Rituximab
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Medical Therapy
Description
Rituximab is a chimeric anti-CD20 monoclonal antibody. This biologic therapeutic serves as a B-lymphocyte inhibitor, depleting mature B-cells.
Rituximab is currently approved for the treatment of adult patients of non-Hodgkin’s lymphoma (NHL), chronic lymphocytic leukemia (CLL), rheumatoid arthritis (RA), Granulomatosis with Polyangiitis (GPA), microscopic polyangiitis (MPA), and pemphigus vulgaris (PV).[1][2] Growing evidence supports the use of rituximab to treat specific ocular conditions and autoimmune diseases with ocular involvement.[1][3]
Rituximab has been demonstrated to be effective and well-tolerated as second- or third-line therapy for patients with refractory noninfectious uveitis (NIU) and scleritis and may reduce reliance on concomitant corticosteroids and/or immunosuppressants.[4][5]
Patient Selection
Indications
Growing evidence supports the use of rituximab for treatment of NIU refractory to steroid therapy and disease-modifying antirheumatic drugs. This option offers a corticosteroid-sparing strategy. Although rituximab use for noninfectious uveitis is presently off-label, it has been extensively used for this indication with documented efficacy in multiple studies.[4][5][6][7]
In a case series of 11 patients with refractory noninfectious posterior uveitis, treatment with rituximab demonstrated control of inflammation in 81% of patients as well as improvement of visual acuity from 20/80 to 20/40.[8] Rituximab therapy has also been successful in treatment of refractory juvenile idiopathic arthritis (JIA)-associated uveitis. Eight of eight patients in a multicenter case series being treated with rituximab achieved complete control of uveitis.[9] While uveitis activity decreased within 4-5 months after the first infusion, rituximab was discontinued in two patients due to inefficiency in treatment of underlying arthritis.
In study of limited sample size, rituximab has showed efficacy in the treatment of children with juvenile idiopathic arthritis associated uveitis, with 7 of 8 patients achieving complete control of the uveitis.[6][10] Rituximab use allowed reduction in concomitant prednisone dosage in all 8 patients, as well as discontinuation of concomitant systemic immunosuppressants in 5 of 8 patients.[11]
Contraindications
The U.S. Food and Drug Administration (FDA) does not list any contraindications for use of this medication at time of compilation (February 2026).[2]
Patients must undergo testing for hepatitis B virus (HBV) infection prior to initiation of rituximab therapy as it may cause HBV reactivation.[1]
Clinical Pharmacology
Rituximab is a chimeric (murine and human) monoclonal antibody that targets CD20. CD20 is an antigen expressed on the surface of pre-B and mature B-lymphocytes, and is found on both normal and malignant B-cells. However, CD20 is not found on normal plasma cells, hematopoietic stem cells, or pro-B-cells. B-cell lysis is mediated by the binding of rituximab to the transmembrane antigen CD20. Proposed mechanisms of cell lysis include the combined effects of antibody-dependent cell-mediated cytotoxicity and phagocytosis, complement-mediated cell lysis, growth arrest, and B-cell apoptosis.[1][2]
Warnings/Precautions
General
Rituximab may cause infusion reactions, tumor lysis syndrome, mucocutaneous reactions, progressive multifocal leukoencephalopathy, Hepatitis B reactivation, infections, cardiac arrhythmias, renal toxicity, and bowel obstruction and perforation.[2]
Refer to Section 5 for further details regarding adverse reactions.
Drug Interactions
The FDA recognizes interaction between rituximab and concomitant cisplatin therapy resulting in renal toxicity.[2] Rituximab products have not undergone formal drug interaction studies.
Patients who have received prior antibody therapies may experience allergic or hypersensitivity reactions when treated with other monoclonal antibodies due to human anti-mouse antibody or anti-drug antibody titres.[12]
Carcinogenesis/Mutagenesis/Impairment of Fertility
Standard tests investigating mutagenicity have not been performed as they are not relevant for monoclonal antibodies. No long-term animal studies have been performed to establish the carcinogenic potential of rituximab nor its effects on fertility. General toxicology animal studies did not reveal deleterious effects on reproductive organs. [2]
Pregnancy
Although there is limited data due to a lack of well-controlled studies in pregnant women, cases of transient B-cell lymphocytopenia have been reported in some infants exposed in utero.[2]
Women of childbearing potential should be counseled regarding the potential risk to a fetus and advised to use effective contraceptive methods during treatment and for 12 months after the final dose of rituximab due to the long retention time in B-cell depleted patients.
Pregnancy status should be confirmed prior to initiation of therapy.
Nursing Mothers
Data on the presence of rituximab in human milk and its effects on the breastfed child is limited. Additionally, there is a lack of data on the effect of milk production. Rituximab has been detected at low concentrations in human breast milk and maternal IgG is known to be excreted in human milk.
Because the clinical significance of infant exposure through breast milk is unknown and the risk for serious adverse reactions, breastfeeding is not recommended during rituximab therapy. Regulatory guidance suggests 6 months of post-treatment avoidance.[2]
Adverse Reactions
Documented adverse reactions to rituximab therapy are listed below.[2]
Infusion reactions: Severe and even fatal infusion-related reactions have been observed within 24 hours of rituximab infusion. Approximately 80% of fatal reactions occurred with first infusion. It is recommended to premedicate patients with an antihistamine and acetaminophen. Patients should be closely monitored and rituximab infusion should be discontinued if severe reactions occur.
