title: Short-term improvement of endothelial function in rituximab-treated rheumatoid arthritis patients refractory to tumor necrosis factor alpha blocker therapy.
abstract: OBJECTIVE
  Cardiovascular disease is the major cause of excessive mortality in rheumatoid arthritis (RA) and endothelial dysfunction plays a key role in atherosclerosis. The aim of the present study was to assess whether rituximab therapy was able to improve endothelial function in RA patients refractory to tumor necrosis factor alpha (TNFalpha) blockers.
  
  
  METHODS
  Six consecutive RA patients (5 women; age range 55-79 years) with active disease refractory to TNFalpha inhibitor therapy were studied. Patients received intravenous rituximab (1 course, consisting of 2 infusions of 1,000 mg each separated by 2 weeks). Flow-mediated endothelium-dependent vasodilatation (FMD%) and endothelium-independent vasodilatation (postnitroglycerin) were measured at day 0 prior to the first rituximab infusion, at week 2 (before the second infusion), and at month 6.
  
  
  RESULTS
  At week 2, a dramatic increase in FMD% values was observed in all patients (mean +/- SD 7.02 +/- 2.31%, median 7.29%, range 3.2-9.75%) compared with those observed before the first infusion (mean +/- SD 3.35 +/- 1.58%, median 3.04%, range 1.69-5.89%). In addition, at month 6, FMD% values in all patients (mean +/- SD 7.66 +/- 1.73%, median 7.64%, range 5.61-9.98%) were greater than those found before the first infusion (P = 0.03). The dramatic improvement of FMD% was associated with a significant decrease in C-reactive protein level and Disease Activity Score in 28 joints.
  
  
  CONCLUSIONS
  Our study demonstrates an active effect of rituximab on endothelial function in RA patients refractory to TNFalpha blockers.
authors.affiliation: Hospital Xeral-Calde, Lugo, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Gonzalez-Juanatey
authors.forename: Javier
authors.initials: J
authors.lastname: Llorca
authors.forename: Tomas R
authors.initials: TR
authors.lastname: Vazquez-Rodriguez
authors.forename: Nicolas
authors.initials: N
authors.lastname: Diaz-Varela
authors.forename: Hermitas
authors.initials: H
authors.lastname: Garcia-Quiroga
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Gonzalez-Gay
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000503:physiopathology*; D004351:Drug Resistance; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D000069283:Rituximab; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D000069283:Rituximab