Introduction
Briumvi (ublituximab-xiiy) is a novel anti-CD20 monoclonal antibody approved for the treatment of relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease. As the first anti-CD20 monoclonal antibody administered as a 1-hour infusion every 6 months, Briumvi represents a significant advancement in MS treatment convenience and accessibility.
Mechanism of Action
Briumvi is a glycoengineered monoclonal antibody that targets the CD20 antigen expressed on pre-B and mature B lymphocytes. The mechanism involves:
- Binding to CD20 surface antigens on B cells
- Recruiting natural killer cells and macrophages via enhanced affinity for FcγRIIIa receptors
- Mediating antibody-dependent cellular cytotoxicity (ADCC)
- Complement-dependent cytotoxicity (CDC)
- Induction of antibody-dependent cellular phagocytosis
The glycoengineering process removes certain sugar molecules from the Fc region, enhancing binding affinity to FcγRIIIa receptors on effector cells, resulting in potent B-cell depletion while potentially allowing for lower dosing compared to other anti-CD20 therapies.
Indications
Briumvi is indicated for the treatment of:
- Relapsing forms of multiple sclerosis in adults
- Clinically isolated syndrome
- Relapsing-remitting multiple sclerosis
- Active secondary progressive multiple sclerosis
Dosage and Administration
Initial Dose:- 150 mg intravenous infusion over 4 hours
- Administered after completion of initial corticosteroid premedication
- 450 mg intravenous infusion over 4 hours
- Administered 2 weeks after the first infusion
- 450 mg intravenous infusion over 1 hour
- Administered every 24 weeks (6 months) after the second dose
- Methylprednisolone 100 mg IV or equivalent corticosteroid
- Antihistamine (e.g., diphenhydramine)
- Antipyretic (e.g., acetaminophen)
- Renal impairment: No dosage adjustment recommended
- Hepatic impairment: Not studied; use with caution
- Elderly: No specific dosage adjustment recommended
- Pediatric: Safety and effectiveness not established
Pharmacokinetics
Absorption:- Administered intravenously, resulting in complete bioavailability
- Steady-state volume of distribution: approximately 3.1-4.5 L
- Binds specifically to CD20-positive B cells
- Expected to be metabolized via proteolytic catabolism into small peptides and amino acids
- No cytochrome P450-mediated metabolism
- Terminal half-life: approximately 22 days
- Clearance: approximately 0.18 L/day
- Linear pharmacokinetics observed at therapeutic doses
Contraindications
- Active hepatitis B virus infection
- History of life-threatening infusion reaction to Briumvi
- Active tuberculosis or other serious infections
- Severe, active hepatic disease
- Hypersensitivity to ublituximab-xiiy or any component of the formulation
Warnings and Precautions
Infusion Reactions:- May occur during and up to 24 hours after infusion
- Symptoms include fever, chills, headache, nausea, pruritus, and bronchospasm
- Premedication required to reduce frequency and severity
- Monitor patients during infusion and for at least 1 hour post-infusion
- Increased risk of bacterial, viral, and fungal infections
- Screen for hepatitis B and tuberculosis prior to initiation
- Delay administration in patients with active infection until resolved
- Consider prophylactic antivirals for herpes virus infections
- Monitor liver function tests before treatment and periodically during therapy
- Cases of drug-induced liver injury reported
- Administer all necessary vaccines prior to treatment initiation
- Avoid live attenuated vaccines during treatment
- Briumvi may reduce effectiveness of non-live vaccines
- Although not reported with Briumvi, PML has occurred with other anti-CD20 antibodies
- Monitor for neurological symptoms suggestive of PML
Drug Interactions
Immunosuppressive Therapies:- Concomitant use may increase risk of immunosuppression and infections
- Avoid concurrent use with other immunosuppressive agents
- Reduced immune response to vaccines
- Avoid live vaccines during and after treatment
- B-cell depletion may affect CYP450 activity
- Monitor drugs with narrow therapeutic index that are metabolized by CYP450 enzymes
Adverse Effects
Most Common Adverse Reactions (≥10%):- Infusion reactions (48%)
- Upper respiratory tract infections (12%)
- Herpes virus infections (10%)
- Serious infections (2.5%)
- Infusion reactions (0.5%)
- Hepatitis B reactivation
- Immunogenicity (anti-drug antibodies in 1.3% of patients)
- Decreased immunoglobulin levels (IgM)
- Decreased neutrophil count
- Increased liver transaminases
Monitoring Parameters
Prior to Initiation:- Complete blood count with differential
- Liver function tests
- Hepatitis B serology
- Tuberculosis screening
- Quantitative immunoglobulins
- Pregnancy testing in women of childbearing potential
- Monitor for infusion reactions during and for at least 1 hour post-infusion
- Regular assessment for signs and symptoms of infection
- Periodic liver function tests
- Monitor immunoglobulin levels (especially IgM)
- Neurological assessment for PML symptoms
- Annual quantitative immunoglobulin assessment
- Regular infection surveillance
- Monitoring for signs of hepatic injury
Patient Education
Treatment Expectations:- Explain the infusion process and time commitment
- Discuss the importance of premedication
- Inform about the 6-month dosing interval after initial loading doses
- Educate about signs and symptoms of infusion reactions
- Emphasize the importance of reporting any symptoms during or after infusion
- Advise prompt reporting of fever or signs of infection
- Discuss strategies to reduce infection risk
- Emphasize importance of avoiding sick contacts
- Complete recommended vaccinations before starting treatment
- Avoid live vaccines during therapy
- Inform healthcare providers about Briumvi treatment before receiving any vaccines
- Discuss family planning before initiation
- Use effective contraception during treatment
- Discuss potential risks with healthcare provider if pregnancy is planned
- Stress importance of regular monitoring appointments
- Encourage reporting of any new or worsening symptoms
References
1. Fox E, Lovett-Racke AE, Gormley M, et al. A phase 2b study of ublituximab in patients with relapsing forms of multiple sclerosis. Mult Scler. 2021;27(3):420-429. 2. TG Therapeutics, Inc. Briumvi (ublituximab-xiiy) prescribing information. 2022. 3. Hauser SL, Waubant E, Arnold DL, et al. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med. 2008;358(7):676-688. 4. FDA Approval Letter: Briumvi (ublituximab-xiiy). December 2022. 5. Cross AH, Stark JL, Lauber J, et al. Rituximab reduces B cells and T cells in cerebrospinal fluid of multiple sclerosis patients. J Neuroimmunol. 2006;180(1-2):63-70. 6. National Multiple Sclerosis Society. Disease-modifying therapies for MS. 2023. 7. Sorensen PS, Lisby S, Grove R, et al. Safety and efficacy of ofatumumab in relapsing-remitting multiple sclerosis: A phase 2 study. Neurology. 2014;82(7):573-581.
This monograph is intended for educational purposes only and should not replace clinical judgment. Always consult prescribing information and current clinical guidelines when making treatment decisions.