Infection and Rituximab-linked Immunoglobulin Deficiency Save

A minority of immune-mediated inflammatory disease (IMID) patients treated with rituximab (RTX) are expected to develop and depressed immunoglobulin (Ig) levels.  A recent cohort analysis suggests that RTX-induced Ig deficiency was not associated with an increased risk of severe infection in IMID patients.

An observational, retrospective single-centre study of IMID patients (mostly RA) receiving at least one RTX, analyzed their risk for Ig deficiency, severe infection or death for at least 12 months after the last infusion or until severe infection or death.

The cohort included 311 RTX treated patients, of whom 10.6% had prevalent and 19.6% acquired Ig deficiency.

Prevalent Ig deficiency was more related to concomitant glucocorticoids (GCs) treatment while acquired Ig deficiency was related to cumulative dose of RTX, DAS28 activity, immunosuppressor or GCs therapy at baseline, diabetes mellitus and obesity.

Severe infection was seen in 14.5% during follow-up, but was unrelated to Ig levels. Instead severe infection was significantly associated with chronic pulmonary disease, GCs dose and DAS28-CRP. In some, the risk of severe infection during RTX treatment was increased in patients with prevalent immunoglobulin deficiency, but was mainly due to confounding factors.

In a time-dependent analysis, risk of severe infection was not associated with Ig deficiency, either acquired or prevalent (adjusted HR 1.04 (95% CI 0.5 to 2.3), p=0.92).

There still may be a concern regarding the risk of severe infection in those who develop hypogammaglobulinaemia.  As some studies have shown the risk of severe infection (SIE) in RA may be elevated in those with or who develop low IgG levels. When RTX has been used in other autoimmune or IMIDs, there has been variable and inconsistent low IgM and IgG levels, making their predictive value equally inconsistent. 

This study points out that beyond changes in Ig levels, the safe use of RTX should focus on individual patients infectious risk, especially in those on GC or with chronic lung disease.