title: Low immunoglobulin levels increase the risk of severe hypogammaglobulinemia in granulomatosis with polyangiitis patients receiving rituximab.
abstract: BACKGROUND
  Randomized controlled trials and retrospective studies in ANCA-associated vasculitis (AAV) concurred that rituximab (RTX) is effective to induce and maintain remission. Infections and hypogammaglobulinemia during RTX were usually infrequent and uncomplicated. But in the Tromsø study cohort, 45% of patients with granulomatosis with polyangiitis (GPA) developed hypogammaglobulinemia during RTX maintenance leading to its discontinuation in 62%.
  
  
  METHODS
  To explain these differences in outcome when using RTX in AAV to maintain remission, we used statistical structural methods to compare the Tromsø study cohort with other published cohorts.
  
  
  RESULTS
  GPA patients' characteristics of the Tromsø study cohort were not so different compared with other cohorts. Rates of hypogammaglobulinemia and discontinuation of RTX seemed closely related to the cut-off used and to the levels of immunoglobulin (Ig) at baseline. Combination of low IgG serum levels at baseline (7.7 g/L) and low cut-off to define hypogammaglobulinemia in the Tromsø study cohort explained the high rate of hypogammaglobulinemia and discontinuation of RTX.
  
  
  CONCLUSIONS
  Patients' characteristics in the Tromsø study cohort were not skewed, apart from IgG levels. Low IgG level at baseline seemed to contribute the most to hypogammaglobulinemia and its complications.
authors.affiliation: Bone and Joint Research Group, Institute of Clinical Medicine, UiT The Arctic University of Norway, 9037, Tromsø, Norway. emilio.besada@uit.no.
authors.forename: Emilio
authors.initials: E
authors.lastname: Besada
mesh_terms: D000328:Adult; D000361:Agammaglobulinemia / Q000097:blood* / Q000139:chemically induced* / Q000453:epidemiology; D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005260:Female; D014890:Granulomatosis with Polyangiitis / Q000097:blood* / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009664:Norway / Q000453:epidemiology; D012307:Risk Factors; D000069283:Rituximab / Q000009:adverse effects*; D012720:Severity of Illness Index
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; D007074:Immunoglobulin G; D000069283:Rituximab