What to do for Systemic JIA with severe neutropenia on Anakinra?

Management of Neutropenia in Systemic JIA Patient on Anakinra

Initial Assessment and Recommendation

For a systemic JIA patient on anakinra with neutrophil count of 0.96, the recommended next step is to temporarily discontinue anakinra and consider switching to tocilizumab once the neutropenia resolves. 1

Understanding the Situation

Neutropenia (neutrophil count <1.0 × 10^9/L) in this patient represents a significant adverse effect of anakinra therapy. The American College of Rheumatology (ACR) guidelines recommend monitoring complete blood counts (CBC) within the first 1-2 months of anakinra usage and every 3-4 months thereafter due to the risk of cytopenias 1.

Management Algorithm

Step 1: Immediate Management

• Temporarily discontinue anakinra due to severe neutropenia
• Monitor CBC closely (every 1-2 days) until neutrophil recovery
• Assess for signs of infection (fever, chills, malaise)
• Consider prophylactic antibiotics if clinically indicated

Step 2: After Neutrophil Recovery (>1.5 × 10^9/L)

• Option A: Switch to tocilizumab

  • Preferred option based on evidence
  • Tocilizumab has been shown to be effective in systemic JIA after anakinra treatment 1
  • Although tocilizumab can also cause neutropenia, research shows that neutropenia during tocilizumab treatment is not associated with increased infection risk in JIA patients 2

• Option B: Rechallenge with anakinra at lower dose

  • Consider only if patient had excellent disease control with anakinra
  • Start at 50% of previous dose with more frequent monitoring
  • Not recommended if neutropenia was severe or recurrent

Step 3: Long-term Monitoring

• Monitor CBC counts every 2-4 weeks initially after starting new therapy
• If stable, continue monitoring every 3-4 months as per guidelines 1

Evidence-Based Rationale

1. Safety concerns with anakinra: The ACR guidelines recommend regular monitoring of CBC counts during anakinra treatment due to risk of neutropenia 1.

2. Efficacy of alternative agents: Tocilizumab is recommended by ACR guidelines for systemic JIA patients with active disease following treatment with anakinra (level B evidence) 1.

3. Tocilizumab and neutropenia: While tocilizumab can also cause neutropenia, research shows that neutropenia during tocilizumab treatment is transient and not associated with increased infection risk in JIA patients 2. In a 2019 study, neutropenia occurred in 25% of systemic JIA patients on tocilizumab but was not associated with increased infection rates 2.

4. Comparative efficacy: A 2021 Bayesian network meta-analysis showed that both anakinra and tocilizumab are effective for systemic JIA, with canakinumab having the highest probability of being the best treatment in terms of ACRpedi30 response rate 3.

Important Considerations

• Infection risk: Carefully evaluate for signs of infection during neutropenic period
• Disease flare: Systemic JIA may flare when anakinra is discontinued; consider bridging with short-term glucocorticoids if necessary
• Treatment alternatives: If both anakinra and tocilizumab are not tolerated, canakinumab is another IL-1 inhibitor option for systemic JIA 1
• Monitoring requirements: For tocilizumab, monitor CBC counts and liver function tests within the first 1-2 months of usage and every 3-4 months thereafter 1

Pitfalls to Avoid

• Don't continue anakinra at same dose despite severe neutropenia as this may increase infection risk
• Don't delay treatment switch if neutropenia is recurrent or severe with anakinra
• Don't overlook signs of macrophage activation syndrome (MAS) which can present with cytopenias and is a life-threatening complication of systemic JIA 1
• Don't forget to monitor liver function with both anakinra and tocilizumab, as both can cause elevated liver enzymes 1