Jens Thiel1, Arianna Troilo1, Ulrich Salzer1, Theresa Schleyer1, Kirsten Halmschlag1, Marta Rizzi1, Natalie Frede1, Ana Venhoff1, Reinhard E Voll1, Nils Venhoff2. 1. Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. 2. Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. Electronic address: nils.venhoff@uniklinik-freiburg.de.
Abstract
BACKGROUND: Rituximab (RTX) is approved for induction therapy of granulomatosis with polyangiitis and microscopic polyangiitis. In eosinophilic granulomatosis with polyangiitis (EGPA), organ-threatening manifestations are mainly treated with cyclophosphamide (CYC). RTX as treatment in EGPA has been described in small case series; however long-term data and the efficacy of RTX in EGPA refractory to CYC have not been reported yet. OBJECTIVES: To investigate the efficacy and safety of RTX and conventional immunosuppressive therapy with CYC in EGPA as induction therapy and during long-term follow-up. METHODS: Retrospective analysis of 28 patients with EGPA was done. Treatment response and disease activity were determined by Birmingham Vasculitis Activity Score, C-reactive protein, eosinophils, antineutrophil cytoplasmic antibody, and peripheral CD19+ B cells. RESULTS: Fourteen patients with EGPA treated with RTX were compared with 14 age- and sex-matched patients with EGPA treated with CYC for remission induction; 64% of the RTX-treated patients with EGPA had previously failed CYC treatment. Disease duration was longer and the number of previous immunosuppressants higher in RTX-treated patients. Five RTX-treated patients (36%) and 4 CYC-treated patients (29%) achieved complete remission. All other patients were in partial remission. There was no difference between both groups in respect to treatment response and partial and complete remission. In both treatment groups, eosinophils, C-reactive protein, and IgE levels dropped. Relapse-free survival within an observation period of 36 months was comparable between RTX- and CYC-treated patients. RTX was well tolerated, but resulted in a decline in serum immunoglobulin levels. CONCLUSIONS: RTX was effective in inducing remission and during long-term follow-up in patients with EGPA, even when previously refractory to standard immunosuppressive therapy including CYC. RTX-treated patients should be monitored for hypogammaglobulinemia.
BACKGROUND:Rituximab (RTX) is approved for induction therapy of granulomatosis with polyangiitis and microscopic polyangiitis. In eosinophilic granulomatosis with polyangiitis (EGPA), organ-threatening manifestations are mainly treated with cyclophosphamide (CYC). RTX as treatment in EGPA has been described in small case series; however long-term data and the efficacy of RTX in EGPA refractory to CYC have not been reported yet. OBJECTIVES: To investigate the efficacy and safety of RTX and conventional immunosuppressive therapy with CYC in EGPA as induction therapy and during long-term follow-up. METHODS: Retrospective analysis of 28 patients with EGPA was done. Treatment response and disease activity were determined by Birmingham Vasculitis Activity Score, C-reactive protein, eosinophils, antineutrophil cytoplasmic antibody, and peripheral CD19+ B cells. RESULTS: Fourteen patients with EGPA treated with RTX were compared with 14 age- and sex-matched patients with EGPA treated with CYC for remission induction; 64% of the RTX-treated patients with EGPA had previously failed CYC treatment. Disease duration was longer and the number of previous immunosuppressants higher in RTX-treated patients. Five RTX-treated patients (36%) and 4 CYC-treated patients (29%) achieved complete remission. All other patients were in partial remission. There was no difference between both groups in respect to treatment response and partial and complete remission. In both treatment groups, eosinophils, C-reactive protein, and IgE levels dropped. Relapse-free survival within an observation period of 36 months was comparable between RTX- and CYC-treated patients. RTX was well tolerated, but resulted in a decline in serum immunoglobulin levels. CONCLUSIONS:RTX was effective in inducing remission and during long-term follow-up in patients with EGPA, even when previously refractory to standard immunosuppressive therapy including CYC. RTX-treated patients should be monitored for hypogammaglobulinemia.
Authors: Zachary M Dong; Edwin Lin; Michael E Wechsler; Peter F Weller; Amy D Klion; Bruce S Bochner; Don A Delker; Mark W Hazel; Keke Fairfax; Paneez Khoury; Praveen Akuthota; Peter A Merkel; Anne-Marie Dyer; Carol Langford; Ulrich Specks; Gerald J Gleich; Vernon M Chinchilli; Benjamin Raby; Mark Yandell; Frederic Clayton Journal: Am J Pathol Date: 2020-04-03 Impact factor: 4.307
Authors: Hans-Hartmut Peter; Hans D Ochs; Charlotte Cunningham-Rundles; Donald C Vinh; Peter Kiessling; Bernhard Greve; Stephen Jolles Journal: J Allergy Clin Immunol Date: 2020-09 Impact factor: 10.793