title: 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.
authors.forename: Helena
authors.initials: H
authors.lastname: Marco
authors.affiliation: Department of Medicine, School of Clinical Medicine, University of Cambridge, Cambridge, UK. ronasmith@doctors.net.uk.
authors.forename: Rona M
authors.initials: RM
authors.lastname: Smith
authors.forename: Rachel B
authors.initials: RB
authors.lastname: Jones
authors.forename: Mary-Jane
authors.initials: MJ
authors.lastname: Guerry
authors.forename: Fausta
authors.initials: F
authors.lastname: Catapano
authors.forename: Stella
authors.initials: S
authors.lastname: Burns
authors.forename: Afzal N
authors.initials: AN
authors.lastname: Chaudhry
authors.forename: Kenneth G C
authors.initials: KG
authors.lastname: Smith
authors.forename: David R W
authors.initials: DR
authors.lastname: Jayne
mesh_terms: D000293:Adolescent; D000328:Adult; D000361:Agammaglobulinemia / Q000097:blood* / Q000139:chemically induced* / Q000175:diagnosis; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000009:adverse effects / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D000069283:Rituximab; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D007136:Immunoglobulins; D007155:Immunologic Factors; D000069283:Rituximab