status. Live vaccines should not be administered during treatment, and non-live vaccines should preferably be given prior to therapy initiation. Special caution is required in elderly patients and those with hepatic impairment or recurrent infections. Drug interactions are primarily related to additive immunosuppressive effects when used with other immunomodulatory or immunosuppressive therapies.
Expert Tips
Appropriate patient selection for ofatumumab requires assessment of disease activity, prior treatment history, and infection risk. Baseline laboratory testing should be completed before initiation and repeated periodically during treatment. Patients should be counselled on recognizing early signs of infection and adhering to prescribed dosing schedules. For subcutaneous administration, proper injection technique and storage conditions should be explained clearly. Coordination with other therapies is important to minimize cumulative immunosuppression and ensure safe long-term management.