title: Depletion of B-cells with rituximab improves endothelial function and reduces inflammation among individuals with rheumatoid arthritis.
abstract: BACKGROUND
  Individuals with rheumatoid arthritis (RA) are at increased risk for cardiovascular disease, partly due to systemic inflammation and endothelial dysfunction. B-cells play an important pathogenic role in the inflammatory process that drives RA disease activity. Rituximab, a chimeric murine/human monoclonal antibody that depletes B-cells, is an effective therapy for RA. The purpose of this study was to determine whether B-cell depletion with rituximab reduces systemic inflammation and improves macrovascular (brachial artery flow-mediated dilation, FMD) and microvascular (reactive hyperemia) endothelial function in RA patients.
  
  
  RESULTS
  RA patients received a single course of rituximab (1000 mg IV infusion at baseline and on day 15). FMD, reactive hyperemia, inflammatory markers, and clinical assessments were performed at baseline, week 12, and week 24. Twenty patients (95% female, median age 54 years) completed the study. Following treatment, FMD improved from a baseline of 4.5±0.4% to 6.4±0.6% at 12 weeks (mean±SE; P<0.0001), followed by a decline at week 24; a similar pattern was observed for hyperemic velocity. Significant decreases in RA disease scores, high-sensitivity C-reactive protein, erythrocyte sedimentation rate, and circulating CD19+ B-cells were sustained through week 24. Cholesterol and triglycerides became significantly although modestly elevated during the study.
  
  
  CONCLUSIONS
  Depletion of B-cells with rituximab improved macrovascular and microvascular endothelial function and reduced systemic inflammation, despite modest elevation in lipids. Given these results, rituximab should be evaluated in the future for its possible role in reducing excess cardiovascular risk in RA.
  
  
  BACKGROUND
  URL http://ClinicalTrials.gov. Unique identifier: NCT00844714.
authors.affiliation: Division of Cardiology, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, CA (P.Y.H., Y.W., E.N., A.S.H., P.G.).
authors.forename: Priscilla Y
authors.initials: PY
authors.lastname: Hsue
authors.affiliation: San Francisco Veterans Affairs Medical Center, Department of Medicine UCSF, University of California, San Francisco, CA (R.S., C.G., J.S.).
authors.forename: Rebecca
authors.initials: R
authors.lastname: Scherzer
authors.affiliation: San Francisco Veterans Affairs Medical Center, Department of Medicine UCSF, University of California, San Francisco, CA (R.S., C.G., J.S.).
authors.forename: Carl
authors.initials: C
authors.lastname: Grunfeld
authors.affiliation: Division of Rheumatology, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, CA (J.I., G.P., J.G.).
authors.forename: John
authors.initials: J
authors.lastname: Imboden
authors.affiliation: Division of Cardiology, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, CA (P.Y.H., Y.W., E.N., A.S.H., P.G.).
authors.forename: Yuaner
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Division of Rheumatology, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, CA (J.I., G.P., J.G.).
authors.forename: Gus
authors.initials: G
authors.lastname: Del Puerto
authors.affiliation: Division of Cardiology, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, CA (P.Y.H., Y.W., E.N., A.S.H., P.G.).
authors.forename: Elaine
authors.initials: E
authors.lastname: Nitta
authors.affiliation: San Francisco Veterans Affairs Medical Center, Department of Medicine UCSF, University of California, San Francisco, CA (R.S., C.G., J.S.).
authors.forename: Judy
authors.initials: J
authors.lastname: Shigenaga
authors.affiliation: Division of Cardiology, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, CA (P.Y.H., Y.W., E.N., A.S.H., P.G.).
authors.forename: Amanda
authors.initials: A
authors.lastname: Schnell Heringer
authors.affiliation: Division of Cardiology, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, CA (P.Y.H., Y.W., E.N., A.S.H., P.G.).
authors.forename: Peter
authors.initials: P
authors.lastname: Ganz
authors.affiliation: Division of Rheumatology, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, CA (J.I., G.P., J.G.).
authors.forename: Jonathan
authors.initials: J
authors.lastname: Graf
mesh_terms: D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment; D000069283:Rituximab; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D015415:Biomarkers; D000069283:Rituximab; D002097:C-Reactive Protein
keywords: B‐cells; endothelial function; inflammation; rheumatoid arthritis