What are the indications and toxicities of RTX (Rituxan)?
- • FDA-approved rheumatologic indications: RA after MTX and anti-TNF failure; ANCA-associated vasculitis (granulomatosis with polyangiitis [GPA], microscopic polyangiitis [MPA]).
- • Available formulation: single-use vial of 100 mg and 500 mg.
- • Dosage. RA: 1000-mg IV infusion repeated once 2 weeks later. Some physicians feel 500-mg dose is as effective as 1000 mg particularly on subsequent infusions. Can be used with concomitant csDMARDs (e.g., MTX).
- • ANCA-associated vasculitis: 375 mg/m 2 IV infusion once weekly for 4 weeks. Can also use RA dosage (1 g on days 1 and 15). Maintenance dose: 500 mg IV every 6 months.
- • First infusion lasts 3 to 5 hours, subsequent infusions 1.5 to 3 hours. Patients are typically premedicated 30–60 minutes before each infusion with acetaminophen 1000 mg and an antihistamine to decrease the chance of infusion reaction. Some physicians also premedicate with an IV glucocorticoid particularly with the first infusion or in patients with three or more drug allergies.
- • Follow-up: CBC every 2 to 4 months to monitor for late-onset neutropenia. Get IgG level prior to RTX infusions to make sure not hypogammaglobulinemic.
- • Adverse reactions:
- • Infusion reaction (10%–35%): usually not severe if use premedication. Respond to stopping infusion until symptoms gone, then restart at slower rate. Stop infusion if patients start clearing their throat due to a scratchy feeling. Serious reactions (1%). Risk does not increase with subsequent infusions. May not need premedication with subsequent infusion if tolerated well.
- • Infection: any (35% or 78 events/100 patient years); serious (2% or 3 events/100 patient years); opportunistic (0.05/100 patient years, very low rate).
- • Viral infections: reactivation of resolved hepatitis B (HBsAg–, HBcAb + ) occurs in 5%–10%. Patients with chronic and inactive hepatitis B (HBsAg + ) should either not receive RTX or must receive concomitant antiviral prophylaxis (lamivudine, other) starting 2 to 4 weeks before and continuing while on RTX and for 1 month after stopping. Patients with hepatitis C can receive RTX without antiviral therapy but need hepatic enzymes and viral RNA load monitoring. The risk of JC virus infection resulting in progressive multifocal leukoencephalopathy (PML) may vary by disease being treated and previous immunosuppressive medications (1:25,000 RA patients, 1:4000 SLE patients compared with 1:200,000 in the general population). Owing to frequency of JC virus exposure (60%–70%) and low rate of PML in RA patients treated with RTX, it is not recommended to screen patients with antibody testing for previous JC virus exposure. Herpes zoster appears increased.
- • Hypogammaglobulinemia: only occurs in patients after multiple courses of RTX therapy. IgG becomes low in 3.5% to 12% of patients, IgM low in 22% to 26%. Patients who develop low IgG (<600 mg/dL) are more likely (2–4×) to get a serious infection.
- • Late-onset neutropenia: occurs in 3% of patients with RA and up to 20% of SLE or ANCA-associated vasculitis patients treated. Occurs an average of 3 to 4 months post-therapy and is associated with increased infection risk (16%). Neutropenia can last several weeks. Cause is unclear. Tends to recur with subsequent doses.
- • Immunizations: response to T-cell-independent antigen vaccines (influenza, pneumococcal) is severely decreased if given after RTX. Give vaccines 2 to 4 weeks before or 6 months post-RTX infusion. Tetanus vaccination is not impaired.
- • Other: severe mucocutaneous reactions, hypertension/arrhythmias/myocardial infarction during infusions. Note that CHF, demyelinating disease, malignancy (except skin cancer), and mycobacterial infections were not increased over placebo. RTX may be used ahead of TNF inhibitors in patients with one of these conditions that make TNF inhibitors contraindicated.
- • Precautions: do not use in patients with active infection. However, many physicians regard RTX as the safest therapy in RA patients with ongoing chronic infections (e.g., osteomyelitis), recently treated cancer, or history of lymphoma. Use P. jirovecii prophylaxis for patients with ANCA-associated vasculitis and lung disease.
- • Other diseases that RTX has been used for: SLE, antiphospholipid antibody syndrome, extraglandular Sjögren’s syndrome, IgG4 disease, neuromyelitis optica spectrum disorder, idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, pemphigus vulgaris, Castleman’s disease, cryoglobulinemia, inflammatory myopathies, others. Does not work in spondyloarthropathies.
