Peter A Merkel1, John L Niles2, Lester E Mertz3, Patricia B Lehane4, Pooneh Pordeli5, Félix Erblang6. 1. Division of Rheumatology, Department of Medicine, Division of Clinical Epidemiology, Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, PA, USA. 2. Massachusetts General Hospital, Boston, MA, USA. 3. Mayo Clinic, Scottsdale, AZ, USA. 4. Roche Products Limited, Welwyn Garden City, UK. 5. F. Hoffmann-La Roche Ltd, Mississauga, ON, Canada. 6. F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Abstract
OBJECTIVE: A Phase IV, open-label, prospective study was conducted to characterize the long-term safety of rituximab in a 4-year observational registry of adult patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) within the United States. METHODS: Patients initiating treatment with rituximab were evaluated every 6 months for up to 4 years. Outcomes were the incidence of serious adverse events (SAEs), infusion-related reactions (IRRs), and SAEs of specific interest, including serious infections, serious cardiac events, serious vascular events, and malignancies. RESULTS: Overall, 97 patients (72 with GPA and 25 with MPA) received rituximab through a median of 8 (range, 1-28) infusions, and were followed up for a median of 3.94 (range, 0.05-4.32) years. The estimated incidence rates (95% CI) of serious infections, serious cardiac events, and serious vascular events were 7.11 (4.55 to 10.58), 5.03 (2.93 to 8.06) and 2.37 (1.02 to 4.67) per 100 patient-years (PYs), respectively. No IRRs or SAEs occurred within 24 hours of an infusion of rituximab. None of the 9 deaths reported (crude mortality rate, 2.67 [95% CI, 1.22 to 5.06] per 100 PYs) were considered to be related to use of rituximab. CONCLUSION: The safety profile of long-term treatment with rituximab in patients with GPA or MPA was consistent with that of rituximab administered for shorter durations and with rituximab's known safety profile in other autoimmune disease for which it has received regulatory approval. These findings provide clinicians with long-term, practice-level safety data for rituximab in the treatment of GPA or MPA. This article is protected by copyright. All rights reserved.
OBJECTIVE: A Phase IV, open-label, prospective study was conducted to characterize the long-term safety of rituximab in a 4-year observational registry of adult patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) within the United States. METHODS:Patients initiating treatment with rituximab were evaluated every 6 months for up to 4 years. Outcomes were the incidence of serious adverse events (SAEs), infusion-related reactions (IRRs), and SAEs of specific interest, including serious infections, serious cardiac events, serious vascular events, and malignancies. RESULTS: Overall, 97 patients (72 with GPA and 25 with MPA) received rituximab through a median of 8 (range, 1-28) infusions, and were followed up for a median of 3.94 (range, 0.05-4.32) years. The estimated incidence rates (95% CI) of serious infections, serious cardiac events, and serious vascular events were 7.11 (4.55 to 10.58), 5.03 (2.93 to 8.06) and 2.37 (1.02 to 4.67) per 100 patient-years (PYs), respectively. No IRRs or SAEs occurred within 24 hours of an infusion of rituximab. None of the 9 deaths reported (crude mortality rate, 2.67 [95% CI, 1.22 to 5.06] per 100 PYs) were considered to be related to use of rituximab. CONCLUSION: The safety profile of long-term treatment with rituximab in patients with GPA or MPA was consistent with that of rituximab administered for shorter durations and with rituximab's known safety profile in other autoimmune disease for which it has received regulatory approval. These findings provide clinicians with long-term, practice-level safety data for rituximab in the treatment of GPA or MPA. This article is protected by copyright. All rights reserved.