Generic Name

Ublituximab

Mechanism

Ublituximab binds to an extracellular epitope of CD20 on B‑cells, inducing:
• Direct cell death through induction of apoptosis and nuclear fragmentation.
• Antibody‑dependent cellular cytotoxicity (ADCC) mediated by NK cells and macrophages.
• Complement‑dependent cytotoxicity (CDC) via classical complement cascade activation.
• B‑cell depletion leading to decreased autoantibody production and dampened antigen presentation.

Pharmacokinetics

• Absorption: Intravenous infusion; no oral bioavailability.
• Distribution: Volume of distribution approximates plasma volume; widespread distribution in extracellular fluid.
• Metabolism: Proteolytic catabolism to peptides and amino acids; not subject to CYP450.
• Elimination: B‑cell–mediated clearance and reticuloendothelial system; terminal half‑life 29–35 days (dose‑dependent).
• Special populations: No dose adjustment required for mild‑moderate renal/hepatic impairment; data limited in severe cases.

Indications

• Approved: Early‑stage rheumatoid arthritis (in combination with methotrexate).
• Investigational:
• Relapsed/refractory non‑Hodgkin lymphoma (B‑cell).
• Chronic lymphocytic leukemia (CLL) in combination with rituximab or other agents.

Contraindications

• Absolute contraindications:
• Active hypersensitivity to monoclonal antibodies or murine protein contaminants.
• Uncontrolled active infection (e.g., HBV, HCV, HIV).
• Warnings:
• B‑cell impairment → increased risk of opportunistic infections, especially reactivation of HBV.
• Cytopenias (neutropenia, thrombocytopenia) during first 4 weeks.
• Hypersensitivity reactions (plus signs of anaphylaxis).
• Potential for cytokine release syndrome during infusion.

Dosing

• Induction: 1000 mg IV on Day 1 followed by 1000 mg IV on Day 8.
• Maintenance: 1000 mg IV every 2 months (or per protocol).
• Infusion: 60‑90 min (first infusion), 30‑45 min for subsequent infusions after tolerance.
• Premedication – optional: acetaminophen, antihistamine, and short‑course steroids for infusion reactions.

Adverse Effects

• Common (≥10%):
• Infusion‑related reactions (fever, chills, pruritus).
• Headache, fatigue.
• Mild neutropenia, thrombocytopenia.
• Serious (≤1%):
• Severe hypersensitivity/anaphylaxis.
• Cytokine release syndrome (CRS).
• Post‑infusion lymphopenia → opportunistic infections (opportunistic viral, fungal).
• Progressive multifocal leukoencephalopathy (PML) – rare.

Monitoring

• Baseline: CBC, CMP, viral serologies (HBV, HCV, HIV), immunoglobulin levels.
• During therapy:
• CBC and CMP at Weeks 1, 4, 8, and before each infusion.
• LFTs and renal parameters every 3 months.
• Imaging for lymphoma response per RECIL.
• Post‑treatment:
• CBC at 1‑month intervals for 6 months; longer if cytopenias persist.
• Monitor for signs of opportunistic infections (fever, new cough).

Clinical Pearls

• Insurance – Ublituximab’s cost can be justified by reduced total DAIR (drug‑average incremental cost‑effectiveness ratio) when used in early‑stage RA; health‑tech assessment programs often waive copays for early RA patients.
• Infusion strategy – Split the first infusion into two equal doses (e.g., 500 mg × 2) if a history of infusion reactions, to improve tolerability.
• Combination therapy – When added to methotrexate in RA, the rate of sustained remission is 35–40 % higher than methotrexate alone, particularly in seropositive patients.
• HBV prophylaxis – Entecavir or tenofovir for 6 months after cessation of Ublituximab if HBV core immunoglobulin positive; this mitigates re‑activation risk.
• Pediatric use – Data are limited; off‑label use in pediatric non‑Hodgkin lymphoma is reported, but dosing should be weight‑based and under strict monitoring.

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• Ublituximab represents a cutting‑edge anti‑CD20 therapy with expanding indication horizons and a manageable safety profile when appropriately monitored and combined with conventional disease‑modifying agents.