Dimitrios Vassilopoulos1, Evie M Delicha2, Loukas Settas3, Alexandros Andrianakos4, Spyros Aslanidis5, Panagiota Boura6, Marios Katsounaros7, Panagiotis Athanassiou8, Konstantinos Tempos9, Grigorios Skarantavos10, Christodoulos Antoniadis11, Sotirios Papazoglou12, Lazaros Sakkas13, Vassiliki Galanopoulou14, Fotini Skopouli15, Kyriaki Boki16, Dimitrios Daoussis17, Eleni Vritzali18, Petros P Sfikakis19. 1. 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. 2. 1st Department of Propedeutic & Internal Medicine, Laikon Hospital, National and Kapodistrian University of Athens Medical School, Athens, Greece. 3. Rheumatology Unit, AHEPA Hospital, University of Thessaloniki, Thessaloniki, Greece. 4. Hellenic Foundation of Rheumatology, Athens, Greece. 5. 2nd Department of Internal Medicine, Hippokratio Hospital, Thessaloniki, Greece. 6. 2nd Department of Internal Medicine, University of Thessaloniki, Thessaloniki, Greece. 7. 2nd Department of Internal Medicine, Papanikolaou Hospital, Thessaloniki, Greece. 8. Rheumatology Division, St. Paul Hospital, Thessaloniki, Greece. 9. Rheumatology Division, KAT Hospital, Athens, Greece. 10. Rheumatology and Bone Metabolic Diseases Clinic, Attikon Hospital, Athens, Greece. 11. Rheumatology Division, Asclepieion Hospital, Athens, Greece. 12. Rheumatology Division, Georgios Gennimatas General Hospital, Athens, Greece. 13. Rheumatology Division, University Hospital of Thessaly, Larissa, Greece. 14. 1st Internal Medicine Department, Department of Rheumatology, Papageorgiou Hospital, Thessaloniki, Greece. 15. 2nd Department of Internal Medicine, Euroclinic Hospital, Athens, Greece. 16. Rheumatology Clinic, Sismanoglio Hospital, Athens, Greece. 17. Patras University Rheumatology Department, Patra, Greece. 18. Immunology Franchise, Medical Department, Roche Hellas SA, Greece. 19. 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.
Abstract
OBJECTIVES: 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.
OBJECTIVES: 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: A Krause; P M Aries; S Berger; C Fiehn; H Kellner; H-M Lorenz; L Meier; G A Müller; U Müller-Ladner; A Schwarting; H-P Tony; M A Peters; J Wendler Journal: Z Rheumatol Date: 2019-11 Impact factor: 1.372