Mechanism of Action: Mycophenolate mofetil (MMF), a csD-MARD, is converted to mycophenolic acid, the active form of the drug. The active product inhibits inosine monophosphate dehydrogenase, leading to suppression of Tand B-lymphocyte proliferation. Downstream, it interferes with leukocyte adhesion to endothelial cells through inhibition of E-selectin, P-selectin, and intercellular adhesion molecule 1. MMF’s pharmacokinetics and toxicities are discussed in Chapter 55.
2.
Indications: MMF is effective for the treatment of renal disease due to SLE and may be useful in vasculitis and Wegener’s granulomatosis. Although MMF is occasionally used at a dosage of 2 g/d to treat RA, there are no well-controlled data regarding its efficacy in this disease.
3.
Adverse Effects: MMF is associated with nausea, dyspepsia, and abdominal pain. Like azathioprine, it can cause hepatotoxicity. MMF can also cause leukopenia, thrombocytopenia, and anemia. MMF is associated with an increased incidence of infections. It is only rarely associated with malignancy.
1. Mechanism of Action: Rituximab is a chimeric monoclonal antibody biologic agent that targets CD20 B lymphocytes (see Chapter 55). Depletion of these cells takes place through cell-mediated and complement-dependent cytotoxicity 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.
2.
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 acetaminophen, an antihistamine, and intravenous glucocorticoids (usually 100 mg of methylprednisolone) given 30 minutes prior to infusion decreases the incidence and severity of infusion reactions.
3.
Indications: Rituximab is indicated for the treatment of moderately to severely active RA in combination with methotrexate in patients with an inadequate response to one or more TNF-α antagonists. Rituximab in combination with glucocorticoids is also approved for the treatment of adult patients with granulomatosis with polyangiitis (previously known as Wegener’s granulomatosis) and microscopic polyangiitis and is used in other forms of vasculitis as well (see Chapter 54 for its use in lymphomas and leukemias).
4.