Is Rituximab (rituximab) safe for patients with rheumatoid arthritis (RA) and pulmonary fibrosis?

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Last updated: May 1, 2025View editorial policy

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From the Guidelines

Rituximab is a conditionally recommended treatment option for rheumatoid arthritis (RA) patients with pulmonary fibrosis, particularly for those with active inflammatory arthritis, as it may provide benefits for both joint and lung disease. The standard dosing regimen consists of two 1000 mg intravenous infusions separated by two weeks, typically repeated every 6 months 1. For patients with pulmonary involvement, rituximab may be preferred over other biologics like TNF inhibitors because it has not been associated with worsening interstitial lung disease and may actually help stabilize or improve pulmonary fibrosis in some cases. This benefit stems from rituximab's mechanism of action as a B-cell depleting agent that targets CD20-positive cells, reducing autoantibody production and inflammatory cytokines that contribute to both joint inflammation and lung fibrosis.

Some key points to consider when using rituximab for RA patients with pulmonary fibrosis include:

  • Screening for hepatitis B, tuberculosis, and assessment of immunoglobulin levels before initiating treatment 1
  • Premedication with acetaminophen, antihistamines, and sometimes corticosteroids to reduce infusion reactions
  • Monitoring for infections, neutropenia, and changes in pulmonary function during treatment
  • Potential use in combination with alternative DMARDs like leflunomide or hydroxychloroquine, rather than methotrexate, due to the latter's potential for lung toxicity

According to the 2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) guideline for the treatment of interstitial lung disease in people with systemic autoimmune rheumatic diseases, rituximab is one of the conditionally recommended treatment options for RA-ILD progression despite first ILD treatment 1. The guideline emphasizes the importance of shared decision-making and co-management with pulmonologists, particularly for initiation of ILD treatment.

It is essential to weigh the potential benefits and risks of rituximab treatment for each individual patient, considering factors such as disease severity, risk factors for progression, and patient preferences. As the evidence is conditional, and the certainty of evidence is frequently downgraded for small sample size and use of surrogate outcomes, a cautious approach is necessary, prioritizing patient safety and close monitoring.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Rituximab for Rheumatoid Arthritis with Pulmonary Fibrosis

  • Rituximab is a B-cell depleting monoclonal antibody used to treat rheumatoid arthritis (RA) and has been reported to cause pulmonary toxicity, although mainly during polychemotherapy of malignant lymphoma 2.
  • A study found that rituximab treatment in patients with RA led to a progressive decline in diffusion capacity of the lung for carbon monoxide (DLCO) with a maximum reduction of 6.1% at 26 weeks compared to baseline, indicating subclinical rituximab-induced pulmonary toxicity 2.
  • Another study found that immunosuppression with rituximab, azathioprine, or mycophenolate improved pulmonary function trajectory in patients with RA-associated interstitial lung disease (ILD), with an improvement in forced vital capacity (FVC) and DLCO at 12 months 3.
  • A review of rituximab therapy in RA patients found that low-dose rituximab therapy (2 × 500 mg) seems as effective as standard dose (2 × 1000 mg), safer, and more cost-effective, but may cause side effects such as de novo infections and infusion reactions 4.
  • A longitudinal multicentre study found that rituximab exposure resulted in a lower risk of functional impairment in RA-ILD patients, with a hazard ratio of 0.51 compared to non-exposure 5.
  • A study on the use of rituximab as a first-line biologic therapy for DMARD-resistant RA found that rituximab improved disease activity and reduced rheumatoid factor and antinuclear antibody levels, with significant improvements in DAS28 and EULAR response criteria at all time points 6.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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