Tumor Lysis Syndrome: Acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, or hyperphosphatemia may occur as a result of tumor lysis within 12-24 hours after first infusion.
Severe mucocutaneous reactions: Onset of mucocutaneous reactions, some fatal, have been reported with onset ranging between 1-13 weeks after rituximab exposure.
Progressive multifocal leukoencephalopathy (PML): Cases of PML, including fatal events, have been reported in patients with hematologic malignancies or autoimmune diseases treated with rituximab. Diagnosis of PML was made within 12 months of the last rituximab infusion in most cases.
Infections: Reactivation of Hepatitis B virus (HBV) has been observed, with some cases progressing to fulminant hepatitis, hepatic failure, and death. Other viral, bacterial, and fungal infections can develop following rituximab exposure in the context of B-cell depletion.
Cardiac arrhythmias: Patients with a known history of or new development of cardiac arrhythmia should undergo cardiac monitoring during and after infusions.
Dosage and Administration
Relevant case series and clinical trials typically employed rheumatologic protocol consisting of two 1000mg infusions administered 14 days apart, followed by maintenance dosing at 6 months.[4][5]
A study of rituximab therapy for refractory scleritis did not demonstrate a significant difference in efficacy, toxicity, or likelihood of re-treatment between patients given 500 mg vs. 1000 mg of rituximab intravenous infusions.[11]
Rituximab should only be administered as an intravenous infusion. Do not administer as an intravenous push or bolus.[2]
Patients should be given acetaminophen and antihistamines before each infusion.[11]
How Supplied
Patients must be prescribed rituximab by a physician. It is administered in infusion centers or hospital outpatient infusion units.
Patient’s Instructions for Use
Rituximab should not be administered independently. Rituximab should only be administered by trained healthcare personnel in settings equipped to recognize and manage severe infusion-related reactions that can be fatal if they occur.[2]
References
- ↑ 1.0 1.1 1.2 1.3 Thomas AS. Biologics for the treatment of noninfectious uveitis: current concepts and emerging therapeutics. Curr Opin Ophthalmol. 2019;30(3):138. doi:10.1097/ICU.0000000000000562
- ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 U.S. Food and Drug Administration. Rituxan (rituximab) Label. Accessed January 19, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/103705s5311lbl.pdf
- ↑ Pelegrin L, Jakob E, Schmidt-Bacher A, et al. Experiences with Rituximab for the Treatment of Autoimmune Diseases with Ocular Involvement. J Rheumatol. 2014;41(1):84-90. doi:10.3899/jrheum.130206
- ↑ 4.0 4.1 4.2 Al Ghulaiga FM, Alharbi I, Albloushi AF, Dheyab AM, Abouammoh MA, Abu El-Asrar AM. Safety and efficacy of rituximab in refractory noninfectious uveitis and scleritis. J Ophthalmic Inflamm Infect. 2025;15(1):70. doi:10.1186/s12348-025-00522-5
- ↑ 5.0 5.1 5.2 Ng CC, Sy A, Cunningham ET. Rituximab for non-infectious Uveitis and Scleritis. J Ophthalmic Inflamm Infect. 2021;11(1):23. doi:10.1186/s12348-021-00252-4
- ↑ 6.0 6.1 Miserocchi E, Pontikaki I, Modorati G, Bandello F, Meroni PL, Gerloni V. Rituximab for Uveitis. Ophthalmology. 2011;118(1):223-224. doi:10.1016/j.ophtha.2010.07.031
- ↑ Cao H, Ma X. Rituximab in the Treatment of Non-Infectious Uveitis: A Review. J Inflamm Res. 2024;17:6765-6780. doi:10.2147/JIR.S477708
- ↑ Lasave AF, You C, Ma L, et al. LONG-TERM OUTCOMES OF RITUXIMAB THERAPY IN PATIENTS WITH NONINFECTIOUS POSTERIOR UVEITIS REFRACTORY TO CONVENTIONAL IMMUNOSUPPRESSIVE THERAPY. Retina. 2018;38(2):395-402. doi:10.1097/IAE.0000000000001563
- ↑ Miserocchi E, Modorati G, Berchicci L, Pontikaki I, Meroni P, Gerloni V. Long-term treatment with rituximab in severe juvenile idiopathic arthritis-associated uveitis. Br J Ophthalmol. 2016;100(6):782-786. doi:10.1136/bjophthalmol-2015-306790
- ↑ Miserocchi E, Pontikaki I, Modorati G, Gattinara M, Meroni PL, Gerloni V. Anti-CD 20 monoclonal antibody (rituximab) treatment for inflammatory ocular diseases. Autoimmun Rev. 2011;11(1):35-39. doi:10.1016/j.autrev.2011.07.001
- ↑ 11.0 11.1 11.2 Suhler EB, Lim LL, Beardsley RM, et al. Rituximab Therapy for Refractory Scleritis: Results of a Phase I/II Dose-Ranging, Randomized, Clinical Trial. Ophthalmology. 2014;121(10):1885-1891. doi:10.1016/j.ophtha.2014.04.044
- ↑ Ali SB, Yuson C, Hissaria P. Rituximab hypersensitivity reactions and tolerance of ofatumumab therapy. Clin Exp Rheumatol. 2021;39(3):648-650. doi:10.55563/clinexprheumatol/z3mbin
