What is the most common reason for discontinuing rituximab?

October 6, 2025 •

6 min read

According to studies on patients with rheumatoid arthritis, ineffectiveness accounts for a significant portion of rituximab discontinuations, sometimes as high as 46%. However, pinpointing the single most common reason for discontinuing rituximab is more complex, as the primary drivers vary considerably depending on the specific disease being treated and individual patient factors.

Quick Summary

The most common reason for stopping rituximab varies by medical condition. While ineffectiveness is a leading cause for rheumatoid arthritis, pregnancy or adverse events may be more frequent in other autoimmune diseases like multiple sclerosis. Individual patient tolerance and disease progression are also key factors.

Key Points

Ineffectiveness in RA: For rheumatoid arthritis, the most common reason for discontinuing rituximab is that it stops working, either from the start or over time.
Varies by Condition: The main reason for stopping rituximab differs greatly depending on the treated disease; for instance, in MS, pregnancy is a major factor.
Adverse Events are Common: Infusion-related reactions and serious infections are significant drivers of discontinuation across different conditions.
Risk of Hepatitis B Reactivation: Patients with past or current Hepatitis B infection face a risk of the virus reactivating, which necessitates stopping treatment.
Rare but Severe Complications: Rare but potentially fatal side effects like PML and certain cardiac events can force immediate discontinuation.
Disease Progression in Lymphoma: In non-Hodgkin's lymphoma, disease progression is a common reason for ending rituximab maintenance therapy.
Patient-Specific Factors: Individual patient health, past medication history, and personal life changes like planning a family play a large role in the decision to discontinue treatment.

The monoclonal antibody rituximab is a powerful treatment used for a variety of conditions, including certain types of cancer and autoimmune diseases such as rheumatoid arthritis (RA) and relapsing-remitting multiple sclerosis (RRMS). While often effective, its use is sometimes discontinued. A closer look at clinical data reveals that the leading cause for discontinuation is not universal and depends on the patient's specific diagnosis.

Discontinuation in Rheumatoid Arthritis (RA)

In patients with RA, studies have identified ineffectiveness as the primary driver for stopping rituximab. Research published in Rheumatology indicated that among patients with RA, the largest reason for discontinuation was primary inefficacy, meaning the drug failed to produce a sufficient response from the start. A further breakdown reveals that discontinuation can also occur due to secondary inefficacy, where the drug initially works but loses its effectiveness over time. A study published in Arthritis Research & Therapy reported that ineffectiveness was the most common reason for discontinuation for biologic DMARD-experienced patients with RA, at 50%.

Other factors in RA discontinuation

While efficacy is paramount, other factors also play a role in RA. A separate study focusing on RA found that adverse events were responsible for a smaller but still significant portion of discontinuations. Factors like seronegativity (testing negative for autoantibodies) and a history of failing other biologic DMARDs were associated with a higher risk of needing to discontinue rituximab.

Discontinuation in Relapsing-Remitting Multiple Sclerosis (RRMS)

For patients with RRMS, the landscape of discontinuation reasons is quite different. A study conducted at the Karolinska University Hospital found that pregnancy was the most common reason for discontinuing rituximab, affecting nearly 29% of those who stopped treatment. Adverse events followed closely behind at 28%, and lack of efficacy was reported by a small minority (<1%). The low rate of discontinuation due to ineffectiveness highlights the drug's high efficiency in this specific condition.

Discontinuation in Non-Hodgkin's Lymphoma (NHL)

Rituximab is a standard component of treatment for NHL, often used in combination with chemotherapy. In this context, reasons for discontinuation can be related to the severity of the illness and the intensity of the treatment regimen. Studies in NHL patients have indicated that toxicity (adverse events) and disease progression are significant reasons for stopping maintenance rituximab. Infusion reactions, particularly with the first dose, are a well-documented risk and can lead to discontinuation in severe cases.

Factors in NHL discontinuation

For NHL, the complexity of care is a factor. One study found that less experience among oncologists with rituximab was associated with a higher risk of early discontinuation in Medicare beneficiaries. This suggests that provider expertise can influence treatment persistence, especially when managing severe or complex side effects.

A comparison of discontinuation reasons across diseases


Reason for Discontinuation	Rheumatoid Arthritis	Relapsing-Remitting Multiple Sclerosis	Non-Hodgkin's Lymphoma
Ineffectiveness	High (e.g., 46-50% in bDMARD-experienced)	Very Low (<1%)	Can occur (disease progression)
Adverse Events	Significant (e.g., 17-29%)	High (e.g., 28%)	Significant (e.g., 45%)
Pregnancy	Less common (not a primary factor)	High (e.g., 29%)	Less common (contraindicated)
Stable Disease / Protocol	Reported, but not a primary driver	Common in some contexts (e.g., 10-25%)	Common in some contexts
Toxicity / Infusion Reactions	Contributes to adverse event category	Part of adverse events, relatively frequent but rarely severe enough for withdrawal	High, especially infusion reactions and cytopenias

Common adverse events leading to discontinuation

Several specific adverse events frequently contribute to the decision to stop rituximab, regardless of the underlying disease.

