title: B-cell depletion with rituximab in patients with primary biliary cirrhosis refractory to ursodeoxycholic acid.
abstract: OBJECTIVE
  Rituximab, an anti-CD20 monoclonal antibody that selectively depletes B cells, has shown promise in autoantibody-associated, immune-mediated disorders. As ursodeoxycholic acid (UDCA) is not successful in all patients with primary biliary cirrhosis (PBC), additional treatment options are necessary. The objective of this study was to assess the safety and efficacy of rituximab in patients with PBC refractory to UDCA.
  
  
  METHODS
  Fourteen PBC patients refractory to UDCA received two rituximab infusions (1,000 mg) 2 weeks apart. The primary efficacy outcome was normalization and/or 25% improvement in serum alkaline phosphatase (ALP) concentration at 6 months.
  
  
  RESULTS
  The median age was 53 years, and 92% were female and antimitochondrial antibody (AMA) positive. The median UDCA dosage was 15.3 mg/kg/day (interquartile range 14.5-17.8). Although rituximab was well tolerated, one patient withdrew due to an asthma exacerbation during the first infusion. Effective B-cell depletion was observed in the remaining 13 patients, including three that developed human anti-chimeric antibodies. ALP normalization and/or ≥ 25% improvement was observed in three patients (23%) at 6, 12, and 18 months. Significant reductions in median ALP (from 259 U/l at baseline to 213 U/l at 6 months; median decrease 16%), and serum IgM and AMA levels were observed at 6 months. Although fatigue was stable, pruritus improved in 60% of patients at 12 months (vs. 8% with worsening pruritus).
  
  
  CONCLUSIONS
  Selective B-cell depletion with rituximab was safe and associated with a significant decrease in autoantibody production, but had limited biochemical efficacy in PBC patients with an incomplete response to UDCA.
authors: Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada. rpmyers@ucalgary.ca
authors: Robert P
authors: RP
authors: Myers
authors: Mark G
authors: MG
authors: Swain
authors: Samuel S
authors: SS
authors: Lee
authors: Abdel Aziz M
authors: AA
authors: Shaheen
authors: Kelly W
authors: KW
authors: Burak
mesh_terms: D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D058846:Antibodies, Monoclonal, Murine-Derived / Q000009:adverse effects / Q000627:therapeutic use*; D001323:Autoantibodies / Q000097:blood; D001402:B-Lymphocytes; D002756:Cholagogues and Choleretics / Q000627:therapeutic use; D004351:Drug Resistance; D005221:Fatigue / Q000209:etiology; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008137:Longitudinal Studies; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000276:immunology; D010865:Pilot Projects; D011537:Pruritus / Q000209:etiology; D011788:Quality of Life; D000069283:Rituximab; D012720:Severity of Illness Index; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D001323:Autoantibodies; D002756:Cholagogues and Choleretics; D007075:Immunoglobulin M; D007155:Immunologic Factors; D000069283:Rituximab; D014580:Ursodeoxycholic Acid; D000469:Alkaline Phosphatase