Is the proposed medication or surgery medically indicated for a patient with relapsing-remitting Multiple Sclerosis (MS) who is currently stable or improving on Ublituximab-xiiy (Briumvi) (Ublituximab) 450 milligrams by Intravenous (IV) route every 180 days?

Continuation of Ublituximab (Briumvi) is Medically Indicated for This Stable Patient

For a patient with relapsing-remitting multiple sclerosis who is experiencing disease stability or improvement on Ublituximab-xiiy (Briumvi) 450 mg IV every 180 days, continuation of this therapy is medically indicated and represents appropriate standard of care. 1

FDA-Approved Indication and Dosing

• Briumvi is FDA-approved specifically for the treatment of relapsing forms of multiple sclerosis, including relapsing-remitting disease, in adults 1
• The prescribed regimen of 450 mg IV every 180 days (24 weeks) matches the FDA-approved maintenance dosing schedule exactly 1
• The standard dosing consists of: initial 150 mg infusion, followed by 450 mg two weeks later, then 450 mg every 24 weeks thereafter 1

Evidence Supporting Continuation in Stable Patients

The ULTIMATE I and II phase 3 trials demonstrated that ublituximab produces sustained disease control with continued treatment:

• Ublituximab resulted in an annualized relapse rate of 0.08-0.09 over 96 weeks of treatment, representing an approximately 50-60% reduction compared to teriflunomide 2
• The mean number of gadolinium-enhancing lesions was reduced to 0.01-0.02 with ublituximab versus 0.25-0.49 with teriflunomide (96-97% reduction) 2
• Patients who achieved disease stability maintained this benefit with continued treatment: 82.1% of ublituximab-treated patients achieved NEDA (no evidence of disease activity) during weeks 24-96 when re-baselined 3
• Even among patients who had some disease activity in the first year, 41.8% achieved NEDA in the second year of continued ublituximab treatment 3

Clinical Rationale for Continuation

Discontinuing effective B-cell depleting therapy in a stable MS patient would be inappropriate and contraindicated:

• B-cell depletion with ublituximab is maintained at >99% throughout the treatment period, and this sustained depletion is the mechanism of therapeutic benefit 4
• The phase 2 study demonstrated that 74% of patients maintained NEDA status with continued ublituximab therapy 4
• There is no evidence supporting treatment discontinuation in stable patients, and doing so would risk disease reactivation 2, 3

Safety Profile Supporting Long-Term Use

• The most common adverse events are infusion-related reactions (47.7%), which are typically grade 1-2 and manageable with premedication 2
• Serious infections occurred in 5.0% of ublituximab-treated patients over 96 weeks, a rate comparable to other disease-modifying therapies 2
• The FDA label requires infection assessment before each infusion, with treatment delay only if active infection is present 1
• No treatment-related deaths occurred in the ULTIMATE trials with ublituximab 2

Required Monitoring and Safety Assessments

Before each infusion, the following assessments are mandated by the FDA label:

• Screen for active infections and delay infusion if infection is present 1
• Pregnancy testing for females of reproductive potential 1
• Premedication with 100 mg IV methylprednisolone (or equivalent) approximately 30 minutes before infusion 1
• Premedication with antihistamine (e.g., diphenhydramine) 30-60 minutes before infusion 1
• Post-infusion observation is at physician discretion for subsequent infusions unless prior infusion reactions occurred 1

Critical Contraindications to Verify

• Active hepatitis B virus infection is an absolute contraindication to Briumvi 1
• Patients who are HBsAg negative but HBcAb positive require consultation with liver disease experts before continuing treatment 1
• Patients with low serum immunoglobulins require immunology consultation before continuing treatment 1

Common Pitfalls to Avoid

Do not discontinue ublituximab in a stable patient based on:

• Concerns about "overtreatment" - MS is a chronic disease requiring continuous disease-modifying therapy 2, 3
• Misinterpretation of stable disease as "cured" - relapsing MS requires ongoing immunomodulation to prevent relapses 2, 3
• Cost considerations alone - efficacy and patient outcomes must drive treatment decisions 2, 3

Do not delay scheduled infusions unnecessarily:

• If an infusion is missed, administer as soon as possible and reset the schedule to 24 weeks from that dose 1
• Infusions must be separated by at least 5 months (20 weeks) 1