How to manage fever in a patient on Remicade (Infliximab)?

Management of Fever in Patients on Remicade (Infliximab)

When a patient on Remicade (infliximab) develops fever, it should be considered a medical emergency requiring immediate evaluation and management due to the increased risk of serious infections. 1

Initial Assessment

Immediate Evaluation

• Check temperature (fever defined as ≥38°C/100.4°F)
• Assess for signs of infection:
  • Respiratory symptoms: cough, shortness of breath
  • Urinary symptoms: dysuria, frequency
  • Skin: redness, warmth, discharge from wounds
  • Gastrointestinal: abdominal pain, diarrhea
  • Neurological: headache, neck stiffness, altered mental status

Laboratory Workup

• Complete blood count with differential
• Comprehensive metabolic panel
• C-reactive protein and erythrocyte sedimentation rate
• Blood cultures (at least two sets)
• Urinalysis and urine culture
• Chest radiograph

Management Algorithm

Step 1: Assess Severity and Risk

• High Risk Features:
  • Temperature >38.3°C
  • Neutropenia (ANC <500/mm³)
  • Hypotension (systolic BP <90 mmHg)
  • Altered mental status
  • Respiratory distress

Step 2: Initiate Empiric Treatment

• For all febrile patients on infliximab:
  • Start broad-spectrum antibiotics immediately after cultures are obtained 2
  • Consider hospital admission for IV antibiotics if any high-risk features present
  • Temporarily discontinue infliximab until infection is ruled out or controlled 1

Step 3: Targeted Management Based on Suspected Source

For respiratory infections:

• Consider empiric coverage for common respiratory pathogens including Streptococcus pneumoniae, Haemophilus influenzae, and atypical organisms
• Recommended regimens:
  • Co-amoxiclav 625 mg three times daily orally, or
  • Doxycycline 200 mg initially then 100 mg daily orally 2
  • For severe cases: IV antibiotics (co-amoxiclav 1.2g three times daily or cefuroxime 1.5g three times daily) 2

For urinary tract infections:

• Empiric coverage for gram-negative organisms
• Consider fluoroquinolones or trimethoprim-sulfamethoxazole if not contraindicated

For skin and soft tissue infections:

• Coverage for Staphylococcus aureus and Streptococcus species
• Consider MRSA coverage based on local prevalence

Step 4: Special Considerations

Opportunistic Infections

• Evaluate for opportunistic infections including:
  • Tuberculosis (reactivation risk is higher with infliximab)
  • Fungal infections (histoplasmosis, coccidioidomycosis)
  • Viral infections (CMV, EBV, hepatitis B reactivation) 2, 3

Monitoring

• Daily assessment of fever trends and clinical status
• Monitor complete blood count every 2-3 days
• Continue close monitoring until resolution of symptoms 4

Important Caveats

Drug Fever

• Consider drug fever as a diagnosis of exclusion
• Characteristics:
  • Onset typically after 7-10 days of drug administration
  • Rapid resolution after drug discontinuation
  • No source of infection identified despite thorough workup 5
• Rechallenge with infliximab should be performed with extreme caution and only if benefits outweigh risks

Hepatitis B Reactivation

• Patients with history of hepatitis B are at risk for reactivation
• Monitor for signs of hepatitis:
  • Jaundice
  • Dark urine
  • Right upper quadrant pain
  • Fatigue 1

Neutropenic Fever

• For patients who develop neutropenia (ANC <500/mm³) while on infliximab:
  • Immediate hospitalization
  • Broad-spectrum antibiotics (anti-pseudomonal coverage)
  • Consider G-CSF if neutropenia is severe and prolonged 4

Return to Therapy Considerations

• Resolution of fever and infection should be documented before restarting infliximab
• Consider the risk-benefit ratio of continuing infliximab in patients with recurrent infections
• The safety of resuming TNF blocker therapy after hepatitis B reactivation is not well established 1

Patient Education

Instruct patients on infliximab to:

• Check temperature frequently and report fever immediately
• Report signs of infection promptly (cough, chills, wounds with redness/discharge, painful urination)
• Report shortness of breath or changes in breathing
• Understand the importance of seeking immediate medical attention for fever >38.3°C 2, 1

Remember that fever in patients on TNF inhibitors like infliximab should never be dismissed as minor, as these medications significantly increase the risk of serious and potentially life-threatening infections that require prompt evaluation and management.