Understanding Rituxan and the Need for Substitutes
Rituxan (rituximab) is a monoclonal antibody medication that targets CD20, a protein found on the surface of B-cells, which are a type of white blood cell [1.3.1]. By targeting these cells, it helps to treat certain types of blood cancers and autoimmune conditions [1.3.1]. It is commonly used for non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL), and rheumatoid arthritis (RA) [1.2.2]. The primary substitutes for Rituxan are its biosimilars, which are highly similar versions of the original biologic drug, as well as other medications that work through different mechanisms [1.4.8].
What are Biosimilars?
A biosimilar is a biologic medical product that is almost an identical copy of an original product that is manufactured by a different company [1.4.8]. They are approved based on a finding that they are highly similar to an already-approved biologic product, known as the reference product [1.2.3]. Biosimilars have been shown to have no clinically meaningful differences from the reference product in terms of safety, purity, and potency [1.5.6]. The main driver for their development and use is to increase access and provide more affordable treatment options [1.3.1, 1.4.8].
FDA-Approved Rituximab Biosimilars
The U.S. Food and Drug Administration (FDA) has approved several biosimilars to Rituxan. These are considered direct substitutes and are often used interchangeably based on institutional and insurance preferences [1.3.1, 1.3.6].
- Truxima (rituximab-abbs): Approved in 2018, Truxima was the first rituximab biosimilar to receive FDA approval [1.3.1]. It is approved for adult patients with NHL, CLL, RA, Granulomatosis with Polyangiitis (GPA), and Microscopic Polyangiitis (MPA) [1.3.1, 1.3.7].
- Ruxience (rituximab-pvvr): This became the second rituximab biosimilar approved by the FDA in 2019 [1.3.1]. It shares the same indications as Truxima, offering another alternative for the same patient populations [1.3.7].
- Riabni (rituximab-arrx): The third biosimilar, Riabni, was approved in 2020 [1.2.1, 1.3.1]. Like the others, it has demonstrated comparable efficacy and safety to Rituxan for its approved uses, including various forms of NHL, CLL, RA, GPA, and MPA [1.2.2, 1.2.5].
Clinical studies for each of these biosimilars have demonstrated equivalence or non-inferiority to Rituxan in terms of treatment outcomes and safety profiles [1.5.3]. The choice between Rituxan and its biosimilars often comes down to cost and insurance coverage [1.3.1].
Comparison of Rituxan and its Biosimilars
| Feature | Rituxan (rituximab) | Truxima (rituximab-abbs) | Ruxience (rituximab-pvvr) | Riabni (rituximab-arrx) |
|---|---|---|---|---|
| Mechanism of Action | CD20-directed cytolytic antibody [1.3.4] | CD20-directed cytolytic antibody [1.3.4] | CD20-directed cytolytic antibody [1.3.4] | CD20-directed cytolytic antibody [1.3.4] |
| First FDA Approval | Original Biologic | 2018 [1.3.1] | 2019 [1.3.1] | 2020 [1.3.1] |
| Approved Adult Uses | NHL, CLL, RA, GPA, MPA, Pemphigus Vulgaris [1.3.2] | NHL, CLL, RA, GPA, MPA [1.3.1] | NHL, CLL, RA, GPA, MPA [1.3.1, 1.3.2] | NHL, CLL, RA, GPA, MPA [1.2.2, 1.2.5] |
| Clinical Similarity | Reference Product | Highly similar, no clinically meaningful differences [1.5.6] | Highly similar, no clinically meaningful differences [1.3.1] | Highly similar, no clinically meaningful differences [1.2.3] |
Other Alternative Medications
Beyond direct biosimilars, other medications with different mechanisms of action can be considered substitutes for Rituxan depending on the specific condition being treated.
For Non-Hodgkin's Lymphoma (NHL) and CLL:
- Gazyva (obinutuzumab): This is another anti-CD20 monoclonal antibody, but it is considered a second-generation drug engineered to have stronger effects than rituximab [1.7.3, 1.7.7]. Studies have shown it may offer superior progression-free survival in certain contexts compared to rituximab [1.7.2, 1.7.7].
- Arzerra (ofatumumab): A fully human anti-CD20 antibody that binds to a different part of the CD20 protein than rituximab [1.6.1, 1.6.7]. It is designed to have stronger complement-dependent cytotoxicity (CDC), a method of cell-killing [1.6.1].
- Other Therapies: Depending on the type and stage of lymphoma, other treatments like chemotherapy combinations (e.g., CHOP), stem cell transplants, and targeted therapies may be used [1.5.2, 1.5.4].
For Rheumatoid Arthritis (RA):
For RA patients who have an inadequate response to other treatments, Rituxan is an option. However, many other classes of drugs are available:
- TNF Inhibitors: Medications like Humira (adalimumab), Enbrel (etanercept), and Remicade (infliximab) work by blocking Tumor Necrosis Factor, a substance that causes inflammation [1.4.1, 1.4.3].
- Other Biologics: Drugs like Orencia (abatacept), which blocks T-cell activation, and Actemra (tocilizumab), an IL-6 inhibitor, offer alternative mechanisms for controlling RA [1.4.1].
- Janus Kinase (JAK) Inhibitors: Oral medications like Xeljanz (tofacitinib) and Rinvoq (upadacitinib) are targeted synthetic DMARDs that can be used if biologics are not effective [1.4.2].
Conclusion
Substitutes for Rituxan fall into two main categories: direct biosimilars and alternative therapeutic agents. The FDA-approved biosimilars—Truxima, Ruxience, and Riabni—are designed to be as safe and effective as Rituxan and are often chosen based on cost and availability [1.3.1]. For patients who may not respond to rituximab or require a different approach, other medications like Gazyva, Arzerra, or various classes of RA drugs provide distinct mechanisms of action. The decision on which substitute to use is complex and must be made by a healthcare professional based on the patient's specific diagnosis, treatment history, and overall health.
For more information on non-Hodgkin lymphoma treatment options, you can visit the National Cancer Institute [1.5.2].
