title: Safety profile of repeated rituximab cycles in unselected rheumatoid arthritis patients: a long-term, prospective real-life study.
abstract: OBJECTIVE
  To evaluate the long-term safety of rituximab (RTX) in rheumatoid arthritis (RA) patients in daily clinical practice.
  
  
  METHODS
  This was a multicentre (17 Greek Rheumatology sites), prospective, long-term, pharmacovigilance study of patients with moderate to severe RA and an inadequate response or intolerance to ≥1 anti-tumour necrosis factor (TNF) agents. Adverse events (AEs) were recorded and collected prospectively every 2-6 months.
  
  
  RESULTS
  234 patients (mean age: 59±12.5, 79.5% women, mean DAS28: 5.35±1.32) were included and followed for 27.7 months (median). The overall AEs, serious AE (SAEs) and serious infection (SIEs) rate were 48.36, 6.68 and 2.53/100 patient-years, respectively. Three cases of hepatitis B virus (HBV) reactivation were recorded (two in chronic and one in past HBV infection). Withdrawals due to AEs (5.6%) occurred more frequently during the first cycles of RTX therapy while repeated RTX cycles were not associated with an increased risk of AEs. There were 3 deaths with an incidence rate of 0.69/100 patient-years. Age ≥65 years was associated with a higher incidence rate ratio of AEs and SAEs as compared to <65 years (1.53, p=0.002 and 2.88, p=0.005, respectively). Drug retention rate during 434.28 patient-years of follow-up was 57.3%. Factors associated with drug discontinuation by multivariate analysis included age, baseline swollen joint count and no use of concomitant methotrexate therapy.
  
  
  CONCLUSIONS
  Long-term RTX therapy in a real-life RA cohort, did not reveal any new safety issues. Advanced age was associated with increased risk of AEs and premature drug discontinuation.
authors.affiliation: 2nd Department of Internal Medicine and Laboratory, Clinical Immunology-Rheumatology Unit, Hippokration General Hospital; and Joint Rheumatology Program, National and Kapodistrian University of Athens Medical School, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Vassilopoulos
authors.affiliation: 1st Department of Propedeutic & Internal Medicine, Laikon Hospital, National and Kapodistrian University of Athens Medical School, Athens, Greece.
authors.forename: Evie M
authors.initials: EM
authors.lastname: Delicha
authors.affiliation: Rheumatology Unit, AHEPA Hospital, University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Loukas
authors.initials: L
authors.lastname: Settas
authors.affiliation: Hellenic Foundation of Rheumatology, Athens, Greece.
authors.forename: Alexandros
authors.initials: A
authors.lastname: Andrianakos
authors.affiliation: 2nd Department of Internal Medicine, Hippokratio Hospital, Thessaloniki, Greece.
authors.forename: Spyros
authors.initials: S
authors.lastname: Aslanidis
authors.affiliation: 2nd Department of Internal Medicine, University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Panagiota
authors.initials: P
authors.lastname: Boura
authors.affiliation: 2nd Department of Internal Medicine, Papanikolaou Hospital, Thessaloniki, Greece.
authors.forename: Marios
authors.initials: M
authors.lastname: Katsounaros
authors.affiliation: Rheumatology Division, St. Paul Hospital, Thessaloniki, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Athanassiou
authors.affiliation: Rheumatology Division, KAT Hospital, Athens, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Tempos
authors.affiliation: Rheumatology and Bone Metabolic Diseases Clinic, Attikon Hospital, Athens, Greece.
authors.forename: Grigorios
authors.initials: G
authors.lastname: Skarantavos
authors.affiliation: Rheumatology Division, Asclepieion Hospital, Athens, Greece.
authors.forename: Christodoulos
authors.initials: C
authors.lastname: Antoniadis
authors.affiliation: Rheumatology Division, Georgios Gennimatas General Hospital, Athens, Greece.
authors.forename: Sotirios
authors.initials: S
authors.lastname: Papazoglou
authors.affiliation: Rheumatology Division, University Hospital of Thessaly, Larissa, Greece.
authors.forename: Lazaros
authors.initials: L
authors.lastname: Sakkas
authors.affiliation: 1st Internal Medicine Department, Department of Rheumatology, Papageorgiou Hospital, Thessaloniki, Greece.
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Galanopoulou
authors.affiliation: 2nd Department of Internal Medicine, Euroclinic Hospital, Athens, Greece.
authors.forename: Fotini
authors.initials: F
authors.lastname: Skopouli
authors.affiliation: Rheumatology Clinic, Sismanoglio Hospital, Athens, Greece.
authors.forename: Kyriaki
authors.initials: K
authors.lastname: Boki
authors.affiliation: Patras University Rheumatology Department, Patra, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Daoussis
authors.affiliation: Immunology Franchise, Medical Department, Roche Hellas SA, Greece.
authors.forename: Eleni
authors.initials: E
authors.lastname: Vritzali
authors.affiliation: Joint Rheumatology Program, National and Kapodistrian University of Athens Medical School; and 1st Department of Propedeutic & Internal Medicine, Laikon Hospital, National and Kapodistrian University of Athens Medical School, Greece.
authors.forename: Petros P
authors.initials: PP
authors.lastname: Sfikakis
mesh_terms: D000367:Age Factors; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006115:Greece; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060735:Pharmacovigilance; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D000069283:Rituximab / Q000008:administration & dosage* / Q000009:adverse effects; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D000069283:Rituximab