Is Ublituximab-xiiy (Briumvi) medically necessary for a patient with relapsing forms of multiple sclerosis?

Medical Necessity of Ublituximab-xiiy (Briumvi) for Relapsing Multiple Sclerosis

Yes, ublituximab-xiiy (Briumvi) is medically necessary for this patient with relapsing forms of multiple sclerosis, as the diagnosis and prescriber specialty criteria are met, and the medication has demonstrated significant reductions in relapse rates and MRI disease activity compared to active comparators. 1, 2

Indication and Approval Status

• Ublituximab is FDA-approved specifically for relapsing forms of MS, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease in adults. 1
• The patient's diagnosis of relapsing MS meets the labeled indication criteria. 1
• The prescriber specialty requirement (neurologist or MS specialist consultation) appears to be satisfied based on the documentation provided. 1

Evidence of Clinical Efficacy

Relapse Rate Reduction

• In the pivotal ULTIMATE I and II trials, ublituximab reduced annualized relapse rates by 59% (rate ratio 0.41) and 49% (rate ratio 0.51) respectively compared to teriflunomide, with both results highly statistically significant (P<0.001 and P=0.002). 2
• The annualized relapse rate with ublituximab was 0.08-0.09 across both trials, demonstrating profound disease control. 2
• In phase 2 studies, ublituximab achieved an annualized relapse rate of 0.07, with 93% of patients remaining relapse-free. 3

MRI Disease Activity

• Ublituximab reduced gadolinium-enhancing lesions by 97% (rate ratio 0.03) in ULTIMATE I and 96% (rate ratio 0.04) in ULTIMATE II compared to teriflunomide (P<0.001 for both). 2
• The mean number of gadolinium-enhancing lesions was 0.01-0.02 with ublituximab versus 0.25-0.49 with teriflunomide. 2
• Phase 2 data showed complete elimination of T1 gadolinium-enhancing lesions at weeks 24 and 48 (p=0.003), with a 10.6% decrease in T2 lesion volume (p=0.002). 3

No Evidence of Disease Activity (NEDA)

• In phase 2 studies, 74% of patients achieved NEDA status on ublituximab. 3
• Network meta-analysis demonstrated no statistically significant difference between ublituximab and other high-efficacy monoclonal antibodies (ocrelizumab, ofatumumab, natalizumab, alemtuzumab) for relapse rates or disability progression. 4

Critical Pre-Treatment Requirements

Laboratory Screening (UNSURE IF MET - Requires Verification)

• Hepatitis B virus screening is mandatory before the first dose, including HBsAg and anti-HBV core antibody testing. 1
• Quantitative serum immunoglobulin levels must be measured before initiating therapy. 1
• The documentation indicates these tests were ordered (page 12), but results must be documented and reviewed before proceeding with infusion. 1
• If HBsAg is positive, ublituximab is contraindicated. 1
• If HBcAb is positive but HBsAg is negative, consult hepatology before proceeding. 1
• If immunoglobulin levels are low, consult immunology before initiating treatment. 1

Premedication Protocol (MET)

• Methylprednisolone 100 mg IV (or equivalent corticosteroid) must be administered approximately 30 minutes before each infusion. 1
• An antihistamine (e.g., diphenhydramine) must be given orally or IV approximately 30-60 minutes before each infusion. 1
• Addition of an antipyretic (e.g., acetaminophen) may be considered. 1

Dosing Schedule (MET)

• First infusion: 150 mg IV (MET - documented on page 18). 1
• Second infusion: 450 mg IV two weeks after the first infusion (MET - documented on page 22). 1
• Subsequent infusions: 450 mg IV every 24 weeks thereafter. 1

Safety Considerations

Infusion-Related Reactions

• Infusion-related reactions occurred in 47.7% of patients in the ULTIMATE trials, but all were grade 1-2 in severity. 2
• Patients must be observed for at least one hour after completion of the first two infusions. 1
• Post-infusion monitoring of subsequent infusions is at physician discretion unless reactions have occurred. 1

Infection Risk

• Serious infections occurred in 5.0% of ublituximab-treated patients versus 2.9% with teriflunomide. 2
• Active infection must be ruled out before every infusion; delay infusion until infection resolves. 1
• Live or live-attenuated vaccines should be administered at least 4 weeks before starting ublituximab. 1
• Non-live vaccines should be given at least 2 weeks before initiation whenever possible. 1

Mechanism and B-Cell Depletion

• Ublituximab is a glycoengineered anti-CD20 monoclonal antibody with enhanced antibody-dependent cellular cytotoxicity (ADCC). 3, 5
• Median B-cell depletion exceeds 99% by week 4 and is maintained through weeks 24 and 48. 3

Comparative Effectiveness

• Network meta-analysis showed no statistically significant difference between ublituximab and other high-efficacy anti-CD20 monoclonal antibodies (ocrelizumab, ofatumumab) for annualized relapse rate or confirmed disability progression. 4
• Ublituximab offers the advantage of shorter infusion times (1-4 hours for first dose, 1-3 hours for subsequent doses) compared to other anti-CD20 therapies due to its enhanced ADCC mechanism. 3
• Treatment discontinuation rates were comparable between ublituximab and other monoclonal antibodies except alemtuzumab. 4

Critical Action Items Before Approval

1. Verify and document Hepatitis B screening results (HBsAg and HBcAb). 1
2. Verify and document quantitative serum immunoglobulin results. 1
3. Confirm premedication orders are in place (methylprednisolone and antihistamine). 1
4. Ensure infusion will occur under supervision with access to manage severe reactions. 1
5. Confirm pregnancy testing for females of reproductive potential. 1