Rituximab

RITUXIMAB

Mechanism of Action

Rituximab is a chimeric monoclonal antibody biologic agent that targets CD20 B lymphocytes . This depletion takes place through cell-mediated and complement-dependent cytotoxic-ity and stimulation of cell apoptosis. Depletion of B lymphocytes reduces inflammation by decreasing the presentation of antigens to T lymphocytes and inhibiting the secretion of proinflammatory cytokines. Rituximab rapidly depletes peripheral B cells, although this depletion correlates neither with efficacy nor with toxicity.

Pharmacokinetics

Rituximab is given as two intravenous infusions of 1000 mg, separated by 2 weeks. It may be repeated every 6–9 months, as needed. Repeated courses remain effective. Pretreatment with intravenous glucocorticoids given 30 minutes prior to infusion (usually 100 mg of methylprednisolone) decreases the incidence and severity of infusion reactions.

Indications

Rituximab is indicated for the treatment of moderately to severely active rheumatoid arthritis in combination with methotrexate in patients with an inadequate response to one or more TNF-α antagonists.

Adverse Effects

About 30% of patients develop rash with the first 1000 mg treat-ment; this incidence decreases to about 10% with the second infusion and progressively decreases with each course of therapy thereafter. These rashes do not usually require discontinuation of therapy but of course an urticarial or anaphylactoid reaction pre-cludes further therapy. Immunoglobulins (particularly IgG and IgM) may decrease with repeated courses of therapy and infections can occur, although they do not seem directly associated with the decreases in immunoglobulins. Rituximab has not been associated with either activation of tuberculosis or the occurrence of lympho-mas or other tumors . Other adverse effects, like cardiovascular events, are rare.