Infusion-Related Reactions (IRRs): IRRs are a very common side effect, especially during the first infusion, and can be severe or even fatal in rare cases. Symptoms can include fever, chills, rash, and shortness of breath. Discontinuation may be necessary for severe reactions.
Serious Infections: Rituximab suppresses the immune system by depleting B-cells, increasing the risk of serious bacterial, fungal, and viral infections. This can lead to discontinuation, particularly if the infections are recurrent or severe. Some patients experience prolonged hypogammaglobulinemia, which heightens this risk over time.
Hepatitis B Virus (HBV) Reactivation: For individuals who are carriers of the hepatitis B virus, rituximab can cause the virus to reactivate, leading to severe liver problems. Screening for HBV is required before starting treatment, and reactivation necessitates immediate discontinuation.
Progressive Multifocal Leukoencephalopathy (PML): This is a rare, but serious and often fatal, brain infection that has been reported in patients treated with rituximab. Diagnosis of PML requires immediate discontinuation of the drug.
Other Side Effects: Cardiovascular events, severe skin and mouth reactions, and kidney problems are also documented reasons for rituximab discontinuation.

Conclusion: A multifaceted answer

In summary, the question "what is the most common reason for discontinuing rituximab" does not have a single, universal answer. For many patients with rheumatoid arthritis, the leading cause is ineffectiveness, both primary and secondary. In contrast, for a condition like relapsing-remitting multiple sclerosis, non-efficacy reasons, such as pregnancy, are the most frequently cited factors. Across all indications, severe adverse events, including infusion reactions, serious infections, and rare but life-threatening complications like PML and HBV reactivation, are also critical drivers of discontinuation. Patient-specific factors, disease response, and risk management all contribute to this complex clinical decision.

For more detailed information on specific side effects, you can consult resources like Drugs.com, which provides a comprehensive overview of reported adverse events.

Summary of Discontinuation Reasons for Rituximab

Ineffectiveness: The primary reason for discontinuing rituximab in patients with rheumatoid arthritis.
Adverse Events: A significant reason across all disease indications, including infections, infusion reactions, and severe organ toxicity.
Pregnancy: The most common reason for stopping treatment in women with relapsing-remitting multiple sclerosis.
Disease Progression: A major factor in discontinuing maintenance rituximab for non-Hodgkin's lymphoma.
Toxicity: Includes severe side effects like infusion-related reactions, Hepatitis B reactivation, and Progressive Multifocal Leukoencephalopathy (PML).
Clinical Protocol/Stable Disease: In some cases, discontinuation is planned, such as for stable disease or per a study protocol.
Provider Experience: Can influence the risk of early discontinuation, particularly in complex conditions like non-Hodgkin's lymphoma.

Why Ineffectiveness is so prevalent in RA

Primary Inefficacy: For some patients, rituximab simply does not produce the desired therapeutic effect from the outset.
Secondary Inefficacy: The treatment may initially provide relief, but the patient's body develops a diminished response over time.
Previous Failures: Patients who have already failed other biologic DMARDs may be more likely to stop rituximab due to lack of efficacy.

Risk of serious infections

Immune Suppression: Rituximab works by depleting B-cells, which are a component of the immune system, thereby increasing susceptibility to infections.
Prolonged Hypogammaglobulinemia: Some patients experience low levels of antibodies for an extended period after treatment, increasing the risk of infection.
Serious Infections: A small but significant risk of serious infections, including pneumonia and sepsis, persists throughout treatment and follow-up.

Infusion reactions: Acute vs. Delayed

Acute Reactions: Occur during or within 24 hours of infusion and are most common during the first dose. Symptoms range from mild (fever, chills) to severe (anaphylaxis).
Delayed Reactions: Rare, but severe delayed hypersensitivity reactions like serum sickness can occur.

Patient management

Pre-screening: Patients should be screened for Hepatitis B before starting rituximab to prevent reactivation.
Premedication: Patients are typically pre-medicated with antihistamines and acetaminophen to reduce the risk of infusion reactions.
Monitoring: Close monitoring during and after infusion is crucial for detecting and managing adverse events promptly.
Patient Education: Ensuring patients understand the potential side effects and what symptoms to report is essential for early intervention.

The long-term picture

Long-term persistence: Despite discontinuation, many patients remain on rituximab for years, indicating good long-term tolerance for many.
Subsequent therapy: For those who discontinue due to ineffectiveness, a switch to an alternative therapy is often initiated.
Disease management: Proper monitoring and management of side effects can help prolong treatment duration and improve patient outcomes.

Frequently Asked Questions

If rituximab is no longer effective, your doctor will likely switch you to an alternative therapy. For example, in RA, other biologic DMARDs like tocilizumab are often considered.

For mild or moderate infusion reactions, the infusion rate is often slowed down. However, if you experienced a severe, life-threatening reaction, the drug is typically permanently discontinued.

PML stands for Progressive Multifocal Leukoencephalopathy. It is a rare, severe brain infection caused by a virus that can occur in patients with weakened immune systems, including those on rituximab. It is an urgent reason for discontinuation.

Before starting rituximab, doctors screen all patients for HBV infection. If there is evidence of current or prior infection, a specialist is consulted, and the patient is monitored closely during and after treatment. Antiviral therapy may be considered.

Older age is a factor associated with a higher rate of serious complications, particularly cardiopulmonary and infectious ones, which can lead to discontinuation. In some lymphoma studies, advanced age was linked to early discontinuation.

Serious infections require immediate discontinuation of rituximab. If the patient has a history of severe infections or prolonged immunosuppression, the decision to resume treatment is made on a case-by-case basis with careful consideration.

In some diseases and specific clinical trial settings, discontinuing rituximab is an option for patients with stable disease. However, in many conditions, ongoing maintenance therapy is necessary to prevent relapse.