E005 The impact of hypogammaglobulinaemia with rituximab treatment

Abstract

Background: Hypogammaglobulinaemia is known complication of B cell depletion therapy but the impact of the low globulins in these group of patients is far from clear. We carried out an audit to check how well these rheumatoid arthritis (RA) patients were monitored and also try to correlate low globulins levels with significant infection risks. The normal ranges for UK electrophoresis are: IgG 6-16g/L, IgA 0.9- 4.5g/L and IgM 0.5-2.0g/L. Methods: The list of patients undergoing rituximab infusions in 12 months were collected from the infusion clinic. Then we manually looked at the data on the hospital systems; electronic health records and integrated clinical environment. A total of 75 patients have had rituximab infusions within the year but we randomly chose 60 patients for the audit. Of our 60 patients, only 2 were receiving rituximab for indications other than RA - polychondritis and microscopic polyangiitis. We had strict inclusion criteria of having a minimum of one infusion within the 12 months. Results: We found that 42% (25/60) patients had confirmed hypogammaglobulinaemia on their electrophoresis and 20% did not have blood tests within the year to check their immunoglobulin levels. 64% of patients with hypogammaglobulinaemia had 6 monthly rituximab infusions, which is the most common regimen, however, no correlation could be made between frequency of infusions and hypogammaglobulinaemia. Only 7% (4/60 patients) had some type of infection who had normal immunoglobulin levels. We also found that although IgG is the most abundant immunoglobulin in our body, IgM was the most deficient immunoglobulin with rituximab treatment. In terms of patients presenting with infections, 52% patients with confirmed hypogammaglobulinaemia had some variant of active infections. The ranges of hypogammaglobulinaemia were: IgG 2.6- 5.9, IgA 0.12-0.79 and IgM 0.05-0.35. Infections varied from cellulitis to pneumonia but some of these patients also had other risk factors for infections e.g. diabetes. Most of our patients were not deficient in IgG; this may explain why none of the patients presented with lifethreatening infections. Four patients were panhypogammaglobulinaemic but only one of these patients had an active infection. There was also one patient with herpes keratitis and another with a chest infection whose immunoglobulin statuses were not known to us. Conclusion: This audit shows hypogammaglobulinaemia is a common problem in the rituximab treated patients but the infection risks show more correlation to low IgG levels and panhypogammaglobulinaemia. It is important to emphasize that although some patients did have infections, none of them resulted in mortality or significant morbidity. We need clear guidelines when to use IV immunoglobulins in these group of patients. To look at how rituximab impacts immunoglobulin levels and if it increases risk of infections, larger studies need to be carried out.