RISK OF SEVERE INFECTIONS IN IMMUNE MEDIATED INFLAMMATORY DISEASES WITH IMMUNOGLOBULIN DEFICIENCY UNDER RITUXIMAB THERAPY
Authors: Morel J et al.
Rituximab (RTX) is effective in treating immune-mediated inflammatory diseases (IMID). Hypogammaglobulinemia may occur under RTX and may increase infection risk. Since data are controversial, this retrospective single-center study evaluated the risk of severe infection in patients with IMID and hypogammaglobulinemia under RTX therapy.
311 patients were analyzed. Mean follow-up was 62.6 months. Exposure was 1623.7 patient-years. 15% of patients developed at least 1 severe infection. Incidence rate was 2.77/100 PY. 29 patients had prevalent Ig deficiency before being treated with RTX. 68 patients developed hypogammaglobulinemia, mainly for IgM (12%) and IgG (8%). Severe infection rate was higher in patients with prevalent Ig deficiency (RR 1.73; 95% CI 0.85-3.53), with significant difference in survival model (Log-Rank test: p=0.033). On the other hand, no excess risk of infection was observed in patients developing Ig deficiency under RTX in univariate analysis (RR 0.68; 95% CI 0.31-1.47) or in survival analyses after adjustment for confounding factors (type of IMID (RA versus other IMID), cumulative dose of RTX, presence of chronic pulmonary comorbidities, use of an immunosuppressive drug at inclusion, and mean dose of GCs collected at each cycle of RTX during follow-up). Chronic lung disease and glucocorticoid (GCs) use during follow-up were associated with an increased risk of severe infection.
In this study there was not an increased risk of severe infection in RTX-induced Ig deficiency after adjustment for confounding factors. However, there was an increased risk of severe infection in cases of prevalent Ig deficiency prior to RTX. Independent of immunoglobulin level chronic lung disease and glucocorticoid (GCs) use during follow-up were associated with an increased risk of severe infection.
RTX management should therefore be discussed on a case-by-case basis, according to an individual assessment of the infectious risk. The automatic administration of immunoglobulins in the case of a low immunoglobulin level (e.g. < 5 g/l IgG) is therefore not necessary. Only when the risk of infection is very high (e.g. in patients with chronic lung diseases and/or simultaneous administration of glucocorticoids) an Immunoglobulin substitution should be considered.