Is rituximab (Rituxan) used in the treatment of rheumatoid arthritis?

Rituximab in Rheumatoid Arthritis

Yes, rituximab is FDA-approved for the treatment of rheumatoid arthritis in patients who have had an inadequate response to one or more TNF antagonist therapies. 1

Mechanism and Approval

Rituximab is a monoclonal antibody that targets CD20 molecules expressed on the surface of pre-B and mature B lymphocytes, causing their apoptosis through antibody- and complement-dependent cytotoxicity. 2 Originally developed for non-Hodgkin's lymphoma, it was later approved for rheumatoid arthritis treatment. 2

Indication in Rheumatoid Arthritis

Rituximab is specifically indicated for:

• Treatment of adults with moderately to severely active rheumatoid arthritis 1
• Patients who have had an inadequate response to one or more TNF antagonist therapies 1
• Must be used in combination with methotrexate 1

Dosing and Administration

• Standard dosing is two 1000 mg intravenous infusions given two weeks apart 1, 3
• Administered as an intravenous infusion (not as push or bolus) 1
• Premedication is required before each infusion 1
• Monitoring for infusion reactions is essential, especially during the first infusion 1

Efficacy in Rheumatoid Arthritis

• In clinical trials, rituximab in combination with methotrexate demonstrated significant improvement in disease activity compared to methotrexate alone 3
• At 24 weeks, 51% of patients on rituximab plus methotrexate achieved ACR20 response compared to 18% on placebo plus methotrexate 4
• Significant improvements were also seen in ACR50 and ACR70 responses 4
• Benefits include reduced disease activity, improved physical function, and a trend toward less radiographic progression 3, 4

Patient Selection Factors

• Rituximab shows better response in seropositive patients (positive for rheumatoid factor or anti-citrullinated protein antibodies) 2
• Particularly useful in patients with certain contraindications to other biologics, such as: 2
  • History of lymphoma
  • Latent tuberculosis with contraindications to chemoprophylaxis
  • Living in TB-endemic regions
  • History of demyelinating disease
  • Recent history of malignancy

Place in Treatment Algorithm

Rituximab is typically used after failure of TNF inhibitors: 2

• First-line therapy usually includes conventional DMARDs (particularly methotrexate)
• If inadequate response, TNF inhibitors are typically the first biologic agents used
• Rituximab is generally recommended after inadequate response to at least one TNF inhibitor
• In certain circumstances (as mentioned above), rituximab may be considered earlier in the treatment algorithm

Safety Considerations

• Most common adverse events are infusion reactions, particularly with the first infusion 1, 4
• Serious potential adverse events include: 1, 5
  • Fatal infusion-related reactions
  • Severe mucocutaneous reactions
  • Hepatitis B virus reactivation
  • Progressive multifocal leukoencephalopathy (PML)
• Screening for hepatitis B infection is required before initiating treatment 1, 5
• Rituximab depletes peripheral CD20+ B cells, but immunoglobulin levels typically remain within normal ranges 4
• Extended use may lead to hypogammaglobulinemia, which could increase infection risk 5

Retreatment Considerations

• Patients who respond to rituximab may require retreatment when disease flares 6, 7
• The median time to retreatment is approximately 6-9 months 6, 7
• Retreatment has been shown to be effective and generally maintains efficacy 7

Common Pitfalls and Caveats

• Failure to screen for hepatitis B before treatment (including occult infection) 5
• Not monitoring immunoglobulin levels with repeated courses 5
• Underutilizing rituximab in seropositive patients who may have better response 2
• Not providing adequate premedication before infusions 1
• Insufficient monitoring during infusions, particularly the first infusion 1