What is the CD19 count threshold to restart intravenous (IV) rituximab (rituximab)

CD19 Count Threshold for Restarting IV Rituximab

There is no established CD19 count cutoff to guide restarting IV rituximab, and current guidelines conditionally recommend scheduled re-dosing over using CD19+ B cell counts to determine timing of retreatment. 1, 2

Guideline-Based Approach

The American College of Rheumatology (2021) explicitly recommends against using CD19+ B cell counts or ANCA titers to guide rituximab re-dosing in patients with GPA/MPA receiving maintenance therapy. 1 Instead, scheduled re-dosing is preferred because:

• Disease flares can occur even when patients have complete CD19+ B cell depletion 1, 2
• CD19 counts do not accurately predict disease flare potential 1, 2
• A randomized trial showed similar relapse rates between scheduled dosing versus biomarker-guided dosing, though the study had limited sample size 1

Recommended Dosing Schedule (Not CD19-Guided)

For maintenance therapy in GPA/MPA, use fixed-interval dosing: 1, 2

• 500 mg IV every 6 months (FDA-approved) 1
• 1,000 mg IV every 4 months 1
• 1,000 mg IV every 6 months 1

What the Research Shows About CD19 Monitoring

While guidelines recommend against CD19-guided dosing, research studies have examined various thresholds:

Rheumatoid Arthritis Data:

• CD19 repopulation >0.1% of lymphocytes preceded clinical relapse by approximately 4 months 3
• Most relapses occurred within 4 months of total B cell, transitional B cell, and memory B cell repopulation 3

Minimal Change Disease Data:

• 71% of relapses occurred when CD19 counts exceeded 100 cells/µL 4

NMOSD/MOGAD Data:

• Switching from CD19 monitoring (>0.1% of lymphocytes) to CD27+ B cell monitoring (>0.05-0.1% of lymphocytes) allowed longer inter-dose intervals without compromising efficacy 5

Critical Pitfalls to Avoid

Do not delay scheduled rituximab re-dosing based on persistently low or undetectable CD19 counts, as disease can flare despite complete B-cell depletion. 1, 2

Do not assume B-cell repopulation automatically indicates need for immediate re-treatment, as the timing of repopulation does not reliably correlate with clinical relapse across all conditions. 1, 2

Do not use CD19 counts as the primary determinant for retreatment timing in vasculitis, as this approach is not supported by current guidelines and may lead to suboptimal disease control. 1, 2

Practical Clinical Algorithm

For GPA/MPA maintenance: 2

1. Use scheduled dosing (500-1,000 mg IV every 4-6 months)
2. Monitor clinical disease activity, symptoms, and organ function
3. Ignore CD19 counts for dosing decisions

For other conditions (RA, nephrotic syndrome) where CD19 monitoring is sometimes used: 3, 4

1. If monitoring CD19, consider >0.1% of lymphocytes or >100 cells/µL as thresholds associated with increased relapse risk
2. However, recognize this is not guideline-recommended for vasculitis
3. Clinical assessment remains paramount over laboratory values

Monitor for treatment response using clinical parameters rather than CD19 counts to assess need for continuation. 2