The effect of rituximab therapy on immunoglobulin levels in patients with multisystem autoimmune disease

Abstract

Background: Rituximab is a B cell depleting anti-CD20 monoclonal antibody. CD20 is not expressed on mature plasma cells and accordingly rituximab does not have immediate effects on immunoglobulin levels. However, after rituximab some patients develop hypogammaglobulinaemia.

Methods: We performed a single centre retrospective review of 177 patients with multisystem autoimmune disease receiving rituximab between 2002 and 2010. The incidence, severity and complications of hypogammaglobulinaemia were investigated.

Results: Median rituximab dose was 6 g (1-20.2) and total follow-up was 8012 patient-months. At first rituximab, the proportion of patients with IgG <6 g/L was 13% and remained stable at 17% at 24 months and 14% at 60 months. Following rituximab, 61/177 patients (34%) had IgG <6 g/L for at least three consecutive months, of whom 7/177 (4%) had IgG <3 g/L. Low immunoglobulin levels were associated with higher glucocorticoid doses during follow up and there was a trend for median IgG levels to fall after ≥ 6 g rituximab. 45/115 (39%) with IgG ≥ 6 g/L versus 26/62 (42%) with IgG <6 g/L experienced severe infections (p=0.750). 6/177 patients (3%) received intravenous immunoglobulin replacement therapy, all with IgG <5 g/L and recurrent infection.

Conclusions: In multi-system autoimmune disease, prior cyclophosphamide exposure and glucocorticoid therapy but not cumulative rituximab dose was associated with an increased incidence of hypogammaglobulinaemia. Severe infections were common but were not associated with immunoglobulin levels. Repeat dose rituximab therapy appears safe with judicious monitoring.

Figure 1

The effect of rituximab on median immunoglobulin levels. Median immunoglobulin levels are represented as a continuous line and interquartile ranges as dashed lines, according to time after first rituximab treatment, from 0 to 60 months. A. IgG, IgM and IgA levels for all 177 patients. B. Comparison of IgG levels for all patients with those patients with IgG <6 g/L before first rituximab (N = 18). C. Comparison of IgG levels for patients who received <6 g of rituximab in total (N = 79) and patients who received ≥6 g of rituximab (N = 98). D. Comparison of IgG levels for patients with (N = 71) and without (N = 106) severe infection.

Figure 2

Time to first severe infection following first rituximab. Time to first severe infection according to IgG levels. The time to first severe infection was not different when patients with IgG levels ≥6 g/L (N = 116) and IgG levels <6 g/L (N = 61) (p = 0.953) were compared.