Should tocilizumab (interleukin-6 receptor inhibitor) be stopped in a patient with pneumonia who is receiving it for conditions like rheumatoid arthritis (RA) or COVID-19?

Management of Tocilizumab in Patients with Pneumonia

In patients with rheumatoid arthritis or other rheumatic diseases who develop non-COVID pneumonia, tocilizumab should be temporarily stopped until the infection is controlled, as IL-6 inhibition can mask early symptoms of pneumonia and increase infection risk. 1, 2

Context-Specific Recommendations

For Non-COVID Pneumonia in Rheumatic Disease Patients

• Stop tocilizumab immediately when bacterial, fungal, or other non-COVID pneumonia is diagnosed or suspected 1, 2
• The FDA black box warning explicitly states that serious infections including bacterial and invasive fungal infections have occurred with tocilizumab, requiring interruption until infection is controlled 2
• Tocilizumab can suppress inflammatory symptoms and C-reactive protein elevation, potentially masking the severity of pneumonia and delaying appropriate treatment 3
• In two documented cases, patients on tocilizumab developed severe pneumonia that initially presented with only minimal clinical symptoms due to IL-6 blockade suppressing early inflammatory responses 3

For COVID-19 Pneumonia (Special Circumstance)

The guidance differs substantially for COVID-19:

• In select circumstances with severe COVID-19 pneumonia requiring high-flow oxygen, non-invasive ventilation, or mechanical ventilation, tocilizumab may be continued or initiated as part of shared decision-making with the treating team 1, 2
• The American College of Rheumatology guidance (2020-2021) specifically states that "in select circumstances, as part of a shared decision-making process, IL-6 receptor inhibitors may be continued" in documented COVID-19 1
• This exception exists because tocilizumab targets the cytokine storm mechanism in severe COVID-19, potentially reducing mechanical ventilation requirements 4, 5
• However, even in COVID-19, careful monitoring for opportunistic infections (Pneumocystis jirovecii, Aspergillus) is essential, as tocilizumab can weaken anti-infectious immunity 6

Critical Safety Considerations

Infection Risk Profile

• Tocilizumab carries FDA black box warning for serious infections including tuberculosis, bacterial, invasive fungal, viral, and opportunistic infections that may lead to hospitalization or death 2
• IL-6 blockade is a double-edged sword: while it may reduce hyperinflammation, it simultaneously weakens anti-infectious immunity 6
• Patients with rheumatic diseases on chronic immunosuppression are at particularly high risk when tocilizumab is combined with other immunosuppressive agents 6

Monitoring Requirements

• Before stopping tocilizumab for pneumonia, ensure laboratory parameters are documented: absolute neutrophil count, platelet count, and liver enzymes 1, 2
• Monitor closely for opportunistic infections, particularly in patients who have received long-term immunosuppressive therapy 6
• Be aware that tocilizumab masks fever and acute phase responses, making clinical assessment more challenging 1, 3

Reinitiation After Infection Resolution

Timing for Restarting Tocilizumab

• For uncomplicated pneumonia treated in the ambulatory setting: consider restarting 7-14 days after symptom resolution 1
• For severe pneumonia requiring hospitalization: decisions should be made case-by-case based on complete clinical recovery and resolution of infection 1
• Do not require negative inflammatory markers before restarting, as prolonged delays may lead to rheumatic disease flare 1

Pre-Initiation Laboratory Thresholds

When restarting tocilizumab after pneumonia:

• Absolute neutrophil count should be ≥2000/mm³ 1
• Platelet count should be ≥100,000/mm³ 1
• ALT/AST should be ≤1.5 times upper limit of normal 1

Common Pitfalls to Avoid

• Do not continue tocilizumab during non-COVID bacterial or fungal pneumonia simply because the patient's rheumatic disease is well-controlled—infection control takes priority 1, 2
• Do not rely solely on fever or CRP elevation to assess pneumonia severity in patients on tocilizumab, as these may be blunted 3
• Do not assume all pneumonias in tocilizumab-treated patients are typical bacterial infections—maintain high suspicion for opportunistic pathogens including Pneumocystis and Aspergillus 6
• Do not automatically restart tocilizumab after COVID-19 pneumonia without considering the severity of illness and potential for opportunistic co-infections 6