UBLITUXIMAB-XIIY INJ,SOLN
Clinical Criteria Summary
Document 468
Indications
- • Relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), and active secondary progressive MS (active SPMS).
Dosing & Administration
- • Intravenous infusion via single-dose vial.
- • First infusion: 150 mg; second infusion: 450 mg administered two weeks after the first.
- • Maintenance dosing: 450 mg every 24 weeks, starting 24 weeks after the first infusion.
- • Initial infusion duration approximately 4 hours; subsequent infusions approximately 1 hour.
Efficacy Outcomes
- • Significantly lower adjusted annualized relapse rate (ARR) compared to teriflunomide over 96 weeks.
- • Significant reduction in average number of contrast enhancing lesions and new or enlarged non-enhancing lesions.
- • No statistically significant difference in delay of disability progression or confirmed disability progression compared to teriflunomide.
Safety, Contraindications & Monitoring
- • Contraindicated in patients with active hepatitis B infection or a history of life-threatening infusion reaction to ublituximab.
- • Infusion reactions (e.g., fever, chills, headache, flu-like symptoms, tachycardia, nausea, erythema, anaphylaxis) occurred in 48% of patients, primarily with the first infusion. Pre-medication with a steroid, antihistamine, and acetaminophen is recommended; careful observation with pausing or discontinuation based on severity is warranted.
- • Infections were the most common adverse reaction (56% incidence), with approximately 5% classified as serious. Monitor for bacterial, fungal, and viral infections.
- • Decreased immunoglobulins (IgG and IgM) observed; declines below the lower limit of normal are associated with higher infection rates. Monitor immunoglobulins during treatment as clinically indicated.
- • Vaccination requirements: Administer live vaccines at least 4 weeks prior to initiation; administer non-live vaccines at least 2 weeks prior. Do not administer live vaccines while on therapy. Non-live vaccines may be administered during treatment.
- • Fetal risk: Transient B-cell depletion and lymphocytopenia reported in infants of mothers exposed to anti-CD20 antibodies. Recommend pregnancy testing for individuals of childbearing potential prior to each infusion. Counsel to use effective contraception during treatment and for at least 6 months after the last infusion.
Patient Selection & Trial Eligibility Criteria
- • Age 18–55 years with a relapsing form of MS.
- • Baseline Expanded Disability Status Scale (EDSS) score of 0 to 5.5.
- • Requirement for neurologic stability for 30 days prior to enrollment.
- • Excludes patients with ≥10 years disease duration and EDSS ≤2.
- • Requires washout periods for prior disease-modifying therapies (DMTs): anti-CD20 antibodies, alemtuzumab, natalizumab, teriflunomide, leflunomide, stem cell transplant; cladribine within 24 months; daclizumab, azathioprine, methotrexate, cyclophosphamide within 6 months; fingolimod, experimental S1P modulators, IVIg, plasmapheresis within 90 days; glatiramer, interferons, dimethyl fumarate, laquinimod, glucocorticoids within 30 days.
Place in Therapy & Clinical Considerations
- • Classified as a high-efficacy disease-modifying therapy (DMT) for MS.
- • May be considered for patients with highly active MS or those who have experienced therapeutic inefficacy from other DMTs.
- • Comparative efficacy data show no statistically significant difference in ARR between ublituximab, ocrelizumab, ofatumumab, and off-label rituximab.
- • Has one of the shorter infusion times among IV infused anti-CD20 antibodies.
Document 604
Exclusion Criteria
- Diagnosis of primary progressive multiple sclerosis (PPMS) or secondary progressive multiple sclerosis without activity (i.e., non-active SPMS)
- History of life-threatening infusion reaction to another anti-CD20 antibody (e.g., ocrelizumab, rituximab)
- Untreated active hepatitis B infection
- Untreated latent or active tuberculosis infection
- Concurrent use of another disease modifying therapy (DMT) to treat multiple sclerosis (MS) unless the previous agent will be discontinued when ublituximab is initiated
- Active infection or receiving chemotherapy
- Pregnancy
Inclusion Criteria
- Care provided by a VA/VA Community Care neurologist or locally designated MS expert (e.g., Spinal Cord Injury)
- Diagnosis of a relapsing form of multiple sclerosis established (relapsing-remitting MS, active secondary progressive MS, and clinically isolated syndrome)
- Screening for hepatitis B virus (HBV) completed (HBsAg, HBsAb, and HBcAb); if HBsAb negative and HBcAb positive or HBsAg positive, consultation with a liver disease expert is required first
- Quantitative serum immunoglobulins tested; if low, neurologist documentation of risk/benefit assessment and/or immunology expert consultation prior to initiation
- Administration of all guideline-recommended eligible immunizations at least 4 weeks prior to treatment for live or live-attenuated vaccines, and whenever possible at least 2 weeks prior for inactivated vaccines
Additional Inclusion Criteria (One of the following must be met)
- Current treatment with natalizumab combined with elevated risk factors for progressive multifocal leukoencephalopathy (PML) (anti-JC virus antibody positive, duration of therapy > 24 months, or prior immunosuppressant therapy)
- Ineffectiveness with at least one other MS DMT, defined as continued clinical relapses, central nervous system (CNS) lesion progression on MRI, or continued worsening of disability
- Highly active disease demonstrated by heavy burden of gadolinium enhancing and/or T2 lesions on MRI at onset of disease, high accumulation of CNS lesions on MRI, or rapid accrual of disability
Pregnancy & Reproductive Management
- For patients who can become pregnant: Pregnancy must be excluded prior to receiving ublituximab
- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and requirement for effective contraception during therapy and for 6 months after stopping treatment
Document 626
Administration & Dosing
- IV infusion daily for 5 days then 1 year later, IV infusion daily for 3 days
- Repeat 3-day courses can be considered if clinically indicated and if at least 12 months after last dose
- Typical pre-medication: high dose corticosteroid as methylprednisolone 1000mg immediately prior to first alemtuzumab dose and for the first 3 days of each treatment course
Monitoring & Laboratory Requirements
- Baseline: HIV, VZV, TB, HBV, HCV, CBC w/ diff, CMP, UA w/ cell counts and adult onset Still's disease, thyroid function tests, autoimmune encephalitis, and acquired hemophilia
- Routine: CBC w/ diff, CMP, TSH, LFT, and UA
- Has a REMS program which also provides lab and imaging frequency guidance
Contraindications & Precautions
- Delay treatment if active skin infection
- Instruct patients to avoid potential sources of Listeria and monocytegenes VZV antibodies
- Give antivirals for herpes prophylaxis starting the first day of treatment until 2 months or CD4+ lymphocyte count is > 200 cells/microliter
Adverse Events
- Serious: Secondary autoimmune diseases (including autoimmune hepatitis, thyroid disorders, thrombotic thrombocytopenic purpura, hemophagocytic lymphohistiocytosis, protein, thyroid infusion reactions, stroke or cervicocephallic arterial dissection, malignancy, PML)
- Common: rash, headache, pyrexia, nasopharyngitis, nausea/vomiting, minor infections, fatigue, insomnia, urticaria, pruritus, thyroid disorders, arthralgia, pain in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pian, flushing
Pregnancy & Lactation
- Avoid if pregnant
- Use contraception during and for 4 months after treatment course
- Avoid breastfeeding during treatment and at least 3 months after last dose
Washout & Switching Considerations
- An appropriate washout time from previous DMT is unknown
- The risks of a longer washout period should be weighed against the risks of another relapse
- Additive immunosuppression should be considered
- If switching from alemtuzumab to another DMT, lymphocyte counts can help assess magnitude of immunosuppression and additive risks