FDA-Approved Indications for Rituximab (Rituxan) and Biosimilars
Rituximab is FDA-approved for five major disease categories: Non-Hodgkin's Lymphoma (NHL), Chronic Lymphocytic Leukemia (CLL), Rheumatoid Arthritis (RA), ANCA-associated vasculitis (GPA/MPA), and Pemphigus Vulgaris (PV). 1
Complete FDA-Approved Indications
Non-Hodgkin's Lymphoma (NHL)
Adult NHL indications:
- Relapsed or refractory, low-grade or follicular, CD20-positive B-cell NHL as monotherapy
- Previously untreated follicular, CD20-positive B-cell NHL in combination with first-line chemotherapy, plus maintenance therapy as single agent for complete or partial responders
- Non-progressing (including stable disease) low-grade, CD20-positive B-cell NHL as monotherapy after first-line CVP chemotherapy
- Previously untreated diffuse large B-cell, CD20-positive NHL in combination with CHOP or other anthracycline-based chemotherapy 1
Pediatric NHL indications (≥6 months of age):
- Previously untreated, advanced stage, CD20-positive diffuse large B-cell lymphoma (DLBCL)
- Burkitt lymphoma (BL)
- Burkitt-like lymphoma (BLL)
- Mature B-cell acute leukemia (B-AL) All in combination with chemotherapy 1
Chronic Lymphocytic Leukemia (CLL)
- Previously untreated CD20-positive CLL in combination with fludarabine and cyclophosphamide (FC)
- Previously treated CD20-positive CLL in combination with FC 1
Rheumatoid Arthritis (RA)
- Moderately to severely active RA in combination with methotrexate in adult patients who have had inadequate response to one or more TNF antagonist therapies 1
The 2021 ACR guidelines note that rituximab is considered a bDMARD option, though recommendations exclude rituximab unless patients have had inadequate response to TNF inhibitors (consistent with FDA approval) or have a history of lymphoproliferative disorder for which rituximab is approved therapy 2.
ANCA-Associated Vasculitis
- Granulomatosis with Polyangiitis (GPA) (Wegener's Granulomatosis) in adult and pediatric patients ≥2 years of age in combination with glucocorticoids
- Microscopic Polyangiitis (MPA) in adult and pediatric patients ≥2 years of age in combination with glucocorticoids 1
Pemphigus Vulgaris (PV)
- Moderate to severe pemphigus vulgaris in adult patients 1
FDA-Approved Biosimilars
All FDA-approved rituximab biosimilars are approved for the same indications as reference rituximab through extrapolation of data. The biosimilars include:
CT-P10 (Truxima™): First rituximab biosimilar approved by FDA (2018) and EMA (2017), with demonstrated pharmacokinetic equivalence and clinical equivalence in RA and follicular lymphoma 3, 4
GP2013 (Rixathon®): Second biosimilar approved in EU (2017), with demonstrated biosimilarity through physicochemical, pharmacodynamic, and pharmacokinetic studies in RA and efficacy equivalence in follicular lymphoma 5, 6
The ACR guidelines explicitly state that "biosimilars are considered equivalent to FDA-approved originator bDMARDs" 2.
Important Clinical Considerations
Rituximab carries boxed warnings for:
- Fatal infusion-related reactions (approximately 80% occur with first infusion)
- Severe mucocutaneous reactions with potential fatal outcomes
- Hepatitis B virus (HBV) reactivation resulting in fulminant hepatitis, hepatic failure, and death
- Progressive multifocal leukoencephalopathy (PML) resulting in death 1
For patients with hepatitis B: Prophylactic antiviral therapy is strongly recommended over monitoring alone for patients initiating rituximab who are hepatitis B core antibody positive, regardless of surface antigen status 7.
Administration requirements: Rituximab should only be administered by healthcare professionals with appropriate medical support to manage severe infusion-related reactions, as intravenous infusion only—never as IV push or bolus 1.