title: Safety of rituximab in rheumatoid arthritis: a long-term prospective single-center study of gammaglobulin concentrations and infections.
abstract: OBJECTIVE
  Rituximab seems well tolerated in patients with rheumatoid arthritis (RA). However, variations in the gammaglobulin profile that might increase the infection risk have been reported. Here, our objective was to evaluate gammaglobulin concentrations and the infection risk in patients receiving rituximab therapy for RA in everyday practice.
  
  
  METHODS
  Prospective single-center observational study of 65 patients with refractory RA (median age, 59 years; range, 26-83) treated with rituximab 1 g twice 15 days apart, with or without a further 1-g dose at least 6 months later depending on the clinical response. Gammaglobulins were assayed before each rituximab dose.
  
  
  RESULTS
  The median cumulative rituximab dose was 4 g (1-16) and the median time to retreatment was 8 months (6-16). Rituximab therapy significantly improved the DAS-28 score. The gammaglobulin concentration decreased significantly between the first and last rituximab dose (from 11.6 g/L [5-26] to 8.2 g/L [3-20], a -2.6 g/L difference; P<0.05). The decrease was larger in the 24 patients with cumulative rituximab doses greater than 5 g than in the 41 other patients (difference of -4 vs. -2.7 g/L; P<0.05). Three patients experienced severe infections, two in the high-dose group and one in the other group (P=0.5).
  
  
  CONCLUSIONS
  These data obtained in everyday practice constitute further evidence that rituximab is well-tolerated in patients with RA. Rituximab therapy was associated with a decrease in gammaglobulin concentrations that was greater in patients receiving higher cumulative doses.
authors.affiliation: Service de rhumatologie A, hôpital Cochin, AP-HP, université Paris Descartes, 27, rue du Faubourg-Saint-Jacques, 75014 Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Isvy
authors.forename: Marine
authors.initials: M
authors.lastname: Meunier
authors.forename: Camille
authors.initials: C
authors.lastname: Gobeaux-Chenevier
authors.forename: Emilie
authors.initials: E
authors.lastname: Maury
authors.forename: Julien
authors.initials: J
authors.lastname: Wipff
authors.forename: Chantal
authors.initials: C
authors.lastname: Job-Deslandre
authors.forename: André
authors.initials: A
authors.lastname: Kahan
authors.forename: Yannick
authors.initials: Y
authors.lastname: Allanore
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000009:adverse effects*; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D001424:Bacterial Infections / Q000097:blood / Q000209:etiology / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006304:Health Status; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D011446:Prospective Studies; D000069283:Rituximab; D012720:Severity of Illness Index; D016896:Treatment Outcome; D005719:gamma-Globulins / Q000032:analysis / Q000378:metabolism*
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D005719:gamma-Globulins; D000069283:Rituximab; D008727:Methotrexate