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Should Immunoglobulins be Monitored with Rituximab Use?

Boston researchers have found that in a large cohort study of patients receiving rituximab (RTX), most were not being monitored for hypogammaglobulinemia, despite the observed significant increase in severe infections and increased mortality in RTX treated patients.

Published analyses of RTX rheumatoid arthritis clinical trial data has shown that while IgM decreases were common (24%), they were of little consequence. On the other hand, less frequent (4%) IgG decreases, for more than 4 mos. (either before or after RTX),  was associated with a significant increased risk for serious infecions. (Citation source: https://buff.ly/2SSCJRf) RTX trials in granulomatosis with polyangiitis (GPA) found 6 month decreases in immunogloblin levels 27% for IgA, 58% for IgG and 51% for IgM.

A cohort study of 4479 patients receiving RTX (up to 12/31/17) in the in a tertiary, academic Partners HealthCare System examined immunoglobulin measurements, infectious complications, and mortality.

They found that 85% of patients did not have immunoglobulin levels checked before rituximab therapy.

In the 15% with Ig levels assessed hypogammaglobulinemia was found in nearly half (48%) and post RTX, worsening hypogammaglobulinemia was often noted.

There was an increase in severe infections after rituximab use in the study cohort (from 17.2% to 21.7%; P < .001).

Increased mortality was associated with increasing age, male sex and severe infectious complications in the 6 months before and after the first rituximab infusion.

A total of 201 patients (4.5%) received immunoglobulin replacement following rituximab, presumeably for hypogammaglobulinemia.  In this subset, higher cumulative immunoglobulin replacement dose was associated with a reduced risk of serious infectious complications (HR, 0.98; 95% CI, 0.96-0.99; P = .002).

These findings suggest there may be a risk reduction benefit to assessing for hypogammaglobulinemia both before and after rituximab administration. Identification of hypogammaglobulinemic patients (especially with low IgG levels) may prompt the need for immunoglobulin replacement therapy to reduce infectious and mortal risks. 

Disclosures: 
The author has received compensation as an advisor or consultant on this subject

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