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Predictors of Serious Infections with Rituximab

The risk of serious infectious events (SIE) with rituximab (RTX) is similar to that seen in other biologics (e.g., RA: 2% or 4.3/100PY), but with prolonged use the risk may change. Recent research says that low IgG levels, RTX induced neutropenia, prior SIE and comorbidities can significantly augment this risk.

A retrospective longitudinal single center study of 700 rheumatic and musculoskeletal diseases (RMDs) treated monitored serum immunoglobulins (at baseline and 4–6 months after each cycle), clinical outcomes and SIE over time.

The patient population included rheumatoid arthritis (72%), systemic lupus erythematosus (13%),  ANCA‐associated vasculitis (7%) and 8% with other RMDs.

The overall SIE rate was 9.8/100 PY - 281 SIEs in 176 patients. Predictors of SIEs included:

  • non‐RTX‐specific comorbidities: prior history of SIE, cancer, chronic lung disease, diabetes, heart failure
  • higher corticosteroid doses
  • RTX‐specific factors;
    • low IgG(<6g/L) at baseline and subsequently
    • RTX‐associated neutropaenia
    • higher IgM
    • longer time‐to‐RTX retreatment

B‐cell depletion numbers were not predictive.

SIEs rates were even higher in those with low baseline IgG (16.4/100 PY) or acquired it during/post‐RTX (21.3/100 PY) when compared to those with normal IgG (9.7/100 PY). 

Monitoring B cell numbers does not appear to be as effective as monitoring serum IgG levels and neutrophils counts in patients who will receive long term or repeated RTX therapy.

Careful patient selection - those with no prior SIE and without comorbidities - may further limit the risk of SIE in such patients.

The author has no conflicts of interest to disclose related to this subject

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