What is the use of Rituximab (Rituxan)?

From the Guidelines

Rituximab is used in patients with refractory immune thrombocytopenia (ITP) primarily based on experience in other autoimmune diseases, as well as uncontrolled studies in ITP, despite being licensed for use in certain hematological malignancies and rheumatoid arthritis, but not in ITP 1. The use of rituximab in ITP is based on its mechanism of action as an anti-CD20 antibody, which depletes B lymphocytes and reduces immune system activity.

• The optimal dosing of rituximab for ITP has not been defined, but it is typically administered at a dose of 375 mg/m2 over 4 consecutive weekly infusions, although lower doses may be sufficient 1.
• A meta-analysis of randomized controlled trials found that the complete response rate to a single course of rituximab by 6 months is 47% versus 32.5% with standard of care, however, no statistically significant difference was found in overall response rate and reduction in bleeding events 1.
• Long-term studies of rituximab have shown disappointing results, with a placebo-controlled long-term study finding no significant benefit of rituximab beyond 1.5 years compared with placebo 1.
• However, for certain patient populations, such as adult females with newly diagnosed or persistent ITP who have shown an initial response to rituximab and high-dose dexamethasone, rituximab may provide durable remissions, with a remarkable percentage of patients (79%) achieving a durable remission (>48 months) 1.
• Rituximab is usually well tolerated in patients with ITP, but infusion reactions and rare but potentially fatal complications, including severe mucocutaneous reactions, reactivation of hepatitis B, and multifocal leukoencephalopathy, can occur 1.

From the FDA Drug Label

RITUXAN is a prescription medicine used to treat: Adults with Non-Hodgkin's Lymphoma (NHL): alone or with other chemotherapy medicines. Children 6 months of age and older with mature B-cell Non-Hodgkin's Lymphoma (NHL) and mature B-cell acute leukemia (B-AL): in combination with chemotherapy medicines Adults with Chronic Lymphocytic Leukemia (CLL): with the chemotherapy medicines fludarabine and cyclophosphamide Adults with Rheumatoid Arthritis (RA): with another prescription medicine called methotrexate, to reduce the signs and symptoms of moderate to severe active RA in adults, after treatment with at least one other medicine called a Tumor Necrosis Factor (TNF) antagonist has been used and did not work well Adults and children 2 years of age and older with Granulomatosis with Polyangiitis (GPA) (Wegener's Granulomatosis) and Microscopic Polyangiitis (MPA): with glucocorticoids, to treat GPA and MPA. Adults with Pemphigus Vulgaris (PV): to treat moderate to severe PV.

The use of Rituximab (Rituxan) includes:

• Non-Hodgkin's Lymphoma (NHL): treatment of adult patients with relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent, and treatment of pediatric patients aged 6 months and older with mature B-cell NHL and B-AL in combination with chemotherapy medicines.
• Chronic Lymphocytic Leukemia (CLL): treatment of adult patients with previously untreated and previously treated CD20-positive CLL in combination with fludarabine and cyclophosphamide.
• Rheumatoid Arthritis (RA): treatment of adult patients with moderately to severely active RA in combination with methotrexate.
• Granulomatosis with Polyangiitis (GPA) and Microscopic Polyangiitis (MPA): treatment of adult and pediatric patients 2 years of age and older with GPA and MPA in combination with glucocorticoids.
• Pemphigus Vulgaris (PV): treatment of adult patients with moderate to severe PV. 2, 2, 2

From the Research

Use of Rituximab

Rituximab is an anti-CD20 monoclonal antibody used in the treatment of various lymphoid malignancies, including:

• Non-Hodgkin's lymphoma (NHL) 3, 4
• Chronic lymphocytic leukaemia (CLL) 3, 4
• Rheumatoid arthritis (RA) 5, 6
• Anti-neutrophilic cytoplasmic antibody (ANCA)-associated vasculitis 5
• Membranous nephropathy 5

Mechanism of Action

Rituximab works by inducing lysis and apoptosis of normal and malignant human B cells, and sensitising malignant B cells to the cytotoxic effect of chemotherapy 4.

Administration and Safety

Rituximab is typically administered intravenously, with initial infusions given slowly over 4-6 hours to minimize the risk of infusion-related toxicity 7. Subsequent doses can be administered over a shorter period, such as 90 minutes or even 60 minutes, in the absence of significant reactions 7. The safety of rapid 60-minute infusions has been demonstrated in patients with malignant and benign haematological disease 7.

Efficacy

Rituximab has been shown to be effective in combination with chemotherapy as first- or second-line therapy for indolent or aggressive B-cell NHL, and as maintenance therapy to prolong tumour remission and patient survival 3, 4. It has also been used to treat CLL, with promising results 3, 4.

Potential Side Effects

Rituximab can cause infusion-related reactions, which are usually mild to moderate but can be severe in some cases 3, 6. Other potential side effects include arrhythmia, angina, and non-ischemic cardiomyopathy, particularly in patients with prior history of cardiovascular diseases 5.