Rituximab is a medication that treats certain blood cancers and autoimmune diseases by selectively destroying a type of immune cell called B cells. It was one of the first targeted cancer therapies when it came to market in the late 1990s, and its uses have expanded significantly since then. Today it is approved for five distinct conditions and used off-label for several more.
How Rituximab Works
B cells are white blood cells that play a central role in the immune system. They produce antibodies, which normally help fight infections. But in certain cancers, B cells multiply uncontrollably, and in certain autoimmune diseases, they produce antibodies that attack the body’s own tissues.
Rituximab locks onto a protein called CD20, which sits on the surface of B cells. Once attached, it triggers the immune system to destroy those cells through several pathways: it recruits other immune cells to attack, activates a chain of proteins that punch holes in the cell membrane, and can directly trigger cell death. The result is a dramatic reduction in B cells throughout the body. This depletion is temporary; B cells gradually repopulate over months after treatment ends.
FDA-Approved Cancer Uses
Rituximab is approved for two types of blood cancer, both involving the abnormal growth of B cells.
Non-Hodgkin lymphoma (NHL) is the condition rituximab was originally developed for. It covers several scenarios: as a standalone treatment for relapsed or slow-growing lymphoma, in combination with chemotherapy for previously untreated follicular lymphoma and diffuse large B-cell lymphoma (the most common aggressive form), and as ongoing maintenance therapy for patients who respond to initial treatment. In follicular lymphoma patients, adding rituximab to chemotherapy has shown statistically significant improvements in how long patients live without their disease worsening.
Chronic lymphocytic leukemia (CLL) is the other approved cancer indication. Rituximab is used alongside two chemotherapy drugs for both newly diagnosed and previously treated CLL.
Approved Autoimmune Uses
Because autoimmune diseases often involve rogue B cells producing harmful antibodies, rituximab has proven effective well beyond oncology. Three autoimmune conditions carry FDA approval.
Rheumatoid arthritis (RA) was rituximab’s first approved autoimmune indication. It is reserved for patients whose joint inflammation hasn’t responded adequately to other biologic therapies. In clinical trials, roughly 51 to 55 percent of patients treated with rituximab achieved meaningful improvement in joint pain and swelling at 24 weeks, compared to about 23 percent on placebo. Treatment involves two infusions spaced two weeks apart, with repeat courses typically every six months.
Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are rare conditions in which the immune system attacks blood vessels, potentially damaging the kidneys, lungs, and other organs. Rituximab is approved for both adults and children aged two and older, used alongside steroids. After an initial induction course of weekly infusions for four weeks, patients transition to maintenance infusions every six months.
Pemphigus vulgaris is a serious skin disease in which the immune system attacks proteins that hold skin cells together, causing painful blistering. Rituximab is approved for moderate to severe cases. The initial course is two infusions two weeks apart, followed by maintenance doses every six months starting at the one-year mark.
Off-Label Use in Multiple Sclerosis
One of the most notable off-label uses of rituximab is for multiple sclerosis, where it has become a widely used treatment despite never receiving formal FDA approval for that condition. In 2023, the World Health Organization added rituximab to its list of essential medicines for MS. A phase III trial demonstrated that it was significantly better than another established MS drug at controlling relapses and inflammatory disease activity.
Rituximab’s popularity in MS stems from a combination of strong effectiveness, good tolerability, and lower cost compared to newer MS medications. Studies show patients stick with rituximab longer than with several other MS therapies, a combined reflection of how well it works, how well it’s tolerated, and how manageable the side effects are. Its affordability makes it particularly valuable for patients with unstable insurance coverage or high out-of-pocket costs.
Rituximab is also used off-label for other conditions, including myasthenia gravis, certain kidney diseases, and other autoimmune blood disorders.
What the Infusion Process Looks Like
Rituximab is given exclusively as an intravenous infusion. It cannot be injected quickly; it must be delivered slowly to reduce the risk of reactions.
The first infusion is the longest. It starts at a slow drip rate and is gradually increased over several hours if you’re tolerating it well. Subsequent infusions can be given faster because the risk of a reaction drops after the first dose. For some lymphoma patients who tolerated their first infusion without problems, later infusions can be completed in about 90 minutes.
Treatment schedules vary widely depending on the condition. For lymphoma, you might receive weekly infusions for four to eight weeks. For rheumatoid arthritis, it’s two infusions two weeks apart, repeated roughly every six months. For pemphigus vulgaris, the pattern is similar but with additional maintenance doses. Your treatment team will typically give you medications before each infusion, such as an antihistamine and a fever reducer, to minimize the chance of a reaction.
Side Effects and Serious Risks
Infusion reactions are the most common side effect. Symptoms can include fever, chills, shaking, dizziness, itching, rash, and difficulty breathing. These reactions are most likely during the first infusion and tend to become less frequent with subsequent treatments. While most reactions are mild to moderate, they can occasionally be severe or life-threatening, which is why rituximab is given in a supervised clinical setting.
Because rituximab depletes B cells, it lowers your immune defenses and increases the risk of infections, including bacterial, viral, and fungal. This heightened vulnerability can persist for months after treatment ends, since B cells take time to recover.
Two risks are serious enough that the FDA highlights them with its strongest safety warnings. The first is reactivation of hepatitis B. If you carry the virus, even without symptoms, rituximab can cause it to flare into active, potentially fatal hepatitis. The median time to diagnosis is about four months after starting treatment. Screening for hepatitis B before starting rituximab is standard practice, and carriers require close monitoring during and for several months after therapy.
The second is progressive multifocal leukoencephalopathy (PML), a rare but often fatal brain infection caused by a virus that takes advantage of the weakened immune system. Symptoms can include changes in thinking, vision problems, weakness, or difficulty walking. Most cases have occurred in cancer patients who received rituximab alongside other immune-suppressing treatments. Any new neurological symptoms during or after rituximab treatment warrant immediate medical evaluation.
Vaccines and Timing
Rituximab’s effect on B cells has important implications for vaccination. Because B cells are essential for building immunity after a vaccine, getting vaccinated while B cells are depleted can result in a weak or absent immune response.
The CDC recommends completing any needed vaccines at least two weeks before starting rituximab. After finishing treatment, you should wait at least six months before receiving most vaccines, and some experts recommend waiting even longer. Live vaccines require the same six-month waiting period. The shingles vaccine is an exception, requiring only a one-month gap after rituximab before it can be given.
Biosimilar Options
Three biosimilars of rituximab are now FDA-approved: Truxima, Ruxience, and Riabni. Biosimilars are near-identical copies of biologic drugs that meet the same standards for safety and effectiveness. They are typically available at a lower cost, which can make treatment more accessible. All three are approved for the same indications as the original rituximab product.