What is the risk of pneumonia in patients treated with Rituximab (rituximab)

From the Guidelines

Rituximab increases the risk of pneumonia due to its immunosuppressive effects, and preventive measures such as pneumococcal vaccination (both PCV13 and PPSV23) and annual influenza vaccination are strongly recommended. Patients receiving rituximab have a higher susceptibility to bacterial, viral, and opportunistic pneumonias because the medication depletes B cells, compromising humoral immunity 1. The risk is particularly elevated in the first 3-6 months after treatment but can persist for up to 12 months or longer.

Key Considerations

• Pneumococcal vaccination should be strongly considered for the majority of patients with autoimmune inflammatory rheumatic diseases, including those receiving rituximab 1.
• Influenza vaccination should also be strongly considered for the majority of patients with autoimmune inflammatory rheumatic diseases, including those receiving rituximab 1.
• A stepwise pneumococcal vaccination approach, with a PCV13 prime-PPSV23 boost strategy, is recommended for patients at risk of pneumococcal disease, including those receiving rituximab 1.
• Patients receiving rituximab should be monitored for respiratory symptoms such as cough, fever, and shortness of breath during and after treatment.
• If pneumonia is suspected, prompt evaluation with chest imaging and appropriate cultures is essential, followed by broad-spectrum antibiotics while awaiting culture results.

Preventive Measures

• Pneumococcal vaccination (both PCV13 and PPSV23) should be administered at least 4 weeks before starting rituximab for optimal antibody response.
• Annual influenza vaccination should be administered to patients receiving rituximab.
• Prophylaxis to prevent P jirovecii pneumonia may be considered for patients receiving rituximab, especially those with GPA or MPA 1.

Patient Education

• Healthcare providers should educate patients about infection risks and advise them to seek immediate medical attention if respiratory symptoms develop.
• Patients should be informed about the importance of preventive measures, such as pneumococcal and influenza vaccination, and the need for prompt evaluation and treatment if pneumonia is suspected.

From the FDA Drug Label

Infections Fourteen patients (37%) in the group treated with non-U.S.-licensed rituximab experienced treatment-related infections compared to 15 patients (42%) in the prednisone group. The most common infections in the group treated with non-U.S. -licensed rituximab were herpes simplex, herpes zoster, bronchitis, urinary tract infection, fungal infection, and conjunctivitis. Three patients (8%) in the group treated with non-U.S. -licensed rituximab experienced a total of 5 serious infections (Pneumocystis jirovecii pneumonia, infective thrombosis, intervertebral discitis, lung infection, Staphylococcal sepsis) and 1 patient (3%) in the prednisone group experienced 1 serious infection (Pneumocystis jirovecii pneumonia)

In GPA/MPA Study 1,62% (61/99) of patients in the RITUXAN group experienced an infection of any type compared to 47% (46/98) patients in the cyclophosphamide group by Month 6. The most common infections in the RITUXAN group were upper respiratory tract infections, urinary tract infections, and herpes zoster The incidence of serious infections was 11% in the RITUXAN-treated patients and 10% in the cyclophosphamide treated patients, with rates of approximately 25 and 28 per 100 patient-years, respectively. The most common serious infection was pneumonia

Pneumonia in Rituximab:

• Pneumonia is a serious infection that can occur in patients treated with rituximab.
• The incidence of pneumonia as a serious infection was reported in the studies, with rates of approximately 25 and 28 per 100 patient-years in the RITUXAN and cyclophosphamide groups, respectively.
• Pneumocystis jirovecii pneumonia was also reported as a serious infection in patients treated with rituximab.
• The most common serious infection reported was pneumonia. 2 2

From the Research

Pneumonia in Rituximab

• Pneumocystis pneumonia (PcP) is an opportunistic fungal infection that can occur in patients treated with rituximab, with the majority of cases having also received cytotoxic chemotherapy or significant doses of glucocorticoids 3.
• The clinical course of PcP in patients treated with rituximab can be quite fulminant, with significant mortality, and primary prophylaxis should be considered in patients at risk 3.
• Severe pneumonia in patients treated with rituximab in the intensive care unit (ICU) is often caused by fungi, bacteria, or Pneumocystis jirovecii pneumonia, and older age and chronic lung disease are significantly associated with mortality 4.

Prognostic Factors and Treatment

• The efficacies of atovaquone, pentamidine, and trimethoprim/sulfamethoxazole for the prevention of Pneumocystis jirovecii pneumonia in patients with connective tissue diseases have been compared, and atovaquone was found to be well tolerated 5.
• The optimal prophylaxis duration for Pneumocystis pneumonia in kidney transplant recipients according to perioperative treatment with rituximab is yet unknown, but maintaining prophylaxis for 12 months may be beneficial in patients treated with rituximab 6.
• Trimethoprim-Sulfamethoxazole (TMP-SMX) dose optimization is important in Pneumocystis jirovecii pneumonia management, and a low dose of TMP-SMX may provide satisfactory outcomes while reducing mortality rate and PCP-associated adverse events 7.

Risk Factors

• Rituximab treatment and acute rejection are significant risk factors for Pneumocystis pneumonia in kidney transplant recipients 6.
• Older age and chronic lung disease are significantly associated with mortality in patients treated with rituximab who develop severe pneumonia in the ICU 4.