Continuation of Briumvi for Relapsing Multiple Sclerosis Without Recent Clinical Evaluation
Yes, continuation of Briumvi (ublituximab) is medically necessary for this patient with relapsing multiple sclerosis, as disease-modifying therapies for RMS should not be interrupted without evidence of treatment failure, serious adverse events, or disease progression, and the absence of recent clinical notes does not constitute grounds for discontinuation. 1
Rationale for Continuous Treatment
Briumvi is FDA-approved for relapsing forms of MS and functions as a B-cell depleting anti-CD20 monoclonal antibody that requires continuous administration to maintain therapeutic B-cell depletion. 1, 2 The mechanism involves sustained suppression of pathogenic B-cells, and interruption of therapy leads to B-cell reconstitution and potential disease reactivation 1, 2.
Critical Evidence Supporting Continuation
The ULTIMATE I and II trials demonstrated that ublituximab significantly reduces annualized relapse rates (0.08-0.09 vs 0.18-0.19 with teriflunomide) and MRI lesion activity in relapsing MS patients 3.
Ublituximab ranks among the three most efficacious disease-modifying therapies for reducing annualized relapse rate in relapsing MS, alongside other monoclonal antibody therapies 4.
The standard dosing regimen for Briumvi after initial loading doses is 450 mg every 24 weeks (twice yearly), and missing scheduled doses compromises disease control 5, 3.
Why Clinical Visit Timing Does Not Justify Treatment Interruption
The absence of a recent doctor's visit does not constitute a valid reason to withhold scheduled disease-modifying therapy in stable MS patients. 6, 7 Here's the algorithmic approach:
Disease Stability Assessment Without Recent Visit
If the patient had documented disease stability at the last clinical evaluation (no new relapses, stable neurological examination, stable or improved MRI findings), continuation is appropriate until the next scheduled assessment 6, 7.
MS disease activity often occurs asymptomatically on MRI - approximately 80% of new lesions in relapsing-remitting MS show gadolinium enhancement during acute phases, but non-enhancing lesions still represent active disease 8, 7.
Clinical relapses represent only a fraction of total disease activity - MRI typically shows 5-10 times more lesions than clinical events would suggest 8.
The Danger of Treatment Interruption
Stopping B-cell depleting therapy allows rapid B-cell reconstitution, which can trigger disease reactivation and rebound inflammatory activity 1, 2.
The FDA label explicitly warns about immunosuppressant effects and the need for careful consideration when discontinuing therapy, emphasizing that treatment decisions should be based on active infection, serious adverse events, or confirmed disease progression - not administrative scheduling 1.
Monitoring Requirements During Continued Therapy
While continuing Briumvi, the following monitoring should occur regardless of visit timing:
Safety Monitoring Parameters
Quantitative serum immunoglobulin levels should be monitored during treatment, especially if the patient develops recurrent infections 1.
Complete blood count monitoring for cytopenias, particularly if any infectious complications arise 1, 3.
Hepatitis B screening status should be confirmed as negative before each infusion cycle 1.
Clinical Red Flags Requiring Immediate Evaluation
New neurological symptoms suggesting relapse (vision changes, weakness, sensory disturbances, coordination problems) require urgent clinical assessment before the next scheduled dose 9, 7.
Signs of progressive multifocal leukoencephalopathy (PML) including progressive weakness, vision disturbances, cognitive changes, or personality changes mandate immediate withholding of therapy and diagnostic workup 1.
Serious or opportunistic infections may require temporary discontinuation until resolution 1.
Infusion-related reactions (occurred in 47.7% of patients in clinical trials) should be managed with premedication but do not typically require discontinuation 3.
Common Pitfalls to Avoid
Do not conflate administrative scheduling gaps with clinical contraindications to therapy. The following are NOT valid reasons to withhold scheduled Briumvi:
- Lack of recent progress notes in the medical record 6, 7
- Scheduling delays for follow-up appointments 6, 7
- Absence of recent MRI if the patient is clinically stable 7
Do not delay treatment based on the timing of the next clinical visit - the scheduled infusion date is determined by pharmacokinetic and pharmacodynamic properties of the medication, not by clinic appointment availability 5, 3.
Specific Situations Requiring Treatment Delay
The only valid reasons to delay or discontinue Briumvi are:
- Active hepatitis B infection (HBsAg positive) 1
- Active serious infection or sepsis requiring treatment 1
- Confirmed PML diagnosis 1
- Pregnancy (requires contraception during treatment and 6 months after last dose) 1
- Severe infusion reactions requiring discontinuation 1, 3
- Documented disease progression to a non-relapsing phenotype 9, 1
Recommended Action Plan
Administer the scheduled Briumvi dose as planned, while simultaneously:
- Ensuring the follow-up appointment occurs within a reasonable timeframe (ideally within 3-6 months of the infusion) 7
- Obtaining updated laboratory monitoring (immunoglobulins, CBC) at the time of infusion 1
- Documenting any interval symptoms or concerns the patient reports at the infusion visit 6, 7
- Scheduling MRI surveillance according to disease activity patterns (every 6-12 months for stable patients) 7
The medical necessity of continuing Briumvi is established by the FDA-approved indication for relapsing MS, the demonstrated efficacy in preventing relapses and MRI activity, and the absence of any documented contraindications or treatment failure. 1, 3