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B-Cell Depletion With Rituximab in Patients With Primary Biliary Cirrhosis Refractory to Ursodeoxycholic Acid
- Source :
- American Journal of Gastroenterology. 108:933-941
- Publication Year :
- 2013
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2013.
-
Abstract
- 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.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.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).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.
- Subjects :
- Adult
Male
Cholagogues and Choleretics
medicine.medical_specialty
Drug Resistance
Pilot Projects
Severity of Illness Index
Gastroenterology
Lymphocyte Depletion
Antibodies, Monoclonal, Murine-Derived
Primary biliary cirrhosis
Refractory
immune system diseases
hemic and lymphatic diseases
Internal medicine
medicine
Humans
Immunologic Factors
Longitudinal Studies
Fatigue
Autoantibodies
B-Lymphocytes
Hepatology
biology
Liver Cirrhosis, Biliary
business.industry
Pruritus
Ursodeoxycholic Acid
Autoantibody
Middle Aged
Alkaline Phosphatase
medicine.disease
Ursodeoxycholic acid
Mitochondria
Immunoglobulin M
Immunology
Monoclonal
Quality of Life
biology.protein
Female
Rituximab
Antibody
business
medicine.drug
Subjects
Details
- ISSN :
- 00029270
- Volume :
- 108
- Database :
- OpenAIRE
- Journal :
- American Journal of Gastroenterology
- Accession number :
- edsair.doi.dedup.....916f47c50501a4a762594164b914d1af